FIBRO*

Endocrine. 2003 Oct;22(1):67-76.

Fibromyalgia: symptom constellation and potential therapeutic options.

Shuer ML. Mood & Menopause Clinic, P.O. Box 462223, Escondido, CA 92046-2223, USA. MLShuer@ispwest.com

Fibromyalgia (FM) is a disease entity consisting of a heterogeneous cluster of symptoms that has thus far eluded identification of a causative etiology. The disease onset appears to follow physiological and/or psychological stressors and involves a subset of symptoms that are consistent with varied disorders found in multiple medical specialties to include rheumatology, immunology, endocrinology, neurology, and psychiatry. Owing to the heterogeneity of the symptom complex and the heretofore absence of serum markers that might serve as concrete diagnostic criteria, this disease has baffled clinicians and basic scientists alike. Recent findings regarding sleep architecture, immunology, and endocrinology have provided clues that may help in the understanding and resultant treatment of this entity.

Women with fibromyalgia tend to present with an alpha-delta sleep anomaly, which when treated with a growth hormone secretagogue (GHS), reduces the rheumatological pain and restores slow-wave sleep architecture. These findings suggest the somatotrophic axis may be involved in the etiology and the treatment of this disorder. Those diagnosed with FM respond to various stressors with increased disruption of their physiological homeostasis. When compared to healthy age-matched cohorts, there are quantitative differences in various neuroactive steroid levels, immunological markers, and feedback mechanisms. The varied physiological alterations in patients diagnosed with fibromyalgia when compared to controls will be discussed along with the potential treatment options for this population.

Anesth Analg. 2003 Dec;97(6):1730-9.

Ketamine in chronic pain management: an evidence-based review.

Hocking G, Cousins MJ. Pain Management and Research Centre, University of Sydney, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia.

Ketamine has diverse effects that may be of relevance to chronic pain including: N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, gamma-aminobutyric acid(A) receptors; inhibition of voltage gated Na(+) and K(+) channels and serotonin, dopamine re-uptake. Ketamine has been in clinical practice for over 30 yr; however, there has been little formal research on the effectiveness of ketamine for chronic pain management. In this review we evaluate the available clinical data as a basis for defining the potential use of ketamine for chronic pain. Literature referenced in this review was obtained from a computer search of EMBASE and MEDLINE from 1966 through August, 2002. Search terms included ketamine, ketalar, pain, painful, analgesic, and analgesia. Abstracts were screened for relevance and publications relating to chronic pain use were obtained. Levels of evidence were stratified according to accepted guidelines (level I-IV). For central pain, there is level II and level IV evidence of efficacy for parenteral and oral ketamine. For complex regional pain syndromes, there is only level IV evidence of efficacy of epidural ketamine. For fibromyalgia, there is level II evidence of pain relief, reduced tenderness at trigger points, and increased endurance. For ischemic pain, a level II study reported a potent dose-dependent analgesic effect, but with a narrow therapeutic window. For nonspecific neuropathic pain, level II and level IV studies reported divergent results with questionable long-term effects on pain. For phantom limb pain and postherpetic neuralgia, level II and level II studies provided objective evidence of reduced hyperpathia and pain relief was usually substantial either after parenteral or oral ketamine. Acute on chronic episodes of severe neuropathic pain represented the most frequent use of ketamine as a "third line analgesic," often by IV or subcutaneous infusion (level IV). In conclusion, the evidence for efficacy of ketamine for treatment of chronic pain is moderate to weak. However, in situations where standard analgesic options have failed ketamine is a reasonable "third line" option. Further controlled studies are needed.

Curr Pain Headache Rep. 2003 Dec;7(6):433-42.

Evaluation of treatments for myofascial pain syndrome and fibromyalgia.

Rudin NJ. nj.rudin@hosp.wisc.edu

Myofascial pain syndrome (MPS) and fibromyalgia (FM) are complex conditions and pose significant challenges to clinicians and patients. This chapter explores available treatments for MPS and FM in the context of pathophysiology, clinical evidence, and experimental support. This information may prove to be helpful in designing individualized treatment for patients with these complex syndromes. New treatments should be critically and carefully evaluated as they appear.

Curr Pain Headache Rep. 2003 Dec;7(6):426-32.

Hypersensitivity in muscle pain syndromes.

Henriksson KG. karl-g@telia.com

The aim of this review is to present research that has a bearing on the pathogenesis of hypersensitivity in muscle pain syndromes. Allodynia and hyperalgesia in these syndromes can be segmental or generalized and temporary or permanent. Hypersensitivity in muscle pain conditions in the clinic is best diagnosed by determining the pressure pain threshold. In a disorder such as fibromyalgia, decreased pain thresholds also are found at sites where there is no tenderness. Pathogenetic mechanisms for allodynia and hyperalgesia can be identified at several levels of the nociceptive system, from the nociceptors in the muscle to the cortex. Central sensitization of nociceptive neurons in the dorsal horn and a disturbed balance between inhibitory and facilitatory impulses in the descending tracts from the brain stem to the dorsal horn are the main mechanisms for pain hypersensitivity. Changes in function, biochemical make-up, and synaptic connections in the nociceptive neurons in the dorsal horn are considered to be caused by neuronal plasticity.

Orthop Nurs. 2003 Sep-Oct;22(5):353-60. Related Articles, Links

Effects of T'ai Chi exercise on fibromyalgia symptoms and health-related quality of life.

Taggart HM, Arslanian CL, Bae S, Singh K. Armstrong Atlantic State University, Savannah, GA, USA.

BACKGROUND: Fibromyalgia (FM), one of the most common musculoskeletal disorders, is associated with high levels of impaired health and inadequate or limited symptom relief. The cause of this complex syndrome is unknown, and there is no known cure. Numerous research results indicate that a combination of physical exercise and mind-body therapy is effective in symptom management. T'ai Chi, an ancient Chinese exercise, combines physical exercise with mindbody therapy. PURPOSE: To investigate the effects of T'ai Chi exercise on FM symptoms and health-related quality of life. DESIGN: Pilot study, one group pre-to-post posttest design. METHODS: Participants with FM (n = 39) formed a single group for 6 weeks of 1-hour, twice weekly T'ai Chi exercise classes. FM symptoms and health-related quality of life were measured before and after exercise. FINDINGS: Twenty-one participants completed at least 10 of the 12 exercise sessions. Although the dropout rate was higher than expected, measurements on both the Fibromyalgia Impact Questionnaire (FIQ) (Buckhardt, Clark, & Bennett, 1991) and the Short Form-36 (SE-36) (Ware & Sherbourne, 1992) revealed statistically significant improvement in symptom management and health-related quality of life. IMPLICATIONS FOR NURSING RESEARCH: Knowledge of interventions to enhance health for the patient with musculoskeletal problems is a National Association of Orthopaedic Nurses priority. Tai Chi is potentially beneficial to patients with FM. Further research is needed to support evidence-based practice.

Ann Pharmacother. 2003 Nov;37(11):1561-5.

Venlafaxine treatment of fibromyalgia.

Sayar K, Aksu G, Ak I, Tosun M. mkemalsayar@superonline.com

BACKGROUND: Although the pathophysiology of fibromyalgia is unknown, central monoaminergic transmission may play a role. Antidepressants have proved to be successful in alleviating symptoms of fibromyalgia. Medications that act on multiple neurotransmitters may be more effective in symptom management. OBJECTIVE: To assess the efficacy of venlafaxine, a potent inhibitor of both norepinephrine and serotonin reuptake, in the treatment of patients with fibromyalgia. METHODS: Fifteen patients with fibromyalgia were assessed prior to and after treatment with fixed-dose venlafaxine 75 mg/d. Before initiation of pharmacotherapy, patients were interviewed with the Structured Clinical Interview for Axis I disorders in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The study lasted for 12 weeks, and patients were evaluated in weeks 6 and 12. The primary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ) total score and pain score. The anxiety and depression levels of the patients were measured with the Beck Depression, the Beck Anxiety, the Hamilton Anxiety, and the Hamilton Depression scales. RESULTS: There was a significant improvement in the mean intensity of pain (F = 14.3; p = 0.0001) and in the disability caused by fibromyalgia (F = 42.7; p = 0.0001) from baseline to week 12 of treatment. The depression and anxiety scores also decreased significantly from baseline to week 12. The improvement in the FIQ scores did not correlate with the decrease of scores in both patient- and physician-rated depression and anxiety inventories. Change in pain scores also was not correlated with the change in depression and anxiety scores. CONCLUSIONS: Venlafaxine was quite promising in alleviating the pain and disability associated with fibromyalgia. This effect seems to be independent of its anxiolytic and antidepressant properties. Blockade of both norepinephrine and serotonin reuptake might be more effective than blockade of either neurotransmitter alone in the treatment of fibromyalgia.

J Med Virol. 2003 Dec;71(4):540-7.

Detection of enterovirus in human skeletal muscle from patients with chronic inflammatory muscle disease or fibromyalgia and healthy subjects.

Douche-Aourik F, Berlier W, Feasson L, Bourlet T, Harrath R, Omar S, Grattard F, Denis C, Pozzetto B.

Enterovirus RNA has been found previously in specimens of muscle biopsy from patients with idiopathic dilated cardiomyopathy, chronic inflammatory muscle diseases, and fibromyalgia or chronic fatigue syndrome (fibromyalgia/chronic fatigue syndrome). These results suggest that skeletal muscle may host enteroviral persistent infection. To test this hypothesis, we investigated by reverse transcription-polymerase chain reaction (RT-PCR) assay the presence of enterovirus in skeletal muscle of patients with chronic inflammatory muscle diseases or fibromyalgia/chronic fatigue syndrome, and also of healthy subjects. Three of 15 (20%) patients with chronic inflammatory muscle diseases, 4 of 30 (13%) patients with fibromyalgia/chronic fatigue syndrome, and none of 29 healthy subjects was found positive. The presence of VP-1 enteroviral capsid protein was assessed by an immunostaining technique using the 5-D8/1 monoclonal antibody; no biopsy muscle from any patient or healthy subject was found positive. The presence of viral RNA in some muscle biopsies from patients exhibiting muscle disease, together with the absence of VP-1 protein, is in favor of a persistent infection involving defective viral replication.

J ECT. 2003 Dec;19(4):226-9.

Electroconvulsive therapy in complex regional pain syndromes.

McDaniel WW. Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, USA. mcdaniww@evms.edu

Three cases are presented in which electroconvulsive therapy (ECT) for depression led to the relief of comorbid complex regional pain syndrome as well as depression. In one of the cases, concomitant fibromyalgia was not relieved during 2 separate series of ECT. The literature regarding the role of ECT in the management of chronic pain is reviewed and discussed in light of recent findings about ECT and changes in neurotransmission associated with seizures.

Best Pract Res Clin Rheumatol. 2003 Aug;17(4):667-83.

Complementary and alternative medicine in fibromyalgia and related syndromes.

Holdcraft LC, Assefi N, Buchwald D. holdcraf@u.washington.edu

Complementary and alternative medicine (CAM) has gained increasing popularity, particularly among individuals with fibromyalgia syndrome (FMS) for which traditional medicine has generally been ineffective. A systematic review of randomized controlled trials (RCTs) and non-RCTs on CAM studies for FMS was conducted to evaluate the empirical evidence for their effectiveness. Few RCTs achieved high scores on the CONSORT, a standardized evaluation of the quality of methodology reporting. Acupuncture, some herbal and nutritional supplements (magnesium, SAMe) and massage therapy have the best evidence for effectiveness with FMS. Other CAM therapies have either been evaluated in only one RCT with positive results (Chlorella, biofeedback, relaxation), in multiple RCTs with mixed results (magnet therapies), or have positive results from studies with methodological flaws (homeopathy, botanical oils, balneotherapy, anthocyanidins, dietary modifications). Lastly, other CAM therapies have neither well-designed studies nor positive results and are not currently recommended for FMS treatment (chiropractic care).

J Rheumatol. 2003 Oct;30(10):2257-62.

The efficacy of mindfulness meditation plus Qigong movement therapy in the treatment of fibromyalgia: a randomized controlled trial.

Astin JA, Berman BM, Bausell B, Lee WL, Hochberg M, Forys KL. jastin@cooper.cpmc.org

OBJECTIVE: To test the short and longterm benefits of an 8 week mind-body intervention that combined training in mindfulness meditation with Qigong movement therapy for individuals with fibromyalgia syndrome (FM). METHODS: A total of 128 individuals with FM were randomly assigned to the mind-body training program or an education support group that served as the control. Outcome measures were pain, disability (Fibromyalgia Impact Questionnaire), depression, myalgic score (number and severity of tender points), 6 minute walk time, and coping strategies, which were assessed at baseline and at 8, 16, and 24 weeks. RESULTS: Both groups registered statistically significant improvements across time for the Fibromyalgia Impact Questionnaire, Total Myalgic Score, Pain, and Depression, and no improvement in the number of feet traversed in the 6 minute walk. However, there was no difference in either the rate or magnitude of these changes between the mind-body training group and the education control group. Salutary changes occurring by the eighth week (which corresponded to the end of the mind-body and education control group sessions) were largely maintained by both groups throughout the 6 month followup period. CONCLUSION: While both groups showed improvement on a number of outcome variables, there was no evidence that the multimodal mind-body intervention for FM was superior to education and support as a treatment option. Additional randomized controlled trials are needed before interventions of this kind can be recommended for treatment of FM.

Arthritis Rheum. 2003 Oct;48(10):2916-22.

Subgrouping of fibromyalgia patients on the basis of pressure-pain thresholds and psychological factors.

Giesecke T, Williams DA, Harris RE, Cupps TR, Tian X, Tian TX, Gracely RH, Clauw DJ. University of Michigan, Ann Arbor, USA.

OBJECTIVE: Although the American College of Rheumatology (ACR) criteria for fibromyalgia are used to identify individuals with both widespread pain and tenderness, individuals who meet these criteria are not a homogeneous group. Patients differ in their accompanying clinical symptoms, as well as in the relative contributions of biologic, psychological, and cognitive factors to their symptom expression. Therefore, it seems useful to identify subsets of fibromyalgia patients on the basis of which of these factors are present. Previous attempts at identifying subsets have been based solely on psychological and cognitive features. In this study, we attempt to identify patient subsets by incorporating these features as well as the degree of hyperalgesia/tenderness, which is a key neurobiologic feature of this illness. METHODS: Ninety-seven individuals meeting the ACR criteria for fibromyalgia finished the same battery of self-report and evoked-pain testing. Analyzed variables were obtained from several domains, consisting of 1) mood (evaluated by the Center for Epidemiologic Studies Depression Scale [for depression] and the State-Trait Personality Inventory [for symptoms of trait-related anxiety]), 2) cognition (by the catastrophizing and control of pain subscales of the Coping Strategies Questionnaire), and 3) hyperalgesia/tenderness (by dolorimetry and random pressure-pain applied at suprathreshold values). Cluster analytic procedures were used to distinguish subgroups of fibromyalgia patients based on these domains. RESULTS: Three clusters best fit the data. Multivariate analysis of variance (ANOVA) confirmed that each variable was differentiated by the cluster solution (Wilks' lambda [degrees of freedom 6,89] = 0.123, P < 0.0001), with univariate ANOVAs also indicating significant differences (all P < 0.05). One subgroup of patients (n = 50) was characterized by moderate mood ratings, moderate levels of catastrophizing and perceived control over pain, and low levels of tenderness. A second subgroup (n = 31) displayed significantly elevated values on the mood assessments, the highest values on the catastrophizing subscale, the lowest values for perceived control over pain, and high levels of tenderness. The third group (n = 16) had normal mood ratings, very low levels of catastrophizing, and the highest level of perceived control over pain, but these subjects showed extreme tenderness on evoked-pain testing. CONCLUSION: These data help support the clinical impression that there are distinct subgroups of patients with fibromyalgia. There appears to be a group of fibromyalgia patients who exhibit extreme tenderness but lack any associated psychological/cognitive factors, an intermediate group who display moderate tenderness and have normal mood, and a group in whom mood and cognitive factors may be significantly influencing the symptom report.

Pain. 2003 Oct;105(3):385-6.

Hyperalgesia versus response bias in fibromyalgia.

Fillingim RB. These results extend a large body of work demonstrating that FM is characterized by generalized hyperalgesia. The vestiges of Cartesian dualism remain evident as scientists and clinicians debate whether these findings should be attributed to neurobiological mechanisms or psychological influences. Petzke et al. (2003) provide a helpful redefinition of this issue by addressing whether enhanced pain responses in FM patients are explained by psychological influences on ‘ reporting’ Their sophisticated psychophysics revealed that psychological factors, such as expectancy or hypervigilance, do not explain the greater pain responding by FM patients. Does this imply that psychological factors are unimportant in the hyperalgesia of FM patients? In answering this question, it is important to recognize that in addition to their impact on pain reporting, psychological factors also alter pain responses through direct effects on nociceptive processing. For example, abundant literature on placebo responses indicates that expectations of imminent pain relief produce an endogenous opioid-mediated reduction in pain (Benedetti and Amanzio, 1997). Also, distraction reduces pain reporting in humans, and several studies in behaving monkeys have demonstrated that attentional redirection decreased activity in both spinal and thalamic nociceptive neurons (Villemure and Bushnell, 2002). This distinction between psychological influences on responding versus pain processing often goes unnoticed. Petzke et al. (2003) demonstrated no group differences in the impact of psychological factors specifically on pain reporting; however, group differences in nociceptive processing were observed and psychological factors may well have contributed to these differences. Indeed, the authors point this out in the last paragraph of the paper. Thus, an important implication of these findings is that any contribution of psychological factors to altered pain sensitivity in FM patients may be due to direct effects on nociceptive processing rather than to influences on pain reporting behavior.

The findings of Petzke et al. (2003) further indicate that individuals with FM process nociceptive information differently than controls. There are inevitably multiple biopsychosocial factors that interact in complex ways to produce these alterations in pain sensitivity. The results of their research suggest that measures of pain sensitivity that are freer of response bias still demonstrate enhanced pain responses in FM. The mechanisms underlying the enhanced pain responses of FM patients remain to be determined, but the careful and systematic research described by Petzke et al. (2003) informs us that the enhanced pain sensitivity in FM is not an artifact of response bias. A more thorough understanding of the hyperalgesia observed in FM will help elucidate its pathophysiology, ultimately leading to more effective diagnosis and treatment of this complex and disabling syndrome.

**Pain. 2003 Oct;105(3):403-13.

Increased pain sensitivity in fibromyalgia: effects of stimulus type and mode of presentation.

Petzke F, Clauw DJ, Ambrose K, Khine A, Gracely RH.

Fibromyalgia (FM) is defined in part by sensitivity to blunt pressure. Pressure pain sensitivity in FM is evaluated typically by the use of 'ascending' testing methods such as tender point counts or dolorimetry, which can be influenced by response bias of both the subject and examiner. Methods that present stimuli in a random, unpredictable fashion might minimize the influence of these factors. In this study, we compared the results of ascending and random assessments of both pressure and thermal pain sensitivities in 43 FM patients and 28 age- and gender-matched controls. Even though FM is defined on the basis of pressure sensitivity, this group was also more sensitive to heat stimuli, presented in either ascending or random paradigms. In both the patient and control groups, the pain ratings to painful sensations evoked by both thermal and pressure stimuli were significantly greater in the random, compared with the ascending method. The number of subjects classified as 'expectant' because they rated pain higher in ascending than random paradigms was similar for FM and control groups. Both patients and controls exhibited a similar degree of sensitization to pressure and thermal stimuli. The increased sensitivity to both pressure and thermal stimuli for threshold and suprathreshold stimuli in FM patients is consistent with central augmentation of pain processing.

Expert Opin Pharmacother. 2003 Oct;4(10):1687-95.

Current trends in fibromyalgia research.

Marcus DA. Pain Evaluation & Treatment Institute, 5750 Centre Avenue, Pittsburgh, PA 15206, USA. dawnpainmd@yahoo.com

The development of standardised criteria for the diagnosis of fibromyalgia in 1990 has allowed careful study of this chronically painful syndrome. Epidemiological studies show increased symptoms and disability in patients with fibromyalgia, compared with other conditions associated with chronic, widespread pain. In addition, prevalence and severity of fibromyalgia symptoms are increased in women. Current studies have identified strong evidence for central sensitisation in fibromyalgia. Data from these studies may expand effective treatment options for fibromyalgia.

J Hand Surg [Am]. 2003 Nov;28(6):894-7.

Diagnosis of compressive neuropathies in patients with fibromyalgia.

Dellon AL, Shookster LA, Maloney CT Jr, Ducic I. Division of Plastic Surgery and Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, USA

The hand surgeon relies on the Tinel sign in the physical examination of the patient suspected of having a peripheral nerve entrapment. Fibromyalgia is recognized by the American College of Rheumatology as a condition characterized by having tender points on physical examination. This article reviews the location of the 9 bilateral critical diagnostic fibromyalgia points as they relate to known sites of anatomic entrapment of peripheral nerves in the upper extremity. The interpretation of this article is that the Tinel sign may be used with validity to identify the site of a peripheral nerve compression in the upper extremity in the patient with fibromyalgia.

Yonsei Med J. 2003 Aug 30;44(4):619-22. Related Articles, Links

The role of tendinitis in fibromyalgia syndrome.

Genc H, Saracoglu M, Duyur B, Erdem HR. hakangenc06@hotmail.com

Fibromyalgia Syndrome (FS) is a common disease characterized by diffuse, widespread pain and multiple tender points. The syndrome has been subclassified as primary (PFS) and secondary (SFS) fibromyalgia. The aim of this study was to evaluate the role of common tendinitis (rotator cuff tendinitis, bicipital tendinitis, lateral epicondylitis, De-Quervain's tendinitis and pes anserinus tendinitis) in FS. Twenty female patients with PFS, 20 with SFS and 20 female controls, matched by age and body mass index, participated in the study. Existence of common tendinitis was evaluated with specific examination methods. Right and left rotator cuff tendinitis, pes anserinus tendinitis and left lateral epicondylitis were significantly more common in patients with PFS and SFS than in control subjects. As a result, considering the central hyperexcitability present in the fibromyalgia patients, concomitant pathologies such as tendinitis which lead to shoulder, arm, and leg pain must be evaluated. Follow up and therapy for the disease must be planned according to these factors which are not only probable symptoms of FS, but also leading causes for the occurrence and continuity of the pain in this disease.

Brain. 2004 Apr;127(Pt 4):835-43. Epub 2004 Feb 11.

Pain catastrophizing and neural responses to pain among persons with fibromyalgia.

Gracely RH, Geisser ME, Giesecke T, Grant MA, Petzke F, Williams DA, Clauw DJ. dclauw@med.umich.edu

Pain catastrophizing, or characterizations of pain as awful, horrible and unbearable, is increasingly being recognized as an important factor in the experience of pain. The purpose of this investigation was to examine the association between catastrophizing, as measured by the Coping Strategies Questionnaire Catastrophizing Subscale, and brain responses to blunt pressure assessed by functional MRI among 29 subjects with fibromyalgia. Since catastrophizing has been suggested to augment pain perception through enhanced attention to painful stimuli, and heightened emotional responses to pain, we hypothesized that catastrophizing would be positively associated with activation in structures believed to be involved in these aspects of pain processing. As catastrophizing is also strongly associated with depression, the influence of depressive symptomatology was statistically removed. Residual scores of catastrophizing controlling for depressive symptomatology were significantly associated with increased activity in the ipsilateral claustrum (r = 0.51, P < 0.05), cerebellum (r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.47, P < 0.05), and parietal cortex (r = 0.41, P < 0.05), and in the contralateral dorsal anterior cingulate gyrus (ACC; r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.41, P < 0.05), medial frontal cortex (r = 0.40, P < 0.05) and lentiform nuclei (r = 0.40, P < 0.05). Analysis of subjects classified as high or low catastrophizers, based on a median split of residual catastrophizing scores, showed that both groups displayed significant increases in ipsilateral secondary somatosensory cortex (SII), although the magnitude of activation was twice as large among high catastrophizers. Both groups also had significant activations in contralateral insula, SII, primary somatosensory cortex (SI), inferior parietal lobule and thalamus. High catastrophizers displayed unique activation in the contralateral anterior ACC, and the contralateral and ipsilateral lentiform. Both groups also displayed significant ipsilateral activation in SI, anterior and posterior cerebellum, posterior cingulate gyrus, and superior and inferior frontal gyrus. These findings suggest that pain catastrophizing, independent of the influence of depression, is significantly associated with increased activity in brain areas related to anticipation of pain (medial frontal cortex, cerebellum), attention to pain (dorsal ACC, dorsolateral prefrontal cortex), emotional aspects of pain (claustrum, closely connected to amygdala) and motor control. These results support the hypothesis that catastrophizing influences pain perception through altering attention and anticipation, and heightening emotional responses to pain. Activation associated with catastrophizing in motor areas of the brain may reflect expressive responses to pain that are associated with greater pain catastrophizing.

Adv Nurse Pract. 2003 Nov;11(11):34-8, 41-3.

Evidence-based management of the fibromyalgia patient. In search of optimal functioning.

Wassem RA, Stillion-Allen KA. University of Utah College of Nursing, Salt Lake City, USA.

Theor Med Bioeth. 2003;24(4):345-54.

Signification and pain: a semiotic reading of fibromyalgia.

Quintner J, Buchanan D, Cohen M, Taylor A. quintner@aceonline.com.au

Patients with persistent pain who lack a detectable underlying disease challenge the theories supporting much of biomedical body-mind discourse. In this context, diagnostic labeling is as inherently vulnerable to the same pitfalls of uncertainty that beset any other interpretative endeavour. The end point is often no more than a name rather than the discovered essence of a pre-existent medical condition. In 1990 a Committee of the American College of Rheumatology (ACR) formulated the construct of Fibromyalgia in an attempt to rectify a situation of diagnostic confusion faced by patients presenting with widespread pain. It was proposed that Fibromyalgia existed as a "specific entity", separable from but curiously able to co-exist with any other painful condition. Epistemological and semiotic analyses of Fibromyalgia have failed to find any sign, clinical or linguistic, which could differentiate it from other diffuse musculoskeletal pain states. The construct of Fibromyalgia sought to define a discernable reality outside the play of language and to pass it off as a natural phenomenon. However, because it has failed both clinically and semiotically, the construct also fails the test of medical utility for the subject in persistent pain.

Health Psychol. 2003 Nov;22(6):592-7.

Biological and psychological factors associated with memory function in fibromyalgia syndrome.

Sephton SE, Studts JL, Hoover K, Weissbecker I, Lynch G, Ho I, McGuffin S, Salmon P. sephton@louisville.edu

Fibromyalgia is a stress-related disorder characterized by chronic pain, memory impairment, and neuroendocrine aberrations. With the hypothesis that biological and psychological symptoms may underlie the cognitive problems, the relative influences of neuroendocrine function and psychological factors on declarative memory were examined among 50 women with fibromyalgia. This within-group analysis controlled for age, education, pain, and relevant medications. Neuroendocrine function and depression had significant independent associations with memory function. Higher log-transformed mean salivary cortisol levels were associated with better performance on both immediate and delayed visual recall and with delayed verbal recall. Depressive symptoms were negatively associated with verbal recall. These findings suggest that a basic disorder of endocrine stress responses may contribute to the cognitive symptoms experienced by fibromyalgia patients.

Rheumatology, In Press

Does psychological vulnerability determine health-care utilization in fibromyalgia?

P. L. Dobkin, M. De Civita, S. Bernatsky, H. Kang, and M. Baron; patricia.dobkin@mcgill.ca.

Objectives. Patients with fibromyalgia (FM) undergo multiple testing and referral to specialists, and often use complementary/alternative medicine (CAM) services. The objectives of the study were: (i) to document health service utilization, and (ii) to examine whether psychological vulnerability was associated with visits to physicians and CAM providers. Methods. Women (N = 178) with a diagnosis of primary FM completed a psychosocial test measuring pain, perceived stress, global psychological distress, sexual abuse history, co-morbidity and disability due to FM. Subjects also completed a health services questionnaire, documenting visits to physicians and CAM providers during the previous 6 months.

Psychological vulnerability was operationalized as obtaining high scores on psychological distress, perceived stress and reporting at least one abusive event. Results. The average number of visits was 7.2 to physicians and 11.3 to CAM providers. Conclusions. The number of physician visits was significantly associated with more co-morbidity. Psychologically vulnerable subjects were more likely to use CAM services than those not so classified.

Curr Pain Headache Rep. 2003 Oct;7(5):362-8. Related Articles, Links

Epidemiology of fibromyalgia.

Neumann L, Buskila D. Department of Epidemiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. lily@bgumail.bgu.ac.il

Chronic widespread pain, the cardinal symptom of fibromyalgia (FM), is common in the general population, with comparable prevalence rates of 7.3% to 12.9% across different countries. The prevalence of FM in the general population was reported to range from 0.5% to 5% and up to 15.7% in the clinic. The common association of FM with other rheumatic disorders, chronic viral infections, and systemic illnesses has been well documented in several studies. Up to 65% of patients with systemic lupus erythematosus meet the criteria for FM. FM is considered a member of the family of functional somatic syndromes. These syndromes are very common and share a similar phenomenology, epidemiologic characteristics, high rates of occurrence, a common pathogenesis, and similar management strategies. A high prevalence of FM was demonstrated among relatives of patients with FM and it may be attributed to genetic and environmental factors.

Central Sensitization in Fibromyalgia and Other Musculoskeletal Disorders

Lars Arendt-Nielsen PhD and Thomas Graven-Nielsen PhD Laboratory for Human Experimental Pain Research, Fredrik Bajers Vej 7 Building D3, Center for -Sensory-Motor Interaction Aalborg University, Aalborg, DK-9220, Denmark Current Pain and Headache Reports 2003 7:355-361 (published 1 October 2003)

Muscle hyperalgesia and referred pain play an important role in chronic musculoskeletal pain. New knowledge on the involved basic mechanisms and better methods to assess muscle pain in the clinic are needed to revise and optimize treatment regimens. Increased muscle sensitivity is manifested as pain evoked by a normally non-nociceptive stimulus (allodynia), increased pain intensity evoked by nociceptive stimuli (hyperalgesia), or increased referred pain areas with associated somatosensory changes. Some manifestations of sensitization, such as expanded referred muscle pain areas in patients with chronic musculoskeletal pain, can be explained from animal experiments showing extrasegmental spread of sensitization. An important part of the pain manifestations (eg, tenderness and referred pain) related to chronic musculoskeletal disorders may result from peripheral and central sensitization, which may play a role in the transition from acute to chronic pain.

Schmerz. 2003 Dec;17(6):459-63. [What is different about muscle pain?] [Article in German]

Mense S. mense@urz.uni-heidelberg.de

BACKGROUND: The bulk of available knowledge about pain mechanisms is derived from studies on cutaneous pain. However, deep somatic pain (from muscle, fascia, tendon, joint) is clinically of much greater importance. The existing subjective differences between muscle and skin pain (e.g. muscle pain is poorly localized and shows referral) suggest that muscle and skin pain do not share the same mechanisms. AIMS OF THE STUDY: To answer the question if the nociceptive information from muscle has neuroanatomical connections and mechanisms that are distinct from those of cutaneous nociception. MATERIALS AND METHODS: The results were obtained partly in animal experiments on anaesthetised rats, partly in studies with healthy subjects or fibromyalgia patients. RESULTS: 1. At the spinal level, the excitatory effects of unmyelinated afferent fibres from muscle are subject to a strong segmental inhibition by myelinated afferent fibres, which is largely absent in the effects of cutaneous C fibres. 2. At the cortical level, experimental muscle pain excites other regions than does cutaneous pain. 3. At the level of descending pain-modulating pathways, interruption of the activity in these pathways leads to higher activity of nociceptive neurones caudal to the site of interruption. The activity was higher in neurones with input from deep nociceptors than in cells mediating cutaneous nociception. CONCLUSIONS: The data demonstrate that at all central nervous levels the connections and processing of nociceptive information from muscle and skin are different. The findings regarding descending pain-modulating pathways suggest that a dysfunction of this system could lead to chronic deep pain as in fibromyalgia.

Schmerz. 2003 Dec;17(6):464-74.

[Diagnosis and clinical signs of fibromyalgia] [Article in German]

Conrad I. conrad.ingomar@mh-hannover.de

According to the criteria of the American College of Rheumatology (ACR 1990) fibromyalgia can be classified as a complex of clinical symptoms. It is characterised by widespread muscle pain, and pain in at least 11 out of 18 defined so-called tender points. The widespread muscle pain must be present for at least 3 months. For the diagnosis of fibromyalgia many other rheumatological, neurological and psychiatric diseases have to be excluded; additional autonomic or functional symptoms are usual. Routine laboratory or radiological examinations yield normal results. From a pathogenetic point of view endocrine disturbances and psychosocial stress factors are found. In most cases the clinical course shows a slow development of generalised pain.

Rev Enferm. 2003 Oct;26(10):24-32. [Fibromyalgia, or whole body pain] [Article in Spanish] Ortega Fernandez JA, Poza Vacas BM, Ortiz Jimenez MA, Marin Moreno ME. Psicologia Clinica, USM Alzira, Valencia.

Fibromyalgia is a rheumatic syndrome which is being recognized and diagnosed more often all the time. Its symptoms include a general state of pain not localized in the joints, combined with tremendous tiredness and sleep alterations. Although its exact etiology is still unknown, medical professionals speculate on the existence of multiple cause factors.

Therefore, an integrated therapeutic treatment having the coordinated participation of medical professionals from different fields of expertise is necessary. Mental health professionals play an important role since it is proven the existence of psychological and socio-psychological factors at the start, during the duration of and in the evolution of this syndrome.

J Negat Results Biomed. 2003 Aug 23;2(1):4.

Prospective Epidemiological Observations on the Course of the Disease in Fibromyalgia Patients.

Noller V, Sprott H. Switzerland. haiko.sprott@usz.ch

OBJECTIVES: The aim of the study was to carry out a survey in patients with fibromyalgia (FM), to examine their general health status and work incapacity (disabilitypension status), and their views on the effectiveness of therapy received, over a two-year observation period. METHODS: 48 patients diagnosed with FM, according to the American College of Rheumatology (ACR) criteria, took part in the study. At baseline, and on average two years later, the patients underwent clinical investigation (dolorimetry, laboratory diagnostics, medical history taking) and completed the Fibromyalgia questionnaire (Dettmer and Chrostek 1). RESULTS: 27/48 (56%) patients participated in the two-year follow-up. In general, the patients showed no improvement in their symptoms over the observation period, regardless of the type of therapy they had received. General satisfaction with quality of life improved, as did satisfaction regarding health status and the family situation, although the degree of pain experienced remain unchanged. In comparison with the initial examination, there was no change in either work-capacity or disability-pension status. CONCLUSIONS: The FM patients showed no improvement in pain, despite the many various treatments received over the two-year period. The increase in general satisfaction over the observation period was believed to be the result of patient instruction and education about the disease. To what extent a population of patients with FM would show similar outcomes if they did not receive any instruction/education about their disorder, cannot be ascertained from the present study; and, indeed, the undertaking of a study to investigate this would be ethically questionable. As present, no conclusions can be made regarding the influence of therapy on the primary and secondary costs associated with FM.

Fibromyalgia, Hepatitis C Infection, and the Cytokine Connection

Mollie E Thompson MD and André Barkhuizen MD Current Pain and Headache Reports 2003 7:342-347

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints. This review discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years; increased gp130, which is a neutrophil cytokine transducing protein; increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and IL-1 ß, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia. In addition, this review describes the mechanism by which alterations in

cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and theinfluence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively. The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.

Pain. 2003 Aug;104(3):665-72.

The effect of combined therapy (ultrasound and interferential current) on pain and sleep in fibromyalgia.

Almeida TF, Roizenblatt S, Benedito-Silva AA, Tufik S.

Multidisciplinary treatment has proven to be the best therapeutic option to fibromyalgia (FM) and physiotherapy has an important role in this approach. Considering the controversial results of electrotherapy in this condition, the aim of this study was to assess the effects of combined therapy with pulsed ultrasound and interferential current (CTPI) on pain and sleep in FM. Seventeen patients fulfilling FM criteria were divided into two groups, CTPI and SHAM, and submitted to pain and sleep evaluations. Pain was evaluated by body map (BM) of the painful areas; quantification of pain intensity by visual analog scale (VAS); tender point (TP) count and tenderness threshold (TT). Sleep was assessed by inventory and polysomnography (PSG). After 12 sessions of CTPI or SHAM procedure, patients were evaluated by the same initial protocol. After treatment, CTPI group showed, before and after sleep, subjective improvement of pain in terms of number (BM) and intensity (VAS) of painful areas (P<0.001, both); as well as objective improvement, with decrease in TP count and increase in TT (P<0.001, both). Subjective sleep improvements observed after CTPI treatment included decrease in morning fatigue and in non-refreshing sleep complaint (P<0.001, both). Objectively, PSG in this group showed decrease in sleep latency (P<0.001) and in the percentage of stage 1 (P<0.001), increase in the percentage of slow wave sleep (P<0.001) and in sleep cycle count (P<0.001). Decrease in arousal index (P<0.001), number of sleep stage changes (P<0.05) and wake time after sleep onset (P<0.05), were also observed and no difference regarding pain or sleep parameters were verified after SHAM procedure. This study shows that CTPI can be an effective therapeutic approach for pain and sleep manifestations in FM.

J Affect Disord. 2003 Jun;75(1):77-82.

Altered dopamine D2 receptor function in fibromyalgia patients: a neuroendocrine study with buspirone in women with fibromyalgia compared to female population based controls.

Malt EA, Olafsson S, Aakvaag A, Lund A, Ursin H. eva.albertson@psych.uib.no BACKGROUND: To what extent fibromyalgia belongs to affective spectrum disorders or anxiety spectrum disorders remains disputed. Buspirone induces a hypothermic response, which most likely is due to 5-HT(1A) autoreceptor stimulation, and growth hormone (GH) release, which probably is related to postsynaptic 5-HT(1A) receptor stimulation. The prolactin response to buspirone has been suggested to be mediated through dopamine (DA) antagonistic effects. OBJECTIVES: Based on the assumption that fibromyalgia is more strongly related to stress and anxiety than affective spectrum disorders, we hypothesized that compared to population controls, fibromyalgia patients should demonstrate an increased prolactin response (DA sensitivity) to buspirone challenge test, but no difference in hypothermic response or GH release (5HT sensitivity). METHOD: A 60-mg dose of buspirone was given orally to 22 premenopausal women with fibromyalgia and 14 age and sex matched healthy control subjects. Core body temperature, growth hormone and prolactin levels were analyzed at baseline and after 60, 90, and 150 min. RESULTS: Fibromyalgia patients showed an augmented prolactin response to buspirone compared to controls. Temperature and growth hormone responses did not differ from controls. CONCLUSIONS: Dopaminergic rather than serotonergic neurotransmission is altered in fibromyalgia, suggesting increased sensitivity or density of dopamine D(2) receptors in fibromyalgia patients. Stress and anxiety is an important modulator of dopaminergic neurotransmission. Our results suggest that fibromyalgia is related to anxiety and associated with disturbance in the stress response systems.

Neuroreport. 2003 Mar 24;14(4):619-21.

Retrosplenial cortical activation in the fibromyalgia syndrome.

Wik G, Fischer H, Bragee B, Kristianson M, Fredrikson M. gustav.wik@psyk.uib.no

To study the CNS in chronic muscular pain typical of fibromyalgia we compared PET measures of regional cerebral blood flow (rCBF) in eight fibromyalgic patients and controls at rest. Higher rCBF for patients than controls was found bilaterally in the retrosplenial cortex. Lower rCBF for patients than controls were seen in the left frontal, temporal, parietal, and occipital cortices. The higher retroplenial rCBF in patients than controls may reflect increased attention towards sub-noxious somatosensory signaling, and agrees with the notion that fibromyalgic pain reflects secondary hyperalgesia. The brain regions with lower rCBF in fibromyalgic patients than controls participate in the normal cognitive processing of pain, which may be dysfunctional in fibromyalgia.

***CES Treatment Efficacy STUDIES (Several...)

Eur J Pain. 2004;8(2):163-71.

Peripheral effects of needle stimulation (acupuncture) on skin and muscle blood flow in fibromyalgia.

Sandberg M, Lindberg LG, Gerdle B.

Acupuncture has become a widely used treatment modality in various musculoskeletal pain conditions. Acupuncture is also shown to enhance blood flow and recovery in surgical flaps. The mechanisms behind the effect on blood flow were suggested to rely on vasoactive substances, such as calcitonin gene-related peptide, released from nociceptors by the needle stimulation. In a previous study on healthy subjects, one needle stimulation into the anterior tibial muscle was shown to increase both skin and muscle blood flow. The aim of this study was to examine the effect of needle stimulation on local blood flow in the anterior tibial muscle and overlying skin in patients suffering from a widespread chronic pain condition. Fifteen patients with fibromyalgia (FM) participated in the study. Two modes of needling, deep muscle stimulation and subcutaneous needle insertion were performed at the upper anterior aspect of the

tibia, i.e., in an area without focal pathology or ongoing pain in these patients. Blood flow changes were assessed non-invasively by photoplethysmography (PPG). The results of the present study were partly similar to those earlier found at a corresponding site in healthy female subjects, i.e., deep muscle stimulation resulted in larger increase in skin blood flow (mean (SE)): 62.4% (13.0) and muscle blood flow: 93.1% (18.6), compared to baseline, than did subcutaneous insertion (mean (SE) skin blood flow increase: 26.4% (6.2); muscle blood flow increase: 46.1% (10.2)). However, in FM patients subcutaneous needle insertion was followed by a significant increase in both skin and muscle blood flow, in contrast to findings in healthy subjects where no significant blood flow increase was found following the subcutaneous needling. The different results of subcutaneous needling between the groups (skin blood flow: [Formula: see text]; muscle blood flow: [Formula: see text] ) may be related to a greater sensitivity to pain and other somatosensory input in FM.

J Endocrinol Invest. 2004 Jan;27(1):42-6.

Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome.

Calis M, Gokce C, Ates F, Ulker S, Izgi HB, Demir H, Kirnap M, Sofuoglu S, Durak AC, Tutus A, Kelestimur F.

Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system, fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6 nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/- 26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than overactivated.

Minerva Med. 2004 Feb;95(1):35-52.

Fibromyalgia: state of the art.

Fietta P. Rheumatic Disease and Internal Medicine Unit, Osteo-Articular Department, Hospital of Parma, Parma, Italy.

Fibromyalgia (FM) is a common and complex condition, defined as long lasting, widespread musculoskeletal pain, in the presence of tender points (TPs) at specific anatomical sites. Dysautonomic and functional symptoms, such as orthostatic hypotension, tachycardia, effort intolerance, marked fatigue, sleep disorders, cognitive disturbances, psychological distress, paresthesias, headache, genitourinary manifestations, irritable bowel syndrome and bladder dyskinesia, frequently occur. The etiopathogenesis of FM is presently unknown, but nociceptor, autonomic and neuro-endocrine system dysfunctions have been found in patients. Since specific serological or instrumental markers of the syndrome are not yet identifiable, TP search is the only useful diagnostic hallmark. The development of an effective therapy of FM has hitherto been hampered by the incomplete knowledge of its pathogenic mechanisms. In this paper, the most recent information on FM is reviewed.

Psychother Psychosom Med Psychol. 2004 Mar;54(3-4):137-47.

[Fibromyalgia as a dysfunction of the central pain and stress response] [Article in German]

Egle UT, Ecker-Egle ML, Nickel R, Van Houdenhove B. egle@psychosomatik.klinik.uni-mainz.de Fibromyalgia is often understood as a syndrome mainly characterised by widespread pain and tenderness and "unexplained" etiology and pathogenesis. In the last years evidence is growing that biological as well as psychosocial stress play a pathogenetic key-role. Beginning with the general function and development of the stress response system the actual knowledge of its relationship with central pain-processing mechanisms is reviewed. Early adverse childhood experiences can impair the function of the stress system all over the lifespan. Subsequently, research evidence for the role of stress in the etiopathogenesis of fibromyalgia is summarised. Psychological as well as psychobiological consequences are outlined. Finally, an integrative model of fibromyalgia is proposed, which may put several pieces of a biopsychosocial puzzle together. This model offers an approach for the differentiation of subgroups and a clinical orientation for developing an adequate therapy for the individual patient.

Arthritis Rheum. 2004 Mar;50(3):944-52.

Family study of fibromyalgia.

Arnold LM, Hudson JI, Hess EV, Ware AE, Fritz DA, Auchenbach MB, Starck LO, Keck PE Jr. Lesley.Arnold@uc.edu

OBJECTIVE: To assess for familial aggregation of fibromyalgia (FM) and measures of tenderness and pain, and for familial coaggregation of FM and major mood disorder (major depressive disorder or bipolar disorder). METHODS: Probands meeting the American College of Rheumatology criteria for FM and control probands with rheumatoid arthritis (RA) and no lifetime diagnosis of FM were recruited from consecutive referrals to 2 community-based rheumatology practices. Probands were ages 40-55 years and had at least 1 first-degree relative age 18 years or older who was available for interview and examination. All probands and interviewed relatives underwent a dolorimeter tender point examination and a structured clinical interview. Interviewed relatives were asked about first-degree relatives who were not available for interview, using a structured family interview. Logistic and linear regression models, adjusting for the correlation of observation within families, were applied to study the aggregation and coaggregation effects. RESULTS: Information was collected for 533 relatives of 78 probands with FM and 272 relatives of 40 probands with RA. FM aggregated strongly in families: the odds ratio (OR) measuring the odds of FM in a relative of a proband with FM versus the odds of FM in a relative of a proband with RA was 8.5 (95% confidence interval [95% CI] 2.8-26, P = 0.0002). The number of tender points was significantly higher, and the total myalgic score was significantly lower in the relatives of probands with FM compared with the relatives of probands with RA. FM coaggregated significantly with major mood disorder: the OR measuring the odds of major mood disorder in a relative of a proband with FM versus the odds of major mood disorder in a relative of a proband with RA was 1.8 (95% CI 1.1-2.9, P = 0.013). CONCLUSION: FM and reduced pressure pain thresholds aggregate in families, and FM coaggregates with major mood disorder in families. These findings have important clinical and theoretical implications, including the possibility that genetic factors are involved in the etiology of FM and in pain sensitivity. In addition, mood disorders and FM may share some of these inherited factors.

Ann Rheum Dis. 2004 Apr;63(4):450-452.

A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing.

Pimentel M, Wallace D, Hallegua D, Chow E, Kong Y, Park S, Lin HC.

BACKGROUND: An association between irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) has been found. OBJECTIVE: To compare the prevalence and test results for bacterial overgrowth between IBS and fibromyalgia. METHODS: Subjects with independent fibromyalgia and IBS were compared with controls in a double blind study. Participants completed a questionnaire, and a lactulose hydrogen breath test was used to determine the presence of SIBO. The prevalence of an abnormal breath test was compared between study participants. Hydrogen production on the breath test was compared between subjects with IBS and fibromyalgia. The somatic pain visual analogue score of subjects with fibromyalgia was compared with their degree of hydrogen production. RESULTS: 3/15 (20%) controls had an abnormal breath test compared with 93/111 (84%) subjects with IBS (p<0.01) and 42/42 (100%) with fibromyalgia (p<0.0001 v controls, p<0.05 v IBS). Subjects with fibromyalgia had higher hydrogen profiles (p<0.01), peak hydrogen (p<0.0001), and area under the curve (p<0.01) than subjects with IBS. This was not dependent on the higher prevalence of an abnormal breath test. The degree of somatic pain in fibromyalgia correlated significantly with the hydrogen level seen on the breath test (r = 0.42, p<0.01). CONCLUSIONS: An abnormal lactulose breath test is more common in fibromyalgia than IBS. In contrast with IBS, the degree of abnormality on breath test is greater in subjects with fibromyalgia and correlates with somatic pain.

J Psychosom Res. 2004 Feb;56(2):185-8.

Psychological aspects of fibromyalgia; Research vs. clinician impressions.

Sansone RA, Levengood JV, Sellbom M. Department of Internal Medicine, Kettering Medical Center, Kettering, OH, USA.

Objective: This study was designed to compare the psychological features of patients with fibromyalgia, as described in the research literature, with physicians' clinical impressions. Method: Using a survey method, physicians (n=44) and physicians-in-training (n=54) were polled regarding their clinical impressions of 18 psychological features, culled from the research literature, which are attributed to fibromyalgia patients. Results: Over 90% of respondents reported that fatigue, muscle tension, pain proneness, depression and anxiety were clinically associated with fibromyalgia patients "frequently" or "very frequently." The majority of respondents (52%) endorsed 10 of 18 items as occurring "frequently" or "very frequently." Conclusions: Physicians and physicians-in-training appear to observe in fibromyalgia patients over half of the psychological features identified in the research literature. For the remainder of items, we discuss possible explanations for the disparity.

Pain Med. 2004 Mar;5(1):33-41.

Comorbidity of fibromyalgia and posttraumatic stress disorder symptoms in a community sample of women.

Raphael KG, Janal MN, Nayak S.

OBJECTIVE: To test alternative explanations for the comorbidity between fibromyalgia (FM), a medically unexplained syndrome involving widespread pain, and posttraumatic stress disorder (PTSD). In contrast to a default "risk factor" hypothesis, tested hypotheses were that: A) The association is due to a sampling bias introduced by the study of care-seeking individuals; B) FM is an additive burden that strains coping resources when confronting life stress; and C) Arousal symptoms of PTSD and FM are confounded. DESIGN: Community-dwelling women in the New York/New Jersey metropolitan area (N=1,312) completed a telephone survey regarding FM-like symptoms prior to September 11, 2001. Approximately 6 months after the World Trade Center terrorist attacks, they again completed the survey, to which questions regarding PTSD symptoms were added. RESULTS: The odds of probable PTSD were more than three times greater in women with FM-like symptoms, both assessed after 9/11. The odds ratio was not reduced by controlling for FM-like symptoms before 9/11 or for the potentially confounded symptoms of PTSD specifically related to arousal. CONCLUSIONS: These findings lead us to reject alternate explanations for the comorbidity between FM and PTSD. Speculations that FM and PTSD share psychobiological risk factors remain plausible.

Psychol Med. 2004 Feb;34(2):363-8.

Post-traumatic stress disorder among patients with chronic pain and chronic fatigue.

Roy-Byrne P, Smith WR, Goldberg J, Afari N, Buchwald D. Department of Psychiatry and Behavioral Science, University of Washington, Seattle, WA, USA.

BACKGROUND: Fibromyalgia (FM), a chronic pain condition of unknown aetiology often develops following a traumatic event. FM has been associated with post-traumatic stress disorder (PTSD) and major depression disorder (MDD). METHOD: Patients seen in a referral clinic (N=571) were evaluated for FM and chronic fatigue syndrome (CFS) criteria. Patients completed questionnaires, and underwent a physical examination and a structured psychiatric evaluation. Critical components of the diagnostic criteria of FM (tender points and diffuse pain) and CFS (persistent debilitating fatigue and four of eight associated symptoms) were examined

for their relationship with PTSD. RESULTS: The prevalence of lifetime PTSD was 20% and lifetime MDD was 42%. Patients who had both tender points and diffuse pain had a higher prevalence of PTSD (OR=3.4, 95% CI 2.0-5.8) compared with those who had neither of these FM criteria. Stratification by MDD and adjustment for sociodemographic factors and chronic fatigue revealed that the association of PTSD with FM criteria was confined to those with MDD. Patients with MDD who met both components of the FM criteria had a threefold increase in the prevalence of PTSD (95% CI 1.5-7.1); conversely, FM patients without MDD showed no increase in PTSD (OR=1.3, 95% CI 0.5-3.2). The components of the CFS criteria were not significantly associated with PTSD. CONCLUSION: Optimal clinical care for patients with FM should include an assessment of trauma in general, and PTSD in particular. This study highlights the importance of considering co-morbid MDD as an effect modifier in analyses that explore PTSD in patients with FM.

J Rheumatol. 2004 Mar;31(3):598-600.

Clues to pathogenesis of fibromyalgia in patients with sickle cell disease.

Schlesinger N. schlesna@umdnj.edu

OBJECTIVE: To investigate the association between sickle cell disease (SCD) and fibromyalgia (FM). METHODS: Nine patients with SCD for whom a rheumatology consult was requested were assessed for FM by retrospective chart review. Eleven inpatients with other forms of anemia referred for rheumatology consult were also assessed for FM. RESULTS: Eight of 9 patients with SCD fulfilled classification criteria for FM compared to one of 11 patients without SCD (p < 0.001). CONCLUSION: Awareness of the high frequency of FM in SCD can improve treatment of sickle cell crisis. Some pain that is labeled as sickle cell crisis pain may be due to FM, and may improve with tender point injections.

Rheumatol Int. 2004 Feb 21 [Epub ahead of print]

Auditory event-related brain potentials in fibromyalgia syndrome.

Alanoglu E, Ulas UH, Ozdag F, Odabasi Z, Cakci A, Vural O. Physical Therapy and Rehabilitation Department, Social Security Hospital of Ankara, Diskapi, Ankara, Turkey.

OBJECTIVE. The aim of this study was to investigate cognitive functions using auditory event-related brain potentials (ERP) in fibromyalgia syndrome (FMS). METHODS. The P300 component of ERP was studied in 36 female FMS patients and 22 control subjects. The short form 36 (SF-36) medical outcome study was used to determine quality of life. Number of tender points and disease duration were noted. Cognitive functions were evaluated with P300. RESULTS. The symptoms were discrepant in FMS ( P<0.001). The scores of the eight SF-36 subgroups in FMS patients were significantly lower than in the control group ( P<0.001). Fibromyalgia syndrome patients had prolonged latency and reduced amplitude of P300 ( P<0.001). No correlation was found between the subgroups of SF-36, tender point count, disease duration, and P300. CONCLUSION. The results of our study reveal that FMS affects quality of life and dysfunction in cognitive abilities can be determined by brain event-related potentials.

Med Hypotheses. 2004 Mar;62(3):420-4.

Stress and dopamine: implications for the pathophysiology of chronic widespread pain.

Wood PB. Department of Family Medicine, LSU Health Science Center - Shreveport, 1501 Kings Highway Shreveport, LA 71103, USA.

Fibromyalgia has been called a "stress-related disorder" due to the onset and exacerbation of symptoms in the context of stressful events. Evidence suggests that inhibition of tonic pain is mediated by activation of mesolimbic dopamine neurons, arising from the cell bodies of the ventral tegmental area and projecting to the nucleus accumbens. This pain-suppression system is activated by acute stress, via the release of endogenous opioids and substance P within the ventral tegmental area. However, prolonged exposure to unavoidable stress produces both reduction of dopamine output in the nucleus accumbens and development of persistent hyperalgesia. It is proposed that a stress-related reduction of dopaminergic tone within the nucleus accumbens contributes to the development of hyperalgesia in the context of chronic stress and thus plays a role in the pathogenesis of fibromyalgia. A stress-related dysfunction of mesolimbic dopaminergic activity might serve as the basis for other fibromyalgia-associated phenomena as well.

Ann Rheum Dis. 2004 Mar;63(3):290-6.

Fibromyalgia: a randomised, controlled trial of a treatment programme based on self management.

Cedraschi C, Desmeules J, Rapiti E, Baumgartner E, Cohen P, Finckh A, Allaz AF, Vischer TL. Christine.Cedraschi@hcuge.ch

OBJECTIVE: To evaluate the efficacy of a treatment programme for patients with fibromyalgia (FM) based on self management, using pool exercises and education. METHODS: Randomised controlled trial with a 6 month follow up to evaluate an outpatient multidisciplinary programme; 164 patients with FM were allocated to an immediate 6 week programme (n = 84) or to a waiting list control group (n = 80). The main outcomes were changes in quality of life, functional consequences, patient satisfaction and pain, using a combination of patient questionnaires and clinical examinations. The questionnaires included the Fibromyalgia Impact Questionnaire (FIQ), Psychological General Well-Being (PGWB) index, regional pain score diagrams, and patient satisfaction measures. RESULTS: 61 participants in the treatment group and 68 controls completed the programme and 6 month follow up examinations. Six months after programme completion, significant improvements in quality of life and functional consequences of FM were seen in the treatment group as compared with the controls and as measured by scores on both the FIQ (total score p = 0.025; fatigue p = 0.003; depression p = 0.031) and PGWB (total score p = 0.032; anxiety p = 0.011; vitality p = 0.013,). All four major areas of patient satisfaction showed greater improvement in the treatment than the control groups; between-group differences were statistically significant for "control of symptoms", "psychosocial factors", and "physical therapy" No change in pain was seen. CONCLUSION: A 6 week self management based programme of pool exercises and education can improve the quality of life of patients with FM and their satisfaction with treatment. These improvements are sustained for at least 6 months after programme completion.

Ann Rheum Dis. 2004 Mar;63(3):245-51.

Increased DNA fragmentation and ultrastructural changes in fibromyalgic muscle fibres.

Sprott H, Salemi S, Gay RE, Bradley LA, Alarcon GS, Oh SJ, Michel BA, Gay S. haiko.sprott@usz.ch

OBJECTIVE: To determine whether there is evidence of increased DNA fragmentation and ultrastructural changes in muscle tissue of patients with fibromyalgia (FM) compared with healthy controls. METHODS: Muscle tissues from 10 community residents with FM and 10 age and sex matched healthy controls were examined "blindly" for the presence of DNA fragmentation by two different methods: terminal deoxynucleotidyl transferase (TdT) staining (TUNEL) and the FragEL-Klenow DNA fragmentation detection kit. Ultrastructural analysis of tissue was performed by electron microscopy. RESULTS: DNA fragmentation was detected by both methods in 55.4 (SEM 2.5)% of the nuclei in muscle tissue of patients with FM compared with 16.1 (4.1)% (p<0.001) of the nuclei in healthy controls. Contrary to expectation, no typical features of apoptosis could be detected by electron microscopy. The myofibres and actin filaments were disorganised and lipofuscin bodies were seen; glycogen and lipid accumulation were also found. The number of mitochondria was significantly lower in patients with FM than in controls and seemed to be morphologically altered. CONCLUSION: The ultrastructural changes described suggest that patients with FM are characterised by abnormalities in muscle tissue that include increased DNA fragmentation and changes in the number and size of mitochondria. These cellular changes are not signs of apoptosis. Persistent focal contractions in muscle may contribute to ultrastructural tissue abnormalities as well as to the induction and/or chronicity of nociceptive transmission from muscle to the central nervous system.

Arthritis Rheum. 2004 Feb 15;51(1):9-13.

Treatment of fibromyalgia with cyclobenzaprine: A meta-analysis.

Tofferi JK, Jackson JL, O'Malley PG.

OBJECTIVE: To systematically review the effectiveness of cyclobenzaprine in the treatment of fibromyalgia. METHODS: Articles describing randomized, placebo-controlled trials of cyclobenzaprine in people with fibromyalgia were obtained from Medline, EMBase, Psyclit, the Cochrane Library, and Federal Research in Progress Database. Unpublished literature and bibliographies were also reviewed. Outcomes, including global improvement, treatment effects on pain, fatigue, sleep, and tender points over time, were abstracted. RESULTS: Five randomized, placebo-controlled trials were identified. The odds ratio for global improvement with therapy was 3.0 (95% confidence interval [95% CI] 1.6-5.6) with a pooled risk difference of

0.21 (95% CI 0.09-0.34), which calculates to 4.8 (95% CI 3.0-11) individuals needing treatment for 1 patient to experience symptom improvement. Pain improved early on, but there was no improvement in fatigue or tender points at any time. CONCLUSION: Cyclobenzaprine-treated patients were 3 times as likely to report overall improvement and to report moderate reductions in individual symptoms, particularly sleep.

Curr Opin Rheumatol. 2004 Mar;16(2):157-63.

Fibromyalgia pain: do we know the source?

Staud R. staudr@ufl.edu

PURPOSE OF REVIEW: Fibromyalgia Syndrome (FMS) is a chronic pain condition of unknown origin. Multiple abnormalities have been described, including peripheral tissue and central nervous system changes. The relation of these mechanisms, however, is likely bidirectional. FMS pain clearly depends on peripheral nociceptive input as well as abnormal central pain processing. This review will focus on the role of peripheral nociceptive input for pain in FMS. RECENT FINDINGS: There is strong evidence for abnormal central pain processing in FMS. Sensitized spinal cord neurons in the dorsal horn are responsible for augmented pain processing of nociceptive signals from the periphery. In addition, glial activation, possibly by cytokines and excitatory amino acids may play a role in the initiation and perpetuation of this sensitized state. SUMMARY: Nociceptive input clearly plays an important role in FMS. Acute or repetitive tissue injury has been associated with FMS pain. Cytokines related to such injuries may be responsible for long-term activation of spinal cord glia and dorsal horn neurons, thus resulting in central sensitization. A better understanding of these important neuro-immune interactions may provide relevant insights into future effective therapies.

J Rheumatol. 2004 Feb;31(2):379-89.

Aspects of diurnal rhythmicity in pain, stiffness, and fatigue in patients with fibromyalgia.

Bellamy N, Sothern RB, Campbell J. Faculty of Health Sciences, The University of Queensland, Brisbane, Australia.

OBJECTIVE: To determine diurnal rhythm characteristics of pain, stiffness, and fatigue in self-ratings performed by patients with fibromyalgia (FM). METHODS: Twenty-one women with FM made self-measurements of pain, stiffness, and fatigue on 100 mm horizontal visual analog scales at 6 prespecified timepoints at home for 10 consecutive days. Linear and multiple regressions were performed on the original data and the 24-hour means vs FM classifiers (age, disease duration, tender points, dolorimetry score, Fibromyalgia Impact Questionnaire score), respectively. Data were analyzed for 24-hour and 7-day time-effects by ANOVA and for diurnal and weekly rhythms by the cosinor technique. RESULTS: Individual ratings for pain, stiffness, and fatigue correlated highly with each other throughout the day and over the days of the week. Of the FM classifiers, dolorimetry score was found to be inversely related to the pain, stiffness, and fatigue scores. For the group of subjects with a low dolorimetry score (< 2.25 kg), a significant diurnal rhythm was found in each self-rated variable, with greater pain, stiffness, and fatigue observed in the morning and least in the late afternoon. No rhythm in pain or stiffness was observed in those subjects with a higher threshold for pain (dolorimetry score > 2.25 kg), while fatigue showed the same significant diurnal pattern as in the first group. For the group as a whole, the possible presence of a weekly variation was found with ratings for pain, stiffness, and fatigue higher on Sunday and Monday and lower on Friday. CONCLUSION: Ratings of pain, stiffness, and fatigue in FM are significantly correlated, and show diurnal and possibly weekly rhythmicity, especially when pain threshold is low (dolorimetry score < 2.25 kg), and are thus predictive of each other over these time spans. This has important implications for scheduling activities of daily living, for measurement in clinical trials, and possibly for timing the administration of medications.

J Rheumatol. 2004 Feb;31(2):364-78.

Functional imaging of pain in patients with primary fibromyalgia.

Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH. cookdb@njneuromed.org

OBJECTIVE: To examine the function of the nociceptive system in patients with fibromyalgia (FM) using functional magnetic resonance imaging (fMRI). METHODS: Two groups of women, 9 with FM and 9 pain-free, volunteered to participate. In Experiment 1, we assessed psychophysical responses to painful stimuli and prepared participants for fMRI testing. For Experiment 2, subjects underwent fMRI scanning while receiving painful and nonpainful heat stimuli. Conventional and functional MR images were acquired using a 1.5 T MR scanner. Scanning occurred over 5 conditions. Condition 1 served as a practice session (no stimuli). Conditions 2 and 5 consisted of nonpainful warm stimuli. Conditions 3 and 4 consisted of an absolute thermal pain stimulus (47 degrees C) and a perceptually equivalent pain stimulus delivered in counterbalanced order. RESULTS: Experiment 1 indicated that subjects with FM were significantly more sensitive to experimental heat pain than controls (p < 0.001). In Experiment 2, fMRI data indicated that the FM group exhibited greater activity than controls over multiple brain regions in response to both nonpainful and painful stimuli (p < 0.01). Specifically, in response to nonpainful warm stimuli, FM subjects had significantly greater activity than controls in prefrontal, supplemental motor, insular, and anterior cingulate cortices (p < 0.01). In response to painful stimuli, FM subjects had greater activity in the contralateral insular cortex (p < 0.01). Data from the practice session indicated brain activity in pain-relevant areas for the FM group but not for controls. CONCLUSION: Our results provide further evidence for a physiological explanation for FM pain.

Rheumatology (Oxford). 2004 Jan 20

Improved clinical status in fibromyalgia patients treated with individualized homeopathic remedies versus placebo.

Bell IR, Lewis II DA, Brooks AJ, Schwartz GE, Lewis SE, Walsh BT, Baldwin CM.

OBJECTIVE: To assess the efficacy of individualized classical homeopathy in the treatment of fibromyalgia. METHODS: This study was a double-blind, randomized, parallel-group, placebo-controlled trial of homeopathy. Community-recruited persons (N = 62) with physician-confirmed fibromyalgia (mean age 49 yr, s.d. 10 yr, 94% women) were treated in a homeopathic private practice setting. Participants were randomized to receive oral daily liquid LM (1/50 000) potencies with an individually chosen homeopathic remedy or an indistinguishable placebo. Homeopathic visits involved joint interviews and concurrence on remedy selection by two experienced homeopaths, at baseline, 2 months and 4 months (prior to a subsequent optional crossover phase of the study which is reported elsewhere). Tender point count and tender point pain on examination by a medical assessor uninvolved in providing care, self-rating scales on fibromyalgia-related quality of life, pain, mood and global health at baseline and 3 months, were the primary clinical outcome measures for this report. RESULTS: Fifty-three people completed the treatment protocol. Participants on active treatment showed significantly greater improvements in tender point count and tender point pain, quality of life, global health and a trend toward less depression compared with those on placebo. CONCLUSIONS: This study replicates and extends a previous 1-month placebo-controlled crossover study in

fibromyalgia that pre-screened for only one homeopathic remedy. Using a broad selection of remedies and the flexible LM dose (1/50 000 dilution factor) series, the present study demonstrated that individualized homeopathy is significantly better than placebo in lessening tender point pain and improving the quality of life and global health of persons with fibromyalgia.

Pain. 2004 Jan;107(1-2):7-15.

Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia.

Banic B, Petersen-Felix S, Andersen OK, Radanov BP, Villiger PM, Arendt-Nielsen L, Curatolo

M.

Patients with chronic pain after whiplash injury and fibromyalgia patients display exaggerated pain after sensory stimulation. Because evident tissue damage is usually lacking, this exaggerated pain perception could be explained by hyperexcitability of the central nervous system. The nociceptive withdrawal reflex (a spinal reflex) may be used to study the excitability state of spinal cord neurons. We tested the hypothesis that patients with chronic whiplash pain and fibromyalgia display facilitated withdrawal reflex and therefore spinal cord hypersensitivity. Three groups were studied: whiplash (n=27), fibromyalgia (n=22) and healthy controls (n=29). Two types of transcutaneous electrical stimulation of the sural nerve were applied: single stimulus and five repeated stimuli at 2 Hz. Electromyography was recorded from the biceps femoris muscle. The main outcome measurement was the minimum current intensity eliciting a spinal reflex (reflex threshold). Reflex thresholds were significantly lower in the whiplash compared with the control group, after both single (P=0.024) and repeated (P=0.035) stimulation. The same was observed for the fibromyalgia group, after both stimulation modalities (P=0.001 and 0.046, respectively). We provide evidence for spinal cord hyperexcitability in patients with chronic pain after whiplash injury and in fibromyalgia patients. This can cause exaggerated pain following low intensity nociceptive or innocuous peripheral stimulation. Spinal hypersensitivity may explain, at least in part, pain in the absence of detectable tissue damage.

Rheumatol Int. 2003 Dec 20

Free radicals and antioxidants in primary fibromyalgia: an oxidative stress disorder?

Bagis S, Tamer L, Sahin G, Bilgin R, Guler H, Ercan B, Erdogan C.

The role of free radicals in fibromyalgia is controversial. In this study, 85 female patients with primary fibromyalgia and 80 age-, height-, and weight-matched healthy women were evaluated for oxidant/antioxidant balance. Malondialdehyde is a toxic metabolite of lipid peroxidation used as a marker of free radical damage. Superoxide dismutase is an intracellular antioxidant enzyme and shows antioxidant capacity. Pain was assessed by visual analog scale. Tender points were assessed by palpation. Age, smoking, body mass index (BMI), and duration of disease were also recorded. Malondialdehyde levels were significantly higher and superoxide dismutase levels significantly lower in fibromyalgic patients than controls. Age, BMI, smoking, and duration of disease did not affect these parameters. We found no correlation between pain and number of tender points. In conclusion, oxidant/antioxidant balances were changed in fibromyalgia. Increased free radical levels may be responsible for the development of

fibromyalgia. These findings may support the hypothesis of fibromyalgia as an oxidative disorder.

Schmerz. 2003 Dec;17(6):399-404.

[Psychosomatic aspects in the diagnosis and treatment of fibromyalgia]

[Article in German] Blumenstiel K, Eich W. Abteilung fur Allgemeine Klinische und Psychosomatische Medizin, Medizinische Klaus_Blumenstiel@med.uni-heidelberg.de

The fibromyalgia syndrome (FMS) is a chronic pain condition of the musculoskeletal system defined by criteria of the American College of Rheumatology in 1990. Despite this definition, etiology and pathogenesis of FMS are still unknown, and consequently the therapy aims mainly at relieving symptoms. The favourite hypothesis is a multietiological concept including genetic, central nervous, muscular, and psychological issues. This article focuses on current psychological aspects as to etiology, process of chronification, and therapy of FMS. Regarding etiology there are diverging hypotheses rather than a general agreement, e.g. specific personality traits, traumatic events, psychodynamic explanations on the basis of a depressive conflict, or the subsumption under somatoform disorders. However, psychological aspects are evident to influence the course and treatment of FMS. In the chronification process behavioural aspects like avoidance behaviour with subsequent physical impairment, attitudes towards subjective theories of illness and therapeutic options, social factors like effects on work, interpersonal conditioning, and coping strategies play an important role. Therapeutic options of FMS comprise exercise, drugs, and psychotherapy. An integrated approach combining these options, a sustainable doctor-patient relationship, and a continuous support of the patient seem to be beneficial.

Schmerz. 2003 Dec;17(6):437-40. [What's new in the therapy of fibromyalgia?] [Article in German] Spath M. Friedrich-Baur-Institut, Ludwig-Maximilians-Universitat Munchen. michael.spaeth@lrz.uni- muenchen.de

Modern management of fibromyalgia (FM) requires a holistic approach, which includes nonpharmacologic strategies (both exercise and behavioral strategies) and pharmacologic treatment. Despite only partial effects in some patients, tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal antiinflammatory drugs, analgesics and opioids are in use. The use of antiepileptic drugs and antispasticity agents is mainly supported by anecdotal data. Three other classes of agents are currently thought to have useful potentials. N-methyl-D-aspartate-(NMDA-)mediated neurotransmission may play an important role in mediating windup and related phenomena in pain pathways. Recent studies have demonstrated that NMDA receptor antagonists improve pain symptoms in FM. But a poor side effect profile represents a significant problem. Cerebrospinal fluid substance P concentrations are significantly elevated in FM patients, but the analgesic potential of neurokinin-1 (NK1) receptor antagonists did not meet early expectations. Tropisetron, a 5-HT3 receptor antagonist, was tested in a multicenter, double-blind, randomized, placebo-controlled trial including 403 patients. In those receiving 5 mg tropisetron, 39.2% fulfilled the response criterion (pain reduction 35%) as compared to 26.2% in the placebo group (p=0.033). On 10 and 15 mg, the responder rates were smaller and statistically not significant. A total of 78 responders to therapy were followed up for 12 months. After the end of treatment, pain intensity rose within one month in all 4 groups. Patients having received 5 or 10 mg showed a less pronounced increase in pain. In addition, even 12 months after stopping treatment, pain was still markedly below baseline levels in the 5 and 10 mg groups.

 

Gerson, A. and Fox, D. (2003).

Fibromyalgia revisited: Axis II factors in MMPI and historical Data in compensation claimants.

American Journal of Forensic Psychology, 21(3), 21-25.

The current study examined differences between 20 fibromyalgia (FIBRO) and 22 chronic pain (PAIN), litigating, women by comparing history of trauma, previous psychiatric treatment, and personality variables as measured by the MMPI-2. After exclusion of protocols with questionable validity, mean T scores on scales Hy and Hs were significantly higher for the FIBRO group, suggesting greater somatic preoccupation. Scores on MMPI-2 personality disorder scales did not significantly differentiate the two groups but there was a high rate of one or more elevations on these scales in both groups. The FIBRO patients had a higher rate of previous psychiatric treatment but not a higher incidence of being a victim of physical abuse.

 

J Rheumatol. 2001 Aug;28(8):1892-9.

Effort testing in patients with fibromyalgia and disability incentives.

Gervais RO, Russell AS, Green P, Allen LM 3rd, Ferrari R, Pieschl SD.

OBJECTIVE: To examine whether symptom exaggeration is a factor in complaints of cognitive dysfunction using 2 new validated instruments in patients with fibromyalgia (FM). METHODS: Ninety-six patients with FM and 16 patients with rheumatoid arthritis (RA) were administered 2 effort or symptom validity tests designed to detect exaggerated memory complaints as part of a battery of psychological tests and self-report questionnaires. RESULTS: A large percentage of patients with FM who were on or seeking disability benefits failed the effort tests. Only 2 patients with FM who were working and/or not claiming disability benefits and no patient with RA scored below the cutoffs for exaggeration of memory difficulties. CONCLUSION: This study illustrates the importance of assessing for exaggeration of cognitive symptoms and biased responding in patients with FM presenting for disability related evaluations.

 

Clin J Pain. 2004 Mar-Apr;20(2):103-10. Related Articles, Links

Confirmatory factor analysis of the Tampa Scale for Kinesiophobia: invariant two-factor model across low back pain patients and fibromyalgia patients.

Goubert L, Crombez G, Van Damme S, Vlaeyen JW, Bijttebier P, Roelofs J. Liesbet.Goubert@rug.ac.be

OBJECTIVES: (1) To investigate the factor structure of the Tampa Scale for Kinesiophobia (TSK) in a Dutch-speaking sample of chronic low back pain (CLBP) patients using confirmatory factor analysis, (2) to examine whether the internal structure of the TSK extends to another group of fibromyalgia (FM) patients, and (3) to investigate the stability of the factor structure in both patient groups using multi-sample analysis. PATIENTS AND METHODS: TSK-data from 8 studies collected in Dutch and Flemish chronic pain patients were pooled. For 188 CLBP patients and 89 FM patients, complete data were available. Confirmatory factor analyses were performed to assess 4 models of kinesiophobia, and to examine which factor model provided the best fit. Furthermore, a multi-sample analysis was performed to investigate the stability of the factor structure in both patient groups. RESULTS: For both CLBP and FM patients, the 2factor model containing the factors "activity avoidance" and "pathologic somatic focus" was superior as compared with the 4-factor model containing the factors "harm," "fear of (re)injury." "importance of exercise," and "avoidance of activity". Moreover, the 2-factor model was found to be invariant across CLBP and FM patients, indicating that this model is robust in both pain samples. DISCUSSION: As the 2-factor structure provided the best fit of the data in both patient samples, we recommend to use this version of the TSK and its 2 subscales in both clinical practice and research. Based on the content of the items, the subscales were labeled "Harm" and "Fear-avoidance."

Evidence of augmented central pain processing in idiopathic chronic low back pain Arthritis Rheum. 2004 Feb;50(2):613-23. Giesecke T, Gracely RH, Grant MA, Nachemson A, Petzke F, Williams DA, Clauw DJ.

OBJECTIVE: For many individuals with chronic low back pain (CLBP), there is no identifiable cause. In other idiopathic chronic pain conditions, sensory testing and functional magnetic resonance imaging (fMRI) have identified the occurrence of generalized increased pain sensitivity, hyperalgesia, and altered brain processing, suggesting central augmentation of pain processing in such conditions. We compared the results of both of these methods as applied to patients with idiopathic CLBP (n = 11), patients with widespread pain (fibromyalgia; n = 16), and healthy control subjects (n = 11). METHODS: Patients with CLBP had low back pain persisting for at least 12 months that was unexplained by MRI/radiographic changes.

Experimental pain testing was performed at a neutral site (thumbnail) to assess the pressure-pain threshold in all subjects. For fMRI studies, stimuli of equal pressure (2 kg) and of equal subjective pain intensity (slightly intense pain) were applied to this same site. RESULTS: Despite low numbers of tender points in the CLBP group, experimental pain testing revealed hyperalgesia in this group as well as in the fibromyalgia group; the pressure required to produce slightly intense pain was significantly higher in the controls (5.6 kg) than in the patients with CLBP (3.9 kg) (P = 0.03) or the patients with fibromyalgia (3.5 kg) (P = 0.006). When equal amounts of pressure were applied to the 3 groups, fMRI detected 5 common regions of neuronal activation in pain-related cortical areas in the CLBP and fibromyalgia groups (in the contralateral primary and secondary [S2] somatosensory cortices, inferior parietal lobule, cerebellum, and ipsilateral S2). This same stimulus resulted in only a single activation in controls (in the contralateral S2 somatosensory cortex). When subjects in the 3 groups received stimuli that evoked subjectively equal pain, fMRI revealed common neuronal activations in all 3 groups.

CONCLUSION: At equal levels of pressure, patients with CLBP or fibromyalgia experienced significantly more pain and showed more extensive, common patterns of neuronal activation in pain-related cortical areas. When stimuli that elicited equally painful responses were applied (requiring significantly lower pressure in both patient groups as compared with the control group), neuronal activations were similar among the 3 groups. These findings are consistent with the occurrence of augmented central pain processing in patients with idiopathic CLBP.

Hypervigilance to Pain in Fibromyalgia: The Mediating Role of Pain Intensity and Catastrophic Thinking About Pain

Crombez, Geert PhD, Eccleston, Chris, Van den Broeck, Annelies, Goubert, Liesbet, Van Houdenhove, Boudewijn Clinical Journal of Pain. 20(2):98-102, March/April 2004

Objective: To investigate the mediating role of pain intensity, catastrophic thinking about pain, and negative affectivity in explaining enhanced attention for pain in patients with fibromyalgia. Methods: Sixty-four patients with fibromyalgia and 46 patients with chronic low back pain completed self-report instruments of vigilance to pain, negative affectivity, and catastrophic thinking about pain. These measures, along with diagnostic group and pain intensity, were entered into a partial correlational analysis to investigate which variables mediate the relationship between diagnostic group (fibromyalgia vs. chronic low back pain) and vigilance to pain. Results: Fibromyalgia patients reported significantly greater vigilance to pain than patients with chronic low back pain. They also reported higher pain intensity, more negative affectivity, and more catastrophic thinking about pain than patients with chronic low back pain. Vigilance to pain was correlated significantly with pain intensity, negative affectivity, and catastrophic thinking about pain. Further analyses revealed that pain intensity and catastrophic thinking about pain, but not negative affectivity, mediated the relationship between diagnostic group and vigilance to pain. Conclusion: Fibromyalgia patients report a heightened vigilance to pain. This vigilance is not a unique characteristic of fibromyalgia but is related to the intensity of pain and catastrophic thinking about pain.

*** PAIN®, Vol. 107 (1-2) (2004) pp. 7-15

Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia

Borut Banic, Steen Petersen-Felix, Ole K. Andersen, Bogdan P. Radanov, P.M. Villiger, Lars Arendt-Nielsen and Michele Curatolo: michele.curatolo@insel.ch

Patients with chronic pain after whiplash injury and fibromyalgia patients display exaggerated pain after sensory stimulation. Because evident tissue damage is usually lacking, this exaggerated pain perception could be explained by hyperexcitability of the central nervous system. The nociceptive withdrawal reflex (a spinal reflex) may be used to study the excitability state of spinal cord neurons. We tested the hypothesis that patients with chronic whiplash pain and fibromyalgia display facilitated withdrawal reflex and therefore spinal cord hypersensitivity. Three groups were studied: whiplash (n=27), fibromyalgia (n=22) and healthy controls (n=29). Two types of transcutaneous electrical stimulation of the sural nerve were applied: single stimulus and five repeated stimuli at 2 Hz. Electromyography was recorded from the biceps femoris muscle. The main outcome measurement was the minimum current intensity eliciting a spinal reflex (reflex threshold). Reflex thresholds were significantly lower in the whiplash compared with the control group, after both single (P=0.024) and repeated (P=0.035) stimulation. The same was observed for the fibromyalgia group, after both stimulation modalities (P=0.001 and 0.046, respectively). We provide evidence for spinal cord hyperexcitability in patients with chronic pain after whiplash injury and in fibromyalgia patients. This can cause exaggerated pain following low intensity nociceptive or innocuous peripheral stimulation. Spinal hypersensitivity may explain, at least in part, pain in the absence of detectable tissue damage.

J Rheumatol. 2004 Feb;31(2):359-63.

Clinical profile of rheumatic disease patients referred to a multidisciplinary pain center.

Fitzcharles MA, Almahrezi A, Ware MA. Division of Rheumatology, McGill University, Montreal, Quebec, Canada. mary- ann.fitzcharles@muhc.mcgill.ca

OBJECTIVE: Good pain control is a prerequisite for success in the management of many rheumatological diseases. However, some rheumatology patients may present challenges in terms of pain management and be subsequently referred to a specialized pain clinic. We examined the characteristics and assessed the outcome of patients with rheumatic diseases who were referred to a tertiary care pain center. METHODS: All new patients with a primary rheumatological diagnosis referred over a 9 year period to the McGill University Pain Centre were studied. Patients were identified through a computer search according to both diagnoses and symptoms. Demographic information, clinical and pain characteristics, and subsequent management and final outcome were assessed. RESULTS: Out of a total of 1120 new patients, 60 (5%) had a primary rheumatologic diagnosis to account for pain and referral. The diagnoses were as follows: fibromyalgia in 26 (43%), inflammatory arthritis 17 (28%), degenerative arthritis 9 (15%), and soft tissue rheumatism 8 (13%). The median age at presentation was 52 years and 47 (78%) were female. The median duration of pain was 5 years. The mean pain scores according to the McGill Pain Questionnaire and the visual analog scale were 27 +/- 15 and 7 +/- 2, respectively. Patients were followed a mean duration of 10.6 +/- 15 months. Seventy-two percent were assessed by a psychologist and 52% by a physiotherapist or occupational therapist. New pharmacologic treatments were prescribed for 47 (78%)

patients, with 47% receiving opioids, 37% antidepressants, 12% nonsteroidal antiinflammatory drugs, 8% tranquillizers, and 18% other medications. Final outcome was described as follows: improved in 55%, no change in 43%, and worsened in 2%. CONCLUSION: Although patients with a primary rheumatologic process to account for pain constituted a small proportion of patients evaluated, improvement was considerable in over half. Further study should address the selection of patients that are most likely to benefit from referral to multidisciplinary pain centers and the longterm outcome of such interventions.

Disabil Rehabil. 2004 Jan 7;26(1):46-53.

Recovery from fibromyalgia - previous patients' own experiences.

Mengshoel AM, Heggen K. a.m.mengshoel@helsefag.uio.no

PURPOSE: To explore what patients that had completely recovered from fibromyalgia (FM) experienced as being important for their recovery. METHODS: Five women, aged between 37 and 49 were interviewed individually. The interviews were aimed at finding out about the recovery process and the women's daily lives at the time of the interview and before and after their diagnosis, with a special emphasis on social relationships and obligations. The interviews were analysed by qualitative thematic content analysis. RESULTS: These five women reported that they recovered irrespective of specific treatment. The study shows that resistance to the unpleasantness of the sick role and the stigmatization associated with the uncertain nature of the FM diagnosis promoted recovery. Instead of adapting their activities to pain, they used pain as a warning signal of too much stress in life. This significantly developed their ability to alter their life goals and everyday obligations. At the same time they managed to maintain a social role they considered to be consistent with their self-image. CONCLUSIONS: Patients can recover from FM. The information from these informants suggests that to struggle against a role of chronic patient and keep up with their social obligations and goals were of great importance.

OLDER

ARTHRITIS & RHEUMATISM Vol. 46, No. 5, May 2002, pp 1333-1343

Functional Magnetic Resonance Imaging Evidence of Augmented Pain Processing in Fibromyalgia

Richard H. Gracely, Frank Petzke Julie M. Wolf and Daniel J. Clauw Objective. To use functional magnetic resonance imaging (fMRI) to evaluate the pattern of cerebral activation during the application of painful pressure and determine whether this pattern is augmented in patients with fibromyalgia (FM) compared with controls. Methods. Pressure was applied to the left thumbnail beds of 16 right-handed patients with FM and 16 right-handed matched controls. Each FM patient underwent fMRI while moderately painful pressure was being applied. The functional activation patterns in FM patients were compared with those in controls, who were tested under 2 conditions: the "stimulus pressure control" condition, during which they received an amount of pressure similar to that delivered to patients, and the "subjective pain control" condition, during which the intensity of stimulation was increased to deliver a subjective level of pain similar to that experienced by patients. Results. Stimulation with adequate pressure to cause similar pain in both groups resulted in 19 regions of increased regional cerebral blood flow in healthy controls and 12 significant regions in patients. Increased fMRI signal occurred in 7 regions common to both groups, and decreased signal was observed in 1 common region. In contrast, stimulation of controls with the same amount of pressure that caused pain in patients resulted in only 2 regions of increased signal, neither of which coincided with a region of activation in patients. Statistical comparison of the patient and control groups receiving similar stimulus pressures revealed 13 regions of greater activation in the patient group. In contrast, similar stimulus pressures produced only 1 region of greater activation in the control group. Conclusion. The fact that comparable subjectively painful conditions resulted in activation patterns that were similar in patients and controls, whereas similar pressures resulted in no common regions of activation and greater effects in patients, supports the hypothesis that FM is characterized by cortical or subcortical augmentation of pain processing.

Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms.

Clauw DJ; Chrousos GP Neuroimmunomodulation, 1997 May, 4:3, 134-53

Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical literature, although the terms used to describe these symptom complexes have changed frequently. The currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which describe the prominent clinical features of the illness without any attempt to identify the cause. This review delineates the definitions of these syndromes, and the overlapping clinical features. A hypothesis is presented to demonstrate how genetic and environmental factors may interact to cause the development of these syndromes, which we postulate are caused by central nervous system dysfunction. Various components of the central nervous system appear to be involved, including the hypothalamic pituitary axes, pain-processing pathways, and autonomic nervous system. These central nervous system changes lead to corresponding changes in immune function, which we postulate are epiphenomena rather than the cause of the illnesses.

BioMed Central - Factors explaining variance in perceived pain in women with fibromyalgia

BMC

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Musculoskeletal

Disorders

Publishing peer-reviewed

original research papers

with open access

( Submit a manuscript )

Research article

Factors explaining variance in perceived pain in women with fibromyalgia

Eva Albertsen Malt1, Snorri Olafsson2, Anders Lund1

and Holger Ursin3

1Department of Psychiatry, University of Bergen Haukeland University Hospital, N-5022 Bergen, Norway 2Department of Internal Medicine, University of Bergen

Haukeland University Hospital, N-5022 Bergen, Norway 3Department of Biological And Medical Psychology, Division of Physiological Psychology University of Bergen, N-5022 Bergen, Norway

BMC Musculoskeletal Disorders 2002 3: 12

This article is available from: http://www.biomedcentral.com/1471-2474/3/12

Accepted 25 Apr 2002

Published 25 Apr 2002

2002 Malt et al; licensee BioMed Central Ltd. Verbatim copying and redistribution of this article are permitted in any medium for any purpose, provided this notice is preserved

along with the article's original URL.

http://www.biomedcentral.com/1471-2474/3/12 (1 of 30) [9/12/2002 10:13:40 PM]

BioMed Central - Factors explaining variance in perceived pain in women with fibromyalgia

Background

We hypothesized that a substantial proportion of the subjectively experienced variance in pain in fibromyalgia patients would be explained by psychological factors alone, but that a combined model, including neuroendocrine and autonomic factors, would give the most parsimonious explanation of variance in pain.

Methods

Psychometric assessment included McGill Pain Questionnaire, General Health Questionnaire, Hospital Anxiety and Depression Rating Scale, Eysenck personality Inventory, Neuroticism and Lie subscales, Toronto Alexithymia Scale, and Multidimensional Health Locus of Control Scale and was performed in 42 female patients with fibromyalgia and 48 female age matched random sample population controls. A subgroup of the original sample (22 fibromyalgia patients and 13 controls) underwent a pharmacological challenge test with buspirone to assess autonomic and adrenocortical reactivity to serotonergic challenge.

Results

Although fibromyalgia patients scored high on neuroticism, anxiety, depression and general distress, only a minor part of variance in pain was explained by psychological factors alone. High pain score was associated with high neuroticism, low baseline cortisol level and small

http://www.biomedcentral.com/1471-2474/3/12 (2 of 30) [9/12/2002 10:13:40 PM]

BioMed Central - Factors explaining variance in perceived pain in women with fibromyalgia

drop in systolic blood pressure after buspirone challenge test. This model explained 41.5% of total pain in fibromyalgia patients. In population controls, psychological factors alone were significant predictors for variance in pain.

Conclusion

Fibromyalgia patients may have reduced reactivity in the central sympathetic system or perturbations in the sympathetic-parasympathetic balance. This study shows that a biopsychosocial model, including psychological factors as well as factors related to perturbations of the autonomic nervous system and hypothalamic-pituitary-adrenal axis, is needed to explain perceived pain in fibromyalgia patients.

http://www.biomedcentral.com/1471-2474/3/12 (3 of 30) [9/12/2002 10:13:40 PM]

Entrez-PubMed

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?hol...etrieve&db=PubMed&list_uids=9617472&dopt=Abstract (1 of 2) [9/12/2002 10:14:22 PM]

Entrez-PubMed

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?hol...trieve&db=PubMed&list_uids=11760858&dopt=Abstract (1 of 2) [9/12/2002 10:15:25 PM]

Entrez-PubMed

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?hol...trieve&db=PubMed&list_uids=11760858&dopt=Abstract (2 of 2) [9/12/2002 10:15:25 PM]

Entrez-PubMed

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?hol...etrieve&db=PubMed&list_uids=1558082&dopt=Abstract (1 of 2) [9/12/2002 10:16:40 PM]

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Synonyms and related keywords: fibromyositis, fibrositis, idiopathic myalgia, interstitial Workup myofibrositis, muscular hardening, muscular rheumatism,musculorheumatism, Treatment myofibrositis, myogelosis, myositism, nodular rheumatism,nonarticular rheumatism, Medication

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Mechanical Low

not a recently discovered disorder. Descriptions have been found in the medical Back Pain literature as far back as the early 17th century. Many physicians prefer not to deal with patients who have this complicated disorder and question the actual Meralgia existence of the disorder. In the past, poor recognition and lack of treatment for Paresthetica this disorder could be explained by a lack of meaningful research. Today Myofascial Pain

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Teitelbaum J: For physicians. In: From Fatigued to Fantastic! Avery Publishing; 1995:93-115.

Travell JG, Simons DG: In: Myofascial Pain and Dysfunction: The Trigger Point Manual.

Baltimore: Lippincott Williams & Wilkins; 1983. UCLA Sleep Research Society: Basics of Sleep Behavior: What is Sleep. 1997; Available at: http://www.sleephomepages.org/sleepsyllabus.[Full Text].

Vecchiet L, Giamberardino MA: Referred Pain: Clinical Significance, Pathophysiology, and

Treatment. Physical Medicine and Rehabilitation Clinics of North America 1997; 8: 119-136. Wolfe F, Smythe HA, Yunus MB, et al: The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990 Feb; 33(2): 160-72[Medline].

Yunus MB: Fibromyalgia Syndrome: Clinical Features and Spectrum. J Musculoskelet Pain 1994;

2: 5-21.

Zohn DA: Relationship of Joint Dysfunction and Soft-Tissue Problems. Phys Med Rehabil Clin North Am 1997; 8: 69-86.

NOTE:

Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER

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Year 2000 (Some 1999, 2000) Abstracts

The British Journal of Rheumatology, Vol 34, 925-931

Muscle strength, voluntary activation and cross-sectional muscle area in patients with fibromyalgia

J Norregaard, PM Bulow, P Vestergaard-Poulsen, C Thomsen and B Danneskiold-Samoe Department of Rheumatology, Frederiksberg Hospital, Copenhagen, Denmark.

The objectives were to determine whether the low muscle strength in fibromyalgia is due to lack of exertion and to determine the relation between strength and muscle area. Secondarily we examined the voluntary muscle strength of the different muscles of the leg. The twitch interpolation technique was used to estimate the degree of central activation and the 'true' quadriceps muscle strength. Muscle cross- sectional area was determined with magnetic resonance imaging (MRI). The estimated 'true' muscle strength was 91 Nm (S.D. = 34 Nm) in 15 fibromyalgia patients compared with 125 Nm (28 Nm) in 14 healthy controls (P < 0.02). The 'true' strength divided by the sum of the maximal areas of the four bellies of the quadriceps muscle was lower, being 1.56 Nm/cm2 (0.32 Nm/cm2) in fibromyalgia patients compared with

2.11 Nm/cm2 (0.39 Nm/cm2) in the controls (P < 0.001). The voluntary muscle strength of the flexor muscles of the knee and of the plantar flexors of the ankle was markedly reduced in patients, but no significant differences could be observed in the strength of the dorsal flexors of the ankle. In conclusion, a reduction of the estimated 'true' quadriceps muscle strength per unit area of about 35% was found in fibromyalgia patients.

The British Journal of Rheumatology, Vol 29, 174-177

Primary fibromyalgia: clinical parameters in relation to serum procollagen type III aminoterminal peptide

S Jacobsen, LT Jensen, M Foldager and B Danneskiold-Samsoe Department of Rheumatology, Frederiksberg Hospital, Denmark.

Serum concentrations of procollagen type III aminoterminal peptide have previously been reported to be low in some patients with primary fibromyalgia and the aim of this study was to determine if such patients differ clinically from primary fibromyalgia patients with normal levels of procollagen type III aminoterminal peptide. Subjective symptoms, tender points and dynamic muscle strength in 45 women with primary fibromyalgia were related to serum concentrations of procollagen type III aminoterminal peptide. Patients with low serum concentrations of procollagen type III aminoterminal peptide had more symptoms, a higher frequency of tender points and lesser quality of sleep compared to patients with normal serum concentrations of procollagen type III aminoterminal peptide (P less than 0.05). They also had a lower dynamic muscle strength (P less than 0.0005). We conclude that the serum concentrations of procollagen type III aminoterminal peptide of primary fibromyalgia patients are connected to the disease impact.

Rheumatology 2000; 39: 1121-1125

31P magnetic resonance spectroscopy in fibromyalgic muscle

H. Sprott1,2,, R. Rzanny3, J. R. Reichenbach3, W. A. Kaiser3, G. Hein2 and G. Stein2 1 Department of Rheumatology and Institute of Physical Medicine, University Hospital Zürich, Switzerland, 2 Department of Internal Medicine IV and 3 Institute of Diagnostic and Interventional Radiology, Friedrich Schiller University Jena, Germany

Objective. To measure inorganic phosphate (Pi), phosphocreatine (PCr), ATP and phosphodiesters (PDE) in fibromyalgic muscle tissue by 31P magnetic resonance spectroscopy.

Methods. A 1.5 Tesla scanner with a P 100 surface coil was used to examine 15 patients (mean age 49.9 ± 14.3 yr) with fibromyalgia, according to the American College of Rheumatology criteria, and 17 healthy controls (mean age 30.2 ± 5.8 yr).

Results. Compared with the controls, there were increases in the levels of PDE (+22%, P = 0.032) and Pi (+19%, P = 0.019) in the spectra of fibromyalgia patients, but there was no difference in pH.

Conclusion. The metabolic differences we found may have been related to weakness and fatigue in the fibromyalgia patients, but they do not fully explain the fibromyalgia symptoms.

KEY WORDS: Fibromyalgia, Magnetic resonance spectroscopy, Phosphate, ATP, Phosphocreatine, Phosphodiesters. Correspondence to: H. Sprott, Department of Rheumatology and Institute of Physical Medicine, University Hospital Zürich, Gloriastrasse 25, CH-8091 Zürich, Switzerland.

Rheumatology 2000; 39: 501-505

An observer-blinded comparison of supervised and unsupervised aerobic exercise regimens in fibromyalgia

C. Ramsay, J. Moreland1, M. Ho1, S. Joyce, S. Walker1 and T. Pullar1, Physiotherapy Department and 1 Rheumatic Diseases Unit, Ninewells Hospital, Dundee DD1 9SY, UK

Objective. To compare a supervised 12-week aerobic exercise class with unsupervised home aerobic exercises in the treatment of patients with fibromyalgia.

Methods. This was a 48-week randomized single (observer) blind study in a teaching hospital rheumatology and physiotherapy department. The subjects were 74 patients who fulfilled the American College of Rheumatology criteria for fibromyalgia.

Results and conclusions. A 12-week exercise class programme with home exercises demonstrated no benefit over a single physiotherapy session with home exercises in the treatment of pain in patients with fibromyalgia. Neither group (nor the groups combined) showed an improvement in pain compared with baseline. There was some significant benefit in psychological well- being in the exercise class group and perhaps a slowing of functional deterioration in this group.

KEY WORDS: Fibromyalgia, Exercise, Physiotherapy. Correspondence to: T. Pullar.

The British Journal of Rheumatology, Vol 29, 368-370

Does primary fibromyalgia exist?

K Forslind, E Fredriksson and O Nived Department of Rheumatology, University Hospital, Lund, Sweden.

Twenty-one of 25 consecutive primary fibromyalgia or fibrositis patients, identified during a 5year period in a tertiary care day-ward for pain syndromes, were re-examined. Fifteen fulfilled criteria for fibromyalgia but unexpectedly, all cases had either psychiatric disturbance or thyroid dysfunction. Of the four patients not seen at follow-up, two had developed neurological diseases, another rheumatoid arthritis and one other hypothyroidism. Thus, after 5 years no patient fulfilled the criteria for primary fibromyalgia. Women occupied as manual workers were overrepresented. Most patients reported beneficial effects of physiotherapy. None of the patients has been able to return to full time work.

The British Journal of Rheumatology, Vol 34, 1151-1156

Clustering of sleep electroencephalographic patterns in patients with the fibromyalgia syndrome

AM Drewes, K Gade, KD Nielsen, K Bjerregard, SJ Taagholt and L Svendsen Department of Rheumatology, Aalborg Hospital, Denmark.

Several electroencephalographic (EEG) abnormalities have been observed during sleep in patients suffering from the fibromyalgia syndrome (FMS). In this study, 12 patients with fibromyalgia and 14 control subjects had two polysomnographic recordings obtained at home. Data from the second night were subjected to blinded manual scoring as well as signal processing using linked or 'step-wise clustering for pattern recognition. In this procedure, a common learning set was generated using the spectral information in three 2 min EEG samples from each of the sleep stages selected from five patients with FMS and five controls. In this way, 17 characteristic EEG classes were defined. All 2 s EEG segments from the whole night from all subjects were then assigned to one of these classes. Five of the classes (dominated by 0.5- 4.5 Hz activity) were more frequent in the control group, whereas three other classes (dominated by 811 Hz activity) were prevalent in the patient group. This trend was consistent in all sleep stages, although most striking in non-rapid eye movement (NREM) sleep. The predominance of these classes in the patient group may correspond to the alpha-EEG sleep anomaly previously reported in subjects with FMS. More importantly, as the EEG power in the lowest

frequency range (prevalent in controls) probably is a marker for restorative sleep, the findings may reflect important aspects of sleep disturbances n subjects suffering from FMS, thereby contributing to some of the daytime symptoms in these patients.

The British Journal of Rheumatology, Vol 34, 629-635

Sleep intensity in fibromyalgia: focus on the microstructure of the sleep process

AM Drewes, KD Nielsen, SJ Taagholt, K Bjerregard, L Svendsen and J Gade Department of Rheumatology, Aalborg Hospital, Denmark.

Alpha electroencephalography (EEG) predominance has been described during sleep in patients suffering from the fibromyalgia syndrome (FMS). However, EEG power density in the lower frequency bands probably better reflects the restorative functions of sleep. This study was conducted to describe the energy in all frequency bands in the sleep EEG. Ambulatory sleep recordings were performed on 12 women with FMS and 14 control women. Epochs were classified according to standard criteria. Moreover, all 2-s segments (n = 287,355) of the EEG in non- rapid-eye-movement (NREM) 2-4 sleep were subjected to frequency analysis using autoregressive modelling. Frequency bands were: delta (0.5-3.5 Hz), theta (3.5-8 Hz), alpha (812 Hz), sigma (12-14.5 Hz) and beta (14.5-25 Hz). In patients with FMS, there was a predominance of EEG power in the higher frequency bands [two-way analysis of variance (ANOVA), alpha: P = 0.043; sigma: P = 0.004] at the expense of the lower frequencies (ANOVA, delta: P = 0.005; theta: P = 0.008). The same trends were obtained for the individual sleep cycles. The calculations of total delta power in the time domain showed an exponentially declining curve in healthy subjects, but a flatter decline in FMS. The decreased power in the low-frequency range might reflect a disorder in homoeostatic and circadian mechanisms during sleep and may contribute to daytime symptoms in patients with fibromyalgia.

Rheumatology 2001; 40: 806-810

Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders

M. Nishikai, S. Tomomatsu1, R. W. Hankins1, S. Takagi, K. Miyachi2, S. Kosaka and K. Akiya National Tokyo Medical Center, Tokyo, 1 Health Sciences Research Institute, Yokohama and 2 Keigu Medical Clinic, Yokohama, Japan

Objective. To identify antinuclear antibodies (ANA) specific for chronic fatigue syndrome (CFS), and in related conditions such as fibromyalgia (FM) or psychiatric disorders.

Methods. One hundred and fourteen CFS patients and 125 primary and secondary FM patients were selected based on criteria advocated by the Centers for Disease Control and Prevention and by the American College of Rheumatology, respectively. As controls, healthy subjects and patients with either various psychiatric disorders or diffuse connective tissue diseases were included. Autoantibodies were examined by immunoblot utilizing HeLa cell extracts as the antigen.

Results. Autoantibodies to a 68/48 kDa protein were present in 13.2 and 15.6% of patients with CFS and primary FM, respectively. In addition, autoantibodies to a 45 kDa protein were found in

37.1 and 21.6% of the patients with secondary FM and psychiatric disorders, respectively. Meanwhile, these two autoantibodies were not found at all in connective tissue disease patients without FM, nor in healthy subjects (P<0.05). As a group, the anti-68/48 kDa-positive CFS patients presented more frequently with hypersomnia (P<0.005), short-term amnesia (P<0.07) or difficulty in concentration (P<0.05) than those CFS patients without the antibodies.

Conclusions. The presence of the anti-68/48 kDa protein antibodies in a portion of both CFS and primary FM patients suggests the existence of a common immunological background. These antibodies may find utility as possible markers for a clinicoserological subset of CFS/FM patients with hypersomnia and cognitive complaints.

KEY WORDS: Anti-68/48 kDa protein antibodies, Anti-45 kDa protein antibodies, Chronic fatigue syndrome, Fibromyalgia, Antinuclear antibodies, Sleep disorders, Hypersomnia, Insomnia, Depression, Neurosis.

Correspondence to: M. Nishikai, Department of Internal Medicine, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan.

Rheumatology 2001; 40: 743-749

Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study

D. J. Wallace, M. Linker-Israeli, D. Hallegua, S. Silverman, D. Silver and M. H. Weisman Department of Medicine/Division of Rheumatology, Cedars–Sinai Medical Center/UCLA School of Medicine, Los Angeles, CA, USA

Objective. To measure soluble factors having a possible role in fibromyalgia (FM) and compare the profiles of patients with recent onset of the syndrome with patients with chronic FM.

Methods. The production of cytokines, cytokine-related molecules, and a CXC chemokine, interleukin (IL)-8, was examined. Fifty-six patients with FM (23 with <2 yr and 33 with >2 yr of symptoms) were compared with age- and sex-matched healthy controls. Cytokines and cytokine-related molecules were measured in sera and in supernatants of peripheral blood mononuclear cells (PBMC) that were incubated with and without lectins and phorbol myristate acetate (PMA).

Results. No differences between FMS and controls were found by measuring IL-1ß, IL-2, IL-10, serum IL-2 receptor (sIL- 2R), interferon (IFN-), and tumour necrosis factor (TNF-). Levels of IL-1R antibody (IL-1Ra) and IL-8 were significantly higher in sera, and IL-1Ra and IL-6 were significantly higher in stimulated and unstimulated FM PBMC compared with controls. Serum IL-6 levels were comparable to those in controls, but were elevated in supernatants of in vitro-activated PBMC derived from patients with >2 yr of symptoms. In the presence of PMA, there were additional increases in IL-1Ra, IL- 8 and IL-6 over control values.

Conclusions. In patients with FM we found increases over time in serum levels and/or PBMC-stimulated activity of soluble factors whose release is stimulated by substance P.

Because IL-8 promotes sympathetic pain and IL-6 induces hyperalgesia, fatigue and depression, it is hypothesized that they may play a role in modulating FM symptoms.

Correspondence to: D. J. Wallace, 8737 Beverly Blvd Suite 203, Los Angeles, CA 90048, USA

Rheumatology 2001; 40: 290-296

Cerebrospinal fluid biogenic amine metabolites, plasma-rich platelet serotonin and [3H]imipramine reuptake in the primary fibromyalgia syndrome

E. Legangneux, J. J. Mora1, O. Spreux-Varoquaux2, I. Thorin, M. Herrou3, G. Alvado4 and C. Gomeni5 Department of Psychiatry, University of Caen, 1 Department of Rheumatology, Hospital of Bayeux, 2 Department of Pharmacology, Hospital of Versailles, 3 Department of Pharmacology, University of Caen, 4 Department of Surgery, Hospital of Bayeux and 5 Biotrial, rue Jean-Louis Bertrand, Rennes, France

Background. Primary fibromyalgia syndrome (PFS) is a chronic disorder commonly seen in rheumatological practice. The pathophysiological disturbances of this syndrome, which was defined by the American College of Rheumatology in 1990, are poorly understood. This study evaluated, in 30 patients, the hypothesis that PFS is a pain modulation disorder induced by deregulation of serotonin metabolism.

Objectives. To compare platelet [3H]imipramine binding sites and serotonin (5-HT) levels in plasma-rich platelets (PRP) of PFS patients with those of matched healthy controls and to compare the levels of biogenic amine metabolites in the cerebrospinal fluid (CSF) of PFS patients with those of matched controls.

Methods. Platelet [3H]imipramine binding sites were defined by two criteria, Bmax for their density and Kd for their affinity. PRP 5-HT and CSF metabolites of 5-HT (5hydroxyindoleacetic acid, 5-HIAA), norepinephrine (3-methoxy, 4-hydroxy phenylglycol, MHPG) and dopamine (homovanillic acid, HVA) were assayed by reversed-phase high-performance liquid chromatography with coulometric detection.

Results. [3H]Imipramine platelet binding was similar (P=0.43 for Bmax and P=0.30 for Kd) in PFS patients (Bmax=901±83 fmol/mg protein, Kd=0.682±0.046) and in matched controls (Bmax=1017±119 fmol/mg protein, Kd=0.606±0.056). PRP 5- HT was significantly higher (P=0.0009) in PFS patients (955±101 ng/109 platelets) than in controls (633±50 ng/109 platelets). When adjusted for age, the levels of all CSF metabolites were lower in PFS patients. The CSF metabolite of norepinephrine (MHPG) was lower (P=0.003) in PFS patients (8.33±0.33 ng/ml) than in matched controls (9.89±0.31 ng/ml) and 5-HIAA was lower (P=0.042) in PFS female patients (22.34±1.78 ng/ml) than in matched controls (25.75±1.75 ng/ml). For HVA in females, the difference between PFS patients (36.32±3.20 ng/ml) and matched controls (38.32±2.90 ng/ml) approached statistical significance (P=0.054).

Conclusion. Changes in metabolites of CSF biogenic amines appear to be partially correlated to age but remained diagnosis- dependent. High levels of PRP 5-HT in PFS patients were associated with low CSF 5-HIAA levels in female patients but were not accompanied by any change in serotonergic uptake as assessed by platelet [3H]imipramine binding sites. These findings do not allow us to confirm that serotonin metabolism is deregulated in PFS patients.

KEY WORDS: Primary fibromyalgia syndrome, Matched controls, Serotonin, Norepinephrine, Dopamine, Cerebrospinal fluid.

Correspondence to: E. Legangneux, Sanofi Synthelabo, 1 Av. Pierre Brossolette, F-91380 Chilly-Mazarin, France.

Rheumatology 2000; 39: 917-921

Abnormal microcirculation and temperature in skin above tender points in patients with fibromyalgia

M. Jeschonneck1, G. Grohmann2, G. Hein and H. Sprott1,3, 1 Department of Internal Medicine IV and 2 Department of Internal Medicine III, Friedrich Schiller University, Jena, Germany and 3 Department of Rheumatology and Institute of Physical Medicine, University Hospital, Zürich, Switzerland

Objective. Skin temperature and skin blood flow were studied above different tender points in 20 patients with fibromyalgia (FM) and 20 healthy controls.

Methods. Blood flow was measured by laser Doppler flowmetry and skin temperature was measured with an infrared thermometer.

Results. In the skin above the five tender points examined in each subject, we found an increased concentration of erythrocytes, decreased erythrocyte velocity and a consequent decrease in the flux of erythrocytes. A decrease in temperature was recorded above four of the five tender points.

Conclusion. Vasoconstriction occurs in the skin above tender points in FM patients, supporting the hypothesis that FM is related to local hypoxia in the skin above tender points.

Rheumatology 2000; 39: 620-623

Lupus patients with fatigue—is there a link with fibromyalgia syndrome?

J. Taylor, J. Skan1, N. Erb1, D. Carruthers1, S. Bowman1, C. Gordon1 and D. Isenberg Centre for Rheumatology/Department of Medicine, University College London, London W1P 9PG and 1 Department of Rheumatology, University of Birmingham, Birmingham B15 2TT, UK Objective. To determine whether fibromyalgia syndrome (FMS) was more common in patients with lupus who were complaining of fatigue.

Methods. We interviewed 216 patients attending two lupus clinics, all of whom fulfilled the revised American College of Rheumatology (ACR) criteria for lupus. The patients completed a questionnaire and were examined to determine the presence of fatigue and whether they fulfilled the ACR criteria for FMS. Disease activity was measured using the British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage score. Measurements of erythrocyte sedimentation rate, complement C3, lymphocyte count and DNA titre were also performed.

Results. Fifty per cent of our patients complained of fatigue, but only 10% of these patients fulfilled criteria for FMS. FMS did not correlate with any measure of disease activity although patients with FMS had lower mean DNA antibody titres and mean SLICC/ACR damage scores.

Conclusion. A minority of lupus patients with fatigue fulfil the ACR criteria for FMS. Other possible factors leading to fatigue should be considered.

KEY WORDS: Systemic lupus erythematosus, Fatigue, Fibromyalgia syndrome. Correspondence to: J. Taylor, Department of Rheumatology, The Middlesex Hospital, Arthur Stanley House, 40–50 Tottenham Street, London W1P 9PG, UK.

Rheumatology, Vol 38, 355-361

Determinants of WOMAC function, pain and stiffness scores: evidence for the role of low back pain, symptom counts, fatigue and depression in osteoarthritis, rheumatoid arthritis and fibromyalgia

F Wolfe Arthritis Research Center and University of Kansas School of Medicine, Wichita 67214, USA.

OBJECTIVES: The Western Ontario MacMaster (WOMAC) is a validated instrument designed specifically for the assessment of lower extremity pain and function in osteoarthritis (OA) of the knee or hip. In the clinic, however, we have noted that OA patients frequently have other musculoskeletal and non-musculoskeletal problems that might contribute to the total level of pain and functional abnormality that is measured by the WOMAC. In this report, we investigated back pain and non- articular factors that might explain WOMAC scores in patients with OA, rheumatoid arthritis (RA) and fibromyalgia (FM) in order to understand the specificity of this instrument. METHODS: RA, OA and FM patients participating in long-term outcomes studies completed the WOMAC and were assessed for low back pain, fatigue, depression and rheumatic disease symptoms by mailed questionnaires. RESULTS: Regardless of diagnosis, WOMAC functional and pain scores were very much higher (abnormal) among those complaining of back pain. On average, WOMAC scores for back pain (+) patients exceeded those of back pain (-) patients by approximately 65%,, and 52% of OA patients reported back pain. In regression analyses, study symptom variables explained 42, 44 and 38% of the variance in WOMAC function, pain and stiffness scores, respectively. In the subset of OA patients, radiographic scores added little to the explained variance. The strongest predictor of WOMAC abnormality in bivariate and multivariate analyses was the fatigue score, with correlations of 0.58, 0.60 and 0.53 with WOMAC function, pain and stiffness, respectively. The WOMAC performed well in RA and FM, and correlated strongly with the Health Assessment Questionnaire (HAQ) disability scale and a visual analogue scale (VAS) pain scale. CONCLUSION: The WOMAC captures more than just knee or hip pain and dysfunction, and is clearly influenced by the presence of fatigue, symptom counts, depression and low back pain. WOMAC scores also appear to reflect psychological and constitutional status. These observations suggest the need for care in interpreting WOMAC scores as just a measure of function, pain or stiffness, and indicate the considerable importance of psychological factors in rheumatic disease and rheumatic disease assessments.

The British Journal of Rheumatology, Vol 37, 1279-1286

A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder

P Hannonen, K Malminiemi, U Yli-Kerttula, R Isomeri and P Roponen Department of Medicine, Central Hospital, Jyvaskyla, Finland.

OBJECTIVE: To study the usefulness of moclobemide and amitriptyline in the treatment of fibromyalgia (FM) in females without psychiatric disorder. METHODS: In the present four centre, 12 week study, 130 female FM patients not suffering from psychiatric disorders were randomized to receive amitriptyline (AMI; 25 37.5 mg), moclobemide (MOCLO; 450-600 mg) or identical placebo. RESULTS: Seventy-four, 54 and 49 per cent of patients on AMI, MOCLO and placebo, respectively, were judged as responders. The patients on AMI also managed best regarding the respective improvements during the trial in general health, pain, sleep quality and quantity, and fatigue on visual analogue scales (VAS), the areas of the Nottingham Health Profile (NHP), as well as in the three Sheehan's functional disability scales. In the within-group comparisons, MOCLO also improved pain assessed both on VAS and on the NHP pain dimension, but the improvement was invalidated by the poor success of the drug with regard to sleep. The tolerabilities of all three drugs were comparable. CONCLUSION: The study indicates that MOCLO may not be helpful in FM patients free from clinically meaningful psychiatric problems.

The British Journal of Rheumatology, Vol 36, 1318-1323

A population study of the incidence of fibromyalgia among women aged 26- 55 yr

KO Forseth, JT Gran and G Husby Rikshospitalet, National Hospital, University of Oslo, Norway.

In a population survey, we assessed the incidence of fibromyalgia (FM) among females. A screening questionnaire about pain was distributed twice (in 1990 and 1995) to 2498 females aged 20-49 yr, living in South Norway. A positive answer classified the responder as positive, merely negative answers as negative. One hundred females converting from negative to positive responders and 100 females remaining negative responders (controls) underwent a structural interview and examination for tender points (TP). Of the 870 negative responders in 1990, 717 answered the questionnaire in 1995. Of these, 523 were still negative responders, while 194 were positive converters. Twelve of the converters developed FM and none of the controls. The calculated annual incidence of FM in females was 583/100,000. This rather high incidence is most likely explained by the design of the study, also detecting cases usually not seen in hospital settings.

The British Journal of Rheumatology, Vol 36, 981-985

Fibromyalgia-associated hepatitis C virus infection

J Rivera, A de Diego, M Trinchet and A Garcia Monforte Rheumatology Unit, Hospital General Universitario Gregorio Maranon, Madrid, Spain.

The objective was to determine whether there might be an association between hepatitis C virus (HCV) chronic infection and fibromyalgia (FM). We determined the prevalence of HCV infection in 112 FM patients, in comparison with matched rheumatoid arthritis (RA) patients from the out-patient clinic of a teaching tertiary care general hospital. Furthermore, we looked for evidence of FM in 58 patients diagnosed with chronic hepatitis due to HCV, compared with matched surgery clinic patients, HCV antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA). Serum RNA of HCV (HCV-RNA) was determined by polymerase chain reaction. In the group of FM patients, HCV antibodies were found by ELISA in 17 (15.2%) patients and in six (5.3%) of the RA controls (P < 0.05). RIBA was positive in 16 and indeterminate in one of the FM patients. Serum HCV-RNA was found in 13 of these FM patients. In eight (47%) FM patients, alanine aminotransferase (ALT) was normal, although HCV-RNA was detected in four (50%) of them. In the group of patients with chronic hepatitis due to HCV, all patients had HCV antibodies and the presence of HCV-RNA in serum. Within these patients, 31 (53%) had diffuse musculoskeletal pain, while six (10%) fulfilled FM diagnostic criteria. In the control group, 13/58 (22%) had diffuse musculoskeletal pain (P < 0.001), whereas only one female patient (1.7%) fulfilled FM criteria (P < 0.05). Serum ALT was 51.7 +/- 38.4 in FM patients, whereas it was 122 +/- 76.3 in patients with HCV chronic hepatitis but without FM (P < 0.001). There were no statistical differences in autoimmune markers between patients with and without FM. These data suggest that there exists an association between FM and active HCV infection in some of our patients. FM is not associated with liver damage or autoimmune markers in these patients. HCV infection should be considered in FM patients even though ALT elevations were absent.

The British Journal of Rheumatology, Vol 33, 576-582,

Fluid retention syndrome and fibromyalgia

AA Deodhar, RA Fisher, CV Blacker and AD Woolf Duke of Cornwall Rheumatology Unit, Royal Cornwall Hospital, Truro.

Fluid retention syndrome (FRS) or idiopathic oedema is an unusual clinical entity almost exclusively seen in women, which remains under- diagnosed and poorly understood. It can produce a variety of symptoms ranging from headaches and blurring of vision to abdominal pains and diarrhoea [1]. More commonly it presents with symptoms of bloating, fatigue and generalized weakness. We describe four cases of FRS who presented to the rheumatology clinic with signs and symptoms of fibromyalgia. We also discuss the common features of these two conditions and argue that rheumatologists need to be aware of this condition.

The British Journal of Rheumatology, Vol 32, 484-489,

Patients' beliefs about their lack of pain control in primary fibromyalgia syndrome

MA Pastor, E Salas, S Lopez, J Rodriguez, S Sanchez and E Pascual Department of Health Psychology, University of Alicante, Spain.

This study had two aims, first, to determine the expectancies of control over pain experience ('pain locus of control') of patients with primary fibromyalgia syndrome (PFS) and to compare them with other chronic rheumatic diseases. Second, to analyse the relationships between health status and locus of control. We applied the Multidimensional Health Locus of Control-Pain and the Arthritis Impact Measurement Scales (AIMS), by interviewing 137 out patients (32 PFS, 32 RA, 20 SLE, 22 AS and 31 OA). Data were analysed by ANOVA and partial correlation tests. PFS patients believed that their symptoms depended on uncontrollable events and that they could not influence their disease by themselves. PFS patients were the most disabled on the 'Affect' (P < or = 0.001) and 'Symptom' factors (P < or = 0.01). In the PFS group, patients who showed a 'Fate' locus of control orientation reported more disability on 'Affect' and 'Social Interaction' AIMS factors.

The British Journal of Rheumatology, Vol 32, 479-483

Pathology of skeletal muscle in fibromyalgia: a histo-immuno-chemical and ultrastructural study

AM Drewes, A Andreasen, HD Schroder, B Hogsaa and P Jennum Department of Rheumatology, Viborg County Hospital, Denmark.

The value of muscle biopsy in fibromyalgia is still questioned. In this study we obtained 50 quadriceps biopsies from 20 patients and compared them blindly to 10 biopsies from five normal controls. Using light microscopy, histochemical and immunoenzymatic methods we found no definite evidence of muscle disease. Nevertheless, we subjected biopsies from nine of the patients and five other controls for further ultrastructural evaluations and demonstrated pathologic findings e.g. empty sleeves of basement membrane, many lipofuschin bodies and other degenerative changes. We conclude that ultrastructural evaluation cannot yet be used for diagnostic purposes, but the negative findings with light microscopy, including histochemical and immunoenzymatic techniques, might be of importance in evaluating difficult cases.

Abstract 4 of 7

The British Journal of Rheumatology, Vol 32, 139-142

Primary fibromyalgia syndrome--an outcome study

J Ledingham, S Doherty and M Doherty Rheumatology Unit, City Hospital, Nottingham.

Seventy-two patients (65 F, 7 M; mean age 52, range 18-81 years) fulfilling criteria for primary fibromyalgia syndrome (PFS) were reviewed at a mean of 4 years (range 1.5-6) following diagnosis. Ninety- seven per cent still had symptoms typical of PFS (60% worse, 26% better than at presentation); 85% had multiple hyperalgesic tender sites and still fulfilled criteria for PFS; 8% had more limited, and 7% had no tender sites at review. Many had significant disability (median score 1.0, range 0- 2.75, on the Health Assessment Questionnaire; median 2, range 1-3 on the Steinbrocker index) and 92% scored highly (> 12) on the Hospital Anxiety and Depression index. In no patient did screening investigations reveal development of inflammatory, metabolic, endocrine or muscle disease. This study confirms a poor outcome for PFS patients and association with often marked functional disability and high levels of anxiety and depression. Contrary to one previous study there was no evidence that PFS predates the onset of other disease.

The British Journal of Rheumatology, Vol 32, 55-58

Chlormezanone in primary fibromyalgia syndrome: a double blind placebo controlled study

M Pattrick, A Swannell and M Doherty Rheumatology Unit, City Hospital, Nottingham.

Primary fibromyalgia syndrome (PFS) is a common condition that often proves resistant to health interventions. Chlormezanone combines corrective effects on disturbed sleep with muscle-relaxant properties, and therefore could be of potential benefit in PFS. Forty-two female patients with PFS (mean age 49, range 24-72 years) were randomly and blindly allocated either chlormezanone 400 mg nocte or placebo. Patients were assessed by single observer at 0, 3 and 6 weeks of treatment; assessments included sleep quality, inactivity and morning stiffness, morning alertness, tender point score, mood change and global opinion (patient and observer). No beneficial therapeutic effect could be attributed to chlormezanone. Although there are problems in assessing severity of a predominantly subjective condition, this essentially negative finding is of interest in respect to the pathogenesis of PFS.

The British Journal of Rheumatology, Vol 30, 220-222

Primary fibromyalgia and the irritable bowel syndrome: different expressions of a common pathogenetic process

D Veale, G Kavanagh, JF Fielding and O Fitzgerald Department of Rheumatology, Beaumont Hospital, Dublin, Ireland.

Primary fibromyalgia (PFM) and the irritable bowel syndrome (IBS) are both common conditions which account for 30% or more of referrals to rheumatology and gastroenterology clinics. An association between symptoms in PFM and IBS has been suggested but the frequency with which they coexist has not been assessed. The aim of this study was to examine the prevalence of each condition in groups of patients with PFM and IBS compared to normal and disease control populations. We studied four patient groups, 20 patients in each group, with PFM, IBS, inflammatory arthritis, inflammatory bowel disease and also 20 normal controls. Using strict diagnostic criteria, each group was assessed by two investigators for symptoms and signs of PFM and IBS. Sigmoidoscopy was performed when indicated. Results indicate that 70% (14/20) of the PFM patients had IBS and 65% (13/20) of the IBS patients had PFM. This compared with the control groups where 12% (7/60) and 10% (6/60) had PFM and IBS respectively. In conclusion, these results indicate that PFM and IBS frequently coexist. A common pathogenetic mechanism for both conditions is therefore suggested.

Rheumatology 2002; 41: 454-457

Sex hormonal factors and chronic widespread pain: a population study among women

T. V. Macfarlane, A. Blinkhorn, H. V. Worthington, R. M. Davies1 and G. J. Macfarlane2,3, University Dental Hospital of Manchester, 1 Dental Health Unit, 2 Unit of Chronic Disease Epidemiology and 3 Arthritis Research Campaign Epidemiology Unit, University of Manchester, UK

Objective. The observation of higher rates of chronic widespread pain, the cardinal feature of fibromyalgia, in women has led to hypotheses about the role of sex hormonal factors in the aetiology of symptoms. There is little available evidence from epidemiological studies on their importance or role.

Methods. A population postal survey was carried out involving 1178 female participants living in south-east Cheshire in the north-west of England.

Results. Amongst pre- and peri-menopausal women, the risk of chronic widespread pain was unrelated either to the length of the menstrual cycle or the usual length of period reported by participants. Risk was similar in current users and non-users of the oral contraceptive pill, and amongst users there was no relationship with duration of use. However, the reporting of chronic widespread pain showed a relationship with total score on a premenstrual symptom questionnaire. However, this relationship was explained by pain symptoms. Amongst postmenopausal women, reporting chronic widespread pain was not related to age at menopause. An increased (but non-significant) risk of chronic widespread pain was associated with current hormone replacement therapy (HRT), which may be a consequence of HRT being prescribed for menopausal symptoms.

Conclusion. This study, conducted on a large unselected population, has not demonstrated an association between sex hormonal factors and chronic widespread pain.

The British Journal of Rheumatology, Vol 37, 1215-1219

Referral and diagnosis of common rheumatic diseases by primary care physicians

JI Gamez-Nava, L Gonzalez-Lopez, P Davis and ME Suarez-Almazor Department of Public Health Sciences, Faculty of Medicine and Oral Health Sciences, University of Alberta, Edmonton, Canada.

OBJECTIVE: To describe primary care patterns of referral and diagnoses of patients with rheumatic diseases referred to rheumatologists. METHODS: The medical records of all consecutive patients referred in 1994 by >300 primary care physicians to two rheumatologists at an academic centre were reviewed. The referring physician diagnosis was compared with the rheumatologist's diagnosis. Sensitivity, specificity and predictive values of primary care diagnoses were estimated using the rheumatologist diagnosis as the 'gold standard'. SETTING: University-based rheumatology out-patient clinic. RESULTS: Over half of the patients referred had a rheumatologist diagnosis of soft-tissue rheumatism or a spinal pain syndrome. Three hundred and forty-seven patients (49%) had a primary care diagnosis of a defined rheumatic disease. Of these, 142 (41%) of the primary care diagnoses were subsequently modified by the rheumatologist. The highest agreement between primary care physician and rheumatologist was observed for crystal-induced arthritis (kappa = 0.86), and the lowest agreement for polymyalgia rheumatica (kappa = 0.39) and systemic lupus (kappa = 0.46). Sensitivity was lowest for a primary care diagnosis of fibromyalgia (48%) and highest for ankylosing spondylitis (94%). Positive predictive values were generally low, in particular for systemic lupus erythematosus (33%) and polymyalgia rheumatica (30%). CONCLUSION: Most patients referred to an academic rheumatology centre had soft-tissue rheumatism or other pain syndromes. In general, diagnostic agreement between rheumatologists and primary care physicians was low. Increased emphasis on musculoskeletal disorders should be encouraged in medical education to increase the efficiency of rheumatology referrals.

Rheumatology 2002; 41: 450-453

A case–control study examining the role of physical trauma in the onset of fibromyalgia syndrome

A. W. Al-Allaf, K. L. Dunbar1, N. S. Hallum1, B. Nosratzadeh1, K. D. Templeton1 and T. Pullar Rheumatic Disease Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY and 1 Medical School, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK

Objective. To investigate whether physical trauma may precipitate the onset of fibromyalgia syndrome (FMS).

Design. A case–control study was carried out to compare fibromyalgia out-patients with controls attending non-rheumatology out-patient clinics.

Method. One hundred and thirty-six FMS patients and 152 age- and sex-matched controls completed a postal questionnaire about any physical trauma in the 6 months before the onset of their symptoms.

Results. Fifty-three (39%) FMS patients reported significant physical trauma in the 6 months before the onset of their disease, compared with only 36 (24%) of controls (P<0.007). There was no significant difference between FMS patients who had a history of physical trauma and those who did not have physical trauma with regard to age, sex, disease duration, employment status and whether their job at onset was manual.

Conclusion. Physical trauma in the preceding 6 months is significantly associated with the onset of FMS.

KEY WORDS: Fibromyalgia syndrome, Physical trauma, Occupation. Correspondence to: A. W. Al-Allaf, University Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.

Rheumatology 2001; 40: 95-101

Risk factors for persistent chronic widespread pain: a community-based study

J. McBeth,1, G. J. Macfarlane1,2, I. M. Hunt1 and A. J. Silman1 1 Arthritis Research Campaign (ARC) Epidemiology Unit, and 2 Unit of Chronic Disease Epidemiology, School of Epidemiology and Health Sciences, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK

Background. Chronic widespread pain is the cardinal clinical feature of the fibromyalgia syndrome, which, in the majority of clinic patients, is persistent. By contrast, in community-derived patients, pain is persistent in only half of the affected individuals, particularly those with psychological distress. Whether such distress is a consequence of the pain or a manifestation of a wider process of somatization which is associated with the persistence of pain is unclear.

Objectives. We tested in a large, prospective, population-based study the hypothesis that features of somatization predict the persistence of chronic widespread pain.

Methods. In all, 252 (13%) of 1953 adult subjects selected from a population register were classified as having chronic widespread pain based on a detailed questionnaire which included a pain drawing. The patients also completed a number of psychosocial instruments which measure features known to be associated with somatization. Two hundred and twenty-five (91%) of the patients were successfully followed up after 12 months and provided data on pain status using the same instruments.

Results. In all, 126 (56%) patients reported chronic widespread pain at follow-up, 74 (33%) reported other pain and 25 (11%) reported no pain. Persistent chronic widespread pain was strongly associated with baseline test scores for high psychological distress and fatigue. In addition, these subjects were more likely to display a pattern of illness behaviour characterized by frequent visits to medical practitioners for symptoms which disrupt daily activities. The prevalence of persistent pain increased with the number of risk factors the subjects were exposed to.

Conclusions. Although almost half of the cases of chronic widespread pain resolved within 1 yr, this study has demonstrated for the first time that those subjects who display features of somatization are more likely to have widespread pain which persists. These findings have implications for the identification and treatment of persons with persistent chronic widespread pain.

The British Journal of Rheumatology, Vol 35, 350-356

Anterior pituitary function in patients with newly diagnosed rheumatoid arthritis

E Templ, M Koeller, M Riedl, O Wagner, W Graninger and A Luger Division of Endocrinology and Metabolism, University of Vienna, Austria.

Hormonal dysfunction involving the hypothalamic-pituitary-adrenal (HPA) axis, prolactin (PRL) secretion and sex hormone status has been supposed to contribute to the development or persistence of rheumatoid arthritis (RA). In addition, a reduced number of glucocorticoid receptors on circulating lymphocytes has been found in patients with RA. However, so far most studies have been performed in pre-treated patients. A combined test for total anterior pituitary reserve was performed in 10 patients with newly diagnosed untreated RA. Before and after stimulation with the respective hypothalamic releasing hormones, RA patients showed no difference in plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol, prolactin (PRL) and thyroid-stimulating hormone (TSH) when compared to healthy controls. In contrast, the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) was blunted in RA patients. The hypothalamic-pituitary- thyroid/gonadal and adrenal axes seem to be unaltered in RA. However, if one considers the presence of chronic inflammation, normal plasma ACTH and cortisol concentrations must be considered as inappropriately low. The observed blunted GH release could be mediated by cytokines (e.g. IL-1), which are known to be elevated in RA.

Rheumatology 2000; 39: 624-631

The adrenal steroid status in relation to inflammatory cytokines (interleukin-6 and tumour necrosis factor) in polymyalgia rheumatica

R. H. Straub, T. Glück, M. Cutolo1, J. Georgi2, K. Helmke3, J. Schölmerich, P. Vaith4 and B. Lang

Department of Internal Medicine, University Medical Center Regensburg, D-93042 Regensburg, Germany, 1 Division of Rheumatology, Department of Internal Medicine, University of Genova, I-16136 Genova, Italy, 2 Ostseeklinik, D-24349 Damp, 3 Hospital München-Bogenhausen, D-81925 München and 4 Department of Internal Medicine, University Medical Center Freiburg, D-79106 Freiburg, Germany

Objectives. To determine the correlation between inflammatory cytokines and adrenal hormones in patients with polymyalgia rheumatica (PMR) and to compare the ratio of serum cortisol and androstenedione (ASD) or dehydroepiandrosterone sulphate (DHEAS) in normal subjects with PMR patients.

Methods. In 102 patients with PMR (32 beginning and 70 chronic disease) and 31 age-matched and sex-matched healthy subjects, ASD, cortisol, DHEAS, interleukin-6 (IL-6), and tumour necrosis factor (TNF) were measured by immunometric assays.

Results. Serum levels of IL-6 were elevated in patients with PMR as compared with normal subjects (10.0 ± 1.6 vs 2.1 ± 0.1 pg/ml, P = 0.01), which was not found for TNF. In PMR patients, serum levels of IL-6 were positively correlated with serum levels of ASD (P < 0.001), cortisol (P < 0.001), and DHEAS (P = 0.038) irrespective of corticosteroid treatment. Serum levels of cortisol in relation to IL-6 were significantly lower in patients with chronic disease and long-standing corticosteroid administration as compared with patients with recent onset of the disease and without corticosteroid therapy (P < 0.01).

Conclusions. In PMR, as expected, there was an increase in IL-6 serum levels that was associated with elevated serum levels of ASD, DHEAS, and cortisol which was more marked in patients with recent-onset disease and without corticosteroids. However, serum levels of cortisol in patients with and without corticosteroids were lower than expected by considering the inflammatory status (increased IL-6). This may indicate a change in the hypothalamic–pituitary–adrenal (HPA) axis responsiveness to inflammatory stimuli such as IL-6 during chronic disease. Furthermore, there seems to be a shift of biosynthesis to cortisol in relation to DHEAS or ASD in chronic disease.

Correspondence to: R. H. Straub, Department of Internal Medicine I, University Medical Center, D-93042 Regensburg, Germany.

The British Journal of Rheumatology, Vol 35, 436-440

ORIGINAL PAPERS

Endogenous opioid tone in patients with rheumatoid arthritis

D Kassimos, EH Choy, AB Grossman, IC Chikanza and GS Panayi Rheumatology Unit, Guy's Hospital, United Medical School, London.

We have previously shown that there is deficient hypothalamic-pituitary- adrenal (HPA) responsiveness in rheumatoid arthritis (RA) patients. The basis for this deficient response is not known. The purpose of the project was to investigate whether the defective HPA response in RA patients is the result of increased endogenous opioid tone secondary to chronic pain which can suppress corticotrophin-releasing hormone (CRH) production. We conducted a double-blind placebo-controlled cross-over trial to study the effect of the opiate antagonist, naloxone, on psychometric function together with plasma adrenocorticotrophic hormone (ACTH), cortisol and prolactin. Seven RA patients with active and established disease and eight healthy controls were studied. Each received either a bolus i.v. infusion of 20 mg naloxone or normal saline. After at least 72 h, they received naloxone if they had previously received normal saline or vice versa. The pain score was statistically significantly higher at baseline in the RA group compared with controls (5.7 +/- 3.25 vs 0.35 +/- 0.21, P < 0.001). No difference was found in the other psychometric assessments throughout the study. Patients receiving normal saline did not show any significant change in cortisol or ACTH. Cortisol and ACTH showed a sharp and significant rise after naloxone treatment in both RA and normal subjects (P < 0.001 and P < 0.01), but no difference was observed between the two groups. The mean prolactin level showed no significant change in both groups after any treatment. We conclude that endogenous opioid tone does not appear to be a major contributor to the HPA defect in RA. However, the number of patients studied was small and this result will require confirmation from larger trials.

Rheumatology 2000; 39: 764-771

Onset and severity of inflammation in rats exposed to the learned helplessness paradigm

A. J. Chover-Gonzalez, D. S. Jessop1, P. Tejedor-Real, J. Gibert-Rahola and M. S. Harbuz1, Department of Neuroscience, University of Cadiz, Spain, 1 Division of Medicine, University of Bristol, BRI, Marlborough Street, Bristol BS2 8HW, UK

Objective. To test the hypothesis that there is an association between susceptibility to inflammation and a hyporesponsive hypothalamo-pituitary-adrenal (HPA) axis.

Methods. Animals were separated on the basis of behaviour in the learned helplessness (LH) paradigm into groups of LH(+) (i.e. animals which did not escape footshock) and LH(-) animals. Adjuvant-induced arthritis (AA) was subsequently induced in the LH(+) and LH(-) animals.

Results. Plasma corticosterone was significantly increased in response to the LH test in the LH(-) compared with the LH(+) rats. We observed an earlier onset and increased inflammation in the LH(-) rats in spite of the greater corticosterone response to the acute stress. We noted lower levels of plasma testosterone in the LH(-) animals suggesting a possible influence for this protective factor in AA.

Conclusion. These data suggest that increased onset and severity of inflammation in AA is not a simple consequence of an attenuated HPA axis response to stress as proposed in the Lewis rat.

Indeed we have observed the converse. Together these data suggest that the balance of pro- and anti-inflammatory factors released in response to stress may influence the progress of AA.

KEY WORDS: Learned helplessness, Adjuvant-induced arthritis, Inflammation, HPA axis, Corticosterone, Testosterone, Behaviour.

Correspondence to: M. S. Harbuz, Division of Medicine, University of Bristol, BRI, Marlborough Street, Bristol BS2 8HW, UK.

Rheumatology 1999; 38: 1050-1057

Reviews

Stress system response and rheumatoid arthritis: a multilevel approach

J. G. Walker, G. O. Littlejohn1, N. E. McMurray and M. Cutolo2 School of Behavioural Science, The University of Melbourne, 1 Centre for Inflammatory Diseases, Monash Medical Centre, Melbourne, Australia and 2 Division of Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy

Correspondence to: M. Cutolo, Division of Rheumatology, Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 6, 16132 Genoa, Italy.

A growing body of research indicates that the stress system, and its interactions with the immune system, play a pivotal role in the aetiology and progression of rheumatoid arthritis (RA). The stress system has multiple levels and comprises physiological, psychological and environmental components. However, most investigations in RA that involve the stress system tend to focus on the interrelationships between neuroendocrine and immune function, and related disease activity, with little regard for the role of other aspects of stress system activation, including psychological variables. This is despite the fact that psychological stressors, and related psychological variables, are known to influence RA disease activity. This article aims to explore the multiple levels of stress system activation and how they may ultimately influence disease-related outcomes in RA. Some measurement issues of psychological stress will also be examined.

Rheumatology 2001; 40: 868-875

Original Papers

Systemic lupus erythematosus and rheumatoid arthritis patients differ from healthy controls in their cytokine pattern after stress exposure

R. Jacobs, C. R. Pawlak1, E. Mikeska1, D. Meyer-Olson, M. Martin2, C. J. Heijnen3, M. Schedlowski4 and R. E. Schmidt Division of Clinical Immunology,

1 Division of Medical Psychology, 2 Division of Clinical Molecular Pharmacology, Hannover Medical School, 30623 Hannover, Germany, 3 Division of Immunology, University Hospital for Children and Youth, 3501 CA Utrecht, The Netherlands and 4 Division of Medical Psychology, University of Essen, 45122 Essen, Germany

Objective. To study whether patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) differ from healthy individuals in their immune responses to acute psychological stress.

Methods. The phenotype and function of peripheral blood lymphocytes were analysed before and after stress exposure in patients and healthy subjects.

Results. Natural killer (NK) cell numbers increased transiently in all groups under stress. NK activity, however, increased in healthy controls only. We observed a stress-induced increase in interleukin (IL)-4-producing (IL-4+) cells in SLE patients only, whereas interferon (IFN) + cell numbers increased due to stress in all three groups. An analysis of supernatants from phytohaemagglutinin (PHA) cultures revealed increased IFN and IL-10 levels in healthy subjects but not in SLE or RA patients after stress exposure.

Conclusions. These data demonstrate that RA and SLE patients differ in their immune response to stress from healthy controls. Changes in cytokine patterns might be responsible for stress-induced exacerbation of disease activity in RA and SLE patients.

KEY WORDS: Rheumatoid arthritis, Systemic lupus erythematosus, Stress, Natural killer cells, Cytokines.

The British Journal of Rheumatology, Vol 37, 1077-1083

Alteration of central serotonin modifies onset and severity of adjuvant- induced arthritis in the rat

MS Harbuz, O Marti, SL Lightman and DS Jessop Department of Hospital Medicine, University of Bristol, Bristol Royal Infirmary.

OBJECTIVE: Previous studies have determined that depletion of serotonin reduces the severity of hind-paw inflammation in adjuvant-induced arthritis (AA) in the rat. We wished to (i) test the hypothesis that this effect may be mediated, at least in part, through a central mechanism and (ii) to investigate further the pro-inflammatory role of serotonin we determined whether increasing serotonin using a selective serotonin reuptake inhibitor (SSRI), to increase serotonin availability at the active site of release, would increase inflammation. METHODS: (i) Serotonin was depleted in the brain of rats with the selective neurotoxin 5'7'-dihydroxytryptamine. (ii) Rats were treated with an SSRI on days 10, 11 and 12 following adjuvant injection. Hind-paw inflammation was determined with plethysmometry as an index of severity of inflammation, and brain, pituitaries and blood were collected for assessment of changes in the hypothalamo pituitary adrenal (HPA) axis. RESULTS: (i) Serotonin depletion significantly reduced hind-paw inflammation. (ii) SSRI-treated animals developed hind-paw inflammation sooner, and the severity was increased compared to vehicle-treated AA rats. The changes in the HPA axis associated with inflammation were partly reversed by this treatment. CONCLUSION: These data suggest a pro- inflammatory role for central serotonin in this disease model and indicate that treatment with SSRIs may exacerbate the development of inflammation.

Rheumatology 2002; 41: 423-429

In polymyalgia rheumatica serum prolactin is positively correlated with the number of typical symptoms but not with typical inflammatory markers

R. H. Straub, J. Georgi1, K. Helmke2, P. Vaith3 and B. Lang4 Department of Internal Medicine, University Medical Centre Regensburg, D-93042 Regensburg, 1 Ostseeklinik, D-24349 Damp, 2 Hospital München-Bogenhausen, D-81925 München, 3 Department of Internal Medicine, University Medical Centre Freiburg, D-79106 Freiburg and 4 Centre for Rheumatic Diseases, D-76530 Baden-Baden, Germany

Objectives. Hyperprolactinaemia has been associated with the active phase of human systemic lupus erythematosus and rheumatoid arthritis. In the present study, we investigated the role of prolactin (PRL) in relation to the number of typical symptoms and serum markers of systemic inflammation in patients with polymyalgia rheumatica (PMR).

Methods. One hundred and two PMR patients presented with typical symptoms such as adynamia, bilateral muscular pain in shoulders, upper arms or neck, bilateral muscular pain in the pelvic girdle, headache, morning stiffness, arthralgia, symptoms of depression, fever, initial weight loss (>4 kg/month), and transient visual symptoms. If one of the mentioned symptoms was present, the corresponding item was scored with one point (maximum unweighted item points=10). PRL, interleukin-2 (IL-2), IL-6, IL-1 receptor antagonist (IL-1ra), tumour necrosis factor (TNF), soluble IL-2 receptor (sIL-2R), and soluble vascular cell adhesion molecule (sVCAM) were measured by enzyme-linked immunosorbent assay in patients and 31 age-matched healthy controls.

Results. Fifteen PMR patients with elevated PRL had a higher number of symptoms as compared with patients with normal levels (P=0.003). PRL was correlated with the number of symptoms (all PMR patients: rrank=+0.380, P<0.001) and duration of morning stiffness (all PMR patients: rrank=+0.335, P=0.002) irrespective of prior corticosteroid treatment. However, PRL did not correlate with markers of systemic inflammation such as erythrocyte sedimentation rate, C-reactive protein, serum IL-1ra, IL-2, sIL-2R, IL-6, TNF, and sVCAM.

Conclusion. The number of symptoms in PMR patients was positively correlated with PRL, but PRL was not correlated with serum markers of inflammation. This indicates that PRL is not a pro-inflammatory stimulus in patients with PMR. The inter-relationship between PRL and symptoms or duration of morning stiffness may be more a sign of central nervous system involvement, as it can be observed in people with depressed mood or under psychological stress.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Oct;86(4):416-20.

The relationship between temporomandibular disorders and stress-associated syndromes.

Korszun A, Papadopoulos E, Demitrack M, Engleberg C, Crofford L Department of Psychiatry and School of Dentistry, University of Michigan, Ann Arbor 481090840, USA. OBJECTIVES: The purpose of this study was to determine the comorbidity of temporomandibular disorders and other stress-associated conditions in patients with chronic fatigue syndrome and fibromyalgia. STUDY DESIGN: Of 92 patients who fulfilled the criteria for chronic fatigue syndrome or fibromyalgia (or both), 39 (42%) reported a prior diagnosis of temporomandibular disorder. Further questionnaires were sent to the members of this group, and 30 patients responded. RESULTS: Of the original 92 patients, of whom 42% reported temporomandibular disorders, 46% had histories of irritable bowel syndrome, 42% of premenstrual syndrome, and 19% of interstitial cystitis. Of the patients with temporomandibular disorders, the great majority reported an onset of generalized symptoms before the onset of facial pain. Despite this, 75% had been treated exclusively for temporomandibular disorders, usually with bite splints. CONCLUSIONS: Patients appearing for treatment with chronic facial pain show a high comorbidity with other stress-associated syndromes. The clinical overlap between these conditions may reflect a shared underlying pathophysiologic basis involving dysregulation of the hypothalamic-pituitary-adrenal stress hormone axis in predisposed individuals. A multidisciplinary clinical approach to temporomandibular disorders would improve diagnosis and treatment outcomes for this group of patients.

Pankhurst CL.

Controversies in the aetiology of temporomandibular disorders. Part 1. Temporomandibular disorders: all in the mind?

Prim Dent Care. 1997 Jan;4(1):25-30. Review. King's College Dental Institute, London.

The aetiology of temporomandibular disorders (TMDs) is now considered to be multifactorial but the relative importance of individual aetiological factors is still controversial. Psychosocial factors play an important role in the aetiology of TMDs, in adaptation to pain and eventual recovery. TMD patients exhibit a variety of psychological and behavioural characteristics including increased somatization, stress, anxiety and depression. Subcategorisation of TMD patients into joint-related and muscle-related groups reveals psychological differences. Myogenic patients have increased severity of pain and suffer enhanced psychological distress. Within this group of patients are a minority of refractory cases who show marked overlap with those suffering from chronic pain syndrome; such patients benefit from psychiatric assessment and treatment. However, no common TMD personality profile has emerged from the psychometric test research. Recent knowledge of the molecular pathways induced by stress and the evaluation of stress-response substances may, in the future, provide diagnostically valuable biochemical markers of disease susceptibility. The role of psychological factors in the development of TMDs in the general population is critically examined.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996 Nov;82(5):496-500.

Comorbidity of depression with chronic facial pain and temporomandibular disorders.

Korszun A, Hinderstein B, Wong M School of Dentistry/Department of Psychiatry, University of Michigan Medical Center, Ann Arbor, USA.

OBJECTIVE: The objective of this study was to examine the comorbidity of depressive disorders in patients with chronic facial pain presenting to a multidisciplinary facial pain clinic. STUDY DESIGN: Data were collected from 72 consecutive patients with chronic facial pain who had received a maltidisciplinary evaluation including a psychiatric examination for the presence of depressive disorders. RESULTS: Twenty-eight percent of patients met criteria of the latest Diagnostic and Statistical Manual of Mental Disorders for major depression, and 25% met the criteria for minor depression. A further 22% reported subsyndromal depressive symptoms. Temporomandibular disorders were demonstrable in 71% of these patients, but the remaining 29% had no objective physical findings. There was no statistical difference in comorbidity of depressive disorders in patients with temporomandibular disorders compared with patients without temporomandibular disorders. CONCLUSION: Screening for symptoms of depression should be an integral part of the evaluation of all patients with chronic facial pain, even when masticatory muscle or temporomandibular joint disorders are identified.

QUICK SLEEP, FIBROMYALGIA AND COGNITIVE FUNCTIONING SEARCH

Circa 1999

Sleep, daytime symptoms, and cognitive performance in patients with fibromyalgia.

C oté KA; Moldofsky H University of Toronto Centre for Sleep and Chronobiology, Toronto Hospital, Ontario, Canada. J Rheumatol, 1997 Oct, 24:10, 2014-23

OBJECTIVE: To assess sleep, daytime symptoms, and cognitive performance in patients with fibromyalgia (FM). METHODS: Ten female patients with FM (mean age 32 yrs) and a matched, noncomplaintive comparison group (n = 9; mean age 30 yrs) spent 2 nights in the sleep laboratory. After the 2nd night, subjects completed a computerized 20 min battery of self-assessment and performance tests at hourly intervals from 07:00 to 20:00 h. RESULTS: Patients with FM spent more time in stage 1 sleep; however, there were no group differences on any other sleep measures. They reported greater sleepiness, more fatigue, more pain, more negative mood, and lower accuracy on performance tasks across a 14 h day. The FM group was slower in speed, but not impaired in accuracy, on performance of complex tasks, i.e., grammatical reasoning, serial addition/subtraction, and a simulated multi-task office procedure. CONCLUSION: Patients with FM have diurnal impairment in speed of performance on complex cognitive tasks, which accompany light stage 1 electroencephalographic (EEG) sleep and their experience of diffuse pain and nonrestorative sleep symptoms of sleepiness, fatigue, and negative mood.

Effects of selective slow wave sleep disruption on musculoskeletal pain and fatigue in middle aged women.

Lentz MJ; Landis CA; Rothermel J; Shaver JL

Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle 98195-7266, USA. J Rheumatol, 1999 Jul, 26:7, 1586-92

OBJECTIVE: To determine whether disrupted slow wave sleep (SWS) would evoke musculoskeletal pain, fatigue, and an alpha electroencephalograph (EEG) sleep pattern. We selectively deprived 12 healthy, middle aged, sedentary women without muscle discomfort of SWS for 3 consecutive nights. Effects were assessed for the following measures: polysomnographic sleep, musculoskeletal tender point pain threshold, skinfold tenderness, reactive hyperemia inflammatory flare response), somatic symptoms, and mood state. METHODS: Sleep was recorded and scored using standard methods. On selective SWS deprivation (SWSD) nights, when delta waves (indicative of SWS) were detected on EEG, a computer generated tone maximum 85 decibels) was delivered until delta waves disappeared. Musculoskeletal tender points were measured by dolorimetry; skinfold tenderness was assessed by skin roll procedure; and reactive hyperemia was assessed with a cotton swab test. Subjects completed questionnaires on bodily feelings, symptoms, and mood. RESULTS: On each SWSD night, SWS was decreased significantly with minimal alterations in total sleep time, sleep efficiency, and other sleep stages. Subjects showed a 24% decrease in musculoskeletal pain threshold after the third SWSD night. They also reported increased discomfort, tiredness, fatigue, and reduced vigor. The flare response (area of vasodilatation) in skin was greater than baseline after the first, and again, after the third SWSD night. However, the automated program for SWSD did not evoke an alpha EEG sleep pattern. CONCLUSION: Disrupting SWS, without reducing total sleep or sleep efficiency, for several consecutive nights is associated with decreased pain threshold, increased discomfort, fatigue, and the inflammatory flare response in skin. These results suggest that disrupted sleep is probably an important factor in the pathophysiology of symptoms in fibromyalgia.

The effects of delta wave sleep interruption on pain thresholds and fibromyalgia-like symptoms in healthy subjects; correlations with insulin-like growth factor I.

Older SA; Battafarano DF; Danning CL; Ward JA; Grady EP; Derman S; Russell IJ Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6272, USA. J Rheumatol, 1998 Jun, 25:6, 1180-6

OBJECTIVE: To assess the effects of delta wave sleep interruption (DWSI) on pain thresholds and fibromyalgia-like symptoms. To examine the potential correlations between DWSI and serum insulin-like growth factor 1 (IGF-1). METHODS: Thirteen healthy volunteers were subjected to 3 consecutive nights of DWSI (Group 1). Pain thresholds were measured by dolorimetry and symptoms by visual analog scale. Six subjects not undergoing DWSI served as dolorimetry and symptom controls (Group 2). Serum IGF-1 was measured by competitive binding radioimmunoassay before and after DWSI. RESULTS: No significant differences in pain thresholds as a function of condition (baseline, DWSI, recovery) or overnight change were detected between or within groups (p>0.05). Morning mean dolorimeter scores were lower than evening scores in both groups during all 3 conditions, and were lower in Group 1 than in Group 2 during DWSI. Group 1 subjects had higher composite symptom scores during DWSI (p< or =0.005), attributed largely to increases in fatigue. Serum levels of IGF-1 from Group 1 subjects showed no significant change after DWSI (p>0.05). CONCLUSION: In our study subjects, 3 nights of DWSI caused no significant lowering of pain thresholds compared with a control group. Subjects appeared to have lower pain thresholds in the mornings, and DWSI appeared to augment this effect. Symptoms were more apparent during DWSI, but were primarily related to fatigue. IGF-1 was not altered by 3 nights of DWSI. The low levels of IGF-1 seen in patients with fibromyalgia syndrome may result from chronic rather than acute DWSI, or may be dependent on factors other than disturbances of delta wave sleep.

Sleep, psychological distress, and stress arousal in women with fibromyalgia.

Shaver JL; Lentz M; Landis CA; Heitkemper MM; Buchwald DS; Woods NF College of Nursing (M/C 802), University of Illinois at Chicago 60612, USA. Res Nurs Health, 1997 Jun, 20:3, 247-57

The purpose of this investigation was to compare self-reported sleep quality and psychological distress, as well as somnographic sleep and physiological stress arousal, in women recruited from the community with self-reported medically diagnosed fibromyalgia (FM) to women without somatic symptoms. Eleven midlife women with FM, when compared to 11 asymptomatic women, reported poorer sleep quality and higher SCL-90 psychological distress scores. Women with FM also had more early night transitional sleep (stage 1) (p < 0.01), more sleep stage changes (p < 0.03) and a higher sleep fragmentation index (p < 0.03), but did not differ in alpha-EEG-NREM activity (a marker believed to accompany FM). No physiological stress arousal differences were evident. Less stable sleep in the early night supports a postulate that nighttime hormone (e.g., growth hormone) disturbance is an etiologic factor but, contrary to several literature assertions, alpha-EEG-NREM activity sleep does not appear to be a specific marker of FM. Further study of mechanisms is needed to guide treatment options.

Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia.

Bell IR; Baldwin CM; Schwartz GE Department of Psychiatry, University of Arizona, Tucson Veterans Affairs Medical Center, 85723, USA. Am J Med, 1998 Sep, 105:3A, 74S-82S

This article summarizes (1) epidemiologic and clinical data on the symptoms of maladies in association with low-level chemicals in the environment, i.e., environmental chemical intolerance CI), as it may relate to chronic fatigue syndrome (CFS) and fibromyalgia; and (2) the olfactory-limbic neural sensitization model for CI, a neurobehavioral synthesis of basic and clinical research. Severe CI is a characteristic of 20-47% of individuals with apparent CFS and/or fibromyalgia, all patients with multiple chemical sensitivity (MCS), and approximately 46% of the general population. In the general population, 15-30% report at least minor problems with CI. The levels of chemicals reported to trigger CI would normally be considered nontoxic or subtoxic. However, host factors--e.g., individual differences in susceptibility to neurohormonal sensitization amplification) of endogenous responses--may contribute to generating a disabling intensity to the resultant multisystem dysfunctions in CI. One site for this amplification may be the limbic system of the brain, which receives input from the olfactory pathways and sends efferents to the hypothalamus and the mesolimbic dopaminergic [reward] pathway. Chemical, biologic, and psychological stimuli can initiate and elicit sensitization. In turn, subsequent activation of the sensitized limbic and mesolimbic pathways can then facilitate dysregulation of behavioral, autonomic, endocrine, and immune system functions. Research to date has demonstrated the initiation of neurobehavioral sensitization by volatile organic compounds and pesticides in animals, as well as sensitizability of cardiovascular parameters, beta-endorphin levels, resting EEG alpha-wave activity, and divided-attention task performance in persons with

CI.
The ability of multiple types of widely divergent stimuli to initiate and elicit sensitization offers a new perspective on the search for mechanisms of illness in CFS and fibromyalgia with

CI.

Alpha sleep and information processing, perception of sleep, pain, and arousability in fibromyalgia.

Perlis ML; Giles DE; Bootzin RR; Dikman ZV; Fleming GM; Drummond SP; Rose MW Department of Psychiatry, University of Rochester, NY, USA. mperlis@obgyn.rochester.edu Int J Neurosci, 1997 Feb, 89:3-4, 265-80

This study examined the relationship between alpha sleep and information processing during sleep, perception of sleep, musculoskeletal pain, and arousability in patients with fibromyalgia. Patients (n = 20) were allowed to sleep undisturbed for the first 60 minutes of the study to assess amount of alpha sleep and were classified as high or low alpha generators based on quantitative analyses of alpha activity during this period. The groups were compared for performance on two memory tasks, perceptions of polysomnographically-defined sleep and EEG arousals in response to auditory stimuli. Correlations between symptoms of fibromyalgia and alpha activity were also examined. Alpha activity during sleep in fibromyalgic patients was associated with the perception of shallow sleep and an increased tendency to arouse in relation to auditory stimuli. Alpha activity was not associated with increased memory for auditory stimuli presented during sleep, sleep state misperception, or with myalgia symptoms. Alpha sleep appears to be, electrophysiologically, a shallow form of sleep. Our results suggest that it is perceived as such phenomenologically and that it is also associated with increased arousability.

1996 - 1997 ABSTRACTS

Acute sarcoid arthritis: a favourable outcome? A retrospective survey of 49 patients with review of the literature.

Forty-nine patients, 30 males and 19 females with acute sarcoid arthritis admitted to three different hospitals in Norway were studied retrospectively. All patients had peripheral arthritis and hilar adenopathy, and 87.8% also presented with erythema nodosum (EN). Mean duration of arthritis was 3.7 months (0.5-12 months), but in 26% of the cases, duration of the inflammatory joint disease exceeded three months. Radiological bony erosions were not seen. Two patients had recurrence of acute sarcoid arthritis, 14 months and 10 years after the initial episode, respectively. Two other patients developed chronic myalgia and fibromyalgia. Four patients, one female and three males, developed chronic pulmonal sarcoidosis. Of these, two patients had simultaneous onset of acute sarcoid arthritis and parenchymal disease while two patients developed chronic lung disease three months after onset of acute sarcoid arthritis. We thus tentatively suggest that although acute sarcoid arthritis is usually a self-limiting joint disease, recurrences may occasionally occur and some cases develop chronic sarcoidosis of the lungs.

Gran JT, Bohmer E Department of Rheumatology, Central Hospital of Aust Agder, Arendal, Norway. Scand J Rheumatol 1996;25(2):70-3 Publication Types: · Review · Review literature

Alternative medicine use in fibromyalgia syndrome

OBJECTIVE: To record the prevalence, extent, cost, and satisfaction with use of alternative medicine practices by patients with fibromyalgia syndrome (FMS), compared to control rheumatology patients.

METHODS: An interviewer-based questionnaire was administered to 221 consecutive rheumatology patients and 80 FMS patients.

RESULTS: Alternative medicine interventions were currently being used extensively by rheumatology patients overall, and by FMS patients in particular. All categories of alternative practices were used more often by FMS patients, compared to controls, including overall use 91% versus 63% (P = 0.0001), over- the-counter products 70% versus 54% (NS), spiritual practices 48% versus 37% (NS), and alternative practitioners 26% versus 12% (P = 0.003), respectively. Two-thirds of patients using alternative medicine practices were concurrently using multiple interventions. Patient satisfaction ratings were highest for spiritual interventions.

CONCLUSIONS: Alternative medicine practices were currently being used by almost all FMS patients. This observation might indicate that traditional medical therapies are inadequate in providing symptomatic relief to FMS patients.

Pioro-Boisset M •Esdaile JM •Fitzcharles MA Arthritis Care Res 1996;9(1):13-7 Comments: •Arthritis Care Res -- 1996 Feb;9(1):1-2

Ambulatory polysomnography using a new programmable amplifier system with on-line digitization of data: technical and clinical findings.

A new system for polysomnographic recording at home is presented. It consists of a 12 to 24channel amplifier system with direct digitization of the polygraph signals using a portable computer. Sampling frequency, amplification and filter settings can be defined by the user, and the signals are evaluated at bedside. Technical testing proved a high signal/noise ratio, linear amplification and a good signal quality. Clinical testing of the first 100 recordings showed that

they were acceptable for conventional sleep scoring in 98 cases. A comparison of two consecutive recordings was done in 9 healthy subjects and 11 patients with rheumatic disorders. Using conventional sleep staging, only a slight "first night effect" (FNE) was demonstrated in the sleep architecture. Power spectral analysis using autoregressive modeling demonstrated only a difference of power between the 2 nights in the beta (14.5-25 Hz) band. In conclusion, the usability and technical advantages make the system very suitable for ambulatory recordings and only a minimal FNE should be considered when results are evaluated.

Drewes AM •Nielsen KD •Taagholt SJ •Svendsen L •Bjerregard K •Nielsson L •Kristensen L Department of Rheumatology, Aalborg Hospital, Denmark. Sleep 96;19(4):347-54

[Analgesic effect of ketamine in a patient with neuropathic pain].

We report the effect of a single daily dose of ketamine in a 54 year old woman with fibromyalgia and severe post-traumatic neuropathic pain. A number of different approaches for pain relief had been tried with little effect.

An intramuscular test dose of 0.4 mg/kg ketamine combined with 0.05 mg/kg midazolam lead to analgesia which lasted for almost two days. Long-term analgesia was also obtained by 250 mg/kg ketamine hydrochloride taken orally in the form of capsules every night at bedtime. The patient has now used this dose for nine months.

Ketamine is an NMDA receptor antagonist. A single sub-anaesthetic dose of ketamine causes a long-term depression of pain intensity in some, but not in all, patients suffering chronic pain. This effect is distinctly different from the short-lasting (10-30 min) analgesic effect in cases of acute nociceptive pain.

The long-term depression of the intensity of chronic pain states may be due to a reversal of NMDA receptor-dependent long-term potentiation of synapses in central pain pathways. By giving ketamine as a single dose at night the mental side-effects are reduced or avoided.

Oye I, Rabben T, Fagerlund TH Farmakologisk Institutt, Blindern, Oslo. Tidsskr Nor Laegeforen 1996 Oct 30;116(26):3130-3131 [Article in Norwegian]

Association between chronic widespread musculoskeletal complaints and thyroid autoimmunity. Results from a community survey.

OBJECTIVE: To test a hypothesis derived from observations in general practice that thyroid antibodies were associated with chronic widespread musculoskeletal complaints.

DESIGN: Cross-sectional study of 40-42 year old men and women based on a self-administered questionnaire and on results of blood tests.

SETTING: Sarpsborg municipality, Norway.

PARTICIPANTS: 737 men and 771 women who attended the National Health Screening Service's mobile unit in 1989 and answered the questionnaire.

MAIN OUTCOME MEASURES: Prevalence of detectable microsomal thyroid antibodies in persons with and without chronic widespread musculoskeletal complaints.

RESULTS: The prevalence of thyroid microsomal antibodies was significantly higher in persons with than without chronic widespread musculoskeletal complaints (16.0% versus 7.3%, p < 0.01). The increase was restricted to women (20.4% versus 11.6%, p = 0.02). Thyroid function tests did not differ significantly between the two groups.

CONCLUSION: The association between chronic widespread musculoskeletal pain complaints and thyroid antibodies in women may reflect a subgroup of patients in which thyroid autoimmunity, rather than thyroid function, is important. A possible relationship to fibromyalgia is discussed as well as a hypothetical role for thyrotropin releasing hormone.

Aarflot T •Bruusgaard D Department of Community Medicine and General Practice, University of Oslo, Norway. Scand J Prim Health Care 1996;14(2):111-15

Bowel dysfunction and irritable bowel syndrome in fibromyalgia patients [see comments]

Fibromyalgia and irritable bowel syndrome are both common conditions which account for most of the referrals to physical medicine and rehabilitation-rheumatology and gastroenterology clinics, and they frequently coexist. In this study, we utilized a previously validated questionnaire to assess the prevalence of symptoms of bowel dysfunction and irritable bowel syndrome, and to survey the range of bowel pattern in 75 patients with fibromyalgia as compared to 50 normal controls. Symptoms associated with irritable bowel syndrome (p < 0.05) were reported in 41.8% of the fibromyalgia patients and 16% of the normal controls. In conclusion, we found that patients with fibromyalgia have a high prevalence of gastrointestinal complaints confirming the results indicating that fibromyalgia and irritable bowel syndrome frequently coexist. This may suggest a common pathogenic mechanism for both conditions.

Sivri A •Cinda[s A •Din[cer F •Sivri B Hacettepe University, Dept. of Physical Medicine and Rehabilitation, Ankara, Turkey. Clin Rheumatol 1996;15(3):283-6

Chronic arthropathy and musculoskeletal symptoms associated with rubella vaccines. A review of 124 claims submitted to the National Vaccine Injury Compensation Program.

OBJECTIVE: To report the outcome of 124 claims of chronic arthropathy associated with rubella vaccine submitted to the National Vaccine Injury Compensation Program.

METHODS: Medical records and testimony were reviewed separately by physicians and Special Masters to determine the clinical diagnosis and eligibility for compensation under the Program.

RESULTS: Among the 124 subjects with chronic arthropathy, the onset occurred between 1 week and 6 weeks after the rubella vaccination in 72, and < 1 week or > 6 weeks after the vaccination in 52. Various conditions developed in the 2 onset groups (1-6 weeks postvaccination, < 1 week or > 6 weeks postvaccination), including, respectively, unspecified arthritis (n = 29, n = 1), specified arthritis (n = 11, n = 19), arthralgia (n = 24, n = 7), fibromyalgia (n = 4, n = 11), and multiple symptoms with minimal arthralgia or myalgia (n = 4, n = 14). Concordance of medical recommendations by Program physicians and Special Masters' decisions in 56 completed claims was 91%, with awards mainly to patients with chronic unspecified arthritis and arthralgia.

CONCLUSION: The Program and the US Court of Federal Claims have accepted a causal relationship between currently used rubella vaccine in the US and some chronic arthropathy with an onset between 1 week and 6 weeks after vaccine administration.

Weibel RE •Benor DE National Vaccine Injury Compensation Program, US Public Health Service, Rockville, Maryland 20857, USA. Arthritis Rheum 1996;39(9)1529-34

Chronic fatigue, chronic fatigue syndrome, and disability and health-care use.

OBJECTIVES: Disabling chronic fatigue that does not meet criteria for chronic fatigue syndrome (CFS) or fibromyalgia (FM) is a condition thought to be associated with substantial disability and an apparently high use of health-care services. The authors compare patients who have chronic fatigue, CFS, FM, or CFS and FM together (CFS+FM) on employment status, self- reported disability, number of medical care visits, type of services obtained, and other diagnoses received.

METHODS: The authors studied 402 patients from a university-based chronic fatigue clinic. All patients underwent an initial structured diagnostic assessment. One hundred forty-seven patients met case criteria for CFS, 28 for FM, 61 for CFS+FM, and 166 fell in the residual chronic fatigue group. Of these patients, 388 completed a follow-up questionnaire an average of 1.7 years later. Chi-squared tests and analysis of variance were used to compare groups on follow-up measures of health-care use and disability.

RESULTS: Patients with chronic fatigue, CFS, FM, and CFS+FM were similar in terms of disability and health-care use, though those with CFS+FM were significantly more likely to be unemployed and to use more chiropractic and "other" provider services. Rates of unemployment ranged from 26% (chronic fatigue) to 51% (CFS+FM). Overall, patients reported a mean of 21 visits to a wide variety health-care providers during the previous year, with no significant differences between groups.

CONCLUSIONS: Chronic fatigue, CFS, and FM are associated with considerable personal and occupational disability and low rates of employment. The potentially large economic burden of these disorders underscores the need for accurate estimates of direct and indirect costs, the relative contribution of individual factors to disability, and the need to develop targeted rehabilitation programs.

Bombardier CH, Buchwald D. Med-Care 1996 Sep;34(9):924-930.

Chronic regional muscular pain in women with precise manipulation work. A study of pain characteristics, muscle function, and impact on daily activities.

Pain characteristics, muscle function and impact on daily activities were studied in 39 women with chronic regional muscular pain (RMP). They were all blue-collar workers in work involving precise manipulations. The main location of the pain was in the neck-shoulder region.

Nineteen age-matched women with fibromyalgia (FM) were studied in the same way as the RMP patients. Thirty-seven women with no pain and with the same age and weight as the RMP patients served as reference group with respect to muscle strength and endurance.

A follow-up study was done with respect to pain distribution and other pain characteristics 20 months after the initial examination. The findings were of the same nature in the RMP and the FM groups. The intensity of pain, the lowering of pain threshold for pressure, and the degree of sleep disturbance were greater in the FM than in the RMP group. Isometric muscle strength and static muscular endurance were reduced in both FM and RMP compared to reference values.

The reduction in strength and endurance was greater in FM than in RMP. Even if the impact on everyday activities were greater in FM than in RMP, the impact was substantial in RMP patients also, for example with regard to work capacity. There were no transitions from RMP to FM during the 20 months to follow- up. Three FM patients, however, did not meet the ACR criteria for FM at follow-up.

Henriksson KG •Backman E •Henriksson C •de Laval JH Neuromuscular Unit and Pain Clinic, University Hospital, Linkoping, Sweden. Scand J Rheumatol 1996;25(4):213-23

Cognitive-educational treatment of fibromyalgia: a randomized clinical trial. I. Clinical effects.

OBJECTIVE: This randomized controlled clinical trial evaluates the effectiveness of outpatient group cognitive/educational treatment for patients with the fibromyalgia (FM) syndrome. We hypothesized that the combination of group education with cognitive treatment aimed at developing pain coping skills would be more effective than group education alone.

METHODS: 131 patients with FM were randomly assigned to 3 conditions: an experimental condition, which was the combined cognitive/educational intervention (ECO); an attention control condition consisting of group education plus group discussion (EDI); and a waiting list control (WLC). For the treatment conditions ECO and EDI, assessments were made 2 weeks before treatment, at start of treatment, at post- treatment, and at 6 and 12 mo followup. WLC patients received only 3 assessments.

RESULTS: There were no pretreatment differences between the groups, or between dropouts and patients who remained in the study. At post-treatment, and compared with the WLC, the ECO patients improved in knowledge about FM (p = 0.007) and pain coping (p < 0.001). EDI patients improved on pain coping (p = 0.005) and pain control (p = 0.002). EDI patients reported significantly less fear than ECO patients (p = 0.005). There were no other differential effects between ECO and EDI at post-treatment or 6 mo or 12 mo followup. Based on the reliability of change index for clinical significance, the relative short term success rates are 6.4 and 18.4% for ECO and EDI, respectively.

CONCLUSION: The surplus value of a highly structured, 12 session group cognitive treatment added to group education cannot be supported by our study. In EDI, fear reduction might have enhanced pain coping and pain control, while poor compliance, the difficulty of homework assignments, and lack of individual support may have limited the effectiveness of ECO.

Vlaeyen JW •Teeken-Gruben NJ •Goossens ME •Rutten-van Molken MP •Pelt RA •van Eek H

•Heuts PH Institute for Rehabilitation Research, Hoensbroek, The Netherlands. J Rheumatol 1996;23(7):1237-45

Cognitive-educational treatment of fibromyalgia: a randomized clinical trial. II. Economic evaluation.

OBJECTIVE: In this 3 year randomized clinical trial the cost effectiveness of a 6 week educational/ cognitive intervention (ECO) is compared with an educational discussion intervention (EDI) and a waiting list condition (WLC).

METHODS: A total of 131 patients with fibromyalgia were randomly allocated to the ECO, EDI, or WLC intervention. The ECO and EDI groups were followed for 12 months, whereas the WLC group was followed for 6 weeks. Direct health care and nonhealth care costs, and the

indirect costs associated with lost production due to illness, were calculated. The effects were measured in terms of utilities, using rating scale and standard gamble methods.

RESULTS: Treatment costs were estimated to be US $980 per patient for both ECO and EDI. The total direct health care costs of ECO treatment were US $1623 higher than those for EDI. This difference was significant. Indirect costs for the 2 groups were not significantly different. At 6 weeks there was a significant difference in rating scale utilities between the 3 groups, caused by a significantly greater improvement in the EDI group compared to the WLC group. However, no significant differences in either rating scale or standard gamble utilities were found between the ECO and EDI groups immediately after treatment, or at the 6 or 12 month followups.

CONCLUSION: The economic evaluation showed that the addition of a cognitive component to the educational intervention led to significantly higher health care costs and no additional improvement in quality of life compared to the educational intervention alone. This conclusion is robust through a range of plausible values used in a sensitivity analysis.

Goossens ME •Rutten-van Molken MP •Leidl RM •Bos SG •Vlaeyen JW •Teeken-Gruben NJ Department of Health Economics, University of Limburg, Maastricht, The Netherlands. J Rheumatol 1996;23(7):1246-54

Coping strategies predict disability in patients with primary fibromyalgia.

We administered the Coping Strategies Questionnaire (CSQ) to 80 patients with fibromyalgia (FM) to determine the relationship between coping strategies and functional disability. A principal components factor analysis revealed two dimensions of patients' CSQ responses: Coping Attempts and Catastrophizing. Coping Attempts consists of five scales: Reinterpreting Pain, Ignoring Pain Sensations, Diverting Attention, Coping Self-Statements and Increasing Activity Level. Catastrophizing is comprised solely of the CSQ Catastrophizing scale. Both coping strategy dimensions were significantly related to patients' disability scores on the Sickness Impact Profile even after controlling for demographic and clinical variables as well as neuroticism. Coping Attempts was associated with higher levels of Physical (P < 0.05) and Total Disability (P < 0.01), and lower levels of Psychosocial Disability (P < 0.05). Catastrophizing was associated with higher levels of Total Disability (P < 0.01). These relationships suggest that investigators should attempt to identify Coping Attempts strategies that best reduce patients' psychological distress in the laboratory. It then may be possible to teach patients to use these strategies to reduce distress in their home and work environments.

Martin MY, Bradley LA, Alexander RW, Alarcon GS, Triana-Alexander M, Aaron LA, Alberts KR University of Alabama School of Medicine, Department of Medicine, Birmingham 35294-0006, USA. Pain 1996 Nov;68(1):45-53

[Diagnosis of fibromyalgia. A critical review of the Scandinavian literature].

A critical review of Nordic literature on fibromyalgia (FMA), undertaken to test the hypothesised inadequacy of the diagnosis, shows the diagnostic criteria to be entirely subjective and arbitrary, and their use to give rise to problems even in controlled studies. Studies have not only shown even small differences in the diagnostic criteria to have profound impact on prevalence figures and to produce apparent fluctuations on the patient population, but also that the prevalence is higher in areas where many cases have already been diagnosed. No common aetiology or pathogenetic mechanism can be identified, and the massive overrepresentation of women remains unexplained. The patient group is characterised by heterogeneity, and no treatment has shown to be specifically beneficial. Papers offering alternative explanations of FMA are concerned with the reasons why FMA is diagnosed, rather than its cause.

Hilden J Afdelingen for Almen medicin, Kobenhavns Universitet, Panuminstituttet. Nord Med 1996 Nov;111(9):308-312 [Article in Danish]

Difference in pain relief after trigger point injections in myofascial pain patients with and without fibromyalgia.

OBJECTIVE: To compare responses to trigger point (TrP) injection between patients having both myofascial pain syndrome (MPS) caused by active TrPs and fibromyalgia syndrome (FMS) and patients with MPS due to TrPs but without FMS. DESIGN: Prospective design blinded measurement, before- after trial.

SETTING: A pain control medical clinic.

PATIENTS: Group 1: MPS + FMS; Group 2: MPS only. All patients (9 in each group) had active TrPs in the upper trapezius muscle.

INTERVENTION: Myofascial TrP injection with 0.5% xylocaine. MAIN

OUTCOME MEASURES: Subjective pain intensity (PI), pain threshold (PT), and range of motion (ROM) were assessed before, immediately after, and 2 weeks after TrP injection.

RESULTS: In a comparison of preinjection measures to immediate postinjection measures, only ROM was significantly improved (p.05) in Group 1 patients; all three parameters were significantly improved (p.05) in the Group 2 patients who had only MPS. Two weeks after injection, both groups showed significant improvement (p.05) in all three measured parameters as compared to preinjection measurements. In a comparison of the two groups, the immediate effectiveness of TrP injection was significantly less (p.05) in Group 1 than in Group 2 for all three parameters. Two weeks after injection, the degree of improvement in PT or ROM (but not PI) was not significantly different between two groups. Postinjection soreness (different from

myofascial pain) was more severe, developed sooner, and lasted longer in Group 1 than in Group

2.

CONCLUSION: Trigger point injection is a valuable procedure for pain relief for patients in both group. Patients with FMS are likely to experience significant but delayed and attenuated pain relief following injection of their active TrPs compared to myofascial pain patients with similar TrPs but without FMS. Also, FMS patients are likely to experience significantly more postinjection soreness for a longer period of time.

Hong CZ •Hsueh TC Department of Physical Medicine and Rehabilitation, University of California, Irvine, USA. Arch Phys Med Rehabil 1996;77(11):1161-66

Effects of aerobic exercise versus stress management treatment in fibromyalgia. A 4.5 year prospective study

To determine and compare short- and long-term effects of aerobic exercise (AE), stress management treatment (SMT), and treatment-as-usual (TAU) in fibromyalgia, 60 patients were randomized to 14 weeks of treatment by either AE, SMT or TAU. Outcome measures at baseline, midway through treatment, at treatment completion, and at 4 year follow up included a patient made drawing of pain distribution, dolorimetry of tender points, ergometer cycle test, global subjective improvement, and VAS registrations of: pain, disturbed sleep, lack of energy, and depression. Both AE and SMT showed positive short-term effects. AE was the overall most effective treatment, despite being subject to the most sceptical patient attitude prior to the study. At follow up, there were no obvious group differences in symptom severity, which for AE seemed to be due to a considerable compliance problem.

Author Wigers SH, Stiles TC, Vogel PA Department of Physical Medicine and Rehabilitation, University Hospital of Trondheim, Norway. Scand J Rheumatol 1996;25(2):77-86

Effects of type of symptom onset on psychological distress and disability in fibromyalgia syndrome patients.

The purpose of the study was to investigate the differences between two types of onset (post- traumatic versus idiopathic) in pain, disability, and psychological distress in patients with fibromyalgia syndrome (FS). Forty-six FS patients with post-traumatic onset and 46 FM patients with idiopathic onset, who were matched in age and pain duration, were included in the study. All participants completed self-report inventories assessing their adaptation to the pain conditions, and during the medical examination, an examining physician completed an inventory (Medical Examination and Diagnostic Information Coding System; MEDICS) to indicate the

degree of physical abnormality. The analysis revealed that the degrees of physical abnormality of the patients were comparable in the two groups.

However, controlling for the involvement with financial compensation issues (e.g. disability, litigation), the post-traumatic FS patients reported significantly higher degrees of pain, disability, life interference, and affective distress as well as lower level of activity than did the idiopathic FS patients. Furthermore, evaluation of the treatment history in these patients revealed that a significantly larger number of the posttraumatic FS patients were receiving opioid medications and had been treated with nerve block, physical therapy, and TENS. The results suggest that (1) post-traumatic onset is associated with high level of difficulties in adaptation to chronic FS symptoms and (2) FS patients are a heterogeneous group of patients.

Turk DC •Okifuji A •Starz TW •Sinclair JD Department of Anesthesiology, University of Washington, Seattle 98195, USA. Pain 1996;68(2-3):423-30

[Epidemiological study of a primary fibromyalgia in pediatric age].

BACKGROUND: The aim of the present epidemiological research was to select paediatric subjects who were suspicious of Primary Fibromyalgia (PF) and estimate its incidence in the students of the schools of Castiglione delle Stiviere (Mantova).

METHODS: The students had to answer Campbell's questionnaire which was varied and simplified in order to make it comprehensive to everybody even if the key answers were unchanged. The questionnaire was distributed in primary schools (3dr up to 5th class), secondary schools and high schools and its compilation was carried out with a doctor's help. The authors collected and examined 2408 forms.

After this evaluation 66 subjects, corresponding to 2.74%, had been considered suspected of PF and had been called to our Paediatric Department to continue the study. In the second phase of the research these 66 students have been submitted to a deep anamnesis, a careful clinical evaluation, a test of tender-points with a digital pressure algometer and some laboratory tests to exclude other rheumatic diseases. The map of the American College of Rheumatology adapted by Wolfe et al. (1990) was used to evaluate tender-points.

RESULTS: After this phase 29 students (1.20%) proved to be affected by primary fibromyalgia.

Sardini S, Ghirardini M, Betelemme L, Arpino C, Fatti F, Zanini F Divisione di Pediatria, Ospedale Civile, Castiglione delle Stiviere, Mantova. Minerva Pediatr 1996 Dec;48(12):543-550 [Article in Italian]

Epidemiology of rheumatic disease in children [Review article]

Major problems associated with interpreting and comparing epidemiologic studies on chronic arthropathies in children include the diversity of classification criteria and selection bias. A new set of classification criteria for peripheral arthritis in children, aiming toward defining biologically homogeneous subgroups, was recently proposed and should be further tested.

Descriptive studies from all over the world are now emerging on childhood rheumatic diseases, increasing the potential for comparing the impact of genetic and environmental factors on disease frequency and manifestations.

Awareness about pain syndromes in children, such as juvenile primary fibromyalgia and reflex sympathetic dystrophy, has increased, and this population now forms a substantial portion of clinic visits in pediatric rheumatology.

The impact of the rheumatic diseases in children on disability and quality of life during childhood and in adult life is still to a large extent unknown and must be further studied in an epidemiologic context.

Boel Andersson Gäre MD, PhD Current Opinion in Rheumatology 1996, 8:449-454.

An Evaluation of Mechanically Induced Neurogenic Flare by Infrared Thermography in Fibromyalgia

Objectives: The purpose of this study was to compare the neurogenic flare between patients with fibromyalgia [FM] and healthy controls [HC] and to compare the visual tracing method [VTM] with thermography.

Methods: The FM and HC groups [16 per group] were matched for age and sex. Two levels of pressure stimulation [3 kg and 6 kg] were applied by a dolorimeter to either side of the upper back of each subject in random order. The neurogenic flare was monitored by thermography for 30 minutes and outlined by the VTM at the second minute after stimulation.

Results: The general baseline back temperature was found to be significantly lower in the FM group than the HC group [P = 0.04]. Significant differences were found between levels of stimulation on peak temperature change, peak area of flare, and flare area measured at the second minute after stimulation by thermography and the VTM [P 0.05]. A significant interaction was found between group and level of stimulation on the peak flare area measured by thermography [P = 0.03].

Conclusions: The significantly lower baseline skin temperature in FM patients implies that adrenergic sympathetic nerve activity in FM may be increased at rest. The significant interaction between group and level of stimulation indicates that the two mechanisms involved in producing

the observable flare [sympathetic nervous system and the neurogenic inflammation] interact differently at different levels of stimulation.

Peggy Pik-Yuk Hau, Roger A. Scudds, and Manfred Harth Address correspondence to: Roger A. Scudds, PhD, PT, Associate Professor and Chair, Department of Physical Therapy, College of Health Professions, Wichita State University, Wichita, Kansas 67260-0043 Journal of Muskuloskeletal Pain, Vol. 4, No. 3, 1996, p.3-4

Peggy Pik-Yuk Hau, BPT, MSc[PT], 1810-88 Erskine Avenue, Toronto, Ontario, Canada M4P I Y3. Roger A. Scudds, PhD, PT, was Assistant Professor, Faculty of Applied Health Sciences, University of Western Ontario, London, Ontario, Canada N6G 1 HI. Manfred Harth, MD, FRCP, is Professor of Medicine, Division of Rheumatology, University Hospital, London, Ontario, Canada.

Exercise in the prevention and treatment of chronic disorders.

The Defense Women's Health Research Initiative commissioned a review of the literature of women's health issues. This was performed and published by the Institute of Medicine. In this publication it was noted that health promotion and disease prevention in women should be an area of high priority for military medicine. This article details some of the ways in which exercise may make substantial contributions to this goal. The available evidence indicates that there is an inverse association between physical activity and a variety of chronic diseases. Moreover, physical activity appears to influence psychological well-being. Aerobic exercise is the mode most frequently studied, and appears to confer positive changes, but other forms of exercise may prove to be equally beneficial. However, the appropriate duration, intensity, and frequency of the exercise have not been determined for any of these chronic health problems and must be considered before global recommendations can be offered. Efforts to promote physical activity within the community, schools, and homes must be initiated to achieve the goals set forth in Healthy People 2000, so the health of our women can improve. Future studies will be required to identify mechanisms whereby physical activity confers benefit.

Deuster PA Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. Womens Health Issues 1996 Nov;6(6):320-331

An exercise program in the treatment of fibromyalgia.

OBJECTIVE: To assess the utility of an exercise program, which included aerobic, flexibility and strengthening elements, in the treatment of fibromyalgia (FM). FM is a chronic

musculoskeletal condition characterized by diffuse musculoskeletal pain and aching. It has been suggested that aerobic exercise is helpful in its treatment.

METHODS: We studied 60 patients who met American College of Rheumatology criteria for FM and had no significant comorbidities. Measurements performed on each patient at the pre and poststudy assessment included the number of tender points (TP), total myalgic scores (TM), aerobic fitness (AF), flexibility and isokinetic strength. After initial evaluation patients were randomly assigned to either an exercise or a relaxation group. Each group met 3 times per week for 6 weeks for 1 h of supervised exercise or relaxation. All patients data were stored in a computerized database and statistical analysis was performed on all pre and poststudy assessments.

RESULTS: Thirty-eight patients (18 exercise and 20 relaxation) completed the study. Analysis of our data showed no significant difference between the groups in their prestudy assessment. Poststudy assessments, however, showed a significant improvement between the exercise and relaxation groups in TP (p < 0.05), TM (p < 0.05), and AF (p < 0.05). Similar improvements were also found when the pre and poststudy assessment of the exercise group were compared.

CONCLUSION: Exercise is helpful in the management of FM in the short term. It also shows that FM patients can undertake an exercise program which includes aerobic, flexibility, and strength training exercises without adverse effects. The long term utility of this type of exercise requires further evaluation.

Martin L •Nutting A •MacIntosh BR •Edworthy SM •Butterwick D •Cook J Faculty of Medicine, University of Calgary, Alberta, Canada. J Rheumatol 1996;23(6):1050-3

Factors predisposing to the resort of complementary therapies in patients with fibromyalgia.

This study examined the factors influencing the use of complementary therapies in patients with fibromyalgia. A postal questionnaire was sent to 90 patients who had attended a rheumatology out-patient clinic in West Yorkshire for their diagnosis or treatment of fibromyalgia. Seventy- one percent of fibromyalgia patients had used or were using complementary therapies. Patients who were using complementary therapies were of a higher socio-economic group (p> 0.001). The most popular therapy was oral supplementation. The duration of complementary therapies ranged from 3 months to 26 years (median = 3). The number of therapies used by each patient ranged from 1 to 10 (median = 3). The duration of fibromyalgia was associated with both the duration of complementary therapies (p> 0.001) and the number of therapies used (p> 0.05). The most popular source of advice for the decision to use complementary therapies was from a magazine (40%). Patients using complementary therapies were less likely to be satisfied with their current hospital treatment and turned to complementary therapies in the chance of relief from their fibromyalgia. The relatively high cost and lack of information on complementary therapies appeared to dissuade those patients who chose not to use it.

Dimmock S •Troughton PR •Bird HA Clinical Pharmacology Unit (Rheumatism Research), University of Leeds, United Kingdom. Clin Rheumatol 1996;15(5):478-482

Familial aggregation in the fibromyalgia syndrome.

The authors studied the familial occurrence of fibromyalgia (FMS) to determine a possible role of genetic and familial factors in this syndrome. Fifty-eight offspring aged 5 to 46 years (35 males and 23 females) from 20 complete nuclear families ascertained through affected mothers with FMS were clinically evaluated for FMS according to the ACR 1990 diagnostic criteria. FMS symptoms, quality of life, physical functioning, and dolorimetry thresholds were assessed in all subjects. Sixteen offspring (28%) were found to have FMS. The M/F ratio among the affected was 0.8 compared with 1.5 in the whole study group. Offspring with and without FMS did not differ on anxiety, depression, global well-being, quality of life, and physical functioning. A high prevalence of FMS was observed among offspring of FMS mothers. Because psychological and familial factors were not different in children with and without FMS, the high familial occurrence of this syndrome may be attributable to genetic factors.

Buskila D, Neumann L, Hazanov I, Carmi R Epidemiology Department, Soroka Medical Center, Ben-Gurion University, Beer Sheva, Israel. Semin Arthritis Rheum 1996 Dec;26(3):605-611

Fibromyalgia: A Study of Thyroid Function and Symptoms

Objectives: Previous studies have suggested an association between fibromyalgia [FS] and thyroid dysfunction. This association was explored in this prospective case-control study.

Methods: One-hundred and eight females with FS and 72 female controls were studied. Patients on medications which interfere with the interpretation of thyroid testing were excluded. Fibromyalgia was diagnosed by a brief history and physical examination using the criteria established by the American College of Rheumatology [ACR]. Thyroid stimulation hormone [TSH], L-thyroxine [T4], 3,5,3'-triiodo-L-thyronine uptake [T3], and T7 [T3U x T4] were determined for each subject.

Results: Females with FS reported a history of thyroid disorder [hypothyroidism, hyperthyroidism] 2.5 times more frequently than control subjects [P

Conclusions: Females with FS reported a history of hypothyroidism or hyperthyroidism more frequently than did females in the control group. Symptoms commonly associated with thyroid dysfunction were reported by fibromyalgics more often than by controls. The data indicates, however, that these symptoms are not specific and a diagnosis of thymid disease should be made only with confirmatomy laboratory tests.

Kathleen C. Jurell, MD, Mary Anne Zanetos, MS, August Orsinelli, MD, Diane Tallo, MD, and George W. Waylonis, MD Departments of Physical Medicine & Rehabilitation, Riverside Methodist Hospitals and the Ohio State University, Columbus, Ohio. Address correspondence to: Kathleen Jurell, MD, Medical College of Wisconsin, 1000 N 92nd Street, Milwaukee, WI 53226. The authors wish to acknowledge Ms. Judy Anderson, MS, MAS for statistical analyses and data management services for this study. Journal of Muskuloskeletal Pain, Vol. 4, No. 3, 1996, p.49-50

Fibromyalgia, depression, and alcoholism: a family history study.

OBJECTIVE: Fibromyalgia (FM) syndrome may be part of an "affective spectrum disorder." The diseases in this group have in common high rates of major depression in first degree relatives (FDR) and a response to antidepressant treatment. In this familial aggregation study, we tested the hypothesis that depression in patients with FM is related to a family history of depression or alcoholism in their FDR.

METHODS: To assess the relationship between FM and lifetime histories of depression (DEP) and alcoholism (ALC), personal and family histories of mood and substance use disorders were obtained from 60 probands with FM. DEP and ALC among the probands were diagnosed using the Schedule for Affective Disorders and Schizophrenia, a standardized, structured psychiatric interview, and the Research Diagnostic Criteria (RDC). Family psychopathology in the FDR (parents, full siblings, children) was assessed using the Family History RDC. The odds ratio (OR) for DEP and/or ALC in FDR of probands with a history of DEP versus those without DEP were calculated. Confidence intervals (CI) not including 1 were significant at p < 0.05 (95% CI).

RESULTS: The odds of identifying FDR with DEP and/or ALC were significantly higher among probands with FM with a lifetime history of DEP than among probands with FM who had no history of DEP (OR = 2.10, 95% CI = 1.23-3.57). This may be accounted for by the significantly higher odds for ALC among the FDR of probands with both FM and DEP compared with the FDR of probands with FM but no history of depression (OR = 2.30, 95% CI = 1.21-4.37). Although alcoholism was increased in the FDR of probands with FM with a history of depression, the odds for DEP were nonsignificantly higher among these FDR (OR = 1.71, 95% CI = 0.87-3.31). OR in the same range of magnitude were obtained when the data were analyzed by family unit, but these results were not statistically significant.

CONCLUSION: Our data suggest that the tendency toward DEP in patients with FM may be a manifestation of a familial depressive spectrum disorder (alcoholism and/or depression in the family members), not simply a "reactive" depression secondary to the pain and other symptoms.

Katz RS •Kravitz HM Department of Internal Medicine, Rush Medical College, Chicago, USA.

J Rheumatol 1996;23(1):149-54

[Fibromyalgia in dentistry]

Fibromyalgia represents one of the most frequent musculoskeletal problems. This condition, associated with widespread pain, is characterized by a number of specific tender points, as well as symptoms such as tiredness, limb stiffness, depression and a lack of refreshing sleep.

Patients suffering from fibromyalgia can also demonstrate the same clinical features as temporomandibular disorders or myofascial pain. Dentists should be aware that certain dental treatments will not be effective in patients suffering from temporal and masseter pain if fibromyalgia has been diagnosed.

Avon SL Faculte de Medecine Dentaire, Universite Laval, Ste-Foy, Quebec. J Can Dent Assoc 1996 Nov;62(11):874-876 [Article in French]

Fibromyalgia. Recognizing and addressing the multiple interrelated factors.

Recognition of fibromyalgia is crucial to avoid extraneous, costly diagnostic testing and ineffective, potentially dangerous therapy. Furthermore, failure to recognize that symptomatic physiologic change does result in a patient's response to stress demeans the legitimate importance of psychiatric disease. The keys to successful therapy are (1) specific pharmacologic manipulation of important processes and prognostic factors, (2) participation in aerobic exercise, which increases time spent in stages 3 and 4 (non-rapid eye movement) sleep and reduces stress, and (3) education, which reduces worry and perceived stress.

Wilke WS Department of Rheumatic and Immunologic Disease, Cleveland Clinic Foundation, OH 44195, USA. Postgrad Med 1996;100(1):153-6, 159, 163-6 passim Number of References: 29

Fibromyalgia syndrome: a review.

Fibromyalgia syndrome includes symptoms of widespread, chronic musculoskeletal aching and stiffness and soft tissue tender points. It is frequently accompanied by fatigue and sleep disturbance. Fibromyalgia is more common in women than in men, and it occurs at a mean age of 49 years.

Differential diagnosis includes myofascial pain syndrome and chronic fatigue syndrome. Fibromyalgia is a multifactorial problem and no universal treatment guidelines apply to all cases.

Pharmacologic therapy may incude tricyclic antidepressants. In addition to commonly used pharmacologic therapies, patient education, reassurance and an exercise program can each play an important role in relieving the symptoms associated with this common musculoskeletal syndrome.

Reiffenberger DH; Amundson LH Brown Clinic, Watertown, South Dakota, USA. Am Fam Physician 1996;53(5):1698-712 Number of References: 34

Fibromyalgia syndrome: overnight falls in arterial oxygen saturation.

PURPOSE: Sleep alterations and muscular changes suggesting hypoxia have been reported in fibromyalgia syndrome (FS) pathophysiology. We tested the hypothesis that patients with FS show falls in the oxygen saturation of hemoglobin in arterial blood (SaO2%) during sleep.

PATIENTS AND METHODS: Overnight SaO2% was measured by digital pulse oximetry in 28 randomly selected women who met 1990 American College of Rheumatology criteria for the diagnosis of FS and 15 similar controls. Considering the results of pulse oximetry and in order to evaluate the possible presence of a sleep apnea syndrome (SAS) as the reason for the nocturnal desaturations, the Epworth Sleepiness Scale (ESS) was mailed to the patients and controls. Patients and controls who had a score higher than 10 on the ESS underwent a polysomnographic study.

RESULTS: Patients with FS showed lower overnight minimum SaO2% (86.8 +/- 1.3 versus 90.7 +/- 0.9 in controls, P < 0.05), greater number of desaturations (8.3 +/- 1.8 versus 2.7 +/- 0.8 in controls, P < 0.05) and more desaturations/hour (1.3 +/- versus 0.4 +/- 0.1 in controls, P < 0.05), more night minutes in SaO2% < 92% (56.3 +/- 12.9 versus 9.1 +/- 3.8 in controls, P < 0.01) and more minutes in SaO2% < 90% (14.7 +/- 3.7 versus 2.4 +/- 1.0 in controls, P < 0.05). There were no differences between patients with FS and controls in ESS scores. Five patients (19.2%) in the FS group and 2 (15.4%) in the control group had ESS scores higher than 10. One patient had 1 control subject showed on apnea-plus-hypopnea index higher than 5 (13 and 9, respectively) in polysomnographic study.

CONCLUSIONS: Patients with FS showed small overnight falls in SaO2% and spent more time during the night in SaO2% below 92% and 90% than did the control group. These alterations that, as a whole, are not due to the presence of an associated SAS could be important in FS musculoskeletal pathophysiology.

Alvarez Lario B •Alonso Valdivielso JL •Alegre Lopez J •Martel Soteres C •Viejo Banuelos JL

•Maranon Cabello A Division de Reumatologia, Hospital General Yague, Burgos, Spain.

Am J Med 1996;101(1):54-60

Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals.

BACKGROUND: Chronic fatigue syndrome (CFS) is a condition that may be associated with substantial disability. The Medical Outcomes Study Short-Form General Health Survey (SF-36) is an instrument that has been widely used in outpatient populations to determine functional status. Our objectives were to describe the usefulness of the SF-36 in CFS patients and to determine if subscale scores could distinguish patients with CFS from subjects with unexplained chronic fatigue (CF), major depression (MD), or acute infectious mononucleosis (AIM), and from healthy control subjects (HC). An additional goal was to ascertain if subscale scores correlated with the signs and symptoms of CFS or the presence of psychiatric disorders and fibromyalgia.

DESIGN: Prospectively collected case series.

SETTING: Patients with CFS and CF were seen in a university-based referral clinic and had undergone a complete medical and psychiatric evaluation. Other study subjects were recruited from the community to participate in research studies.

PARTICIPANTS: The study included 185 patients with CFS, 246 with CF, 111 with AIM, and 25 with MD. There were 99 HC subjects. MEASURES: The SF-36 and a structured psychiatric interview were used. The SF-36 contains 8 subscales: physical, emotional, social, and role functioning, body pain, mental health, vitality, and general health- and a structured psychiatric interview.

RESULTS: Performance characteristics (internal reliability coefficients, convergent validity) of the SF-36 were excellent. A strikingly consistent pattern was found for the physical functioning, role functioning, social functioning, general health, and body pain subscales, with the lowest scores in CFS patients, intermediate scores in AIM patients, and the highest scores in the HC subjects. The CFS patients had significantly lower scores than patients with CF alone on the physical functioning (P < or = 0.01), role functioning (P < or = 0.01), and body pain (P < or = 0.001) subscales. The emotional functioning and mental health scores were worst among those with MD. The presence of fibromyalgia, being unemployed, and increasing fatigue severity all were associated with additional functional limitations across multiple functional domains, with increasing fatigue appearing to have the greatest effect.

CONCLUSIONS: The SF-36 is useful in assessing functional status in patients with fatiguing illnesses. Patients with CFS and CF have marked impairment of their functional status. The severity and pattern of impairment as documented by the SF-36 distinguishes patients with CFS and CF from those with MD and AIM, and from HC, but does not discriminate between CF and CFS.

Buchwald D •Pearlman T •Umali J •Schmaling K •Katon W Department of Medicine, University of Washington, Seattle, USA. Am J Med 1996;101(4):364-70

A guide to the understanding and use of tricyclic antidepressants in the overall management of fibromyalgia and other chronic pain syndromes.

The purpose of this review is to present relatively detailed information on the characteristics of tricyclic antidepressants, mainly amitriptyline hydrochloride and doxepin hydrochloride, for use as an integral part of the safe and effective management of fibromyalgia and, to a lesser extent, other chronic pain syndromes. Data sources include MEDLINE searches in English, relevant reference books and textbooks, my personal database and library, as well as personal clinical experience. I discuss these data with regard to the pharmacologic characteristics, mechanisms of action, adverse effects, and precautions involved with the use of tricyclic antidepressants. Additional information is given on drug selection and dosage titration. Much emphasis is placed on the fact that while tricyclic antidepressants play a major role in the management of fibromyalgia and other chronic pain syndromes, lifestyle alterations (eg. physical reconditioning and exercise), as well as behavior modification, are also vital to a successful outcome in management.

Godfrey RG Department of Medicine, University of Kansas School of Medicine, Kansas City, USA. Arch Intern Med 1996;156(10):1047-52 Number of References: 44

"I've been crying my way"--qualitative analysis of a group of female patients' consultation experiences.

BACKGROUND AND OBJECTIVES: What do women patients, sick-listed for biomedically undefined musculoskeletal disorders, expect and experience when they consult a doctor? With the purpose to learn more about this, a qualitative interview study was conducted.

METHODS: Twenty women participated. They were patients at an urban health care centre in northern Sweden. Data were gained through repeated, semi-structured interviews, and analysed according to grounded theory.

RESULTS: The participants described an atmosphere of distrust in the consultation. They had felt ignored, disregarded and rejected by doctors, and had worked out strategies to keep up medical attention in their search for a creditable diagnosis. They were somatizing, claiming under cover, and pleading, to catch the doctor's interest. In addition, they upheld their self- respect by mystifying and martyrizing themselves and their symptoms, and by condemning physicians as ignorant.

DISCUSSION: The patient's consultation experiences are discussed from different aspects; the biomedical framework, the power asymmetry, and the gendered positions of patient and doctor. The findings indicate the importance of making doctors aware of the context behind frustrations in doctor-patient interaction.

Johansson EE, Hamberg K, Lindgren G, Westman G Department of Family Medicine, Umea University, Sweden. Fam Pract 1996 Dec;13(6):498-503

Insulin-like growth factor-I (somatomedin C) levels in chronic fatigue syndrome and fibromyalgia.

OBJECTIVE. Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are similar conditions characterized by substantial fatigue, diffuse myalgias, sleep disturbances and a variety of other symptoms. Many patients with CFS meet strict criteria for FM. Recently, low insulin-like growth factor-I (IGF-I) levels have been demonstrated in patients with FM, suggesting that disruption of the growth hormone-IGF-I axis might explain the link between the muscle pain and poor sleep. Our goal was to determine whether IGF-I levels are decreased in CFS, and whether such findings are restricted to patients with concurrent FM.

METHODS. Radioimmunoassays were used to determine serum concentrations of IGF-I and its binding protein, (IGFBP-3). Subjects were 3 patients seen in a referral clinic for chronic fatigue: 15 patients with CFS, 15 who met criteria for both CFS and FM (CFS-FM), 27 with FM alone; and 15 healthy control (HC) subjects.

RESULTS. Patients and control subjects had similar demographic and clinical characteristics. No significant differences were observed among any of the 3 patient groups and control subjects in the mean concentration of either IGF-I or IGFBP-3. Likewise, the proportion of subjects with values above or below the laboratory's reference range did not differ for IGF-I or IGFBP-3.

CONCLUSIONS: These findings suggest the disruption of the growth hormone-IGF-I axis previously demonstrated in FM patients is not evident in a referral population of patients with CFS, CFS-FM, or FM.

Buchwald D •Umali J •Stene M Department of Medicine, University of Washington, Seattle, USA. J Rheumatol 1996;23(4):739-42

Lack of correlation between the mean tender point score and self-reported pain in fibromyalgia.

OBJECTIVES: To study the validity and nature of self-assessed symptoms among patients with fibromyalgia syndrome (FMS) and to compare our data with findings reported in the US. To

determine whether tender point scores correlate with self-reported pain and other symptoms and to study the influence of disease duration.

METHODS: Tender point scores were assessed in 113 consecutive patients with FMS. All patients completed 2 self-assessment questionnaires (an extended Campbell list, the Enschede Fibromyalgia Questionnaire, and the Dutch Arthritis Impact Measurement Scales).

RESULTS: The self-assessed symptoms of the Dutch FMS patients seem to be valid and are comparable with those of American patients. No association between disease duration and number of self-reported symptoms was found. An association between self-reported pain and mean tender point score was lacking for patients with disease of shorter duration and was weak for patients with disease of longer duration.

CONCLUSIONS: The use of a self-report questionnaire for patients with FMS is feasible and appears to be valid. Tender point scores and self-reported pain represent very different aspects of pain in FMS.

Jacobs JW •Rasker JJ •van der Heide A •Boersma JW •de Blecourt AC •Griep EN •van Rijswijk MH •Bijlsma JW Arthritis Care Res 1996;9(2):105-11 Special Journal List: Nursing

Middle and long latency somatosensory evoked potentials after painful laser stimulation in patients with fibromyalgia syndrome

Ten female patients with fibromyalgia syndrome (FS) were investigated with laser evoked potentials (LEPs) after hand stimulations and compared with 10 female pain-free and age-matched control patients.

FS patients exhibited significantly lower heat pain thresholds than controls (P < 0.05) and had higher amplitudes of LEP components N170 (P < 0.01) and P390 (P < 0.05) in response to intensities of 20 W (beam diameter 5 mm, duration 20 msec, wavelength 10.6 microns). N170 additionally appeared with additionally appeared with a broader distribution over bilateral central, vertex and fronto-central leads which contrasted to the control group and studies in healthy subjects where N170 was much more restricted to central and midtemporal positions contralateral to the stimulated hand.

Auditory stimuli interspersed between laser impulses that served to announce subjects to rate the perceived pain elicited auditory evoked potentials that were not different between groups indicating no differences of general vigilance level to account for observed LEP effects.

P390 amplitude enhancement might indicate greater attention and cognitive processing of nociceptive stimuli in FS subjects. Effects upon N170 rather point to exogenous factors like peripheral and spinal sensitization or reduced cortical or subcortical inhibition of nociception.

Lorenz J Grasedyck K Bromm B Institute of Physiology, University Hospital Eppendorf, Hamburg Germany. Electroencephalogr Clin Neurophysiol 1996;100(2):165-8

Modulation of pressure pain thresholds during and following isometric contraction in patients with fibromyalgia and in healthy controls.

This study aimed at evaluating the influence of submaximal isometric contraction on pressure pain thresholds (PPTs) in 14 fibromyalgia (FM) patients and 14 healthy volunteers, before and after skin hypoesthesia. PPTs were determined with pressure algometry over m. quadriceps femoris before, during and following an isometric contraction. Maximum voluntary contraction (MVC) was assessed using a computerized dynamometer. A contraction of 22% MVC on average was held until exhaustion (max. 5 min) and PPTs were assessed every 30 sec. A local anesthetic cream and a control cream were applied following a double- blind design and PPTs were reassessed. In healthy volunteers PPTs increased during contraction (P < 0.001), then decreased after the end of contraction (P < 0.001) but remained above precontraction values during the 5 min of post-contraction assessments (P < 0.001). In FM patients PPTs decreased in the middle of the contraction period (P < 0.05) and remained below precontraction levels during the rest of the contraction period (P < 0.05) and during the 5 min of post-contraction assessment (immediately post- contraction NS; 2.5 min post-contraction P < 0.01; 5 min post-contraction P < 0.05). The normalized PPTs were significantly lower in patients than in controls during contraction (start P < 0.01; middle P < 0.001; end P < 0.001) and at all times during post- contraction assessments (P < 0.001). Anesthetic cream raised PPTs at rest in controls (P < 0.01) but not in FM patients, and did not influence contraction or post-contraction PPTs in either group. Therefore, the increased pressure pain sensibility in FM patients is more pronounced deep to the skin. The observed decrease of PPTs during isometric contraction in FM patients could be due to sensitization of mechanonociceptors caused by muscle ischemia and/or dysfunction in pain modulation during muscle contraction.

Kosek E •Ekholm J •Hansson P Department of Rehabilitation Medicine, Karolinska Institute/Hospital, Stockholm (Sweden). Pain 1996;64(3):415-23

Muscle damping measured with a modified pendulum test in patients with fibromyalgia, lumbago, and cervical syndrome.

STUDY DESIGN: Muscle tension with tenderness may be localized or generalized as in fibromyalgia. Wartenberg's pendulum test might be appropriate for quantitating muscle damping, at least in generalized cases.

OBJECTIVE: Damping values provide a quantitative measure of muscle tension and of the response to various treatments.

SUMMARY OF THE BACKGROUND DATA: According to recent anatomic and experimental works, intrafusal muscle fibers are double-innervated by gamma motoneurons and sympathetic fibers. With electromyograph recording, the activity of extrafusal fibers and gamma motoneurons (reflexes) can be assessed and separated from the action of the sympathetic system. METHODS: An electrogoniometer registers the movements of the freely swinging leg. On the oscilloscope, the patient's nodular curve is compared with an ideal calculated dampened curve to find the damping value. Electromyograph surface electrodes from the knee extensors and flexors detect the activity of extrafusal fibers and the occurrence of reflexes.

RESULTS: In longstanding severe fibromyalgia, damping values are almost always elevated, at least in one leg. Half or more of patients with chronic lumbago and cervical syndrome present with increased damping. The surface electromyograph remains silent (in contrast to spastic patients).

CONCLUSION: The findings support the hypothesis that muscle tension in rheumatic patients results from overactivity of the sympathetic system (or part of it). Even in clinically localized pain syndromes, muscle damping is often increased in the legs. The test is valuable for quantitating muscle tension and the effectiveness of therapeutic methods.

Wachter KC •Kaeser HE •Guhring H •Ettlin TM •Mennet P •Muller W Rehabilitation Center, Switzerland. Spine 1996;21(18):2137-42

Muscle force, perceived effort, and voluntary activation of the elbow flexors assessed with sensitive twitch interpolation in fibromyalgia.

OBJECTIVE: To measure maximal voluntary strength and central activation without fatigue, and to assess both peripheral and central components of muscle fatigue of the elbow flexor muscles, during exercise, in a group of patients with fibromyalgia (FM) (n = 11). Results are compared with data from control subjects (n = 36).

METHODS: Maximal voluntary activation and strength of elbow flexors were quantified using twitch interpolation during attempted maximal isometric contractions both in unfatigued muscles and during fatigue produced by 45 min of submaximal exercise.

RESULTS: Maximal voluntary strength of the elbow flexors before and during exercise was within the normal range. Central fatigue did not develop to a greater extent in the patient group. No patient had a decline in twitch amplitude during exercise below the 95% confidence limit for the decline in control subjects. However, the increment in perceived effort (Borg Scale) was abnormally large in 5 patients during the fatiguing exercise.

CONCLUSION: Neither poor motivation, reflex pain inhibition, nor muscle contractile failure are important in the pathogenesis of fatigue in patients with FM. However, the subjective response to exercise is commonly excessive.

Miller TA •Allen GM •Gandevia SC Prince of Wales Medical Research Institute, Prince of Wales Hospital, Sydney, Australia. J Rheumatol 1996;23(9):1621-27

Musculoskeletal complaints and fibromyalgia in patients attending a respiratory sleep disorders clinic.

OBJECTIVE: To determine the frequency of fibromyalgia (FM) syndrome and reporting of pain in an unselected group of patients attending a respiratory sleep disorders clinic, and to examine the association of physical activity and levels of reported pain.

METHODS: 108 consecutive patients attending a respiratory sleep disorders clinic were interviewed and examined, blind to sleep disorder status. Assessment of musculoskeletal pain symptoms included patient history of pain, painful sites marked on a mannequin, visual analog scale (VAS) pain score, and tender point count. Daily physical activity was recorded, and all patients underwent nocturnal polysomnography, blind to clinical status.

RESULTS: FM was identified in 3 patients (2.7%). Pain reporting was more strongly associated with reduced physical activity than with a specific sleep disorder. Patients with reduced physical activity were more likely to have pain symptoms than physically active patients: tender point count > or = 6 (p = 0.002), > or = 3 sites marked on mannequin (p = 0.008), axial pain (p = 0.003), and VAS pain score (p = 0.008).

CONCLUSION: FM by defined criteria was uncommon in patients with a primary complaint of disturbed sleep, and in particular, patients with sleep apnea. Reduced physical activity was strongly associated with reported pain symptoms.

Donald F •Esdaile JM •Kimoff JR •Fitzcharles MA Rheumatic Diseases Unit, McGill University, Montreal, Quebec, Canada. J Rheumatol 1996;23(9):1612-16

The natural history of chronic pain in the community: a better prognosis than in the clinic?

OBJECTIVE: To evaluate the predictors of improvement at 2 years in subjects with chronic widespread

pain ascertained from a community survey.

METHODS: As part of a community based epidemiological survey on the occurrence of pain, 141 subjects (age range 24-74 years; 44 men, 97 women) were selected for more detailed assessment. Followup information on pain experience was collected at a median of 27 months (range 15-35). Subjects were categorized according to whether they had no pain, chronic widespread pain (according to the American College of Rheumatology criteria), or regional pain, both at initial assessment and followup. In addition, subjects were examined at both time periods for tender points.

RESULTS: Of those with chronic widespread pain at initial assessment, 35% still had chronic widespread pain at followup, 50% regional pain, and 15% no pain. Of those originally with regional pain, 65% still had regional pain, 19% chronic widespread pain, and 16% no pain at followup. Logistic regression analysis was conducted to examine factors among those with chronic widespread pain associated with still having these symptoms at followup. Female sex, older age, leaving school at a young age, high tender point count, high levels of fatigue, or additional physical or psychological symptoms were all associated with symptoms being less likely to resolve.

CONCLUSION: Chronic widespread pain in the community has a generally good prognosis. However, those with additional symptoms associated with the fibromyalgia syndrome were more likely still to have chronic widespread pain 2 years later.

MacFarlane GJ •Thomas E •Papageorgiou AC •Schollum J •Croft PR •Silman AJ Arthritis and Rheumatism Council Epidemiology Research Unit, School of Epidemiology and Health Sciences, University of Manchester, UK. J Rheumatol 1996;23(9):1617-20

Neurohormonal perturbations in fibromyalgia.

Fibromyalgia (FM) falls into the spectrum of what might be termed 'stress-associated syndromes' by virtue of frequent onset after acute or chronic stressors and apparent exacerbation of symptoms during periods of physical or emotional stress. Patients with FM exhibit disturbances of the major stress-response systems, the HPA axis and the sympathetic nervous system. Integrated basal cortisol levels measured by 24-hour urine- free cortisol are low. FM patients display a unique pattern of HPA axis perturbation characterized by exaggerated ACTH response to exogenous CRH or to endogenous activators of CRH such as insulin- induced hypoglycaemia. The cortisol response to increased ACTH in these stress paradigms is blunted, as is the the cortisol response to exercise. Functional analysis suggests that FM patients may also exhibit disturbed autonomic system activity. For example, plasma NPY, a peptide co-localized with norepinephrine in the sympathetic nervous system, is low in patients with FM. Abnormalities of related neuronal systems, particularly decreased serotonergic activity, may contribute to the observed neuroendocrine perturbations in FM. Finally, other neuroendocrine systems, including the growth hormone axis, are also abnormal in FM patients. Many clinical features of FM and related disorders, such as widespread pain and fatigue, could be related to the observed neuroendocrine perturbations. This hypothesis is supported by the observation that many useful

treatments for FM affect the function of these central nervous system centres. Further clarification of the role of neuroendocrine abnormalities in patients with FM, and the relationship of these disturbances with particular symptoms, may lead to improved therapeutic strategies.

Crofford LJ •Engleberg NC •Demitrack MA Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109, USA. Baillieres Clin Rheumatol 1996;10(2):365-78 Number of References: 84

Otoneurologic and audiologic findings in fibromyalgia.

Patients with fibromyalgia were studied with otoneurological and audiological tests. Altogether 168 patients (141 women) participated. Vertigo/dizziness was reported by 72% of the patients. Sensorineural hearing loss was found in 15% of the cases. Auditory brainstem responses (ABR) and oculomotor tests were applied, and statistical comparisons between patients and controls were performed. Significant differences were found for the absolute latency of wave V and for the I-V and III-V interpeak latencies, indicating brainstem dysfunction. Abnormal ABR recordings were found in 30% of the cases. In the oculomotor study the mean velocity gain for the smooth pursuits and the mean saccadic latency were significantly different between patients and controls. Abnormal saccades were seen in 28% and pathological smooth pursuit eye movements in 58% of the patients. Electronystagmography was pathological in 45% of the cases. The findings indicate that CNS dysfunction frequently occurs in patients with fibromyalgia, although proprioceptive disturbances might also explain some of the abnormalities observed.

Rosenhall U •Johansson G •Orndahl G Department of Audiology Karolinska Hospital, Sweden. Scand J Rehabil Med 1996;28(4):225-32

Pain coping strategies in children with juvenile primary fibromyalgia syndrome: correlation with pain, physical function, and psychological distress.

OBJECTIVES: The purpose of this study was twofold: 1) to describe the coping strategies used by children with juvenile primary fibromyalgia syndrome (JPFS), and 2) to examine how pain coping relates to measures of pain, disability/function, psychological distress, and pain behavior.

METHODS: Sixteen children with JPFS completed the Child Version of the Coping Strategies Questionnaire (CSQ-C), the visual analog scale for pain, the McGill Pain Questionnaire, the Fibromyalgia Impact Questionnaire modified for children, the Arthritis Impact Measurement Scales 2, and the Symptom Checklist-90-Revised. Subjects also also underwent pain behavior observation. Pearson's product moment correlations were conducted to examine the relationship of coping to measures of pain and disability.

RESULTS: The Pain Control and Rational Thinking composite factor score on the CSQ-C correlated with measures of pain severity, functional disability, and psychological distress. Results supported the internal reliability of the CSQ-C in assessing pain coping.

CONCLUSIONS: These results suggest that the CSQ-C may provide a reliable measure for assessing variations in pain coping in JPFS patients. Behavioral interventions aimed at increasing the perception of pain control may be beneficial in treating JPFS.

Schanberg LE •Keefe FJ •Lefebvre JC •Kredich DW •Gil KM Arthritis Care Res 1996;9(2):89-96

Pain, disability, and physical functioning in subgroups of patients with fibromyalgia.

OBJECTIVE: To investigate (1) whether patients with fibromyalgia (FM) could be subgrouped on the basis of psychosocial and behavioral responses to pain, and (2) the relationships among pain severity, perceived disability, and observed physical functioning, as measured by cervical spinal mobility.

METHODS: 117 patients with FM received a comprehensive examination, underwent physical performance tasks during the evaluation, and completed self-report inventories.

RESULTS: About 87% of the patients could be classified into the Multidimensional Pain Inventory clustering groups identified and validated in patients with a range of chronic pain problems (Dysfunctional, Interpersonally Distressed, and Adaptive Copers). Although the 3 groups exhibited comparable levels of physical functioning, the Dysfunctional and Interpersonally Distressed patients reported higher levels of pain, disability, and depression. Interpersonally Distressed patients also reported significantly lower levels of marital satisfaction than the other 2 subgroups. There were significant associations between pain severity and perceived disability, and pain severity and physical functioning, defined by spinal mobility tests. The relationship between disability and physical functioning did not reach statistical significance. Correlational analyses by subgroups revealed a significant association between patient perceived disability and physical functioning in the Adaptive Copers, but not the Dysfunctional or Interpersonally Distressed patients.

CONCLUSIONS: Patients with FM can be classified into 3 subgroups based on psychosocial and behavioral characteristics. These subgroups show substantial differences in clinical presentation of their symptoms. Although the results should be considered preliminary due to the narrow range of physical functioning, the differential relationships between perceived disability and physical functioning across cluster groups suggest the importance of FM syndrome as a heterogeneous disorder. Treating patients with FM as a homogeneous group may compromise research results, impede understanding of the mechanisms underlying this condition, and deter development of effective treatment.

Turk DC •Okifuji A •Sinclair JD •Starz TW

Pain Evaluation and Treatment Institute, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA. J Rheumatol 1996;23 (7):1255-62

Pain intensity and health locus of control: a comparison of patients with fibromyalgia syndrome and rheumatoid arthritis.

The major purpose of this study was to determine if 31 patients with fibromyalgia syndrome (FS) reported different pain intensity and Health Locus of Control (HLC) scores than 30 patients with rheumatoid arthritis (RA). Another purpose was to determine the relationship among experienced actual pain (present, usual, worse, least), recalled prior episodes of pain (worse toothache, headache, and stomach ache), HLC orientation, age and the duration of the actual pain. Visual Analogue Scales were used to measure pain intensity. The Health Locus of Control Scale was used to determine external/internal orientation. The results showed that the FS patients reported significantly more intense actual pain, recalled pain for worse toothache and headache, and were more externally oriented than the RA patients. Present pain intensity was significantly correlated to actual intensity ratings, but not to reported earlier experienced pain, except for worse stomach ache in the RA group. The findings' implications for treatment and education are discussed.

Gustafsson M •Gaston-Johansson F Goteborgs University, Department of Rehabilitation Medicine, Sweden. Patient Educ Couns 1996;29(2):179-88

Perceived control: a comparison of women with fibromyalgia, rheumatoid arthritis, and systemic lupus erythematosus using a Swedish version of the Rheumatology Attitudes Index.

This study compared the attitudes of women with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or fibromyalgia (FM) regarding their perceptions of control and ability to cope with their disease. We also report the validation of a Swedish version of the Rheumatology Attitudes Index (RAI). One hundred thirty-nine women participated in the study by completing the RAI two or three times along with several other self-report and disease severity measures. The Swedish version RAI was found to have acceptable reliability, evidence of validity, sensitivity to change, and two distinct factors of internality and helplessness. In general, patients with RA or SLE perceived higher control over their symptoms than those with FM. FM patients who participated in a self-management experimental program significantly changed their scores on the RAI in a positive direction.

Burckhardt CS •Bjelle A Department of Mental Health Nursing Oregon Health Science University, Portland 97201, USA. Scand J Rheumatol 1996;25(5):300-6

Periodic K-alpha sleep EEG activity and periodic limb movements during sleep: comparisons of clinical features and sleep parameters.

The K-alpha sleep electroencephalographic (EEG) phenomenon is characterized by periodic (approximately 20-40 seconds) K-complexes, immediately followed by alpha-EEG activity (7.5-11 Hz) of 0.5- to 5.0- second duration. A group of 14 subjects with the periodic K-alpha anomaly was found to have a similar distribution pattern of interevent intervals as compared with previously published data for sleep-related periodic limb movements during sleep (PLMS). Sleep parameters and somatic symptoms of 30 patients with K-alpha were compared with 30 patients with PLMS. The periodic K-alpha group was predominantly female, younger, exhibiting more slow-wave sleep, gastrointestinal symptoms and muscular complaints and fewer movement arousals on overnight polysomnography. The K-alpha group presented uniformly with complaints of unrefreshing sleep, often associated with fibromyalgia and chronic fatigue syndrome. The PLMS group was predominantly male, showed greater sleep disruption and presented with a variety of sleep-related symptoms.

MacFarlane JG •Shahal B •Mously C •Moldofsky H University of Toronto, Centre for Sleep and Chronobiology, Toronto Hospital (Western Division), Ontario, Canada. Sleep 1996;19(3):200-4

A prospective long-term study of fibromyalgia syndrome

OBJECTIVE: To ascertain the long-term natural history of fibromyalgia syndrome (FMS).

METHODS: Patients with a history of FMS, seen in an academic rheumatology referral practice, were originally surveyed soon after onset of symptoms, and then were reinterviewed 10 years later in a prospective followup cohort study. A validated telephone survey was administered that inquired into current symptoms, medical care and treatments used, and work disability. The results were compared with the prior surveys.

RESULTS: Of the original 39 patients, there were 4 deaths. Of the remaining 35 patients, 29 (83%) were reinterviewed. Mean age at current survey was 55 years, and mean duration of symptoms was 15.8 years. All patients had persistence of some fibromyalgia symptoms, although almost half (48%) had not seen a doctor for them in the last year. Moderate to severe pain or stiffness was reported in 55% of patients; moderate to a lot of sleep difficulty was noted in 48%; and moderate to extreme fatigue was noted in 59%. These symptoms showed little change from earlier surveys. In 79% of patients, medications were still being taken to control FMS symptoms. Despite continuing symptoms, 66% of patients reported that FMS symptoms were a little or a lot better than when first diagnosed. Fifty-five percent of patients said they felt well or very well in terms of FMS symptoms, and only 7% felt they were doing poorly. With the exception of sleep trouble, which was persistent, baseline survey symptoms correlated poorly with symptoms at the 10-year followup.

CONCLUSION: FMS symptoms last, on average, at least 15 years after illness onset. However, most patients experience some improvement in symptoms after FMS onset.

Kennedy M Felson DT Boston University Arthritis Center, Massachusetts, USA. Arthritis Rheum 1996;39(4):682-5

Protein peroxidation, magnesium deficiency and fibromyalgia.

Lipid and protein peroxidations were investigated in female patients with magnesium deficit (MD), fibromyalgia (FM) and age matched controls: malondialdehyde and protein carbonyls (PC), as well as serum, leucocyte and erythrocyte magnesium (EMg) were assessed in 20 controls, 25 FM and 16 MD patients. MDA are unchanged in MD and FM. PC are significantly increased (P < 0.01) in FM. EMg is significantly decreased in MD. There is a slight, but not significant, negative correlation between PC and EMg, in controls and MD. Protein peroxidations are demonstrated in FM. Further studies are needed in MD.

Eisinger J, Zakarian H, Pouly E, Plantamura A, Ayavou T Department of Rheumatology, C.H.I. Toulon/La Seyne sur Mer BP, France. Magnes Res 1996 Dec;9(4):313-6

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1998 ABSTRACTS

Index

Poster Presentations

Opioids for managing patients with chronic pain: pharmacists’ perspectives and concerns [abstract] Quality of well-being in patients with osteoarthritis and fibromyalgia [abstract] A survey of the use and effectiveness of conventional and alternative therapies for fibromyalgia [abstract]

Medline and Pre-medline Abstracts

5-Hydroxytryptophan: a clinically-effective serotonin precursor.[abstract] Abnormal functional activity of the central nervous system in fibromyalgia syndrome. [abstract] Advances in fibromyalgia: possible role for central neurochemicals.[abstract]

Advances in the treatment of fibromyalgia: current status and future directions. [abstract] Affective distress in fibromyalgia syndrome is associated with pain severity. [abstract] The association of functional gastrointestinal disorders and fibromyalgia. [abstract] The association of soft-tissue rheumatism and hypermobility. [abstract] Biofeedback/relaxation training and exercise interventions for fibromyalgia: a prospective trial. [abstract] Chronic fatigue and chronic fatigue syndrome: shifting boundaries and attributions. [abstract] Chronic fatigue syndrome and fibromyalgia. Dilemmas in diagnosis and clinical management. [abstract] Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome. [abstract] Chronic myofascial pain: knowledge of diagnosis and satisfaction with treatment. [abstract] Chronic orofacial muscle pain: a new approach to diagnosis and management. [abstract] Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. [abstract] Clinical diagnosis found in patients with Raynaud's phenomenon: a multicentre study. [abstract] [Clinical experiences with the analgesic effects of citalopram]. [abstract] Collagen cross-links in fibromyalgia syndrome. [abstract] Comorbidity between myofascial pain of the masticatory muscles and fibromyalgia. [abstract] Comparison of integrated group therapy and group relaxation training for fibromyalgia. [abstract] Comparison of clinical and psychologic features of fibromyalgia and masticatory myofascial pain. [abstract] A comparison of three types of neck support in fibromyalgia patients. [abstract] The connection between chronic fatigue syndrome and neurally mediated hypotension. [abstract] Current concepts in the pathophysiology of abnormal pain perception in fibromyalgia. [abstract] The detoxification enzyme systems. [abstract] Differential responses by psychosocial subgroups of fibromyalgia syndrome patients to an interdisciplinary treatment. [abstract] Disordered growth hormone secretion in fibromyalgia: a review of recent findings and a hypothesized etiology. [abstract] Doctors' attitudes to fibromyalgia: a phenomenological study. [abstract] Dyspnea resulting from fibromyalgia. [abstract] Early life stress, negative paternal relationships, and chemical intolerance in middle-aged women: support for a neural sensitization model. [abstract] Effect of gamma-hydroxybutyrate on pain, fatigue, and the alpha sleep anomaly in patients with fibromyalgia. Preliminary report. [abstract] Effect of local glucocorticoid injection on masseter muscle level of serotonin in patients with chronic myalgia. [abstract] The effect of pain on memory for affective words. [abstract] The effects of delta wave sleep interruption on pain thresholds and fibromyalgia-like symptoms in healthy subjects; correlations with insulin-like growth factor I. [abstract] The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome. [abstract] Ehlers-Danlos syndrome, fibromyalgia and temporomandibular disorder: report of an unusual combination. [abstract]

Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. [abstract] Ethnocultural and educational differences in Israeli women correlate with pain perception in fibromyalgia. [abstract] [Etiologic factors in temporomandibular joint disorders and pain]. [abstract] Evaluation of multimodal treatment program for fibromyalgia. [abstract] Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. [abstract] Evolving concepts of diagnosis, pathogenesis, and therapy of Sjogren's syndrome. [abstract] Examination for tenderness: learning to use 4 kg force. [abstract] Familial painful restless legs syndrome correlates with pain dependent variation of blood flow to the caudate, thalamus, and anterior cingulate gyrus. [abstract] Fatigue in lupus is not correlated with disease activity. [abstract] [Fibromyalgia. A critical review]. [abstract] [Fibromyalgia--a dispensable disease term]? [abstract] Fibromyalgia--a syndrome associated with decreased nocturnal melatonin secretion. [abstract] Fibromyalgia and chronic fatigue: the holistic perspective. [abstract] Fibromyalgia and headache. Failure of serotonergic analgesia and N- methyl- D- aspartate - mediated neuronal plasticity: their common clues. [abstract] Fibromyalgia and its primary care implications. [abstract] Fibromyalgia and the seratonin pathway. [abstract] Fibromyalgia and women's pursuit of personal goals: a daily process analysis. [abstract] Fibromyalgia, chronic fatigue syndrome, and myofascial pain. [abstract] Fibromyalgia in Behcet's syndrome. [abstract] [Fibromyalgia (generalized tendomyopathy) in expert assessment. Analysis of 158 cases]. [abstract] Fibromyalgia in hyperkalemic periodic paralysis. [abstract] Fibromyalgia in Indian patients with SLE. [abstract] Fibromyalgia is a major contributor to quality of life in lupus. [abstract] Fibromyalgia is not a muscle disorder. [abstract] The fibromyalgia problem. [abstract] Fibromyalgia Syndrome. [abstract] The fibromyalgia syndrome as a manifestation of neuroticism? [abstract] Fibromyalgia syndrome in children and adolescents: clinical features at presentation and status at follow-up. [abstract] Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain. [abstract] Functional diagnosis as a tool in rehabilitation: a comparison of teachers and other employees. [abstract] Genetic factors in fibromyalgia syndrome. [abstract] Gulf War illnesses: complex medical, scientific and political paradox. [abstract] Health-related quality of life in chronic disorders: a comparison across studies using the MOS SF-36. [abstract] Hyperexcitability in fibromyalgia. [abstract] Hyperparathyroidism. [abstract]

The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome. [abstract]

Poster Presentation from the American College of Rheumatology's 62nd National Meeting November 8-12, 1998 Abstract: 1546 November 11, 1998 Poster Session E: ARHP Poster Session II

Quality of Well-being in Patients with Osteoarthritis and Fibromyalgia

S. Schmidt, R. Olmedo, E. Groessl1, T. Cronan San Diego State University; 1SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego, CA 92120, USA

Chronic disease and age are both related to a patient's quality of life. It is important to understand the relationships among these variables to develop interventions that can improve quality of life. The present study compared quality of well-being scores for two groups of people with different chronic conditions, osteoarthritis (OA) and fibromyalgia syndrome (FMS). The group of 363 OA participants was 64% women, with 72.5% married, 92.3% caucasian, and a mean age of 69.2 (SD = 5.63). The group of 316 FMS participants was 95.9% women, with 69% married, 88.3% caucasian, and a mean age of 56.4 (SD = 10.51). The participants' quality of life was assessed using the Quality of Well-being (QWB) scale. An overall QWB score is calculated by combining 4 weighted subscales: symptom problem complex (CPX), mobility (MOB), physical activity (PAC), and social activity (SAC). Scores can range from 0 to 1 with 1 representing optimal asymptomatic functioning.

A one-way analysis of variance was used to compare the two groups on overall QWB and on the 4 subscales. The group with OA scored significantly higher than the FMS group on overall QWB (F(1, 677) = 137.28, p < .0001) and on all 4 subscales. A one way analysis of variance was also use to compare the ages of the groups. The OA group was significantly older than the FMS group (F(1, 677) = 394.57, p < .0001).

Increasing age is viewed as a primary factor associated with decreased quality of life, but the results of the present study indicate that a group of people who are 13 years older on average has a better quality of life thana younger group, although both groups suffer from a chronic health problem. Therefore, FMS appears to be a much more debilitating condition than osteoarthritis. Lower quality of life at an earlier age presents difficult challenges for people with FMS and indicates a special need for interventions to improve the quality of life for people with FMS.

Disclosure: work reported in this abstract was supported by: National Institute of Arthritis and Musculoskeletal & Skin Diseases. Osteoarthritis: other, Fibromyalgia, Disability, Quality of life Poster Presentation from the American College of Rheumatology's 62nd National Meeting November 8-12, 1998

Abstract: 1365 November 11, 1998 Poster Session E: Fibromyalgia and Soft Tissue Disease

A Survey of the Use and Effectiveness of Conventional snd Alternative Therapies for Fibromaylgia

Sumedha S. Dalvi, Patricia Bankes, Charles H. Pritchard Abington Memorial Hospital, Abington, PA 19001, USA

Fibromyalgia (FM) pts may explore alternative therapies due to suboptimal results with conventional medications. We conducted a survey of FM pts to gain understanding of alternative modality utilization rates and efficacy of conventional and alternative therapies in relieving common symptoms. Pts were provided a checklist of nonprescription medications and nonpharmacological treatments (NPT) used for the treatment of FM and asked to grade the impact of each modality on pain, fatigue, sleep, well-being and function, using a Likert scale.

Of the 117 surveys obtained (111 females, 6 males), majority of the pts (93%) had used alternative therapies: vitamins 68%, ointments 41%, herbs 38%, magnesium 35%, malic acid 25%, CoQ 21%, lecithin 15%, manganese 15%, selenium 13% and Gingko 12%. Use of NPT was noted; exercise 70%, meditation 34%, massage 54%, chiropractic 41% and acupuncture 20%. Melatonin, homeopathic/ayurvedic medications, magnets, myofascial release therapy etc. were used by <10% pts.

Pain relief was provided by acetaminophen, NSAIDs, tramadol, aspirin, cyclobenzaprine and narcotics. Narcotics provided more pain relief than acetaminophen and had higher well-being scores than NSAIDs, acetaminophen and tramadol. Tricyclic antidepressants and cyclobenzaprine had higher sleep scores than SSRIs. Exercise and massage offered higher pain relief, sleep, well-being and function scores than acupuncture and better function scores than chiropractic treatments. Meditation and malic acid achieved higher scores with regard to wellbeing than acupuncture.

As a significant proportion of FM pts use alternative therapies, more data is needed regarding benefits and risks. NPTs such as exercise, massage and meditation may offer significant symptom relief. Chiropractic manipulations have limited usefulness. Malic acid may be of some benefit. Acupuncture does not offer any significant benefit. No conclusions can be drawn on the usefulness of magnets, ointments, herbs, homeopathic and ayurvedic medications due to a small sample size.

Disclosure: work reported in this abstract was supported by: Dept. of Medicine, Abington Memorial Hospital, Abington, PA.

Exercise physiology, Fibromyalgia, Treatment: other

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Poster Presentation from the Physical Medicine & Rehabilitation conference

Opioids for managing patients with chronic pain: pharmacists’ perspectives and concerns Brian D. Greenwald, M.D.; Elizabeth J. Narcessian, M.D.

Previous studies of pharmacists have elucidated unavailability of opioids and apprehension to dispense opioids. This study explores the perspectives and concerns pharmacists have towards dispensing opioids to manage patients with chronic pain. Fifty-two randomly selected New Jersey pharmacies were surveyed with a 69% (36/ 52) response rate.

The results showed addiction to and diversion of opioids was considered a moderate to serious problem by 72% (26/36) of respondents. The definition of addiction was correctly identified by only 11% (4/36) of respondents.

Moderate to complete reluctance to stock opioids was attributed to concerns about robbery by 14% (5/35) of respondents. Eight percent (3/36) of respondents had incurred a prior robbery. No correlation was found between those respondents who had a high degree of concern about robbery and those who had incurred previous robbery.

Moderate to complete reluctance to stock opioids was attributed to concerns about federal or state investigation by 17% (6/36) of respondents. Interestingly, of the 20% (7/35) of the respondents who had incurred a prior federal or state investigation, none expressed more than minimal concern about opioid regulatory issues.

The highest daily dose of oral morphine that respondents reported being comfortable dispensing ranged from 60 mg/day to 2000 mg/day, with an average of 411 mg/day, despite the fact that there is no pharmacologic ceiling on pure agonist opioids.

Confidence in the acceptability of a physician prescribing opioids for chronic pain was 75% (27/36) for malignant pain in patients with no history of opioid abuse, and declined to 3% (1/36) for non-malignant pain in patients with a history of opioid abuse.

Perceptions about dosing, addiction, and fear of regulatory scrutiny create barriers to effective pain management. Pharmacists may benefit from education regarding issues related to opioid analgesics.

[back to top of page] 5-Hydroxytryptophan: a clinically-effective serotonin precursor.

5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness.

Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin.

5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin.

In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.

Birdsall TC 73541.2166@compuserve.com Altern Med Rev 1998 Aug;3(4):271-80

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Abnormal functional activity of the central nervous system in fibromyalgia syndrome.

The evaluation of pain is one of the major problems facing general practitioners and specialists in medicine. Although the source of pain can be usually be traced to specific abnormalities in a given organ system, some patients present with generalized pain syndromes, such as fibromyalgia, for which no specific source can be found. Some researchers have begun to consider that although there may be a somatic source of such pain at its initiation, over time the pain may be maintained or exacerbated by functional alterations in critical regions of the brain and spinal cord that are involved in pain processing or pain inhibition. This article describes the techniques currently used to measure regional cerebral blood flow (rCBF) in the brain by single photon emission computed tomography (SPECT) imaging, and reviews the SPECT and positron emission tomography literature concerning alterations in functional brain activity associated with pain in healthy individuals and in patients with chronic pain, including those with fibromyalgia. The article concludes by describing the implications of current knowledge about pain and abnormal functional brain activity in the understanding of the pathophysiology of fibromyalgia and in the development of therapeutic strategies to manage patients with this disorder.

Mountz JM, Bradley LA, Alarcon GS Department of Radiology, The University of Alabama at Birmingham, 35233, USA. jmmountz@uab.edu Am J Med Sci 1998 Jun;315(6):385-96 Publication Types: · Review · Review, tutorial

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Advances in fibromyalgia: possible role for central neurochemicals.

The neurophysiologic term allodynia has been applied to fibromyalgia because people with that disorder experience pain from pressure stimuli which are not normally painful. The nociceptive neurotransmitters of animal studies are now relevant to this human model of chronic, widespread pain. Evidence is presented to implicate several chemical pain mediators (including serotonin, substance P, nerve growth factor, and dynorphin A) in the pathogenesis of fibromyalgia. This perception is hopeful because it offers many new options for the development of innovative therapy.

Russell IJ Department of Medicine, The University of Texas Health Science Center, San Antonio 782847868, USA. Am J Med Sci 1998 Jun;315(6):377-84 Publication Types: · Review · Review, tutorial

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Advances in the treatment of fibromyalgia: current status and future directions.

Despite significant efforts devoted to understanding the etiopathogenesis of fibromyalgia, its treatment still presents a challenge to practicing clinicians, who must recognize the disorder and quantify the different symptoms in order to treat it. This article discusses recent research to identify sensitive and reliable measures for determining response to treatment among patients with FM, and the elements of therapeutic programs (pharmacologic and nonpharmacologic) for patients with FM along with the empirical or theoretical basis for their use.

Future directions, including the need for systematic, controlled outcome studies of therapies and evaluation of variables which may mediate the effects of treatment, as well as demonstration that the effects produced in outcome studies generalize to settings beyond those in which the studies are initially conducted, are also discussed.

Alarcon GS, Bradley LA

Division of Clinical Immunology and Rheumatology and the Multipurpose Arthritis and Musculoskeletal Diseases Center, The University of Alabama at Birmingham, 35294, USA. graciela.alacron@ccc.uab.edu Am J Med Sci 1998 Jun;315(6):397-404 Publication Types: · Review · Review, tutorial

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Affective distress in fibromyalgia syndrome is associated with pain severity.

OBJECTIVE: Comparison of low back pain (LBP) patients with and without fibromyalgia syndrome (FMS) with regard to affective distress.

METHODS: Patients with LBP who had been admitted to various clinics in Germany were examined upon admission. Comparisons were done by dividing the patients into groups with and without signs of FMS. Additionally, both groups were compared after being matched according to sex, age, and pain severity.

RESULTS: 15 out of 135 LBP patients met the American College of Rheumatology criteria for fibromyalgia. Patients with FMS showed remarkably higher levels of pain severity and affective distress. After controlling for different levels of pain severity, these pronounced differences disappeared.

CONCLUSION: Affective distress is not a unique feature of FMS, but seem to be caused entirely by higher levels of pain severity.

Walter B, Vaitl D, Frank R Department of Clinical and Physiological Psychology, University of Giessen, Germany. Z Rheumatol 1998;57 Suppl 2:101-4 [Medline record in process]

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The association of functional gastrointestinal disorders and fibromyalgia.

Previous epidemiological studies have confirmed the clinical impression that functional gastrointestinal disorders typically overlap with fibromyalgia (FM) in the same patient, suggesting a common etiology. FM syndrome occurs in up to 60% of patients with functional bowel disorders. Up to 50% of patients with a diagnosis of FM syndrome complain of symptoms characteristic of functional dyspepsia and 70% have symptoms of IBS. These two conditions have common clinical characteristics: (1) the majority of patients associate stressful life events with the initiation or exacerbation of symptoms, (2) the majority of patients complain of disturbed sleep and fatigue, (3) psychotherapy and behavioral therapies are efficacious in treating

symptoms, and (4) low-dose tricyclic antidepressant medication can improve symptoms. Despite these similarities, their perceptual responses to both somatic and visceral stimuli differ. While FM patients characteristically exhibit somatic hyperalgesia, IBS patients without coexistent FM have somatic hypoalgesia to mechanical stimuli. Visceral distention studies have also demonstrated perceptual alterations in patients with IBS and FM although these findings appear to differ in the two conditions. Further studies will help explore the mechanisms which are responsible for the similarities and differences in clinical symptoms and physiologic parameters seen in IBS and FM.

Chang L CURE/Neuroenteric Disease Program, West Los Angeles VA Medical Center, CA 90073, USA. Eur J Surg Suppl 1998;(583):32-6 [Medline record in process]

The association of soft-tissue rheumatism and hypermobility.

Soft-tissue rheumatism (STR--tendinitis, bursitis, fasciitis and fibromyalgia) accounts for up to 25% of referrals to rheumatologists. The estimated prevalence of generalized hypermobility in the adult population is 5-15%. There have previously been suggestions that hypermobile individuals may be predisposed to soft-tissue trauma and subsequent musculoskeletal pain. This study was designed to examine the mobility status and physical activity level in consecutive rheumatology clinic attendees with a primary diagnosis of STR. Of 82 patients up to age 70 yr with STR, 29 (35%) met criteria for generalized hypermobility. Hypermobile compared to non- hypermobile individuals reported significantly more previous episodes of STR (90% vs 51%, P < 0.01), and more recurrent episodes of STR at a single site (69% vs 38%, P < 0.001). Although we were unable to show any difference in the time spent carrying out physical activity between the two groups, the hypermobile patients were performing significantly more repetitive activities. When specific anatomical sites of STR were analysed, small joints (elbows, hands and feet) currently affected with STR were more likely to show localized hypermobility than if those joints were asymptomatic. These findings suggest that hypermobility may be a factor in the development of STR. Repetitive activity may be a contributing factor towards STR in some hypermobile individuals.

Hudson N, Fitzcharles MA, Cohen M, Starr MR, Esdaile JM Rheumatic Disease Unit, McGill University, Montreal, Quebec, Canada. Br J Rheumatol 1998 Apr;37(4):382-6

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Biofeedback/relaxation training and exercise interventions for fibromyalgia: a prospective trial.

OBJECTIVE: To compare the effectiveness of biofeedback/relaxation, exercise, and a combined program for the treatment of fibromyalgia.

METHODS: Subjects (n = 119) were randomly assigned to one of 4 groups: 1) biofeedback/relaxation training, 2) exercise training, 3) a combination treatment, or 4) an educational/attention control program.

RESULTS: All 3 treatment groups produced improvements in self-efficacy for function relative to the control condition. In addition, all treatment groups were significantly different from the control group on tender point index scores, reflecting a modest deterioration by the attention control group rather than improvements by the treatment groups. The exercise and combination groups also resulted in modest improvements on a physical activity measure. The combination group best maintained benefits across the 2-year period.

CONCLUSION: This study demonstrates that these 3 treatment interventions result in improved self-efficacy for physical function which was best maintained by the combination group.

Buckelew SP, Conway R, Parker J, Deuser WE, Read J, Witty TE, Hewett JE, Minor M, Johnson JC, Van Male L, McIntosh MJ, Nigh M, Kay DR Department of Physical Medicine and Rehabilitation, Missouri Arthritis Rehabilitation Research and Training Center, School of Medicine, University of Missouri-Columbia, USA. Arthritis Care Res 1998 Jun;11(3):196-209 [Medline record in process]

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Chronic fatigue and chronic fatigue syndrome: shifting boundaries and attributions.

The subjective symptom of "fatigue" is one of the most widespread in the general population and is a major source of healthcare utilization. Prolonged fatigue is often associated with neuropsychological and musculoskeletal symptoms that form the basis of several syndromal diagnoses including chronic fatigue syndrome, fibromyalgia, and neurasthenia, and is clearly not simply the result of a lack of force generation from the muscle. Current epidemiologic research in this area relies predominantly on self-report data to document the prevalence and associations of chronic fatigue. Of necessity, this subjective data source gives rise to uncertain diagnostic boundaries and consequent divergent epidemiologic, clinical, and pathophysiologic research findings. This review will highlight the impact of the case definition and ascertainment methods on the varying prevalence estimates of chronic fatigue syndrome and patterns of reported psychological comorbidty. It will also evaluate the evidence for a true postinfective fatigue syndrome.

Lloyd AR The Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, Australia. Am J Med 1998 Sep 28;105(3A):7S-10S [Medline record in process]

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Chronic fatigue syndrome and fibromyalgia. Dilemmas in diagnosis and clinical management.

There has been a resurgence of interest in recent years in both chronic fatigue syndrome and fibromyalgia. These perplexing and common clinical conditions are a source of significant patient morbidity and frame one of the more enduring dilemmas of contemporary Western medical thought, namely the ambiguous interface between mind and body.

In this article, the current definitions are reviewed, and a framework for an emerging psychobiological model of these syndromes is presented. These issues are synthesized into a pragmatic approach to clinical management.

Demitrack MA Lilly Research Laboratories, Indianapolis, Indiana, USA. Psychiatr Clin North Am 1998 Sep;21(3):671-92, viii [Medline record in process]

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Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome.

Levels of substance P were determined in the cerebrospinal fluid (CSF) in 15 patients with chronic fatigue syndrome (CFS). All values were within normal range. This is in contrast to fibromyalgia (FM). The majority of patients with FM have increased substance P values in the CSF. The results support the notion that FM and CFS are different disorders in spite of overlapping symptomatology.

Evengard B, Nilsson CG, Lindh G, Lindquist L, Eneroth P, Fredrikson S, Terenius L, Henriksson KG Department of Infectious Diseases, Karolinska Institute at Huddinge Hospital, Stockholm, Sweden. Pain 1998 Nov;78(2):153-5 [Medline record in process]

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Chronic myofascial pain: knowledge of diagnosis and satisfaction with treatment.

OBJECTIVE: To examine the relation between pain patients' knowledge of pain diagnosis and their satisfaction with pain treatment. It was hypothesized that myofascial pain (MP) patients would be less knowledgeable regarding their diagnosis and less satisfied with the results of pain treatment.

DESIGN: Cross-sectional.

SETTING: Multidisciplinary pain clinic.

PATIENTS: Patients (n=65) were divided into two groups after multidisciplinary assessment: MP patients (n=30) and a mixed group of chronic pain patients (MCP) (n=35) with neurologic or rheumatologic disorders.

MAIN OUTCOME MEASURES: Patient self-report of their knowledge of pain diagnosis and scores on standardized measures of pain intensity, depressive symptoms, and functional disability.

RESULTS: MP patients were significantly less accurate in identifying their diagnosis and the source of their pain and were more likely to believe they suffered a physiologic disturbance "more serious and different" than their physicians had suggested.

MP patients were also significantly more dissatisfied with the treatment for pain by physicians and reported particular dissatisfaction with the informational aspects of physician-patient communication. No group differences were obtained for measures of pain severity, depression, disability, pain duration, or compensation/litigation status.

CONCLUSION: MP patients appear to have less accurate beliefs regarding their pain symptoms and express more dissatisfaction with physician efforts to treat their pain. These findings emphasize the importance of patient education as a component of chronic pain intervention, particularly for MP patients.

Roth RS, Horowitz K, Bachman JE Department of Anesthesiology, University of Michigan Medical Center, Ann Arbor 48109, USA. Arch Phys Med Rehabil 1998 Aug;79(8):966-70

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Chronic orofacial muscle pain: a new approach to diagnosis and management.

The initial data from this study indicate that there are clearly identifiable chronic muscle pain conditions in the form of localized pain; myofascial pain or regional pain conditions; and fibromyalgia or generalized pain conditions. A clear difference exists between the prevalence of these conditions in male and female patients, with a higher percentage of female patients suffering generalized pain problems and temporomandibular problems. Generalized or localized pain appears to be an individual variant of a similar problem and pain patients may have a genetically determined vulnerability associated with bacterial toxins, particularly within the genitourinary tract. It appears that in fibromyalgia there is an underlying genetic factor that causes abnormalities in the muscle metabolic cycle, and preliminary data suggest that lipid

anomalies predispose to fibromyalgia and possibly chronic fatigue syndrome. Patients report infectious events at/or around onset in more than 60 percent of cases. Seventy percent of fibromyalgic cases report orofacial pain.

Klineberg I, McGregor N, Butt H, Dunstan H, Roberts T, Zerbes M Faculty of Dentistry, University of Sydney. Alpha Omegan 1998 Jul;91(2):25-8 [Medline record in process]

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Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms.

Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical literature, although the terms used to describe these symptom complexes have changed frequently. The currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which describe the prominent clinical features of the illness without any attempt to identify the cause.

This review delineates the definitions of these syndromes, and the overlapping clinical features. A hypothesis is presented to demonstrate how genetic and environmental factors may interact to cause the development of these syndromes, which we postulate are caused by central nervous system dysfunction.

Various components of the central nervous system appear to be involved, including the hypothalamic pituitary axes, pain-processing pathways, and autonomic nervous system. These central nervous system changes lead to corresponding changes in immune function, which we postulate are epiphenomena rather than the cause of the illnesses.

Clauw DJ, Chrousos GP Department of Medicine, Georgetown University Medical Center, Washington, D.C. 20007, USA. Neuroimmunomodulation 1997 May-Jun;4(3):134-53 Publication Types: · Review · Review, academic

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Clinical diagnosis found in patients with Raynaud's phenomenon: a multicentre study.

A multicentre observational study was conducted in order to detect the major clinical diagnosis found in 761 patients with Raynaud's phenomenon (RP) attending 50 Italian centres for rheumatology and internal medicine. Systemic sclerosis was the most frequent condition

associated with secondary RP, occurring in 216 (28.4%) patients. The other most frequent clinical diagnoses included systemic lupus erythematosus (52 cases: 6.8%) and rheumatoid arthritis (38 cases: 5%). Other RP-related diseases (hypertension, Sjogren's syndrome, mixed connective tissue disease, undifferentiated connective tissue disease, fibromyalgia, carpal tunnel syndrome, cryoglobulinemia, dermatopolymyositis, vasculitis, thoracic outlet syndrome, hypothyroidism, diabetes mellitus) occurred in less than 5% of cases. A total of 130 (48%) out of 268 patients with primary RP showed one or more clinical features indicating a fairly high risk of evolving into fully established systemic sclerosis. None of these patients fulfilled the ACR criteria for systemic sclerosis. This study shows that over 50% of patients with RP attending 50 Italian centres for rheumatology and internal medicine had a connective tissue disease. The large number of patients with primary RP and isolated clinical features of connective tissue disease indicates that more efforts should be focused on developing new criteria for the classification of RP.

Grassi W, De Angelis R, Lapadula G, Leardini G, Scarpa R Clinica Reumatologica, Ospedale A. Murri, Jesi, Italy. Rheumatol Int 1998;18(1):17-20 Publication Types: Multicenter study

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[Clinical experiences with the analgesic effects of citalopram].

Antidepressive drugs influencing the serotonin metabolism have shown some efficacy in treatment of generalised pain syndrome. The aim of the present study was to observe the analgesic effect of citalopram < 1-[3- (dimetilamino)propil]-1-(p-florofenil)-5-ftal+ ++ankarbonitin > in 20 non depressive patients with chronic pain syndrome (fibromyalgy and/or radicular pain). On the base of a short time (6 weeks) observation a limited clinical effect was observed, however, the Seropram seems to have some benefits in the treatment of chronic pain.

Baraczka K, Janko Z, Vargha K, Markus H Orszagos Reumatologiai es Fizioterapias Intezet, Budapest. Orv Hetil 1997 Oct 12;138(41):2605-7 [Article in Hungarian] Publication Types: · Clinical trial · Clinical trial, phase ii · Randomized controlled trial

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Collagen cross-links in fibromyalgia syndrome.

OBJECTIVE: The acceptance of fibromyalgia as a disease entity and its definitive diagnosis have been hampered by a dearth of knowledge concerning the underlying pathophysiology of this disease and the lack of specific biochemical markers applicable to its diagnosis. To

determine whether abnormal collagen metabolism is a characteristic of fibromyalgia, we have analyzed collagen metabolites in the urine and serum of patients with fibromyalgia.

METHODS: The diagnosis of fibromyalgia was made according to the American College of Rheumatology criteria. Urine and serum were collected under standardized conditions from 39 patients and 55 age- and sex-matched controls. Pyridinoline (Pyd) and deoxypyridinoline (Dpyd), which represent products of lysyl oxidase-mediated cross-linking in collagen and are indicators of connective tissue and bone degradation, respectively, were analyzed by ion-paired and gradient HPLC method with fluorescence detection (HPLC). Levels of hydroxypyroline (Hyp), a collagen turnover marker, were also measured. The findings were related to creatinine levels and the Pyd/Dpyd ratio determined.

RESULTS: The Pyd/Dpyd ratios in the urine and serum and the Hyp in the urine were significantly lower in patients with fibromyalgia than in healthy controls.

CONCLUSION: Decreased levels of collagen cross-linking may contribute to remodeling of the extracellular matrix and collagen deposition around the nerve fibers in fibromyalgia and contribute to the lower pain threshold at the tender points. Analysis of altered collagen metabolism either by histologic examination on biopsy or, preferably, by HPLC analysis of collagen metabolites in urine or serum may aid to understand more about the pathogenesis of fibromyalgia.

Sprott H, Muller A, Heine H Dept. Rheumatology, University Hospital Zurich. Z Rheumatol 1998;57 Suppl 2:52-5 [Medline record in process]

Comorbidity between myofascial pain of the masticatory muscles and fibromyalgia.

This study compared myofascial pain of the masticatory muscles to fibromyalgia. Study data show that, in both myofascial pain and fibromyalgia patients, facial pain intensity and its daily pattern and effect on quality of life are very similar. This indicates that fibromyalgia should be included in the differential diagnosis for myofascial pain of the masticatory muscles. However, with the higher prevalence of neurologic and gastrointestinal symptoms, and the stronger words used to describe the affective dimension of pain, it is apparent that fibromyalgia may be a more debilitating condition than myofascial pain of the masticatory muscles. Since the intensity of facial pain was strongly and significantly correlated to the body-pain index in fibromyalgia but not in myofascial pain patients, it can be concluded that facial pain may be part of the clinical manifestations of fibromyalgia, but it is unlikely to be related to body pain in myofascial pain patients. On the other hand, while body pain is episodic in most myofascial pain patients, it is constant and more severe in the majority of fibromyalgia patients. This difference in the pain patterns suggests that body pain in fibromyalgia and myofascial pain could have different etiologies. The lack of correlation between the intensity of pain and the length of time since onset also supports the concept that myofascial pain of the masticatory muscles and fibromyalgia are unlikely to be progressive disorders.

Dao TT, Reynolds WJ, Tenenbaum HC

Department of Prosthodontics, Faculty of Dentistry, University of Toronto, Mount Sinai Hospital, Ontario, Canada. J Orofac Pain 1997 Summer;11(3):232-41

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Comparison of integrated group therapy and group relaxation training for fibromyalgia.

OBJECTIVE: The efficacy of an integrated, psychological treatment program was tested in a controlled study involving 27 patients with chronic musculoskeletal pain (fibromyalgia).

DESIGN: The experimental treatment program consisted of instruction in various self-help techniques (e.g., cognitive behavioral strategies, relaxation, physical exercises) as well as information on chronic pain. Control groups were instructed only in autogenic training. Measures of pain, daily activities, general symptoms, and psychological functioning were assessed before and after treatment, as well as at 4 months after termination of therapy (follow-up).

RESULTS: At the end of treatment, 7 patients from the experimental group and 2 from the control group showed significant clinical improvement in 3 of 6 parameters (NS). At follow-up, the improvement was still present in 5 experimental cases but in none of the controls (p = 0.024). Successful patients had been sick for a shorter period of time and were less impaired by their condition.

CONCLUSIONS: Psychological interventions in combination with physiotherapy can be effective in treating fibromyalgia patients, especially if applied early.

Keel PJ, Bodoky C, Gerhard U, Muller W University Psychiatric Outpatient Clinic, Basel, Switzerland. Clin J Pain 1998 Sep;14(3):232-8 [Medline record in process]

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Comparison of clinical and psychologic features of fibromyalgia and masticatory myofascial pain.

The aim of this study was to investigate common symptoms and divergent features in fibromyalgia (FS) and masticatory myofascial pain (MFP) in patients affected by craniomandibular disorders. Twenty-three women with MFP and 23 women with FS were studied. All patients were examined by a dentist and by a rheumatologist. Craniomandibular disorders were assessed with a subjective symptoms questionnaire, detailed history interview, joint function examination, and manual palpation of masticatory and cervical muscles. The Middlesex Hospital Questionnaire was used to obtain personality profiles of the patients. The

craniomandibular disorders questionnaire revealed various similarities in the two groups, the most striking of which were pain during mandibular function, articular noises, and headache. Both groups had muscle pain upon palpation; the mean scores (on a 0 to 4 scale) did not differ significantly between the two groups and ranged between 1.39 (SD 1.2) and 2.86 (SD 0.75). The mean value of active mouth opening was 40.9 mm (SD 9.1) in MFP patients and 44.6 mm (SD 7.2) in FS patients, while the mean value of passive opening was 49.6 mm (SD 6.0) in MFP patients and 49.8 mm (SD 3.5) in FS patients. These values did not differ significantly between the two groups, but did differ from the normal population, similar to the trend of the psychologic profile. The authors conclude that the physician should be alert to the need to conduct interdisciplinary evaluations in the diagnosis and management of FS and of MFP.

Cimino R, Michelotti A, Stradi R, Farinaro C Department of Orthodontics, School of Dentistry, Faculty of Medicine, University of Naples, Federico II, Italy. J Orofac Pain 1998 Winter;12(1):35-41

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A comparison of three types of neck support in fibromyalgia patients.

OBJECTIVE: To determine the effectiveness of 3 types of neck support for patients with fibromyalgia (FMS) and their preference for the type of support.

METHODS: Thirty-five patients with FMS chose the order of application and used each type of neck support for a 2-week period, followed by a 2-week washout. The same schedule was repeated a second time. The neck supports included a Shape of Sleep pillow, two neck ruffs with one standard pillow, and a single standard pillow. All subjects received a physiotherapy treatment and educational program in the home. Outcome measures included visual analog scales (VAS) for neck pain and quality of sleep, the Fibromyalgia Impact Questionnaire (FIQ), and a neck and shoulder pain distribution diagram.

RESULTS: Analysis using Friedman's 2-way analysis of variance revealed no significant differences in any outcome measure, although there was a trend towards improvement in the FIQ and VAS neck pain and quality of sleep scores for some patients. Most participants (62.9%) preferred the Shape of Sleep pillow, 20.0% preferred cervical ruffs with one standard pillow, and 17.1% preferred a single standard pillow.

CONCLUSIONS: The results of this study are inconclusive due to the small sample size. However, from a patient's perspective, neck support is an important part of a comprehensive physiotherapy program. Most participants preferred the more rigid support of a Shape of Sleep pillow. Further research into the efficacy of the use of neck support in people with FMS is warranted.

Ambrogio N, Cuttiford J, Lineker S, Li L Arthritis Society, Consultation and Rehabilitation Service, London, Ontario, Canada.

Arthritis Care Res 1998 Oct;11(5):405-10 [Medline record in process]

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The connection between chronic fatigue syndrome and neurally mediated hypotension.

Research from several groups of investigators indicates that some patients with chronic fatigue syndrome have abnormal vasovagal or vasodepressor responses to upright posture. If confirmed, these findings may explain some of the symptoms of chronic fatigue syndrome. There is also speculation that neurally mediated hypotension may be present in fibromyalgia. This article discusses the original research in this area, the results of follow-up studies, and the current approach to treating patients with chronic fatigue syndrome in whom neurally mediated hypotension is suspected.

Wilke WS, Fouad-Tarazi FM, Cash JM, Calabrese LH Department of Rheumatic and Immunologic Disease, Cleveland Clinic Foundation, OH 44195, USA. Cleve Clin J Med 1998 May;65(5):261-6 Publication Types: · Review · Review, tutorial

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Current concepts in the pathophysiology of abnormal pain perception in fibromyalgia.

Fibromyalgia is a noninflammatory rheumatic disorder characterized by chronic widespread musculoskeletal pain. Although many studies have described the pain and other clinical symptoms associated with this disorder, the primary mechanisms underlying the etiology of fibromyalgia remain elusive. This article reviews recent data supporting the links among each of three systems--the musculoskeletal system, the neuroendocrine system, and the central nervous system (CNS), all of which appear to play major roles in fibromyalgia pathophysiology--and pain in fibromyalgia, and concludes by presenting a model of the pathophysiology of abnormal pain perception in fibromyalgia which integrates the research findings described.

Weigent DA, Bradley LA, Blalock JE, Alarcon GS Department of Medicine, The University of Alabama at Birmingham, 35294, USA. Am J Med Sci 1998 Jun;315(6):405-12 Publication Types: · Review · Review, tutorial

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Daily activities in women with rheumatoid arthritis. Aspects of patient education, assistive devices and methods for disability and impairment assessment.

The major aims of the study were to identify the difficulties in daily activities (ADL) of women with rheumatoid arthritis (RA) and to demonstrate the effect of interventions. Methods were developed for measuring grip force, the Grippit instrument, and assessing ADL without and with assistive devices. Effects of interventions were explored, and the need for new solutions concerning daily activities was identified. Seventy-three women with RA participated in the study, 14 women with fibromyalgia were included in the grip force measurements, and 187 healthy women and 65 healthy men acted as a reference group. In describing the consequences of the disease with regard to daily activities, the patient's perspective was taken into account.

RESULTS: Grip force (peak value and average value over 10 seconds) was reduced in women with RA compared to the reference values. With an elastic wrist orthosis, pain decreased and grip force increased significantly in defined ADL situations. After a patient education programme in joint protection, designed to influence knowledge, inspiration and action, on average 91% of the assistive devices provided were in use, most frequently for kitchen work and personal care. Pain also decreased significantly with the use of specially designed assistive devices like breadsaws, potato peelers, and scissors compared to using standard tools. The cost of these interventions could be judged to be low in relation to its effectiveness. Using an alternative model of the Health Assessment Questionnaire (HAQ) where the use of assistive devices did not influence the ratings, grip force was correlated to more ADL activities than disclosed by the ordinary HAQ ratings. The difference between these two models for rating HAQ items was demonstrated. The Evaluation of Daily Activity Questionnaire (EDAQ) was developed and can be used to evaluate both intrinsic (without assistive devices) and actual (with such assistance) disability. The EDAQ consists of 102 items arranged in 11 dimensions. The number of activities with perceived difficulty without assistive devices/altered working methods in RA women ranged between 13 and 99 and after interventions between 6 and 57. Assistive devices appeared most effective in the dimensions Eating, Cooking and Toileting. Only a few useful devices were identified in the dimensions Dressing, Washing/Clothes care and Cleaning. The ordinal score from EDAQ was transformed by the Rasch analysis to obtain linear measures. This allowed the construction of an acceptable model with items ranging from "hard" to "easy". The hardest items were found to be shopping and cleaning the kitchen floor, the easiest were walking indoors and using telephone.

CONCLUSIONS: Women with RA have reduced grip force and pain, which affect their performance of daily activities. Usage of assistive devices and altered working methods reduced the perceived difficulty in various activities. The ADL items assessed with the EDAQ questionnaire, which also considers the individuals' own solutions to their problems, could be arranged hierarchically from "hard" to "easy".

Nordenskiold U Department of Rehabilitation Medicine, Institute of Community Medicine, Goteborg University, Sahlgrenska University Hospital, Sweden. Scand J Rehabil Med Suppl 1997;37:1-72

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Depressed fibromyalgia patients are equipped with an emphatic competence dependent self-esteem.

Employing a recently developed questionnaire we studied the self-esteem structure of 61 female fibromyalgia (FM) patients by comparing them with i) 40 healthy psychology students and ii) 37 patients suffering from rheumatoid arthritis. Depressed FM patients (n=36) had a high need to gain self-esteem through competence and others' approval combined with a low basic sense of self-esteem. In this regard they differed significantly from the healthy controls who had a more equal amount of the two types of self-esteem. These patients had also a more demanding and "hard-driving" self-esteem structure than either control group and exhibited a lower self-assertiveness and less emotional candour than the healthy controls. The non-depressed FM patients did not display this self-esteem pattern. In conclusion, FM patients are probably not a homogeneous group. Furthermore, we suggest that an emphatic competence-dependent self-esteem is one vulnerability factor which, in proper genetic and environmental conditions, increases susceptibility to fibromyalgia and depression.

Johnson M, Paananen ML, Rahinantti P, Hannonen P Department of Psychology, Stockholm University, Sweden. Clin Rheumatol 1997 Nov;16(6):578-84

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The detoxification enzyme systems.

The human body is exposed to a wide array of xenobiotics in one s lifetime, from food components to environmental toxins to pharmaceuticals, and has developed complex enzymatic mechanisms to detoxify these substances. These mechanisms exhibit significant individual variability, and are affected by environment, lifestyle, and genetic influences. The scientific literature suggests an association between impaired detoxification and certain diseases, including cancer, Parkinson's disease, fibromyalgia, and chronic fatigue/immune dysfunction syndrome. Data regarding these hepatic detoxification enzyme systems and the body s mechanisms of regulating them suggests the ability to efficiently detoxify and remove xenobiotics can affect these and other chronic disease processes. This article reviews the myriad detoxification enzyme systems, their regulatory mechanisms, and the dietary, lifestyle, and genetic factors influencing their activities, as well as laboratory tests available to assess their functioning.

Liska DJ HealthComm International, Inc. P.O. Box 1729, Gig Harbor, WA 98335, USA. deann@healthcomm.com Altern Med Rev 1998 Jun;3(3):187-98 Publication Types: · Review · Review, tutorial

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Differential responses by psychosocial subgroups of fibromyalgia syndrome patients to an interdisciplinary treatment.

OBJECTIVES: To evaluate differential treatment responses among 3 empirically derived, psychosocial subgroups of patients with fibromyalgia syndrome to a standard interdisciplinary treatment program.

METHOD: Patients were classified into 1 of 3 psychosocial groups on the basis of their responses to the Multidimensional Pain Inventory. Forty-eight patients completed a 6 one-half-day outpatient treatment program consisting of medical, physical, occupational, and psychological therapies spaced over a period of 4 weeks (3 sessions the first week followed by 1 session per week for the next 3 consecutive weeks).

RESULTS: Statistically significant reductions were observed in pain, affective distress, perceived disability, and perceived inteference of pain in the patients characterized by poor coping and high level of pain ("dysfunctional" group). In contrast, individuals who were characterized by interpersonal difficulties ("interpersonally distressed" group) exhibited poor responses to the treatment. "Adaptive copers," the third group, revealed significant improvements in pain but due to low pretreatment levels of affective distress and disability showed little improvement on these outcomes.

CONCLUSIONS: The results provided support for the hypothesis that customizing treatment based on patients' psychosocial needs will lead to enhanced treatment efficacy. They also emphasize the importance of using appropriate outcome criteria, as low levels of problems at baseline are not likely to show significant changes following any treatment.

Turk DC, Okifuji A, Sinclair JD, Starz TW Department of Anesthesiology, University of Washington School of Medicine, Seattle, WA 98195-6540, USA. Arthritis Care Res 1998 Oct;11(5):397-404 [Medline record in process]

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Disordered growth hormone secretion in fibromyalgia: a review of recent findings and a hypothesized etiology.

Growth hormone (GH) deficiency occurs in about 30% of fibromyalgia patients. Treatment of GH deficient fibromyalgia patients with recombinant growth hormone improves several clinical features, including the tender point count. Defective GH secretion in these patients appears to be due to increased somatostatin tone in the hypothalamus. An hypothesis is presented which relates dysfunctional GH secretion to the effects of intermittent hypercortisolemia on upregulating the density of beta-adrenergic receptors in the hypothalamus. The resulting augmentation of beta- adrenergic tone stimulates the release of somatostatin, thus, impairing GH secretion.

Bennett RM Dept. Medicine (L329A), Oregon Health Sciences University, Portland 97201, USA. Z Rheumatol 1998;57 Suppl 2:72-6 [Medline record in process]

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Doctors' attitudes to fibromyalgia: a phenomenological study.

Besides specific technical skills, successful encounters with patients require an understanding of the many ways in which patients may express themselves. This qualitative study reports on the clinical experiences of doctors when meeting patients with fibromyalgia (FM). Ten strategically chosen rheumatologists and 10 GPs in central Sweden were interviewed.

The interviews were taped, transcribed and analysed in accordance with the empirical, phenomenological, psychological method. The analyses indicate that doctors try to comply with the wishes and demands of patients, and at the same time avoid perceptions of personal frustration.

They are inclined to be objective and to act instrumentally, apparently in order to keep in touch with what gave biomedical meaning to an otherwise incomprehensible phenomenon. The meaning structures revealed by doctors' descriptions of FM and of relating to FM patients were characterized mainly by the way in which the doctors were (i) managing their clinical uncertainty,

(ii) adhering to the biomedical paradigm,

(iii) prioritizing diagnostics,

(iv)
establishing an instrumental relationship, and

(v)
avoiding recognizing FM as a possible biomedical anomaly.

Hellstrom O, Bullington J, Karlsson G, Lindqvist P, Mattsson B Department of Family Medicine, Umea University, Sweden. Scand J Soc Med 1998 Sep;26(3):232-7 [Medline record in process]

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Dyspnea resulting from fibromyalgia.

Two patients with chronic, severe, episodic dyspnea underwent prolonged, extensive, and invasive evaluations without a diagnosis being made. Both were subsequently diagnosed with fibromyalgia, and therapy directed at this condition resulted in resolution of their symptoms.

Fibromyalgia is rarely included in the differential diagnosis of dyspnea, and timely diagnosis and treatment may be delayed. However, this condition must be considered because it can only be established by seeking the appropriate history and physical findings.

Weiss DJ, Kreck T, Albert RK Pulmonary and Critical Care Medicine Division, University of Washington School of Medicine, Seattle, USA. Chest 1998 Jan;113(1):246-249

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Early life stress, negative paternal relationships, and chemical intolerance in middle-aged women: support for a neural sensitization model.

This study (ntotal = 35) compared early life stress ratings, parental relationships, and health status, notably orthostatic blood pressures, of middle-aged women with low-level chemical intolerance (CI group) and depression, depressives without CI (DEP group), and normals. Environmental chemical intolerance is a symptom of several controversial conditions in which women are overrepresented, that is, sick building syndrome, multiple chemical sensitivity, chronic fatigue syndrome, and fibromyalgia.

Previous investigators have postulated that people with CI have variants of somatization disorder, depression, posttraumatic stress disorder (PTSD) initiated by childhood abuse or a toxic exposure event. One neurobehavioral model for CI, somatization disorder, recurrent depression, and PTSD is neural sensitization, that is, the progressive amplification of host responses (e.g., behavioral, neurochemical) to repeated intermittent stimuli (e.g., drugs, chemicals, endogenous mediators, stressors).

Females are more vulnerable to sensitization than are males. Limbic and mesolimbic pathways mediate central nervous system sensitization. Although both CI and DEP groups had high levels of life stress and past abuse, the CI group had the most distant and weak paternal relationships and highest limbic somatic dysfunction subscale scores. Only the CI group showed sensitization of sitting blood pressures over sessions.

Together with prior evidence, these data are consistent with a neural sensitization model for CI in certain women. The findings may have implications for poorer long-term medical as well as

neuropsychiatric health outcomes of a subset of women with CI. Subsequent research should test this model in specific clinical diagnostic groups with CI.

Bell IR, Baldwin CM, Russek LG, Schwartz GE, Hardin EE Department of Psychiatry, University of Arizona, Tucson, USA. J Womens Health 1998 Nov;7(9):1135-47 [Medline record in process]

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Effect of gamma-hydroxybutyrate on pain, fatigue, and the alpha sleep anomaly in patients with fibromyalgia. Preliminary report.

OBJECTIVE: To evaluate the effects of using a gamma-hydroxybutyrate (GHB) administered in divided doses at night in 11 patients previously diagnosed with fibromyalgia (FM).

METHODS: Subjects completed daily diaries assessing their pain and fatigue levels and slept in the sleep laboratory before and one month after initiating GHB treatment. Polysomnographic recordings were evaluated for sleep stages, sleep efficiency and the presence of the alpha anomaly in non-REM sleep.

RESULTS: There was a significant improvement in both fatigue and pain, with an increase in slow wave sleep and a decrease in the severity of the alpha anomaly.

CONCLUSION: Further controlled studies are needed to characterize the clinical improvement and the polysomnographic changes we observed.

Scharf MB, Hauck M, Stover R, McDannold M, Berkowitz D Center for Research in Sleep Disorders, Cincinnati, Ohio, USA. J Rheumatol 1998 Oct;25(10):1986-90 [Medline record in process]

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Effect of local glucocorticoid injection on masseter muscle level of serotonin in patients with chronic myalgia.

The aim of this study was to compare the effects on the level of serotonin (5-HT) in the masseter muscle by intramuscular glucocorticoid (GC) administration in patients with fibromyalgia (FM) and localized myalgia (LM), as well as to determine associated changes in pain, tenderness, and microcirculation. The study comprised 22 patients with pain and tenderness in the masseter muscle region. Ten patients (all women) had FNI, and 12 (1 man and 11 women) had LM involving the temporomandibular system. The patients were examined clinically and by microdialysis at 2 visits 2-3 weeks apart and received local glucocorticoid treatment at the first

visit. The ratio (S1/ S2) between the initial level of 5-HT (S1) and steady state level (S2) was used as a relative measure of the intramuscular release of 5-HT. This ratio decreased significantly after treatment in the FM group. In the FM group there was also a negative correlation regarding changes between visits of 5-HT and changes of intramuscular temperature. In the LM group there was a negative correlation regarding changes between visits of 5-HT and changes of pressure pain threshold and pressure pain tolerance level. This study indicates that there is a reduction of the ratio between initial 5-HT and steady state level in the painful masseter muscle after intramuscular GC administration to FM patients, a reduction not present in the LM patients. In addition, 5-HT seems to be involved in the modulation of local muscle microcirculation in FM patients and in hyperalgesia in LM patients.

Ernberg M, Hedenberg-Magnusson B, Alstergren P, Kopp S Department of Clinical Oral Physiology, Faculty of Odontology, Karolinska Institute, Huddinge, Sweden. Acta Odontol Scand 1998 Jun;56(3):129-34

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The effect of pain on memory for affective words.

Memory is a key cognitive variable in pain management, but lacks extensive research. This study is a replication and extension of Seltzer and Yarczower's investigation of pain's influence on memory for affective words, which found fewer positive words and more negative words recalled if subjects were in acute pain (versus no pain). In the present study, two experiments were conducted: one with a recall memory test and one with a recognition memory test. One hundred sixty undergraduate subjects were randomly placed in one of four groups: two groups had the same condition (pain or no pain) for both the encoding task and memory test, and two groups had mixed conditions (pain at encoding-no pain at memory test or no pain at encoding- pain at memory test). Pain was induced by 0 degrees-2 degrees C water immersion. At encoding, subjects categorized words by judging them as either positive or negative. Results of both experiments show that pain impairs memory. In neither experiment were differences found on memory for positive and negative words. These results do not support Seltzer and Yarczower's discriminative effects of pain on word category, but they are consistent with other research using acute pain manipulations and chronic pain populations, suggesting that pain interferes with memory. It is hypothesized that pain depletes scarce attentional resources, thereby interfering with concurrent cognitive tasks such as thinking, reasoning, and remembering.

Kuhajda MC, Thorn BE, Klinger MR Department of Psychology, University of Alabama, Tuscaloosa 35487, USA. Ann Behav Med 1998 Winter;20(1):31-5 Publication Types: Clinical trial; Randomized controlled trial

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The effect of reproductive events and alterations of sex hormone levels on the symptoms of fibromyalgia.

The fibromyalgia syndrome (FS) is a chronic pain disorder frequently affecting women of fertile age. However, the relationship of FS and pregnancy has been given little attention. In the present retrospective analysis, based on personal interviews, the influence on FS symptomatology by pregnancy, abortion, menstruation, use of oral contraceptives, and breast feeding was investigated. Twenty-six women with an established diagnosis of FS and a total of 40 pregnancies during disease were included in the study. With the exception of one patient, all women described worsening fibromyalgia symptoms during pregnancy with the last trimester experienced as the worst period. A new change of fibromyalgia symptoms within 6 months after delivery was reported for 37 of the 40 pregnancies, to the better in four and to the worse in 33 cases, resulting in a prolonged sick leave for 14 patients. An increase in depression and anxiety was a prominent problem in the post partum period. FS had no adverse effect on the outcome of pregnancy or the health of the neonate. In the majority of patients with FS, hormonal changes connected with abortion, use of hormonal contraceptives, and breast feeding did not modulate symptom severity. A pre-menstrual worsening of symptoms was recorded by 72% of the patients. Comparing the 26 patients who had borne children during disease with 18 patients who had all their children before the onset of FS revealed a negative effect of pregnancy and the post partum period of FS and increased functional impairment and disability in the 26 patients.

Ostensen M, Rugelsjoen A, Wigers SH Centre for Mothers with Rheumatic Disease, University Hospital of Trondheim, Norway. Scand J Rheumatol 1997;26(5):355-60

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The effects of delta wave sleep interruption on pain thresholds and fibromyalgia-like symptoms in healthy subjects; correlations with insulin-like growth factor I.

OBJECTIVE: To assess the effects of delta wave sleep interruption (DWSI) on pain thresholds and fibromyalgia- like symptoms. To examine the potential correlations between DWSI and serum insulin-like growth factor 1 (IGF- 1).

METHODS: Thirteen healthy volunteers were subjected to 3 consecutive nights of DWSI (Group 1). Pain thresholds were measured by dolorimetry and symptoms by visual analog scale. Six subjects not undergoing DWSI served as dolorimetry and symptom controls (Group 2). Serum IGF-1 was measured by competitive binding radioimmunoassay before and after DWSI.

RESULTS: No significant differences in pain thresholds as a function of condition (baseline, DWSI, recovery) or overnight change were detected between or within groups (p>0.05). Morning mean dolorimeter scores were lower than evening scores in both groups during all 3

conditions, and were lower in Group 1 than in Group 2 during DWSI. Group 1 subjects had higher composite symptom scores during DWSI (p< or =0.005), attributed largely to increases in fatigue. Serum levels of IGF-1 from Group 1 subjects showed no significant change after DWSI (p>0.05).

CONCLUSION: In our study subjects, 3 nights of DWSI caused no significant lowering of pain thresholds compared with a control group. Subjects appeared to have lower pain thresholds in the mornings, and DWSI appeared to augment this effect. Symptoms were more apparent during DWSI, but were primarily related to fatigue. IGF-1 was not altered by 3 nights of DWSI. The low levels of IGF-1 seen in patients with fibromyalgia syndrome may result from chronic rather than acute DWSI, or may be dependent on factors other than disturbances of delta wave sleep.

Older SA, Battafarano DF, Danning CL, Ward JA, Grady EP, Derman S, Russell IJ Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6272, USA. J Rheumatol 1998 Jun;25(6):1180-6

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The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome.

This article reports the results of a within-subject design. Fifty subjects with a physician diagnosis of fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) were interviewed using a structured interview from. Each subject was interviewed initially, and again nine months later (follow-up). Subjects had, on their own, consumed nutritional supplements including freeze- dried aloe vera gel extract; a combination of freeze-dried aloe vera gel extract and additional plant-derived saccharides; freeze-dried fruits and vegetables in combination with the saccharides; and a formulation of dioscorea complex containing the saccharides and a vitamin/mineral complex. With medical treatments, approximately 25 percent of FM patients improve, but the beneficial effects of medical treatment rarely persist more than a few months. All subjects in this study had received some form of medical treatment prior to taking the nutritional supplements, but none with enduring success. Nutritional supplements resulted in a remarkable reduction in initial symptom severity, with continued improvement in the period between initial assessment and the follow-up. Further research is needed to verify these results, specifically crossover designs in well-defined populations.

Dykman KD, Tone C, Ford C, Dykman RA Mannatech Inc., Coppell Texas 75019, USA. Integr Physiol Behav Sci 1998 Jan-Mar;33(1):61-71 Publication Types: · Clinical trial

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Ehlers-Danlos syndrome, fibromyalgia and temporomandibular disorder: report of an unusual combination.

An unusual case of temporomandibular disorder in the presence of both fibromyalgia and Ehlers-Danlos syndrome is presented. Some of the problems in treating these patients are discussed. It is suggested that early conservative treatment of the temporomandibular disorder with a stabilization splint and physical therapy is effective, and this approach should be attempted before any surgical intervention is chosen.

Miller VJ, Zeltser R, Yoeli Z, Bodner L Department of Conservative Dentistry, Faculty of Health Sciences, School of Oral Health Science, South Africa. Cranio 1997 Jul;15(3):267-9

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Elevated levels of hyaluronic acid in the sera of women with fibromyalgia.

OBJECTIVE: To evaluate serum levels of hyaluronic acid (HA) in patients with fibromyalgia (FM).

METHODS: HA serum levels were evaluated by a radiometric assay in 42 women with FM (ACR criteria), 27 female patients with rheumatoid arthritis (RA) and 36 healthy female controls matched for age.

RESULTS: HA serum levels (mean microg/l +/- SEM) were 41 +/- 8.7 in healthy controls; 113 +/- 15.9 in RA: and 420 +/- 26 in FM.

CONCLUSION: HA serum levels in women with FM were significantly elevated compared to healthy controls and patients with RA. This observation suggests that FM is associated with a biochemical abnormality and that serum HA could be a laboratory marker for its diagnosis.

Yaron I, Buskila D, Shirazi I, Neumann L, Elkayam O, Paran D, Yaron M Department of Rheumatology, Souraski Tel Aviv Medical Center, Tel Aviv University Sackler School of Medicine, Israel. J Rheumatol 1997 Nov;24(11):2221-4

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Establishing a research agenda for investigating alternative medical interventions for chronic pain.

This article describes the University of Maryland School of Medicine's Center for Complementary Medicine Research approach to developing an agenda for investigating alternative medical treatments for chronic pain syndromes. This agenda includes conducting extensive literature searches and analyses to form a knowledge base for making clinical decisions on which chronic pain syndromes are in greatest need of better therapies, as well as which alternative medical therapies offer the greatest therapeutic promise for these specific chronic pain syndromes. To date, the Center has identified back pain, arthritis, and fibromyalgia as the chronic pain syndromes that contribute the greatest clinical and economic burden to overall chronic pain statistics. Not coincidentally, patients with these diagnoses are the greatest users of alternative therapies. The Center has identified acupuncture, homeopathy, manual/manipulative therapies, and mind-body therapies as the alternative medical therapies offering the greatest clinical potential for these three general chronic pain diagnoses. Preliminary data from the Center's ongoing clinical trials programs are presented.

Berman BM, Swyers JP Division of Complementary Medicine, Department of Family Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21207, USA. Prim Care 1997 Dec;24(4):743-58 Publication Types: · Review · Review, tutorial

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Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States.

OBJECTIVE: To provide a single source for the best available estimates of the national prevalence of arthritis in general and of selected musculoskeletal disorders (osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, the spondylarthropathies, systemic lupus erythematosus, scleroderma, polymyalgia rheumatica/giant cell arteritis, gout, fibromyalgia, and low back pain).

METHODS: The National Arthritis Data Workgroup reviewed data from available surveys, such as the National Health and Nutrition Examination Survey series. For overall national estimates, we used surveys based on representative samples. Because data based on national population samples are unavailable for most specific musculoskeletal conditions, we derived data from various smaller survey samples from defined populations. Prevalence estimates from these surveys were linked to 1990 US Bureau of the Census population data to calculate national estimates. We also estimated the expected frequency of arthritis in the year 2020.

RESULTS: Current national estimates are provided, with important caveats regarding their interpretation, for self- reported arthritis and selected conditions. An estimated 15% (40 million) of Americans had some form of arthritis in 1995. By the year 2020, an estimated 18.2% (59.4 million) will be affected.

CONCLUSION: Given the limitations of the data on which they are based, this report provides the best available prevalence estimates for arthritis and other rheumatic conditions overall, and for selected musculoskeletal disorders, in the US population.

Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, Heyse SP, Hirsch R, Hochberg MC, Hunder GG, Liang MH, Pillemer SR, Steen VD, Wolfe F NIAMS, NIH, Bethesda, Maryland 20892, USA. Arthritis Rheum 1998 May;41(5):778-99

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Ethnocultural and educational differences in Israeli women correlate with pain perception in fibromyalgia.

OBJECTIVE: To compare the clinical features of patients with fibromyalgia (FM) in 2 ethnic groups in Israel.

METHODS: One hundred women with FM participated in the study; 70 were of Sephardic (Mediterranean) origin and 30 of Ashkenazic (European-American) origin. Assessment of FM related symptoms, tenderness, quality of life, and physical functioning was conducted in all subjects. Analysis of covariance and multivariate regression were performed to study the association between these measures and ethnicity, controlling for age and education.

RESULTS: Sephardic patients with FM reported more frequent and more severe symptoms than Ashkenazic patients. They had higher point counts and decreased quality of life. When the patients were divided into 2 age groups (age 45 being the cutoff point), the differences were observed only among the older subjects, most of whom were immigrants. Sephardic older patients had significantly higher point counts than Ashkenazic patients, and lower tenderness thresholds. They reported significantly higher levels of pain, fatigue, and stiffness, and were less satisfied with their life. However, these differences observed between the 2 ethnic groups in the univariate data analysis disappeared when age and education were jointly controlled in multivariate regression analysis. Age had significantly contributed to the variation in the point count, the reported pain, and physical functioning. Education made a significant contribution in explaining the point count, quality of life, pain, and fatigue.

CONCLUSION: Education, rather than ethnic identity, has been found to be an important factor in clinical features of FM. Future studies should include ethnocultural and educational assessment, especially in countries with high immigration rates and diverse ethnic groups, such as the USA and Canada.

Neumann L, Buskila D Epidemiology Department, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva, Israel. J Rheumatol 1998 Jul;25(7):1369-73

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[Etiologic factors in temporomandibular joint disorders and pain].

Parallel to the construction of better classifications and the identification of subgroups of temporomandibular disorders, an important development has taken place in research concerning its etiology. The etiological factors implied in muscle problems refer to more generalised disorders as myofascial pain syndrome and fibromyalgia. The role of occlusal and articular factors has been brought down to realistic proportions, indicating a minor contribution. Similarly, doubt has arisen concerning the existence of a vicious cycle of pain/spasm/pain. With regard to internal derangements, emphasis has been put on the high prevalence in an otherwise normal population and the fluctuating character of the symptom. Also here, developments point towards constitutional and systemic factors, more than local influences. Trauma, however, seems to play an increasing role. The development of osteoarthrosis has been studied more in depth revealing local processes of inflammation, neurogenic inflammation and the existence of specific markers which might be important in the future. The relationship between disc derangement and the development of osteoarthrosis remains unclear.

De Laat A Departement d'Odontologie, Universite Catholique de Leuven. Rev Belge Med Dent 1997;52(4):115-23 [Article in French] Publication Types: · Review · Review, tutorial

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Evaluation of multimodal treatment program for fibromyalgia.

A quasi-experimental design was used to assess a multimodal pain treatment program for female patients with fibromyalgia to ascertain immediate and long-term effects. Laboratory and self- report pain measures together with psychological measures were obtained from patients who were tested up to 6 months after treatment. Comparison data were also obtained from fibromyalgia patients who failed to qualify for the treatment program because of insurance coverage. Immediate and long-term treatment effects were evident with the psychological measures and the subjective pain measures but not with the laboratory pain measures. Participants who attended the month-long multimodal program achieved significant and positive changes on most of the outcome measures. However, relapse prevention must be addressed.

Mason LW, Goolkasian P, McCain GA University of North Carolina, Charlotte, USA. J Behav Med 1998 Apr;21(2):163-78 Publication Types: · Clinical trial · Controlled clinical trial

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Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by profound fatigue and an array of diffuse somatic symptoms. Our group has established that impaired activation of the hypothalamic-pituitary-adrenal (HPA) axis is an essential neuroendocrine feature of this condition. The relevance of this finding to the pathophysiology of CFS is supported by the observation that the onset and course of this illness is excerbated by physical and emotional stressors. It is also notable that this HPA dysregulation differs from that seen in melancholic depression, but shares features with other clinical syndromes (e.g., fibromyalgia). How the HPA axis dysfunction develops is unclear, though recent work suggests disturbances in serotonergic neurotransmission and alterations in the activity of AVP, an important co-secretagogue that, along with CRH, influences HPA axis function. In order to provide a more refined view of the nature of the HPA dusturbance in patients with CFS, we have studied the detailed, pulsatile characteristics of the HPA axis in a group of patients meeting the 1994 CDC case criteria for CFS. Results of that work are consistent with the view that patients with CFS have a reduction of HPA axis activity due, in part, to impaired central nervous system drive. These observations provide an important clue to the development of more effective treatment to this disabling condition.

Demitrack MA, Crofford LJ Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. Ann N Y Acad Sci 1998 May 1;840:684-97 Publication Types: · Review · Review, tutorial

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Evolving concepts of diagnosis, pathogenesis, and therapy of Sjogren's syndrome.

Differences in diagnostic criteria for Sjogren's Syndrome (SS) have led to confusion in the research literature and in clinical practice. A particular challenge is the clinical diagnosis of the patients with sicca symptoms, fibromyalgia, chronic fatigue, vague cognitive defects, and a low titer antinuclear antibody. Until recently, many of these patients would have been classified as primary SS using the European criteria.

A suggested revision of the European criteria will require inclusion of anti SS-A antibody or characteristic minor salivary gland biopsy, leading to greater agreement between European and San Diego criteria. Recent studies have emphasized that lacrimal and salivary gland flow involves an entire "functioal" unit that includes the mucosal surface (the site of inflammation),

efferent nerve signals sent to the midbrain (lacrimatory and salvatory nucleus), efferent neural signals from the brain, and acinal/ductal structures in the gland.

Thus, symptoms of dryness or pain can result from interferences with any part of this functional unit. The initiating antigens in SS remain unknown, but immune reactivity against SS-A, SS-B, fodrin, alpha amylase, and carbonic anhydrase have been demonstrated in patients with established disease. The inflammatory process in the gland releases metalloproteinases that alter the relationship of epithelial cells to their matrix, an interaction that is necessary for glandular function and survival. Therapies for SS remain inadequate.

In SS patients with immune-mediated extraglandular manifestation (ie, lung, kidney, skin, nerve), the therapeutic approach his similar to systemic lupus erythematosus, although these therapies have relatively little effect on tear or saliva flow.

Fox RI, Tornwall J, Maruyama T, Stern M Division of Rheumatology, Scripps Clinic, La Jolla, CA 92037, USA. Curr Opin Rheumatol 1998 Sep;10(5):446-56 [Medline record in process]

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Examination for tenderness: learning to use 4 kg force.

OBJECTIVE: To minimize interobserver variation in tender point examination, a training program was developed that focused on learning to deliver 4 kg force.

METHODS: A 3 step process was designed to provide both measurement and feedback, serving both didactic and research functions. There were 5 repetitions within each step. During the first and 3rd steps, the subjects pressed on the footplate of a dolorimeter with no immediate feedback about the force measured. In the 2nd "training" step, they were given immediate feedback about the force delivered, and were taught to watch the amount and pattern of blanching beneath and around the thumbnail.

RESULTS: Twenty-nine observers participated in 30 studies. Initial values varied from 1.78 to

8.92 kg (means within observers), although the mean value was 4.05 kg (means of all observers). The training step reduced observer variation by 65%, with reduction of mean absolute error from

1.25 to 0.44 kg. This improvement was sustained in the 3rd step, in which no feedback was given. Naive participants performed as well as experts, and there were no detectable sex differences. One observer was retested after an interval of 8 months, and performed no better during the the initial phase of the 2nd test than in the first. Each training session required 3 to 5 minutes.

CONCLUSION: Specific training efficiently reduces interobserver variations in pressure used in tender point examinations. These skills should be periodically refreshed to prevent drift into error.

Smythe H Department of Medicine, University of Toronto, ON, Canada. J Rheumatol 1998 Jan;25(1):149-151

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Exteroceptive suppression of temporalis muscle activity in patients with fibromyalgia, tension- type headache, and normal controls.

Changes of the second suppressive period (ES2) of the exteroceptive suppression of the temporalis muscle activity are found in patients with chronic tension-type headache (TTH) and are suggested to reflect an abnormal endogenous pain control system. We investigated whether similar changes are found in patients with the fibromyalgia syndrome (FMS) that is also believed to result from disturbed central pain processing. The ES2 values of 27 patients with FMS were compared with those of 18 patients with TTH and 40 healthy volunteers. The duration of ES2 (+/-SD) in FMS patients was 30.6+/-7.5 ms and was not significantly different from the control group (33.1+/-7.8 ms), whereas it was significantly shortened in TTH patients (22.9+/-11.5 ms). Our results indicate that, despite similar concepts on the pathophysiology of the two chronic pain disorders, there are no comparable changes of this brain stem reflex activity in FMS.

Schepelmann K, Dannhausen M, Kotter I, Schabet M, Dichgans J Department of Neurology, University of Tubingen, Germany. Electroencephalogr Clin Neurophysiol 1998 Sep;107(3):196-9 [Medline record in process]

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Familial painful restless legs syndrome correlates with pain dependent variation of blood flow to the caudate, thalamus, and anterior cingulate gyrus.

To understand the relationship of caudate, thalamic, and anterior cingulate perfusion to pain states, we investigated familial restless legs syndrome in a father and daughter during the state of pain induced by immobility using semiquantitative regional cerebral blood flow (rCBF) brain single photon emission computed tomography (SPECT).

The father underwent 4 brain SPECT scans using the rCBF tracer 99mTc-HMPAO several weeks apart, at different pain levels and after treatment with L-dopa. Caudate, thalamic, and anterior cingulate rCBF indices were measured. The caudate nuclei showed a 13% reduction in rCBF with increasing pain. The thalami and anterior cingulate showed a 7 and 6.6% increase in rCBF, respectively, with increasing pain.

Compared to normal controls at rest, there was a decrease in caudate rCBF by 13% and an increase in thalamic rCBF by 3%. Linear regression for the caudate nuclei revealed a significant reduction in rCBF (p < 0.05), as pain increased.

The daughter underwent an identical rCBF brain SPECT scan procedure at a high pain level induced by immobilization. Her scan showed a 12% reduction in caudate rCBF and a 1.2% increase in the anterior cingulate rCBF compared to healthy controls.

The study supports the association between pain and decreased regional cerebral blood flow to the caudate nucleus as reported in fibromyalgia syndrome. There is increase in anterior cingulate rCBF with increasing pain. Our findings also corroborate that there is increased thalamic rCBF with pain stimulation.

San Pedro EC, Mountz JM, Mountz JD, Liu HG, Katholi CR, Deutsch G Department of Radiology, University of Alabama at Birmingham Medical Center, 35294, USA. J Rheumatol 1998 Nov;25(11):2270-5 [Medline record in process]

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Fatigue in lupus is not correlated with disease activity.

OBJECTIVE: The relationship between fatigue and disease activity in systemic lupus erythematosus (SLE) has been questioned. We examined whether self-reported fatigue in patients with SLE is correlated with disease activity.

METHODS: Consecutive patients with SLE at the University of Toronto Lupus Clinic were evaluated for disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). They were also evaluated for fibromyalgia (FM) by American College of Rheumatology criteria. One hundred patients completed the following health status questionnaires: the Fatigue Severity Score (FSS), Center for Epidemiologic Studies Depression Scale (CES-D), and Medical Outcomes Study Short Form Health Survey (SF-20). Disease activity was measured by the SLEDAI. Statistical correlations were made using the Spearman test.

RESULTS: No significant correlation was found between FSS scores and SLEDAI (p = NS). Fatigue was found to be highly correlated with the presence of FM (p < 0.05) and depression (p < 0.01). In addition, fatigue was significantly associated with lower performance in all 6 domains of the SF-20 (p < 0.001); disease activity correlated with decreases in social function, mental health, and health perception areas of the SF-20. SLEDAI was not found to correlate with FM (p = NS).

CONCLUSION: Fatigue in patients with SLE does not correlate with disease activity. However, fatigue is correlated with FM, depression, and lower overall health status in this population.

Fatigue is a manifestation of these conditions, which are commonly co-expressed in SLE, and may reflect a decreased overall coping ability in these patients, rather than active disease itself.

Wang B, Gladman DD, Urowitz MB University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Disease, The Toronto Hospital, Ontario, Canada. J Rheumatol 1998 May;25(5):892-5

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[Fibromyalgia. A critical review].

Fibromyalgia is a chronic pain syndrome, more common in women. Its prevalence is estimated around 2% in the general population, and up to 20% among rheumatology outpatients. Besides musculoskeletal pain, symptoms as fatigue and sleep disturbance are considered characteristic.

Research criteria have been set up, but their seemingly preciseness is unable to distinguish clearly between fibromyalgia and other functional somatic syndromes (chronic fatigue syndrome, irritable bowel syndrome) and psychiatric disorders (depression, anxiety), with which a striking comorbidity is documented. The diagnosis of fibromyalgia does not theoretically require the exclusion of muscle, joint, or metabolic diseases, but in clinical practice this problem proves to be of crucial importance.

There are numbers of pathophysiological hypothesis for fibromyalgia, but none of them is fully satisfying: muscle is probably innocent; sleep disturbance, although sometimes considered a landmark of the syndrome, is unspecific; stress response studies show subtle anomaly; psychiatric disorders may represent factors of vulnerability and perpetuation rather than causes. We propose to include some of these etiological contributors in vicious circles leading to a "final common pathway" characterized by generalized hyperalgesia.

Treatments of fibromyalgia, whether pharmacological (antidepressants) or psychological (cognitive-behavioral therapies) are of little efficacy, and the global prognosis of fibromyalgia is poor. However, the outcome might prove better outside the specialized clinics in which studies of chronic sufferers with severe abnormal illness behaviors are done. The social consequences of the popularization of the diagnosis of fibromyalgia should not be neglected.

Cathebras P, Lauwers A, Rousset H Service de Medecine Interne, Hopital Nord, Saint-Etienne. Ann Med Interne (Paris) 1998 Nov;149(7):406-14. French. Publication Types: Review; Review, tutorial

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[Fibromyalgia--a dispensable disease term]?

The term of "fibromyalgia" has been used increasingly in the last years for chronic widespread pain in particular concerning soft tissues, muscular and extra-articular system including pain in 11 of 18 tender point sites on digital palpation. Scientific proof of an organic disorder could not be established to this day. Psychological causes are more and more considered to be responsible for this problems. Nowadays a psychosomatic disorder is assumed although as well a depression with somatization or a neurosis are discussed. Therapeutical problems and pain coping strategies are described just as the medico-legal assessment for pension scheme. Because the term "fibromyalgia" suggests an organic disorder which does not exist, it seems instead useful to prefer the terms "somatization disorder" or "pain disorder" to make easier the approach to early psychotherapy and to prevent a further chronification.

Hausotter W Versicherungsmedizin 1998 Feb 1;50(1):13-7 [Article in German]

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Fibromyalgia--a syndrome associated with decreased nocturnal melatonin secretion.

OBJECTIVE: Most patients with fibromyalgic syndrome (FMS) complain of sleep disturbances, fatigue, and pain. These symptoms might be a consequence of changed melatonin (MT) secretion, since MT is known to have sleep promoting properties. Moreover, serum concentrations of two MT precursors (tryptophan and serotonin)-- affecting both sleep and pain perception--appear to be low in patients with FMS. Therefore, the objective of this investigation was to study whether serum MT (s-MT) level is also low in these patients.

DESIGN: Eight patients with FMS and 8 healthy sex-, BMI-, and age-matched controls were included in the study. s-MT concentrations were determined every second hour between 1800 and 0800 h. Urine was collected between 2200 and 0700 h for determination of urinary MT excretion. To evaluate total MT secretion between 1800 and 0800 h and MT secretion during the hours of darkness (between 23 and 07 h) individual MT areas under the curve (AUC) were calculated and expressed as group means.

RESULTS: The FMS patients had a 31% lower MT secretion than healthy subjects during the hours of darkness (MT AUC 2300-0700 h (mean +/- SEM): 1.70 +/- 0.17 vs 2.48 +/- 0.38 nmol/l; P < 0.05). Also the s-MT peak value was significantly lower in the patient group: 0.28 +/- 0.03 vs 0.44 +/- 0.06 nmol/l; P < 0.05).

CONCLUSION: Patients with fibromyalgic syndrome have a lower melatonin secretion during the hours of darkness than healthy subjects. This may contribute to impaired sleep at night, fatigue during the day, and changed pain perception.

Wikner J, Hirsch U, Wetterberg L, Rojdmark S Karolinska Institute, Endocrinology Section, Department of Internal Medicine, Stockholm Soder Hospital. Clin Endocrinol (Oxf) 1998 Aug;49(2):179-83 [Medline record in process]

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Fibromyalgia and chronic fatigue: the holistic perspective.

Fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) are not new conditions, but they are receiving more attention as more research is conducted. These two conditions are primarily women's health problems. In some instances, there may be a genetic predisposition for these conditions. The impact of FMS and CFS can be devastating both physically and emotionally. The treatment plan must be interdisciplinary and holistic and include alternative therapies if the client and family are to be truly supported and helped in coping with these chronic conditions.

Kenner C Department of Parent-Child Health Nursing, College of Nursing and Health University of Cincinnati, Ohio, USA. Holist Nurs Pract 1998 Apr;12(3):55-63 Publication Types: · Review · Review, tutorial

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Fibromyalgia and headache. Failure of serotonergic analgesia and N-methyl-D-aspartate- mediated neuronal plasticity: their common clues.

A defect in serotonergic analgesia and a hyperalgesic state are proposed as features common to headache and fibromyalgia. The benefit to both migraine and fibromyalgia from inhibiting ionotropic N-methyl-D-aspartate receptor activity implies that redundant hyperalgesia-related neuroplastic changes are crucial for severe or chronic migraine and primary fibromyalgia. The fact that migraine and primary fibromyalgia share some pivotal set-up of serotonergic and excitatory amino acid systems led us to analyse epidemiological data supporting the hypothesis that analgesic disruption and a consequent hyperalgesic state are mechanisms of both migraine and fibromyalgia. Beyond demonstrating the comorbidity between migraine and primary fibromyalgia, the data suggest that migraine may represent a risk factor for fibromyalgia.

Nicolodi M, Volpe AR, Sicuteri F Interuniversity Centre of Neurochemistry and Clinical Pharmacology of Idiopathic Headache, Florence, Italy. Cephalalgia 1998 Feb;18 Suppl 21:41-4

Publication Types: · Review · Review, tutorial

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Fibromyalgia and its primary care implications.

Fibromyalgia is a complex condition affecting up to six million patients. In this literature review, the prevalence, proposed etiology, differential diagnosis, and signs and symptoms of the disorder are presented. Diagnostic criteria, treatment options, and the importance of patient education are explored.

Gordon S, Morrison C Johns Hopkins University, Bethesda, MD, USA. Medsurg Nurs 1998 Aug;7(4):207-13, 216 [Medline record in process]

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Fibromyalgia and the serotonin pathway.

Fibromyalgia syndrome is a musculoskeletal pain and fatigue disorder manifested by diffuse myalgia, localized areas of tenderness, fatigue, lowered pain thresholds, and nonrestorative sleep. Evidence from multiple sources support the concept of decreased flux through the serotonin pathway in fibromyalgia patients. Serotonin substrate supplementation, via L-tryptophan or 5- hydroxytryptophan (5-HTP), has been shown to improve symptoms of depression, anxiety, insomnia and somatic pains in a variety of patient cohorts. Identification of low serum tryptophan and serotonin levels may be a simple way to identify persons who will respond well to this approach.

Juhl JH 625 Madison Ave., Suite 10A, New York, NY 10022, USA. Altern Med Rev 1998 Oct;3(5):367-75 [Medline record in process]

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Fibromyalgia and women's pursuit of personal goals: a daily process analysis.

For 30 days, 50 women with primary fibromyalgia syndrome reported daily progress and effort toward a health- fitness and a social-interpersonal goal and the extent to which their pain and fatigue hindered their accomplishment. They also carried palmtop computers to assess their sleep and their pain, fatigue, and positive and negative mood throughout the day.

Analyses of the person-day data set showed that on days during which pain or fatigue increased from morning to evening, participants perceived their goal progress to be more attenuated by pain and fatigue. Unrestorative sleep the night before predicted the following day's effort and progress toward accomplishing health-fitness goals, but not social-interpersonal goals.

Finally, participants who reported more progress toward social-interpersonal goals on a given day were more likely to evidence improvements in positive mood across the day, regardless of any changes in pain or fatigue that day.

Affleck G, Tennen H, Urrows S, Higgins P, Abeles M, Hall C, Karoly P, Newton C Department of Community Medicine, University of Connecticut Health Center, Farmington 06030, USA. affleck@nsol.uchc.edu Health Psychol 1998 Jan;17(1):40-47

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Fibromyalgia, chronic fatigue syndrome, and myofascial pain.

Epidemiologic studies continue to provide evidence that fibromyalgia is part of a spectrum of chronic widespread pain. The prevalence of chronic widespread pain is several times higher than fibromyalgia as defined by the 1990 American College of Rheumatology guidelines. There is now compelling evidence of a familial clustering of fibromyalgia cases in female sufferers; whether this clustering results from nature or nature remains to be elucidated. A wide spectrum of fibromyalgia-associated symptomatology and syndromes continues to be described. During the past year the association with interstitial cystitis has been explored, and neurally mediated hypotension has been documented in both fibromyalgia and chronic fatigue syndrome. Abnormalities of the growth hormone-insulin-like growth factor-1 axis have been also documented in both fibromyalgia and chronic fatigue syndrome. The commonly reported but anecdotal association of fibromyalgia with whiplash-type neck trauma was validated in a report from Israel. However, unlike North America, 100% of Israeli patients with posttraumatic fibromyalgia returned to work. Basic research in fibromyalgia continues to pinpoint abnormal sensory processing as being integral to understanding fibromyalgia pain. Drugs such as ketamine, which block N-methyl-D-aspartate receptors (which are often upregulated in central pain states) were shown to benefit fibromyalgia pain in an experimental setting. The combination of fluoxetine and amitriptyline was reported to be more beneficial than either drug alone in patients with fibromyalgia. A high prevalence of autoantibodies to cytoskeletal and nuclear envelope proteins was found in chronic fatigue syndrome, and an increased prevalence of antipolymer antibodies was found in symptomatic silicone breast implant recipients who often have fibromyalgia.

Bennett R Department of Medicine, Oregon Health Sciences Center, Portland 97201, USA. Curr Opin Rheumatol 1998 Mar;10(2):95-103

Publication Types: Review; Review, tutorial

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Fibromyalgia in Behcet's syndrome.

OBJECTIVE: To ascertain the frequency of fibromyalgia (FM) in Behcet's syndrome (BS) and to evaluate the relationship of FM to Behcet's disease activity.

METHOD: Self-questionnaires were completed by 108 patients with BS. Each patient was evaluated by an observer blinded to diagnosis; evaluation included assessment of tender points by palpation. Another observer determined the disease activity of patients at that time.

RESULTS: Ten of 108 patients (9.2%) met the American College of Rheumatology criteria for FM. Nine of the patients who met the criteria for FM were women. In contrast to patients without FM, patients with FM had mild to moderate disease activity in which musculoskeletal complaints were common.

CONCLUSION: There is a trend for an increased frequency of FM in female BS patients.

Yavuz S, Fresko I, Hamuryudan V, Yurdakul S, Yazici H Department of Rheumatology, Cerrahpasa Medical School, University of Istanbul, Turkey. J Rheumatol 1998 Nov;25(11):2219-20 [Medline record in process]

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[Fibromyalgia (generalized tendomyopathy) in expert assessment. Analysis of 158 cases].

MEDAS-agencies are medical institutions within the Swiss Disability Insurance, which specialize in assessing the working capacity of candidates who apply for a disability pension. Degenerative and other chronic pain disorders of the musculoskeletal system form the majority of cases that we investigate. Fibromyalgia is one of our most frequent diagnoses (8.6%). We become involved in cases on average 8.5 years after the first onset of painful symptoms and on average 2.5 years after the patients have ceased to work. Our experience, tells us that fibromyalgia is usually associated with psychological disturbances; thus our psychiatrists have found important psychological problems in 86.7% of applicants. They found mainly neurotic and depressive syndromes. Our investigations have shown that psychological disturbances precede the onset of musculoskeletal pain in about 70% of patients. Therefore, we don't consider fibromyalgia syndrome as an entity of its own, but regard it as a pain syndrome in which there are underlying psychological problems in most cases.

Kissel W, Mahnig P

MEDAS Zentralschweiz, Luzern. Schweiz Rundsch Med Prax 1998 Apr 15;87(16):538-45. German Comment in: Schweiz Rundsch Med Prax 1998 Jun 10;87(24):856

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Fibromyalgia in hyperkalemic periodic paralysis.

A 43-year-old woman presented at the age of 38 with joint pains and muscle stiffness. Tender points were found fulfilling ACR criteria (1) for fibromyalgia. She had well developed muscles and decreasing muscle power since the age of 35. Muscle pains increased after exercise. Her 10- year-old son had similar symptoms and one paralytic attack.

Muscle pain and fatigue increasing with age were found by history in three close relatives. Forearm cold water test produced myotonia in both mother and son. Electromyography was normal and muscle biopsy showed minor unspecific changes. Biochemical investigation of muscle mitochondrial function was normal. Peroral potassium load test produced complete muscle paralysis at a potassium serum level of 5.0 mmol/l.

Autosomal dominant hyperkalemic periodic paralysis was diagnosed. Frequent carbohydrate enriched meals, peroral bendroflumethiazide and restriction to submaximal exercise improved muscle and joint pain. Salbutamol peroral spray relieved the periodic weakness.

Gotze FR, Thid S, Kyllerman M Department of Internal Medicine/Rheumatology, Sahlgren University Hospital/Ostra, Goteborg, Sweden. Scand J Rheumatol 1998;27(5):383-4 [Medline record in process]

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Fibromyalgia in Indian patients with SLE.

One hundred and fifty-eight patients with SLE were prospectively studied at a tertiary referral centre in India to ascertain the prevalence and clinical profile of fibromyalgia (FM) in Indian patients with lupus. An attempt was made to determine whether socio-demographic factors or disease characteristics differ in SLE patients with and without FM.

Only 13 patients (8.2%) in our cohort were found to have fibromyalgia. Their clinical profiles were similar to that reported in other series. Corticosteroid withdrawal or dose reduction was the probable precipitating factor in nearly one-third of our patients. Age, sex, marital status, educational level, disease duration, disease activity and the organ involvement in patients with SLE and FM were comparable to those in patients not having FM.

Fibromyalgia appears to be distinctly uncommon in Indian patients with lupus. A strong family support system, the virtual lack of disability benefits and/or racial variations in pain threshold could be the likely factors responsible for the low prevalence of the disease observed in Indian patients with SLE.

Handa R, Aggarwal P, Wali JP, Wig N, Dwivedi SN Department of Medicine, All India Institute of Medical Sciences, New Delhi. Lupus 1998;7(7):475-8 [Medline record in process]

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Fibromyalgia is a major contributor to quality of life in lupus.

OBJECTIVE; To determine whether individual variables of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Coordinating Committee/American College of Rheumatology (SLICC/ACR) Damage Index were associated with any of the domains of the Short Form 36 (SF-36) quality of life measure, and to assess the contribution of fibromyalgia (FM) to the quality of life measure.

METHODS: Patients with systemic lupus erythematosus (SLE) seen between December 1994 and May 1995 completed SF-36 questionnaires at the time of their clinical evaluations at the Lupus Clinic. Disease activity was measured by SLEDAI, damage was assessed by the SLICC/ACR Damage Index, and FM was diagnosed in the presence of widespread pain and > or = 11 of 18 FM tender points. The components of SLEDAI and the Damage Index were compared to the domains of the SF-36 using Pearson correlation coefficients. A t test was used to compare the variables in patients with and without FM.

RESULTS: One hundred nineteen patients with SLE participated in the study. Presence of FM, which occurred in 21% of the patients, was not related to either the overall scores or any of the components of SLEDAI or Damage Index, but was highly correlated with all 8 domains of the SF-36. The correlations ranged from -0.26 to -0.43, with associated p values of 0.007 to 0.0001.

CONCLUSION: In a cross sectional study of patients with SLE at one point in time the SF-36 reflected the presence of FM rather than disease activity or damage.

Gladman DD, Urowitz MB, Gough J, MacKinnon A University of Toronto Lupus Clinic, Centre for Prognosis Studies in The Rheumatic Diseases, The Toronto Hospital, Ontario, Canada. J Rheumatol 1997 Nov;24(11):2145-8

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Fibromyalgia is not a muscle disorder.

Originally described as "fibrositis," fibromyalgia has long been considered a muscle disorder, and many studies have investigated the possible pathologic basis of the disorder by examining muscle tissue, using various methodologic approaches. Although initial studies suggested a possible pathologic basis in muscle, most had serious methodologic limitations. More recent studies, however, have avoided methodologic pitfalls and indicate that the muscles of patients with fibromyalgia are normal. When data from studies of tenderness are also taken into account, the weight of evidence suggests that fibromyalgia is a chronic pain syndrome which has a central rather than peripheral or muscular basis.

Simms RW Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA. rsimms@med-med1.bu.edu Am J Med Sci 1998 Jun;315(6):346-50 Publication Types: Review; Review, tutorial

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The fibromyalgia problem.

To the editor:

In recent editorials on fibromyalgia (FM), not one author argued that the widespread pain and other symptoms of this syndrome did not exist (1,2). It is appalling, however, to read that physicians may be more concerned about the legal ramifications of FM syndrome than the medical needs of patients with this diagnosis.

The real "fibromyalgia problem" is that effective treatments for FM do not exist. Instead of worrying about how the medicolegal and disability compensation systems view FM, more researchers ought to be pushing for a greater understanding of the syndrome. (i.e., additional research) so that more effective therapies can be employed.

As a founder and president of two patient organizations, Fibromyalgia Network (which focuses on education) and the American Fibromyalgia Syndrome Association (AFSA, which funds research), I am acutely aware that some physicians would like to psychiatrize FM syndrome, some would like to find a biophysiological basis for the symptoms, and others would prefer to trivialize or ignore it altogether.

Since the 1990 American College of Rheumatology classification criteria for FM were published, the number of physicians in this last catagory continues to shrink. Filling their void (and then some) are the cost-cutting health insurance and private disability companies.

I willnot argue the issue of how much of FM is psychiatric and how much is biophysiological - although I champion the latter explanation. But the insurance and disability companies have the most to gain in the long run for stepping up research efforts on FM.

In June 1994, 35 researchers gathered from around the world to draft a consensus on FM (3). This document charged the insurance/compensation industry with the crucial role of helping to finance FM research. The insurance industry was represented at this event and acknowledged that it was reasonable for them to accept this responsibility. That was three years ago.

Insurance and disability companies have yet to follow through on this recommendation, although they selectively use to their advantage many of the other recommendations listed in this report to aid them in cutting costs on FM.

I emphathize with clinicians who face the dilemma of trying to help patients with FM when the underlying basis for the symptoms of this syndrome are not well understood. There are numerous hypotheses, and based on them, an array of potential treatments have been proposed, although their efficacy is questionable.

It is a problem for both physicians and their patients that effective tools are not available for the treatment of FM. But this problem will never be diminished if physicians and researchers become obsessed with the legal or financial impact of FM to the extent that it impedes progress on the research front.

Wolfe implies patient organizations may engender certain scientifically unproven treatments for FM, which he has written might also "promote medicalization and prolong illness." There is no proof for this claim.

The American Fibromyalgia Syndrome Association has raised over a quarter of a million dollars (all from the generosity of patients) over its three year existence and has directed it towards research. Patients are serious about wanting to feel better and stay employed with the benefit of therapies supported by research.

For once, I can agree with the nay-saying physicians and the insurance/disability industry. No one wants "the fibromyalgia problem" - but at least the patients are stepping up to the plate to take the necessary measures to alleviate it!

American Fibromyalgia Syndrome Association, Fibromyalgia Network, 6380 E. Tanque Verde Road, Suite D, Tuscon, AZ 85715, USA. Kristen Thorson, President

Thorson K J Rheumatol 1998 May;25(5):1023; discussion 1028-30 Publication Types: Comment , Letter Comments: Comment on: J Rheumatol 1997 Jul;24(7):1247-9, Comment on: J Rheumatol 1997 Jul;24(&):1250-1; discussion 1252

REFERENCES

  1. Wolfe F. The fibromyalgia problem [editorial]. J Rhematol 1997;24:1247-9

  2. Hadler N. Fibromyalgia: La maladie est morte. Vive le malade! [editorial]. Wolfe F: [reply] J Rheumatol 1997;24:1250-2

  3. Wolfe F, and the Vancouver Fibromyalgia Consensus Group. The fibromyalgia syndrome: a consensus report on fibromyalgia and disablility. J Rheumatol 1996;23:534-9

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Fibromyalgia Syndrome.

Fibromyalgia syndrome (FMS) is a more common a condition than previously estimated. The most recent estimates are that 3 to 6 million patients have been diagnosed with FMS. The ACR criteria, established in 1990, provide the primary care provider with definitive subjective and objective findings that have shown to be 88% accurate in their ability to diagnose patients with the syndrome. There is no cure for FMS. It is a chronic condition, but patients quality of life can be improved when fatigue and pain are reduced.

The institution of a plan that is developed collaboratively by the patient and the provider is the essence of successful symptom management. The hallmarks of the management plan include: improving the quality of sleep through the judicious use of medications that boost the body's level of serotonin (therefore reducing fatigue), and reducing pain through complimentary modalities such as exercise, physical therapy, relaxation techniques, massage, and biofeedback.

Smith WA Associate Professor of Nursing and Director, Family Nurse Practitioner Program, Sonoma State University, Rohnert Park, California. Nurs Clin North Am 1998 Dec;33(4):653-669 [Record supplied by publisher]

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The fibromyalgia syndrome as a manifestation of neuroticism?

After elucidating the components and theory of neuroticism (N) as well as of psychosomatic complaints and their relationships to personality dimensions and to psychosomatic diseases, comparisons are performed between patients suffering from fibromyalgia syndrome (FMS) or related pain diseases with healthy subjects scoring high on personality dimensions related to neuroticism. FMS and pain patients score high on depression, anxiety, and experience of stress although questionnaire scores on depression are higher in subjects not exhibiting somatic features of the disease. High subjective pain sensitivity and low thresholds for pain perception are also common features in high N subjects and FMS patients. On the endocrinological level cortisol responses to challenge tests with CRH as well as prolactin responses to TRH are higher in FMS patients than in high N healthy subjects indicating an endocrinological difference. A common feature, however, is the lack of adapatability in the two groups, since neurotics are in particular characterized by a low capacity to shift their behavior from one state to the other (waking-sleeping, working-relaxing), to re-adapt to baseline levels after endocrinological or physiological stress responses, or to adjust to conditions of shift work. This is reflected by chronobiological disturbances in FMS patients and could also explain their maintainance of pain perception, because they are incapable of correcting conditioned pain-producing muscle tension.

Netter P, Hennig J Department of Psychology, University of Giessen, Germany. petra.netter@psychol-uni-giessen.de Z Rheumatol 1998;57 Suppl 2:105-8 [Medline record in process]

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Fibromyalgia syndrome in children and adolescents: clinical features at presentation and status at follow-up.

OBJECTIVES: To 1) describe the characteristic features of fibromyalgia syndrome (FS) in a pediatric population, 2) note similarities and differences with FS in adults, and 3) determine outcome after treatment.

SETTING AND DESIGN: The Pediatric Rheumatology Clinic at the University of Rochester Medical Center is staffed by two pediatric rheumatologists and serves as a regional subspecialty referral service with approximately 450 annual patient visits, of which approximately 120 are initial evaluations. A retrospective medical record review from 1989 to 1995 was used to identify and describe the study population, and a structured telephone interview served to determine current status and response to treatment.

RESULTS: A total of 45 subjects were identified (41 female; 42 white; mean age, 13.3 years), of whom 33 were available for telephone interview at a mean of 2.6 years from initial diagnosis

(0.1 to 7.6 years). Of a possible 15 symptoms associated with FS, subjects reported a mean of 8, with >90% experiencing diffuse pain and sleep disturbance. Less frequent were headaches (71%), general fatigue (62%), and morning stiffness (53%). The mean cumulative number of tender points summed over all visits was 9.7 (of 18). Telephone interviews showed improvement in most patients, with a mean positive change of 4.8 on a self-rating scale of 1 to 10 comparing current status to worst-ever condition.

CONCLUSIONS: FS in patients referred to a pediatric rheumatology clinic is characterized by diffuse pain and sleep disturbance, the latter being more common than that in adults. The mean number of tender points summed over all visits is fewer than the criterion of 11 established for adults at a single visit. The majority of patients improved over 2 to 3 years of follow-up.

Siegel DM, Janeway D, Baum J Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, Strong Children's Research Center, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. Pediatrics 1998 Mar;101(3 Pt 1):377-382

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Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain.

OBJECTIVE: We suggested fibromyalgia (FM) is a disorder associated with an altered functioning of the stress- response system. This was concluded from hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin induced hypoglycemia in patients with FM. In this study, we tested the validity and specificity of this observation compared to another painful condition, low back pain.

METHODS: We recruited 40 patients with primary FM (F:M 36:4), 28 patients (25:3) with chronic noninflammatory low back pain (LBP), and 14 (12:2) healthy, sedentary controls. A standard 100 microg CRH challenge test was performed with measurement of ACTH and cortisol levels at 9 time points. They were also subjected to an overnight dexamethasone suppression test, followed by injection of synthetic ACTH1-24. At 9 AM, the patients divided in 2 groups, received either 0.025 or 0.100 microg ACTH/kg body weight to test for adrenocortical sensitivity. Basal adrenocortical function was assessed mainly by measurement of 24 h urinary excretion of free cortisol.

RESULTS: Compared to the controls, the patients with FM displayed a hyperreactive ACTH release in response to CRH challenge (ANOVA interaction effect p = 0.001). The mean ACTH response of the patients with low back pain appeared enhanced also, but to a significantly lesser extent (p = 0.02 at maximum level) than observed in the patients with FM. The cortisol response was the same in the 3 groups. Following dexamethasone intake there were 2 and 4 nonsuppressors in the FM and LBP groups, respectively. The very low and low dose of exogenous ACTH1-24 evoked a dose and time dependent cortisol response, which, however, was not significantly different between the 3 groups. The 24 h urinary free cortisol levels were significantly lower (p = 0.02) than controls in both patient groups; patients with FM also displayed significantly lower (p < 0.05) basal total plasma cortisol than controls.

CONCLUSION: The present data validate and substantiate our preliminary evidence for a dysregulation of the HPA axis in patients with FM, marked by mild hypocortisolemia, hyperreactivity of pituitary ACTH release to CRH, and glucocorticoid feedback resistance. Patients with LBP also display hypocortisolemia, but only a tendency toward the disrupted HPA features observed in the patients with FM. We propose that a reduced containment of the stress- response system by corticosteroid hormones is associated with the symptoms of FM.

Griep EN, Boersma JW, Lentjes EG, Prins AP, van der Korst JK, de Kloet ER Research Department, Jan van Breemen Institute, Amsterdam, The Netherlands. J Rheumatol 1998 Jul;25(7):1374-81

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Functional diagnosis as a tool in rehabilitation: a comparison of teachers and other employees.

Work-related stress and burnout has been observed in primary school teachers in many countries. Functional deficits have been related to certain psychosomatic diagnoses and the work environment. We have compared 100 teachers with a matched group of non-teachers according to diagnostic differences, all attending a 4 week resident stay at a vocational rehabilitation centre in 1993-5. Seventy-five percent were women. The use of ICD-9 diagnoses and a five- dimensional functional diagnostic tool were compared. The five dimensions were defined along the following axes: work environment, family relations, health, personal economy and leisure time activity. There were no significant differences between ICD-9 diagnostic groups between teachers and non-teachers. Indefinite diagnostic entities (fatigue, chronic myalgia, fibromyalgia, etc.) were used in more than half of residents in both groups. Definite musculo-skeletal disorders were the second most prominent diagnosis. On the five- dimensional functional diagnostic tool teachers scored significantly worse than non-teachers on the family relations axis, and on a sum score of all axes. The difference was mainly present in women. The study suggests that work- related stress and signs of burnout in teachers may be higher than in other employees, but the factors contributing to this may be found outside the work environment.

Berg JE, Berg O, Reiten T, Kostveit S Department of Preventive Medicine, University of Oslo, Norway. Int J Rehabil Res 1998 Sep;21(3):273-84

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Genetic factors in fibromyalgia syndrome.

Although familial occurrence of fibromyalgia syndrome (FMS) has been commonly observed, data on a genetic role in this condition are limited. A few studies have reported familial aggregation and association with HLA. We have studied genetic linkage of FMS with HLA in multicase families, and found a rather weak linkage of FMS with HLA (P < 0.029).

Yunus MB University of Illinois College of Medicine, Peoria, Illinois 61605, USA. Z Rheumatol 1998;57 Suppl 2:61-2 [Medline record in process]

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Gulf War illnesses: complex medical, scientific and political paradox.

Gulf War illnesses are a collection of disorders that for the most part can be diagnosed and treated, if effective programmes exist to assist veterans, and in some cases their immediate family members. Although these illnesses are complex and have multi-organ signs and symptoms, a proportion of these patients can be identified as having Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and/or Fibromyalgia Syndrome (FMS). Although there are many possible causes of CSF/ME/FMS, chronic infections can explain, at least in a subset of patients, the apparent transmission of these illnesses to family members and the appearance of chronic, multi-organ and auto-immune signs and symptoms. Unfortunately, many veterans who have been diagnosed with chronic infections, such as mycoplasmal infections, cannot obtain adequate treatment for their condition, resulting in their reliance on private physicians and clinics for assistance. This lack of response may ultimately be responsible for the transmission of the illness to non-veterans.

Nicolson GL, Nicolson NL Institute for Molecular Medicine, Huntington Beach, CA 92649-1041, USA. gnicimm@ix.netcom.com Med Confl Surviv 1998 Apr-Jun;14(2):156-65

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Health-related quality of life in chronic disorders: a comparison across studies using the MOS SF-36.

The purpose of this report is to examine health-related quality of life (HRQoL) as measured by the Medical Outcomes Study Short Form-36, across patient populations with chronic disorders and to compare quality of life (QoL) in these subjects with normative data on healthy persons.

Six studies, within the Center for Research in Chronic Disorders at the University of Pittsburgh School of Nursing, in patients with urinary incontinence, prostate cancer, chronic obstructive pulmonary disease (COPD), acquired immune deficiency syndrome (AIDS), fibromyalgia and hyperlipidaemia provided the data for analysis.

The results demonstrated that not only did the prostate cancer and hyperlipidaemia patients have the highest QoL across the chronic disorders, but their QoL was comparable to normative data on healthy persons. Homebound, elderly, incontinent patients had the lowest QoL for physical functioning, whereas patients hospitalized with AIDS had the lowest QoL in general health and social functioning. Patients with COPD had the lowest QoL in role- physical, role-emotional and mental health.

Patients with fibromyalgia had the lowest QoL in bodily pain and vitality. Compared to normative data, patients with urinary incontinence, COPD, AIDS and fibromyalgia generally had lower QoL. Prostate cancer and hyperlipidaemia patients had QoL comparable to normative data. Compared to normative data, patients with urinary incontinence, COPD, AIDS and fibromyalgia had more variability for role-emotional. AIDS patients had more variability on physical functioning, bodily pain and social functioning compared to the normative data.

These data suggest that patients with various chronic disorders may have QoL that is lower in most domains compared to a healthy population. However, there may be differences in the domains affected as well as the extent of variation across specific chronic disorders.

Schlenk EA, Erlen JA, Dunbar-Jacob J, McDowell J, Engberg S, Sereika SM, Rohay JM, Bernier MJ School of Nursing, University of Pittsburgh, PA 15261-0001, USA. ELS100@VMS.CIS.PITT.EDU Qual Life Res 1998 Jan;7(1):57-65

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Hyperexcitability in fibromyalgia.

OBJECTIVE: Spontaneous chronic widespread pain in combination with hyperalgesia to pressure stimuli is the hallmark of fibromyalgia (FM). We tested whether muscular hyperalgesia can exist in a muscle without spontaneous pain, which could indicate a generalized hyperexcitability of the nociceptive system in patients with FM.

METHODS: Twelve women with FM and 12 age matched female controls participated in this blind study. Patients had no spontaneous pain in the anterior tibial (AT) muscle. The pressure pain threshold was tested on the AT muscle. The pain threshold to electrical single and repeated stimulations of the skin and of the right AT muscle was assessed. Pain was evoked in the left AT muscle by infusion of sterile hypertonic saline (5.7%, 2.8 ml over 480 s). The saline induced muscle pain intensity and duration were assessed by continuous recordings on an electronic visual analog scale (VAS), and the distribution of pain was assessed on drawings. The sequence of electrical sensibility tests and the infusion of hypertonic saline was randomized.

RESULTS: Pressure pain thresholds were lower (p < 0.02) in patients with FM compared to controls. Thresholds for pain evoked by electrical stimulation at the skin were not significantly different in the 2 groups. The pain threshold to repeated intramuscular stimulation was significantly (p = 0.02) lower for the patients with FM compared to the control group, indicating that the temporal nociceptive summation was more pronounced in patients with FM. This is an indication of central sensitization (hyperexcitability). Infusion of hypertonic saline evoked muscle pain with a longer duration (p = 0.01) in patients with FM, and referred pain that spread to a larger area (p = 0.002) than in controls. This is an indication of central hyperexcitability.

CONCLUSION: There is a state of central hyperexcitability in the nociceptive system in FM. This hyperexcitability can be revealed by excitation of intramuscular nociceptors in a muscle with no spontaneous pain.

Sorensen J, Graven-Nielsen T, Henriksson KG, Bengtsson M, Arendt-Nielsen L Department of Anaesthesiology, Pain Clinic, Linkoping Hospital, Sweden. J Rheumatol 1998 Jan;25(1):152-155

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Hyperparathyroidism.

Hyperparathyroidism is a common cause of hypercalcemia. The hypercalcemia usually is discovered during a routine serum chemistry profile. Often, there has been no previous suspicion of this disorder. In most patients initially believed to be asymptomatic, previously unrecognized symptoms resolve with surgical correction of the disorder.

The symptoms of hyperparathyroidism are vague and often similar to symptoms of depression, irritable bowel syndrome, fibromyalgia or stress reaction. Complications of primary hyperparathyroidism include peptic ulcers, nephrolithiasis, pancreatitis and dehydration. Surgical management is usually indicated.

When medical management is used, routine monitoring for clinical deterioration is recommended. Preoperative localization of adenomas with technetium Tc 99m sestamibi scan is possible but may be unnecessary. An experienced surgeon should perform the parathyroidectomy.

Allerheiligen DA, Schoeber J, Houston RE, Mohl VK, Wildman KM University of Wyoming School of Human Medicine Family Practice Residency Program, Casper, USA. Am Fam Physician 1998 Apr 15;57(8):1795-802, 1807-8 Published erratum appears in Am Fam Physician 1998 Jul;58(1):52 Publication Types: Review; Review, tutorial

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The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome.

HPA axis abnormalities in FM, CFS, and other stress-related disorders must be placed in a broad clinical context. We know that interventions providing symptomatic improvement in patients with FM and CFS can directly or indirectly affect the HPA axis. These interventions include

exercise, tricyclic anti-depresssants, and serotonin reuptake inhibitors. There is little direct information as to how the specific HPA axis perturbations seen in FM can be related to the major symptomatic manifestations of pain, fatigue, sleep disturbance, and psychological distress. Since many of these somatic and psychological symptoms are present in other syndromes that exhibit HPA axis disturbances, it seems reasonable to suggest that there may be some relationship between basal and dynamic function of the HPA axis and clinical manifestations of FM and CFS.

Crofford LJ Division of Rheumatology, University of Michigan, Ann Arbor 48109-0680, USA. crofford@umich.edu Z Rheumatol 1998;57 Suppl 2:67-71 [Medline record in process]

1998 Abstracts, Page 2

index

Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia. [abstract] Intestinal and extraintestinal symptoms in functional gastrointestinal disorders. [abstract] Immune markers in fibromyalgia: comparison with major depressed patients and normal volunteers. [abstract] Immunohistochemical and molecular studies of serotonin, substance P, galanin, pituitary adenylyl cyclase- activating polypeptide, and secretoneurin in fibromyalgic muscle tissue. [abstract] Increased capsaicin-induced secondary hyperalgesia as a marker of abnormal sensory activity in patients with fibromyalgia. [abstract] Increased 24-hour urinary cortisol excretion in patients with post-traumatic stress disorder and patients with major depression, but not in patients with fibromyalgia. [abstract] Individually reported effectiveness of therapy for chronic pain. [abstract] [Interdisciplinary group therapy for fibromyalgia]. [abstract] Interdisciplinary treatment for fibromyalgia syndrome: clinical and statistical significance. [abstract] Joint hypermobility in patients with fibromyalgia syndrome. [abstract] Low-dose lidocaine suppresses experimentally induced hyperalgesia in humans. [abstract] Low growth hormone secretion in patients with fibromyalgia--a preliminary report on 10 patients and 10 controls. [abstract] Lower serum activity of prolyl endopeptidase in fibromyalgia is related to severity of depressive symptoms and pressure hyperalgesia. [abstract] Lyme disease update. Current approach to early, disseminated, and late disease. [abstract] Menstrual cycle modulation of tender points. [abstract] Met-enkephalin increase in patients with fibromyalgia under local treatment. [abstract] Migraine chronobiology. [abstract]

Morphologic aspects of fibromyalgia. [abstract] Musculoskeletal manifestations and autoantibody profile in 90 hepatitis C virus infected Israeli patients. [abstract] Musculoskeletal manifestations, pain, and quality of life in Persian Gulf War veterans referred for rheumatologic evaluation. [abstract] Nasal secretion analysis in allergic rhinitis, cystic fibrosis, and nonallergic fibromyalgia/chronic fatigue syndrome subjects. [abstract] Neurochemical pathogenesis of fibromyalgia. [abstract] Neuroendocrine abnormalities in fibromyalgia and related disorders. [abstract] NIH Consensus Conference. Acupuncture. [abstract] [No title available]. [abstract] [No title available]. [abstract] Normal melatonin levels in patients with fibromyalgia syndrome. [abstract] An open clinical trial of venlafaxine treatment of fibromyalgia. [abstract] Other pain syndromes to be differentiated from fibromyalgia. [abstract] Pain treatment of fibromyalgia by acupuncture. [abstract] Pathophysiological mechanisms of central neuropathic pain after spinal cord injury. [abstract] Physical biodynamics and performance capacities of muscle in patients with fibromyalgia syndrome. [abstract] Physical leisure activity level and physical fitness among women with fibromyalgia. [abstract] A pilot study of cognitive behavioral therapy in fibromyalgia. [abstract] A placebo controlled crossover trial of subcutaneous salmon calcitonin in the treatment of patients with fibromyalgia. [abstract] Plasma levels on nociceptin in female fibromyalgia syndrome patients. [abstract] A possible role for saliva as a diagnostic fluid in patients with chronic pain. [abstract] Prevalence of fibromyalgia in children: a clinical study of Mexican children. [abstract] Prevalence of the major rheumatic disorders in the adult population of north Pakistan. [abstract] Primitivism and plasticity of pain--implication of polymodal receptors. [abstract] Private body consciousness, anxiety and pain symptom reports of chronic pain patients. [abstract] A protocol-contract for opioid use in patients with chronic pain not due to malignancy. [abstract] Protocol for verifying expertise in locating fibromyalgia tender points. [abstract] Psychological and behavioral approaches to pain management for patients with rheumatic disease. [abstract] Psychological and psychiatric aspects of fibromyalgia syndrome. [abstract] Psychosocial factors and the fibromyalgia syndrome. [abstract] Psychosocial vulnerability and maintaining forces related to fibromyalgia. In-depth interviews with twenty- two female patients. [abstract] Quantitative rheumatology: a survey of outcome measurement procedures in routine rheumatology outpatient practice in Canada. [abstract] A randomized, double-blind, placebo-controlled study of growth hormone in the treatment of fibromyalgia. [abstract] A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder. [abstract] A randomised double-blind 16-week study of ritanserin in fibromyalgia syndrome: clinical outcome and analysis of autoantibodies to serotonin, gangliosides and phospholipids. [abstract]

Referral and diagnosis of common rheumatic diseases by primary care physicians. [abstract] The relationship between temporomandibular disorders and stress-associated syndromes. [abstract] A research-based guideline for appropriate use of transdermal fentanyl to treat chronic pain. [abstract] A review of cost-effectiveness analyses in rheumatology and related disciplines. [abstract] Rheumatologic disorders in women. [abstract] Rheumatic findings in Gulf War veterans. [abstract] Risk of connective tissue disease and related disorders among women with breast implants: a nation-wide retrospective cohort study in Sweden. [abstract] The role of anxiety and depression in fatigue and patterns of pain among subgroups of fibromyalgia patients. [abstract] Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic - releasing hormones. [abstract] Selenium status in fibromyalgia. [abstract] Self-management of fibromyalgia: the role of formal coping skills training and physical exercise training programs. Self-reported bodily pain in schoolchildren. Self-reported depression, familial history of depression and fibromyalgia (FM), and psychological distress in patients with FM. [abstract] Serum neopterin and somatization in women with chemical intolerance, depressives, and normals. [abstract] Serum nucleotide pyrophosphohydrolase activity; elevated levels in osteoarthritis, calcium pyrophosphate cyrstal deposition disease, scleroderma, and fibromyalgia. [abstract] Sexual and physical abuse in women with fibromyalgia: association with outpatient health care utilization and pain medication usage. [abstract] Silicone breast implants and autoimmune disease. [abstract] Skeletal muscle abnormalities in patients with fibromyalgia. [abstract] Sleep in fibromyalgia patients: subjective and objective findings. [abstract] Social context of pain in children with Juvenile Primary Fibromyalgia Syndrome: parental pain history and family environment. [abstract] Soft tissue problems associated with rheumatic disease. [abstract] Soft tissue problems in older adults. [abstract] Somatized depression as a subgroup of fibromyalgia syndrome. [abstract] Tramadol in the fibromyalgia syndrome: a controlled clinical trial versus placebo. [abstract] [Treatment of fibromyalgia]. [abstract] Tuberculous spondylitis as a cause of inflammatory spinal pain: a report of 4 cases. The use of opioid drugs in management of chronic orofacial pain. [abstract] Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia. [abstract] Utilization and predictive value of laboratory tests in patients referred to rheumatologists by primary care physicians. [abstract] Validation of questionnaire-based response criteria of treatment efficacy in the fibromyalgia syndrome. [abstract] [What is a disease]? [abstract]

What use are fibromyalgia control points? [abstract]

Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia.

This article summarizes (1) epidemiologic and clinical data on the symptoms of maladies in association with low- level chemicals in the environment, i.e., environmental chemical intolerance (CI), as it may relate to chronic fatigue syndrome (CFS) and fibromyalgia; and (2) the olfactory-limbic neural sensitization model for CI, a neurobehavioral synthesis of basic and clinical research. Severe CI is a characteristic of 20-47% of individuals with apparent CFS and/or fibromyalgia, all patients with multiple chemical sensitivity (MCS), and approximately 46% of the general population. In the general population, 15-30% report at least minor problems with CI. The levels of chemicals reported to trigger CI would normally be considered nontoxic or subtoxic. However, host factors--e.g., individual differences in susceptibility to neurohormonal sensitization (amplification) of endogenous responses--may contribute to generating a disabling intensity to the resultant multisystem dysfunctions in CI. One site for this amplification may be the limbic system of the brain, which receives input from the olfactory pathways and sends efferents to the hypothalamus and the mesolimbic dopaminergic [reward] pathway. Chemical, biologic, and psychological stimuli can initiate and elicit sensitization. In turn, subsequent activation of the sensitized limbic and mesolimbic pathways can then facilitate dysregulation of behavioral, autonomic, endocrine, and immune system functions. Research to date has demonstrated the initiation of neurobehavioral sensitization by volatile organic compounds and pesticides in animals, as well as sensitizability of cardiovascular parameters, beta-endorphin levels, resting EEG alpha-wave activity, and divided-attention task performance in persons with

CI.
The ability of multiple types of widely divergent stimuli to initiate and elicit sensitization offers a new perspective on the search for mechanisms of illness in CFS and fibromyalgia with

CI.

Bell IR, Baldwin CM, Schwartz GE Department of Psychiatry, University of Arizona, Tucson Veterans Affairs Medical Center, 85723, USA. Am J Med 1998 Sep 28;105(3A):74S-82S [Medline record in process]

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Intestinal and extraintestinal symptoms in functional gastrointestinal disorders.

Functional gastrointestinal disorders such as irritable bowel syndrome or functional dyspepsia have traditionally been regarded as syndromes limited to the digestive system. However, both clinical experience and published evidence show that patients with such disorders also report a series of other symptoms of physical distress, such as fibromyalgia and irritable bladder and alterations in vital functions, such as sleep, libido, appetite and energy level.

Some of these extraintestinal symptoms can be explained in the context of an evolving comprehensive disease model which views functional gastrointestinal disorders as manifestations of alterations in the interactions between the nervous system, the viscera and the musculoskeletal system.

Alterations in central circuits concerned with arousal, attention and fear, cognitions about bodily symptoms and possible alterations in the hypothalamic pituitary adrenal (HPA) axis may all contribute to the wide range of symptoms reported by affected patients.

Mayer EA, Fass R, Fullerton S UCLA/CURE Neuroenteric Disease Program, UCLA School of Medicine, Los Angeles, CA 90073, USA. emayer@ucla.edu Eur J Surg Suppl 1998;(583):29-31 [Medline record in process]

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Immune markers in fibromyalgia: comparison with major depressed patients and normal volunteers.

BACKGROUND: There is a high degree of comorbidity between fibromyalgia and major depression. The latter is characterized by signs of immune activation, whereas the immune status in fibromyalgia is not yet elucidated. The aims of the present study were to examine (i) neopterin and biopterin excretion in 24-h urine of patients with fibromyalgia compared with normal volunteers and patients with major depression; and (ii) the effects of subchronic treatment with sertraline (11 weeks) on the urinary excretion of neopterin and biopterin.

METHODS: Measurements of neopterin, biopterin, pseudouridine, creatinine and uric acid in 24-h urine were performed by means of HPLC in 14 fibromyalgia and ten major depressed patients and 17 normal volunteers.

RESULTS: There were no significant differences in urine excretion of the above five analytes between patients with fibromyalgia and normal volunteers. Patients with major depression showed significantly higher urinary neopterin excretion than normal volunteers and fibromyalgia patients. Patients with fibromyalgia and major depression had a significantly increased neopterin/creatinine ratio. Fibromyalgia patients had significantly lower urinary excretion of creatinine than patients with major depression. In fibromyalgia patients, there were no significant effects of sertraline treatment on any of the urine analytes.

CONCLUSIONS: The findings suggest that fibromyalgia, in contrast to major depression, may not be accompanied by activation of cell-mediated immunity.

LIMITATION: Other immune markers should be measured in fibromyalgia before drawing definite conclusions.

CLINICAL RELEVANCE: Increased urinary excretion of neopterin can be used as a marker for major depression, but not fibromyalgia.

Bonaccorso S, Lin AH, Verkerk R, Van Hunsel F, Libbrecht I, Scharpe S, DeClerck L, Biondi M, Janca A, Maes M Clinical Research Center for Mental Health, Antwerp, Belgium. J Affect Disord 1998 Feb;48(1):75-82

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Immunohistochemical and molecular studies of serotonin, substance P, galanin, pituitary adenylyl cyclase-activating polypeptide, and secretoneurin in fibromyalgic muscle tissue.

OBJECTIVE: Because former investigations have reported abnormal changes in the expression of serotonin (5- hydroxytryptamine [5-HT]) and substance P (SP) in serum and cerebrospinal fluid, this study sought to determine whether 5-HT and pain-modulating neuropeptides (SP, galanin [GA], pituitary adenylyl cyclase-activating polypeptide, and secretoneurin) were expressed abnormally in the muscle tissue of patients with fibromyalgia (FM).

METHODS: Snap-frozen muscle tissue specimens (deltoid muscles) from 10 patients with FM (mean disease duration 15 years) and from 10 healthy control subjects were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) of RNA preparations from muscle cells, and by immunohistochemistry methods (alkaline phosphatase-anti-alkaline phosphatase and immunogold-silver) using specific primers as well as antibodies. When specific messenger RNA (mRNA) was detected by RT-PCR, in situ RT-PCR was performed for mRNA localization.

RESULTS: Specific mRNA for the examined substances was absent in 9 of 10 FM patients and in 10 of 10 controls. No differences between the FM patients and controls could be detected in the muscle tissue by immunohistochemistry. In 1 FM patient, mRNA for the GA receptor could be shown.

CONCLUSION: This study showed that 5-HT and neuropeptides are not produced in the muscle of patients with FM, and therefore do not appear to be involved in the peripheral induction of pain in this chronic, painful disorder.

Sprott H, Bradley LA, Oh SJ, Wintersberger W, Alarcon GS, Mussell HG, Tseng A, Gay RE, Gay S Friedrich Schiller University of Jena, Germany. Arthritis Rheum 1998 Sep;41(9):1689-94

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Increased capsaicin-induced secondary hyperalgesia as a marker of abnormal sensory activity in patients with fibromyalgia.

In this study, capsaicin-induced secondary hyperalgesia was assessed as a marker of abnormal nociceptive processing in patients with fibromyalgia (FM). The area of mechanical secondary hyperalgesia induced by a standard solution of capsaicin placed on the volar forearm was measured in ten patients with FM and the results compared to those obtained in ten patients with rheumatoid arthritis (RA) and ten normal subjects.

The area of secondary hyperalgesia was found to be substantially increased in both the FM and RA groups compared with controls. In the FM group the area of hyperalgesia correlated with the overall pain score and with the joint tenderness score.

The results suggest that in FM there is enhanced sensitivity of nociceptive neurones at a spinal level, thereby supporting the concept of a generalised disturbance of pain modulation in this disorder.

Morris V, Cruwys S, Kidd B Bone and Joint Research Unit, St Bartholomew's and Royal London Hospital School of Medicine, UK. Neurosci Lett 1998 Jul 10;250(3):205-7 [Medline record in process]

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Increased 24-hour urinary cortisol excretion in patients with post-traumatic stress disorder and patients with major depression, but not in patients with fibromyalgia.

There is now firm evidence that major depression is accompanied by increased baseline activity of the hypothalamic-pituitary-adrenal (HPA) axis, as assessed by means of 24-h urinary cortisol (UC) excretion. Recently, there were some reports that fibromyalgia and post-traumatic stress disorder (PTSD), two disorders which show a significant amplitude of depressive symptoms, are associated with changes in the baseline activity of the HPA axis, such as low 24-h UC excretion. The aim of the present study was to examine 24-h UC excretion in fibromyalgia and PTSD patients compared to normal controls and patients with major depression. In the three patient groups, severity of depressive symptoms was measured by means of the Hamilton Depression Rating Scale (HDRS) score. Severity of fibromyalgia was measured using a dolorimetrically obtained myalgic score, and severity of PTSD was assessed by means of factor analytical scores computed on the items of the Composite International Diagnostic Interview (CIDI), PTSD Module. Patients with PTSD and major depression had significantly higher 24-h UC excretion than normal controls and fibromyalgia patients. At a threshold value of > or = 240 micrograms/24 h, 80% of PTSD patients and 80% of depressed patients had increased 24 h UC excretion with a specificity of 100%. There were no significant differences in 24-h UC excretion either between fibromyalgia patients and normal controls, or between patients with major

depression and PTSD patients. In the three patient groups, no significant correlations were found between 24-h UC excretion and the HDRS score. In fibromyalgia, no significant correlations were found between 24-h UC excretion and the myalgic score. In PTSD, no significant correlations were found between 24-h UC excretion and severity of either depression-avoidance or anxiety- arousal symptoms. In conclusion, this study found increased 24-h UC excretion in patients with PTSD comparable to that in patients with major depression, whereas in fibromyalgia no significant changes in 24-h UC were found.

Maes M, Lin A, Bonaccorso S, van Hunsel F, Van Gastel A, Delmeire L, Biondi M, Bosmans E, Kenis G, Scharpe S Clinical Research Center for Mental Health, Antwerp, Belgium. Acta Psychiatr Scand 1998 Oct;98(4):328-35 [Medline record in process]

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Individually reported effectiveness of therapy for chronic pain.

In 1996, a primary care-based multidisciplinary group model for treating patients with chronic pain was begun in a large HMO. Prior to the visits, patients completed an assessment, which included their description of previous and current therapies and their effectiveness (inventory developed by A. G. Lipman). This article describes the reports of the first 163 patients.

Females were referred three times more often than males; the average age was 52 (range 18 to 88); average years in pain = 11 (range 0.3-50). Most patients reported more than one source of pain.

No therapy was reported to be effective for everyone; what was highly effective for one could actually increase pain in another. Side effects caused patients to discontinue even effective therapy. Costly does not mean more effective. It is, therefore, essential that a systematic process of accessment, evaluation, and titration be employed with every intervention.

Donovan M, Laack KD Kaiser Permanente Northwest, Portland, OR 97232-2099, USA. Clin Nurs Res 1998 Nov;7(4):423-39 [Medline record in process]

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[Interdisciplinary group therapy for fibromyalgia].

Fibromyalgia is present in 2% of the general population and leads to impairment by chronic pain and fatigue. It does not improve without therapy directed at the symptoms of fibromyalgia. We describe our interdisciplinary group treatment for patients with fibromyalgia. They received a

physical examination, ergometry and psychometric tests both at admission and before discharge, and they were questioned to the degree and localization of their pain, to fatigue, sleeping disorders and functional symptoms. Therapy included information about fibromyalgia, learning of coping strategies, relaxation and endurance training. Our results show that our interdisciplinary group treatment is effective for fibromyalgia and improves anxiety, depression and well being after a period of 5 weeks of in-patient rehabilitation.

Strobel ES, Wild J, Muller W Park-Klinik Bad Kissingen. Z Rheumatol 1998 Apr;57(2):89-94. German.

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Interdisciplinary treatment for fibromyalgia syndrome: clinical and statistical significance.

OBJECTIVES: The primary purposes of the study were to: evaluate the treatment efficacy of an outpatient, interdisciplinary treatment program for fibromyalgia syndrome (FMS); examine whether treatment gains would be sustained for 6 months following the treatment; assess whether improvements were clinically significant; and delineate the factors associated with clinically significant improvement in pain severity.

METHODS: Sixty-seven FMS patients completed a 4-week outpatient program consisting of medical, physical, psychologic, and occupational therapies. Six-month followup data were available for 66% of treated patients.

RESULTS: Comparisons between pretreatment and posttreatment measures revealed significant improvements in pain severity, life interference, sense of control, affective distress, depression, perceived physical impairment, fatigue, and anxiety; however, there was no improvement in interpersonal relationships or general activities. Clinically significant improvement in pain severity, using the Reliable Change Index, was obtained by 42% of the sample and was predicted by the pretreatment levels of depression, activity, perceived disability, solicitous responses of significant others, and idiopathic onset. Pretreatment level of pain severity was not a significant predictor of the degree of pain improvement. Comparisons among pretreatment, posttreatment, and 6-month followup data revealed that the patients maintained treatment gains in pain, life interference, sense of control, affective distress, and depression. However, the quadratic polynomial analysis revealed that relapse occurred in the subjective rating of fatigue.

CONCLUSIONS: The results suggest that, overall, an outpatient interdisciplinary treatment program was effective in reducing many FMS symptoms. Treatment gains tended to be maintained for at least 6 months. However, there were large individual differences in response to treatment. These results suggest that identification of subgroups of FMS patients and their specific clinical characteristics may be useful for maximizing treatment efficacy.

Turk DC, Okifuji A, Sinclair JD, Starz TW

University of Washington, Department of Anesthesiology, Seattle 98195-6540, USA. Arthritis Care Res 1998 Jun;11(3):186-95 [Medline record in process]

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Intestinal and extraintestinal symptoms in functional gastrointestinal disorders.

Functional gastrointestinal disorders such as irritable bowel syndrome or functional dyspepsia have traditionally been regarded as syndromes limited to the digestive system. However, both clinical experience and published evidence show that patients with such disorders also report a series of other symptoms of physical distress, such as fibromyalgia and irritable bladder and alterations in vital functions, such as sleep, libido, appetite and energy level. Some of these extraintestinal symptoms can be explained in the context of an evolving comprehensive disease model which views functional gastrointestinal disorders as manifestations of alterations in the interactions between the nervous system, the viscera and the musculoskeletal system. Alterations in central circuits concerned with arousal, attention and fear, cognitions about bodily symptoms and possible alterations in the hypothalamic pituitary adrenal (HPA) axis may all contribute to the wide range of symptoms reported by affected patients.

Mayer EA, Fass R, Fullerton S UCLA/CURE Neuroenteric Disease Program, UCLA School of Medicine, Los Angeles, CA 90073, USA. emayer@ucla.edu Eur J Surg Suppl 1998;(583):29-31 [Medline record in process]

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Joint hypermobility in patients with fibromyalgia syndrome.

OBJECTIVE: To test the hypothesis that joint hyperlaxity can play some role in the pathogenesis of pain in primary fibromyalgia.

METHODS: A total of 66 women with fibromyalgia (according to the 1990 American College of Rheumatology criteria) and 70 women with other rheumatic diseases were examined for joint laxity based on 5 criteria (The Non- Dominant Spanish modification). Individuals meeting 4 or 5 criteria were considered to be hyperlax.

RESULTS: Joint hyperlaxity was detected in 18 (27.3%) of the patients with fibromyalgia and 8 (11.4%) of those with another rheumatic disorder. The statistical analysis revealed significant differences (P < 0.05) between both groups.

CONCLUSION: The results of this study suggest that joint hypermobility and fibromyalgia are associated. Joint hyperlaxity may play a prominent role in the pathogenesis of pain in fibromyalgia.

Acasuso-Diaz M, Collantes-Estevez E Sant Jordi Centro Medico Reus, Tarragona, Spain. Arthritis Care Res 1998 Feb;11(1):39-42

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Low-dose lidocaine suppresses experimentally induced hyperalgesia in humans.

BACKGROUND: The antinociceptive effects of systemically administered local anesthetics have been shown in various conditions, such as neuralgia, polyneuropathy, fibromyalgia, and postoperative pain. The objective of the study was to identify the peripheral mechanisms of action of low-dose local anesthetics in a model of experimental pain.

METHODS: In a first experimental trial, participants (n=12) received lidocaine systemically (a bolus injection of 2 mg/kg in 10 min followed by an intravenous infusion of 2 mg x kg(-1) x h(- 1) for another 50 min). In a second trial, modified intravenous regional anesthesia was administered to exclude possible central analgesic effects. In one arm, patients received an infusion of 40 ml lidocaine, 0.05%; in their other arm, 40 ml NaCl, 0.9%, served as a control. In both trials, calibrated tonic and phasic mechanical and chemical (histamine) stimuli were applied to determine differentially the impairment of tactile and nociceptive perception.

RESULTS: Mechanical sensitivity to touch, phasic mechanical stimuli of noxious intensity, and heat pain thresholds remained unchanged after systemic and regional application of the anesthetic. In contrast, histamine-induced itch (intravenous regional anesthesia), axon reflex flare (systemic treatment), and development of acute mechanical hyperalgesia during tonic pressure (12 N; 2 min) of an interdigital web was significantly suppressed after both treatments.

CONCLUSIONS: Increasing painfulness during sustained pinching has been attributed to excitation and simultaneous sensitization of particular Adelta- and C-nociceptors. This hyperalgesic mechanism seems to be particularly sensitive to low concentrations of lidocaine. These findings confirm clinical experience with lidocaine in pain states dominated by hyperalgesia.

Koppert W, Zeck S, Sittl R, Likar R, Knoll R, Schmelz M Department of Anesthesiology, University of Erlangen-Nuremberg, Nuremberg, Germany. Anesthesiology 1998 Dec;89(6):1345-53 Publication Types: Clinical trial; Randomized controlled trial

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Low growth hormone secretion in patients with fibromyalgia--a preliminary report on 10 patients and 10 controls.

OBJECTIVE: To evaluate the secretion of growth hormone in patients with fibromyalgia (FM).

METHODS: Serum concentrations of growth hormone (24 h profiles), insulin-like growth factor I (IGF), and IGF binding protein-3 were determined in 10 women with FM and in 10 healthy controls. Quality of sleep was assessed by means of a visual analog scale.

RESULTS: Sleep was significantly more disturbed in the patients than in controls. A significantly lower secretion of growth hormone was found in the patients in comparison with healthy controls.

CONCLUSION: These results suggest that growth hormone secretion is decreased in patients with FM. Substitution therapy with low doses of growth hormone may be worth evaluating in the treatment of FM.

Bagge E, Bengtsson BA, Carlsson L, Carlsson J Department of Rheumatology, the Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Goteborg, Sweden. J Rheumatol 1998 Jan;25(1):145-148

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Lower serum activity of prolyl endopeptidase in fibromyalgia is related to severity of depressive symptoms and pressure hyperalgesia.

BACKGROUND: The aims of the present study were to examine serum activities of peptidases,

i.e. prolyl endopeptidase (PEP) and dipeptidyl peptidase IV (DPP IV), in patients with fibromyalgia and to examine the effects of subchronic treatment with sertraline on these variables.

METHOD: Serum PEP and DPP IV activity were measured in 28 normal volunteers and 21 fibromyalgia patients, classified according to the American College of Rheumatology criteria. Tenderness at tender points was evaluated by means of dolorimetry. Fibromyalgia patients had repeated measurements of serum PEP and DPP IV both before and after repeated administration of sertraline or placebo for 12 weeks.

RESULTS: Patients with fibromyalgia had significantly lower serum PEP activity than normal volunteers. There were significantly negative correlations between serum PEP activity and severity of pressure hyperalgesia and the non-somatic, cognitive symptoms of the Hamilton Depression Rating Scale. Fibromyalgia patients with severe pressure hyperalgesia had significantly lower PEP activity than normal controls and fibromyalgia patients with less severe hyperalgesia. Fibromyalgia patients with severe non-somatic depressive symptoms had significantly lower serum PEP activity than normal volunteers. There were no significant changes in serum DPP IV activity in fibromyalgia. There were no significant effects of repeated administration of sertraline on serum PEP and DPP IV activity in patients with fibromyalgia.

CONCLUSIONS: The results show that fibromyalgia, and aberrant pain perception and depressive symptoms in fibromyalgia are related to lower serum PEP activity. It is hypothesized that lower serum PEP activity may play a role in the biophysiology of fibromyalgia through diminished inactivation of algesic and depression-related peptides.

Maes M, Libbrecht I, Van Hunsel F, Lin AH, Bonaccorso S, Goossens F, De Meester I, De Clerck L, Biondi M, Scharpe S, Janca A Department of Medical Biochemistry, University of Antwerp, Belgium. Psychol Med 1998 Jul;28(4):957-65 [Medline record in process]

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Lyme disease update. Current approach to early, disseminated, and late disease.

A rational approach to diagnosis and treatment of Lyme disease requires an understanding of the endemic range of the tick vectors for B burgdorferi, the epidemiologic risk factors, and the spectrum of clinical manifestations. A two-step approach to serologic testing (ELISA followed by Western blot analysis of positive or equivocal results) can be useful if the pretest likelihood of Lyme disease is higher than 20%. Consideration should be given to the possibility of (1) a noninfectious disease with clinical features similar to those of Lyme disease or (2) coinfection with a second tick-transmitted organism. Late Lyme disease must be distinguished by clinical characteristics from fibromyalgia (the commonest source of misdiagnosis in several studies). Antibiotic therapy should be tailored to the extent of disease and limited to 4 weeks in most cases. Human vaccines based on an outer-surface protein from B burgdorferi have been tested in large-scale US clinical trials and may soon be approved for use in persons whose occupational or recreational activities place them at risk for B burgdorferi exposure.

Rahn DW, Felz MW Section of General Internal Medicine, Medical College of Georgia School of Medicine, Augusta 30912-3104, USA. deptmed.drahn@mail.mcg.edu Postgrad Med 1998 May;103(5):51-4, 57-9, 63-4 passim Publication Types: Review; Review, tutorial

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Menstrual cycle modulation of tender points.

Changes in pain sensitivity throughout the menstrual cycle were assessed in 36 normally menstruating women and 30 users of oral contraceptives. Pain sensitivity was measured with palpation of rheumatological tender points and with pressure dolorimetry.

The number of tender points identified by palpation was greater in the follicular (postmenstrual) phase of the cycle as compared to the luteal (intermenstrual) phase in normally cycling women but not in users of oral contraceptives.

These findings are related to previously described physiological and psychological features of the menstrual cycle, with particular emphasis on the role of hormonal events in modulating pain perception, particularly in musculoskeletal disorders such as fibromyalgia.

Hapidou EG, Rollman GB Chronic Pain Management Program, Chedoke Rehabilitation Services, Hamilton Health Sciences Corporation, Ontario, Canada. hapidou@fhs.csu.mcmaster.ca Pain 1998 Aug;77(2):151-61 [Medline record in process]

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Met-enkephalin increase in patients with fibromyalgia under local treatment.

Fibromyalgia is a chronic debilitating condition of unknown etiology. The clinical picture suggests increased activity and/or supersensitivity in nociceptive pathways or inadequate activity in endogenous pain attenuation mechanisms.

One therapeutic approach in the treatment of this syndrome is the administration of serial local injections of lidocaine hydrochloride in the painful points. To evaluate the effect of this treatment on plasma met-enkephalin (ME) levels we studied 15 patients, all women with fibromyalgia under local treatment in the tender points, grouped as follows: 5 were treated with local injection of lidocaine hydrochloride, 5 were treated with local injection of saline and 5 treated with dry needling.

Significant increases in plasma ME concentrations were observed in all groups in the last sampling of each session studied. These results show an increase in plasma ME levels 10 minutes after finishing each session, which is independent of the maneuver employed.

de Lourdes Figuerola M, Loe W, Sormani M, Barontini M Center for Endocrinological Research, Children's Hospital Ricardo Gutierrez, Buenos Aires, Argentina. Funct Neurol 1998 Oct-Dec;13(4):291-5 [Medline record in process]

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Migraine chronobiology.

This study was undertaken to determine whether migraine attacks exhibits circadian, menstrual, or seasonal variations in frequency and, thus, to characterize more precisely this relapsing, remittent, pleomorphic disease.

An analysis of 3582 well-documented migraine attacks in 1698 adults was undertaken. The demographics of the study population accurately represented the known epidemiology of the disease.

Migraine attacks started more frequently between 4 AM and 9 AM and within the first few days after onset of menses; this migraine periodicity is strongest amongst women not using oral contraceptives. Seasonal periodicity, if any, is clearly weaker than circadian or menstrual.

These chronobiological features may assist in the differential diagnosis of migraine from premenstrual headache and fibromyalgia.

Fox AW, Davis RL Clinical Research and Regulatory Affairs, Cypros Pharmaceutical Corporation, Carlsbad, Calf, USA. Headache 1998 Jun;38(6):436-41

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Morphologic aspects of fibromyalgia.

The most common morphological finding in muscle biopsis in longstanding fibromyalgia is type II fiber atrophy. This can be found in many other conditions such as disuse atrophy, affections of the corticospinal tracts, steroid atrophy, and other different neuromuscular disorders. An increase in lipid droplets and a slight proliferation of mitochondria in type I muscle fibers are correlated with the duration of fibromyalgia. In some cases we could find some ragged red fibers (RRF) which histochemically show a pronounced accumulation of lipids and mitochondria and single fiber defects of cytochrome-c-oxidase. In some fibromyalgia patients with RRF, we could find deletions of the mitochondrial genoma.

Pongratz DE, Spath M Friedrich-Baur-Institut, Universitat Munchen, Germany. Z Rheumatol 1998;57 Suppl 2:47-51 [Medline record in process]

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Musculoskeletal manifestations and autoantibody profile in 90 hepatitis C virus infected Israeli patients.

OBJECTIVES: Recent interest has been expressed in rheumatic manifestations in hepatitis C virus (HCV)-infected populations. The aim of this study was to determine the prevalence and characteristics of the musculoskeletal manifestations and serological markers of autoimmunity in HCV-infected patients in Israel.

METHODS: Ninety anti-HCV-positive patients were consecutively interviewed and examined. The prevalence of autoantibodies and their association with rheumatologic symptoms were also determined.

RESULTS: Rheumatic manifestations were found in 28 subjects (31%), and included arthralgias (9%), arthritis (4%), cryoglobulinemia (11%), sicca symptoms (8%), cutaneous vasculitis (2%), polymyositis (1%), and antiphospholipid syndrome (1%). Rheumatic complications were not associated with liver disease severity, or subjects' gender. In addition, myalgia was reported by 22 patients (24%), and fibromyalgia was diagnosed in 14 (16%). Sixty-nine percent of the patients had at least one autoantibody detected in their serum, the most prevalent being rheumatoid factor (RF), 44%; antinuclear antibody (ANA), 38%; and IgM and IgG anticardiolipin antibodies (ac1), 28% and 22%, respectively. The frequency of autoantibodies was not associated with liver disease severity or rheumatic disorders.

CONCLUSIONS: Musculoskeletal manifestations and autoimmune markers are common in HCV infection. An investigation of risk factors for HCV infection is pertinent in a patient presenting new rheumatic manifestations and should be included in the history of present illness. Future studies of these disorders may uncover the full spectrum of these associations and provide new insights into their operating mechanisms.

Buskila D, Shnaider A, Neumann L, Lorber M, Zilberman D, Hilzenrat N, Kuperman OJ, Sikuler E Department of Medicine B, Soroka Medical Center, Beer Sheeva, Israel. Semin Arthritis Rheum 1998 Oct;28(2):107-13 [Medline record in process]

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Musculoskeletal manifestations, pain, and quality of life in Persian Gulf War veterans referred for rheumatologic evaluation.

OBJECTIVE: Pain in the joints and other areas has been a frequent complaint among veterans of Operation Desert Storm who are experiencing unexplained illness. We characterized the rheumatic manifestations of a group of veterans of the Persian Gulf War who were referred to a rheumatology clinic.

METHODS: Consecutive South Texas veterans of the Persian Gulf War who were referred for evaluation of rheumatic manifestations underwent a comprehensive evaluation of their musculoskeletal symptoms, pain, and health related quality of life.

RESULTS: Of 928 veterans evaluated in a screening clinic for unexplained symptoms, 145 had rheumatic manifestations (15.6%) and were referred to a rheumatology clinic. The most common diagnosis was fibromyalgia, present in 49 patients (33.8%), followed by various soft tissue problems in 25 (17.2%), nonspecific arthralgias in 14 (9.6%), and clinical or radiographic osteoarthritis in 16 (11.0%). In 39 patients (26.9%), no symptoms were present at the time of the evaluation, a careful musculoskeletal examination and laboratory tests were normal, and no diagnosis was possible. Two patients had Reiter's syndrome. Four had a positive rheumatoid factor and 3 had antinuclear antibodies, but none of these had clinical evidence of rheumatoid arthritis or systemic lupus erythematosus. Pain was present in nearly all patients and was widely distributed, with no body area spared in this group of patients. The most frequent painful areas were the knees in > 65%, the lower back in > 60%, the shoulders in 50%, and the hands and wrists in 35%. Widespread body pain was present in 65.1% of the veterans. Average values of all 8 scales measured by the SF-36 health survey were below the 25th percentile of published national norms, with pain and the number of nonarticular rheumatic symptoms explaining most of the decreased health related quality of life in the veterans we evaluated.

CONCLUSION: No specific rheumatic diagnosis is characteristic of Gulf War veterans with unexplained illness referred to a rheumatology clinic. However, pain is common and widespread in these patients, and their health related quality of life is poor. Further research is necessary to determine the cause of the symptoms of veterans of the Gulf War.

Escalante A, Fischbach M Department of Medicine, The University of Texas Health Science Center at San Antonio, 78284, USA. escalante@uthscsa.edu J Rheumatol 1998 Nov;25(11):2228-35 [Medline record in process]

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Nasal secretion analysis in allergic rhinitis, cystic fibrosis, and nonallergic fibromyalgia/chronic fatigue syndrome subjects.

Rhinitis symptoms are present in approximately 70% of subjects with fibromyalgia and chronic fatigue syndrome (FM/CFS). Because only 35% to 50% have positive allergy skin tests, nonallergic mechanisms may also play a role.

To better understand the mechanisms of nonallergic rhinitis in FM/CFS, nasal lavages were performed, and markers of vascular permeability, glandular secretion, and neutrophil and eosinophil infiltration measured in 27 nonallergic FM/CFS, 7 allergic rhinitis, 7 cystic fibrosis, and 9 normal subjects.

Allergic rhinitis subjects had significantly increased vascular permeability (IgG) and ECP levels. Cystic fibrosis subjects had significantly higher elastase and total protein levels. There were no significant differences between FM/ CFS and normal lavage fluids.

Analysis of the constituents of nasal mucus provides information about ongoing secretory processes in rhinitis. There were no differences in the basal secretion of these markers of vascular permeability, submucosal gland serous cell secretion, eosinophil and neutrophil degranulation in nonallergic FM/CFS subjects.

This suggests that constitutively active secretory processes that regulate continuous production of nasal secretions are not altered in FM/CFS. Future studies should examine alternative mechanisms such as inducible, irritant- activated, or reflex-mediated effects.

Baraniuk JN, Clauw D, Yuta A, Ali M, Gaumond E, Upadhyayula N, Fujita K, Shimizu T Division of Rheumatology and Immunology and Allergy, Georgetown University, Washington,

D.C. 20007-2197, USA. Am J Rhinol 1998 Nov-Dec;12(6):435-40 [Medline record in process]

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Neurochemical pathogenesis of fibromyalgia.

In contrast with the situation just a few years ago, the most widely accepted model for the pathogenesis of FMS now invokes CNS mechanisms like nociception and allodynia rather than pathologically painful muscles. The levels of platelet serotonin and CSF substance P appear to be abnormal in directions that could logically amplify pain perception. The extent to which these mechanisms are unique to FMS will be critical in determining the direction that future research should take. Certainly, a better understanding of the cause of FMS could represent an important step toward the development of more effective therapy.

Russell IJ Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7868, USA. Z Rheumatol 1998;57 Suppl 2:63-6 [Medline record in process]

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Neuroendocrine abnormalities in fibromyalgia and related disorders.

Fibromyalgia (FM) and related syndromes are poorly understood disorders that share symptoms such as pain, fatigue, sleep disturbances, and psychological distress. These syndromes are more common in women, and they are associated with psychological or physical stressors.

The neuroendocrine axes are essential physiologic systems that allow for communication between the brain and the body. Interconnections among the neuroendocrine axes lead to coordinate regulation of these systems in both a positive and negative fashion. Several neuroendocrine axes have been shown to be dysfunctional in patients with FM.

Although we do not yet understand the relationship between the reported disturbances of neuroendocrine function and the development or maintenance of FM and related syndromes, the authors have proposed that these abnormalities are important in symptomatic manifestations.

This article reviews data showing disturbances of the neuroendocrine axes in FM and proposes a hypothesis of the development and maintenance of FM related to neuroendocrine disturbances.

Crofford LJ Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0680, USA. Am J Med Sci 1998 Jun;315(6):359-66 Publication Types: Review; Review, tutorial

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NIH Consensus Conference. Acupuncture.

OBJECTIVE: To provide clinicians, patients, and the general public with a responsible assessment of the use and effectiveness of acupuncture to treat a variety of conditions.

PARTICIPANTS: A nonfederal, nonadvocate, 12-member panel representing the fields of acupuncture, pain, psychology, psychiatry, physical medicine and rehabilitation, drug abuse, family practice, internal medicine, health policy, epidemiology, statistics, physiology, biophysics, and the representatives of the public. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 1200. Presentations and discussions were divided into 3 phases over 2 1/2 days: (1) presentations by investigators working in areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that were part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of the third. The conference was organized and supported by the Office of Alternative Medicine and the Office of Medical Applications of Research, National Institutes of Health, Bethesda, Md.

EVIDENCE: The literature, produced from January 1970 to October 1997, was searched through MEDLINE, Allied and Alternative Medicine, EMBASE, and MANTIS, as well as through a hand search of 9 journals that were not indexed by the National Library of Medicine. An extensive bibliography of 2302 references was provided to the panel and the conference audience. Expert speakers prepared abstracts of their own conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience.

CONSENSUS PROCESS: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in the open forum and scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions within a few weeks of the conference. The statement is available at http://consensus.nih.gov.

CONCLUSIONS: Acupuncture as a therapeutic intervention is widely practiced in the United States. Although there have been many studies of its potential usefulness, many of these studies provide equivocal results because of design, sample size, and other factors. The issue is further complicated by inherent difficulties in the use of appropriate controls, such as placebos and sham acupuncture groups. However, promising results have emerged, for example, showing efficacy of acupuncture in adult postoperative and chemotherapy nausea and vomiting and in postoperative dental pain. There are other situations, such as addiction, stroke rehabilitation, headache, menstrual cramps, tennis elbow, fibromyalgia, myofascial pain, osteoarthritis, low back pain, carpal tunnel syndrome, and asthma, in which acupuncture may be useful as an adjunct treatment or an acceptable alternative or be included in a comprehensive management program. Further research is likely to uncover additional areas where acupuncture interventions will be useful.

JAMA 1998 Nov 4;280(17):1518-24 Publication Types: Consensus development conference; Consensus development conference, nih; Review

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[No title available].

Fibromyalgia is a chronic pain syndrome, more common in women. Its prevalence is estimated around 2% in the general population, and up to 20% among rheumatology outpatients. Besides musculoskeletal pain, symptoms as fatigue and sleep disturbance are considered characteristic.

Research criteria have been set up, but their seemingly preciseness is unable to distinguish clearly between fibromyalgia and other functional somatic syndromes (chronic fatigue syndrome, irritable bowel syndrome) and psychiatric disorders (depression, anxiety), with which a striking comorbidity is documented.

The diagnosis of fibromyalgia does not theoretically require the exclusion of muscle, joint, or metabolic diseases, but in clinical practice this problem proves to be of crucial importance.

There are numbers of pathophysiological hypothesis for fibromyalgia, but none of them is fully satisfying: muscle is probably innocent; sleep disturbance, although sometimes considered a landmark of the syndrome, is unspecific; stress response studies show subtle anomaly; psychiatric disorders may represent factors of vulnerability and perpetuation rather than causes. We propose to include some of these etiological contributors in vicious circles leading to a "final common pathway" characterized by generalized hyperalgesia.

Treatments of fibromyalgia, whether pharmacological (antidepressants) or psychological (cognitive-behavioral therapies) are of little efficacy, and the global prognosis of fibromyalgia is poor. However, the otucome might prove better outside the specialized clinics in which studies of chronic sufferers with severe abnormal illness behaviors are done. The social consequences of the popularization of the diagnosis of fibromyalgia should not be neglected.

Cathebras P, Lauwers A, Rousset H Service de Medecine Interne, Hopital Nord, Saint-Etienne. Ann Med Interne (Paris) 1998 Nov;149(7):406-14 [Medline record in process] [Article in French]

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[No title available].

Myofascial pain syndrome (MPS) is a very common localized -- sometimes also polytopic -- painful musculoskeletal condition associated with trigger points, for which, however, diagnostic criteria established in well- designed studies are still lacking. These two facts form the basis for differentiating between MPS and the fibromyalgia syndrome. The difference between trigger points (MPS) and tender points (fibromyalgia) is of central importance--not merely in a linguistic sense. A knowledge of the signs and symptoms typically associated with a trigger point often obviates the need for time-consuming and expensive technical diagnostic measures. The assumption that many cases of unspecific complaints affecting the musculoskeletal system may be ascribed to MPS makes clear the scope for the saving of costs.

Pongratz DE, Spath M Friedrich-Baur-Institut bei der Medizinischen Klinik, Klinikum Innenstadt, Universitat Munchen. Fortschr Med 1998 Sep 30;116(27):24-9 [Article in German] [Medline record in process]

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Normal melatonin levels in patients with fibromyalgia syndrome.

OBJECTIVE: To assess urine levels of melatonin measured by 6-sulphatoxymelatonin (aMT6s) in patients with fibromyalgia (FM).

METHODS: Nocturnal aMT6s urine levels were measured by ELISA, in a sample of urine collected from 10 PM to 7 AM from 39 female patients with FM and 39 age matched healthy female controls. All subjects were interviewed and assessed for nonarticular tenderness, FM symptoms, quality of life, and physical functioning.

RESULTS: Nocturnal aMT6s levels of patients with FM were not statistically different from those of controls: 16.7+/-9.2 vs 16.0+/-11.3 microg, respectively. No association was observed between aMT6s levels of patients with FM and disease duration, reproductive status, sleep and mood disturbances.

CONCLUSION: Nocturnal urine aMT6s levels were similar in patients with FM and controls. Studies are needed to elucidate the possible role of melatonin in FM and should include larger samples of newly diagnosed untreated patients with FM.

Press J, Phillip M, Neumann L, Barak R, Segev Y, Abu-Shakra M, Buskila D Epidemiology Department, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva, Israel. J Rheumatol 1998 Mar;25(3):551-5

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An open clinical trial of venlafaxine treatment of fibromyalgia.

Of 15 patients with fibromyalgia who were first evaluated for the presence of Axis I psychiatric diagnoses by use of the Structured Clinical Interview for DSM-IV, 11 completed an open 8-week trial with the novel antidepressant venlafaxine. Six (55%) of 11 completers experienced a > or = 50% reduction of fibromyalgia symptoms. The presence of lifetime psychiatric disorders, particularly depressive and anxiety disorders, predicted a positive response to venlafaxine. These findings suggest that it is important to assess for comorbid psychiatric disorders in patients with fibromyalgia and that venlafaxine may be helpful to some of these patients.

Dwight MM, Arnold LM, O'Brien H, Metzger R, Morris-Park E, Keck PE Jr Department of Psychiatry, University of Cincinnati, Ohio, USA. Psychosomatics 1998 Jan-Feb;39(1):14-7

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Other pain syndromes to be differentiated from fibromyalgia.

Several common chronic pain syndromes come to the attention of the rheumatologist demanding for differentiation from fibromyalgia (FM), although they are often associated with it.

They may mimick FM by (1) the occurance of wide spread pain, (2) the chronicity of complaints,

(3) the preponderance of females in some of these, and (4) the lack of objective data to be derived from imaging techniques and laboratory tests. Pain is produced by the disturbance of normal function ("dysfunctional syndromes", MASI, ref. 6). Recognition requires examination of the locomotor system under biomechanical auspices both at rest and during movement in order to diagnose hyper- and hypomobility syndromes; treatment of these conditions is guided by principles to improve biomechanical function.

In addition, the skin needs to be examined to detect panniculosis (also called "cellulitis"), which may be mixed up with FM due to its preferential occurance in peri- or postmenopausal women. It is concluded that the aforementioned differential diagnosis needs to be considered appropriately in coinciding FM and all studies dealing with FM.

Menninger H Medizinische Klinik, BRK Rheuma-Zentrum, Germany. Z Rheumatol 1998;57 Suppl 2:56-60 [Medline record in process]

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Pain treatment of fibromyalgia by acupuncture.

The lack of objective parameters makes the measurement of pain and the efficacy of pain treatment in patients with chronic pain very difficult. We performed acupuncture therapy in fibromyalgia patients and established a combination of methods to objectify pain measurement before and after therapy. The parameters corresponded to patients' self-report. Twenty-nine fibromyalgia patients as defined by ACR-criteria (25 women, 4 men) with a mean age of 48.2 +/-

2.0 years and a mean disease duration of 6.1 +/- 1.0 years participated in the study. Pain levels and positive tender points were assessed using the visual analogue scale (VAS, i.e., range 0-100 mm) and dolorimetry. Serotonin and substance P levels in serum and the serotonin concentration in platelets were measured concomitantly. During acupuncture therapy no analgesic medication was allowed. The VAS scores decreased from 64.0 +/- 3.4 mm before therapy to 34.5 +/- 4.3 mm after therapy (P < 0.001). Dolorimetry revealed a decreased number of tender points after therapy from 16.0 +/- 0.6 to 11.8 +/- 1.0, P < 0.01. Serotonin levels decreased from 715.8 +/- 225.8 micrograms/10(12) platelets to 352.4 +/- 47.9 micrograms/10(12) platelets (P < 0.01), whereas the serum concentration increased from 134.0 +/- 14.3 ng/ml to 171.2 +/- 14.6 ng/ml (P < 0.01). Substance P levels in serum increased from 43.4 +/- 3.5 pg/ml to 66.9 +/- 8.8 pg/ml (P < 0.01). Acupuncture treatment of patients with fibromyalgia was associated with decreased pain levels and fewer positive tender points as measured by VAS and dolorimetry. This was accompanied by decreased serotonin concentration in platelets and an increase of serotonin and substance P levels in serum. These results suggest that acupuncture therapy is associated with changes in the concentrations of pain-modulating substances in serum. The preliminary results are objective parameters for acupuncture efficacy in patients with fibromyalgia.

Sprott H, Franke S, Kluge H, Hein G Rheumatol Int 1998;18(1):35-6 Publication Types: Letter

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Pathophysiological mechanisms of central neuropathic pain after spinal cord injury.

After spinal cord injury (SCI), between 10% and 20% of the patients may develop central neuropathic pain. This type of chronic pain usually is a very bothersome sequel and represents a major therapeutic challenge since conventional medical and surgical pain therapies generally are ineffective. This review focuses on recent advances in the understanding of the pathophysiology of this pain syndrome. Important clinical features of central neuropathic pain after SCI include loss of sensations mediated by spinothalamic pathways combined with development of abnormal pain perception (spontaneous continuous pain and abnormally evoked pain). Up-regulation of neuronal activity leading to spontaneous and evoked neuronal hyperactivity/hyperexcitability, may be the neurophysiological substrate for development of abnormal pain perception. This paper describes some neurochemical changes that may be important for the induction and maintenance of neuronal hyperactivity and abnormal pain perception: Increased excitatory glutaminergic activity involving N-methyl-D-aspartate (NMDA) receptor activation, may trigger the intracellular cascade reaction leading to upregulation of neuronal activity/excitability. Changes in voltage- sensitive Na+ channels may contribute to changes in nerve membrane excitability. Other important mechanisms may be loss of endogenous inhibition, including reduced gamma-amino-butyric acid (GABA)ergic, opioid and monoaminergic inhibition. These various mechanisms may provide new targets for treatment of a pain syndrome that traditionally has been so difficult to handle.

Eide PK Department of Neurosurgery, National Hospital, Oslo, Norway. Spinal Cord 1998 Sep;36(9):601-12 Publication Types: Review; Review, tutorial

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Physical biodynamics and performance capacities of muscle in patients with fibromyalgia syndrome.

Patients with fibromyalgia complain of muscle pain, increased fatiguability and low physical endurance. However, no signs of specific muscle pathology have been determined in

fibromyalgia. Alterations in muscle function may reflect effects of deconditioning or inhibition of contraction due to spinal or supraspinal mechanisms.

Jacobsen S Department of Rheumatology, Copenhagen University Hospital at Hvidovre, Denmark. soren.jacobsen@dadlnet.dk Z Rheumatol 1998;57 Suppl 2:43-6 [Medline record in process]

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Physical leisure activity level and physical fitness among women with fibromyalgia.

To determine selfreported physical leisure activity level and physical fitness in women with fibromyalgia we sent questionnaires to the female members of a local fibromyalgia association and the same questionnaire to the women in a population based cohort study.

The fibromyalgia patients had higher physical leisure activity level, but lower physical fitness than the women in the population survey.

The difference in physical leisure activity persisted even after controlling for a series of possible confounders, including employment status and work load in a logistic regression analysis.

Natvig B, Bruusgaard D, Eriksen W Institute of general practice and community medicine, University of Oslo, Norway. Scand J Rheumatol 1998;27(5):337-41 [Medline record in process]

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A pilot study of cognitive behavioral therapy in fibromyalgia.

BACKGROUND: Fibromyalgia is a syndrome characterized by widespread musculoskeletal pain and multiple tender points as well as high levels of self-reported disability and poor quality of life.

OBJECTIVES: In this pilot study, a mind-body approach (cognitive-behavioral therapy) was tested that has been successful in treating chronic back pain patients to determine whether it would improve function, decrease perceived pain, and improve mood state for fibromyalgia patients.

PARTICIPANTS: 28 patients recruited from the greater Baltimore area.

INTERVENTION: Eight weekly sessions, 2 1/2 hours each, with three components: an educational component focusing on the mind-body connection, a portion focusing on relaxation response mechanisms (primarily mindfulness meditation techniques), and a qigong movement therapy session.

MAIN OUTCOME MEASURES: Data collection instruments were the Fibromyalgia Impact Questionnaire, the Health Assessment Questionnaire, the Beck Depression Inventory, the Coping Strategies Questionnaire, the helplessness subscale of the Arthritis Attitudes Index, the Medical Outcomes Study Short Form General Health Survey, and a double-anchored 100-mm visual analog scale to assess sleep.

RESULTS: Twenty patients completed the study. Standard outcome measures showed significant reduction in pain, fatigue, and sleeplessness; and improved function, mood state, and general health following an 8-week intervention.

CONCLUSION: A mind-body intervention including patient education, meditation techniques, and movement therapy appears to be an effective adjunctive therapy for patients with fibromyalgia.

Singh BB, Berman BM, Hadhazy VA, Creamer P University of Maryland School of Medicine, Baltimore, USA. bsingh@compmed.ummc.ab.umd.edu Altern Ther Health Med 1998 Mar;4(2):67-70 Comment in: Altern Ther Health Med 1998 Sep;4(5):114, 116

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A placebo controlled crossover trial of subcutaneous salmon calcitonin in the treatment of patients with fibromyalgia.

The objective of this study was to evaluate the relative efficacy and tolerability of subcutaneously (s.c.) administered salmon calcitonin (sCT) in the treatment of patients with fibromyalgia. Eleven patients who fulfilled the American College of Rheumatology classification criteria for fibromyalgia were studied in a double-blind, crossover trial in which they alternatively received salmon calcitonin (100 IU s.c.) and isotonic saline (1 cc s.c.) for four weeks, with a four weeks wash-out period between the treatments.

None of the 11 outcomes measures (seven analog scales, dolorimetry score, and three SIP scores) showed a significant improvement with sCT. The principal side effect observed with sCT was nausea in ten patients and erythema in four patients. These data suggest that sCT given at a dose of 100 IU daily for one month is not effective in the treatment of fibromyalgia.

Bessette L, Carette S, Fossel AH, Lew RA Department of Medicine, Laval University, Quebec, Ste-Foy, Canada.

Scand J Rheumatol 1998;27(2):112-6 Publication Types: Clinical trial; Randomized controlled trial

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Plasma levels on nociceptin in female fibromyalgia syndrome patients.

Fibromyalgia syndrome (FMS) is a frequent pain disorder in women. The pathophysiologic mechanism behind this disorder is still unexplained; however, alterations in both monoamines, neuropeptides and in the stress axis have been found. This study was designed to determine the levels of the newly discovered neuropeptide nociceptin in hormonally different FMS patients and corresponding controls. The results showed that the nociceptin concentrations of the patients were lower than in controls. It also showed decreased levels with significant differences between the cyclic patients in the luteal phase of the menstrual cycle, compared to the corresponding controls. Our results suggest that the perturbed nociceptin concentrations of the FMS patients may be linked to both the sex hormones and to the stress system and that these changes might be one of several possible pathophysiologic mechanisms involved in the FMS.

Anderberg UM, Liu Z, Berglund L, Nyberg F Department of Neuroscience Psychiatry, University Hospital, Uppsala, Sweden. Z Rheumatol 1998;57 Suppl 2:77-80 [Medline record in process]

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A possible role for saliva as a diagnostic fluid in patients with chronic pain.

OBJECTIVES: The focus of this review was on proteins and peptides found in saliva. Of greatest interest were those neuropeptides relevant to nociception and to the pathogenesis of chronic pain syndromes. An additional goal was to develop a standardized protocol to collect saliva for laboratory assessment.

METHODS: Data were obtained through discussion with experts at the medical schools in San Antonio and Heidelberg and a Medline literature search involving all relevant studies from 1966 to 1997. The literature search was based on the following key terms: saliva, serotonin, neuropeptide, substance P (SP), calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF).

RESULTS: The mean concentration of SP in the saliva of healthy normal controls ranged from

9.6 to 220 pg/mL. Generally, the concentration of SP was approximately three times higher in saliva than in plasma. In a number of painful conditions, particularly tension headache, substantial elevations of salivary SP were found. Mean values for salivary CGRP in healthy controls were approximately 22 pmol/L and were significantly elevated in patients with migraine

attacks or cluster headache. There were no data to indicate prior quantitative determination of NGF in human saliva.

CONCLUSIONS: After sampling and processing techniques have been standardized, measurement of neuropeptides in human saliva could provide a valuable tool for study of patients with chronic painful disorders such as rheumatoid arthritis, osteoarthritis, and even fibromyalgia syndrome.

Fischer HP, Eich W, Russell IJ Ruprecht-Karls-Universitat Heidelberg, Medizinische Klinik und Poliklinik, Germany. Semin Arthritis Rheum 1998 Jun;27(6):348-59

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Prevalence of fibromyalgia in children: a clinical study of Mexican children.

OBJECTIVE: To determine the prevalence of fibromyalgia (FM) in schoolchildren according to the 2 stage classification process proposed by the 1990 American College of Rheumatology (ACR) Multicenter Criteria Committee on Fibromyalgia.

METHODS: Stage 1: we administered a pain questionnaire to a sample of 548 schoolchildren (264 boys, 284 girls; mean age 11.9 yrs, range 9-15).

Stage 2: two rheumatologists examined all children with diffuse pain. Using thumb palpation, they examined 18 fibromyalgia tender points and 3 pairs of controls points followed by dolorimetry. Additionally, a random sample of 79 children with no pain were selected as controls, following the same procedures (thumb palpation and dolorimetry).

The Wilcoxon test was used to compare the distribution of tenderness thresholds between FM and non-FM groups. Kappa statistics for multiple raters was used to assess interobserver agreement.

RESULTS: Seven children, all girls, fulfilled the ACR diagnostic criteria for FM. Thus, the prevalence of FM in this group of schoolchildren reached only 1.2%.

The girls with FM had a mean of 14 tender points, whereas controls (n = 79) had 2.4. Pain thresholds were 3.4 kg in children with FM and 5.1 kg in controls (p = 0.004).

CONCLUSION: The prevalence of FM in our study was 5-fold lower than a previous report. This variance may be due to (1) racial and sociocultural differences between populations; and (2) differences in methodological approach. The difficulties of making accurate estimates of FM across different studies are highlighted.

Clark P, Burgos-Vargas R, Medina-Palma C, Lavielle P, Marina FF

Clinical Epidemiology Unit, Hospital General de Especialidades Bernardo Sepulveda, Universidad Nacional Autonoma de Mexico Faculty of Medicine, Mexico DF. J Rheumatol 1998 Oct;25(10):2009-14 [Medline record in process]

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Prevalence of the major rheumatic disorders in the adult population of north Pakistan.

The prevalence of rheumatic diseases in developing countries is largely unknown. Studies which allow comparison of data within the contrasting communities of the Third World and the developed world have the potential to provide insights into disease aetiologies. The current study compared the frequency of rheumatic symptoms (point prevalence) amongst 1997 adults distributed evenly between poor rural and poor urban communities and relatively affluent urban people. Comparisons were also made with similarly but previously derived prevalence rates of rheumatic symptoms and rheumatoid arthritis (RA) in south Pakistan and Pakistanis in England. A significantly higher prevalence of joint pain was seen in the north compared with the south. RA was more common in the north and similar to the frequency amongst Pakistanis resident in England. Ethnic and genetic susceptibility might have accounted for this. There was significantly more soft-tissue rheumatism and back pain in the northern rural population compared with those in the city. Fibromyalgia was almost completely absent from the urban affluent, but osteoarthritis of the knee was significantly more common in this community, perhaps due to relative obesity. RA was least in the urban poor, a phenomenon that might be attributable to earlier death of females or other undetermined factors.

Farooqi A, Gibson T Department of Rheumatology and Physical Medicine, Pakistan Institute of Medical Sciences, Islamabad. Br J Rheumatol 1998 May;37(5):491-5

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Primitivism and plasticity of pain--implication of polymodal receptors.

Bio-warning and defense mechanisms play the most fundamental roles in living organisms. From an evolutionary point of view, nociceptive systems are very primitive and are richly provided with humoral signaling mechanisms of aboriginal humoral defense systems, as reflected in the primitive nature of the polymodal receptor, a poorly differentiated sensory receptor signaling nociceptive information.

Recent advances in studies on pain have made it possible to explain neural mechanisms of pain systems under physiological conditions and reveal that there is a large gap between physiological

and pathological pains. Protracted nociceptive inputs under pathological conditions induce plastic, either functional or structural, alterations in the nociceptive pathways.

These plastic changes lead to crosstalk among the neural networks, including circuits related to motor, autonomic, or psychological functions. These plastic changes, once established, persist even after the original pain sources disappear in a memory-like fashion. Thus, it is revealed that chronic pain cannot be treated by blocking pain pathways, which is effective against acute pain, but require treatment from a multidisciplinary perspective.

Kumazawa T Research Institute of Environmental Medicine, Nagoya University, Japan. kum@kinjo-u.ac.jp Neurosci Res 1998 Sep;32(1):9-31 Publication Types: Review; Review, tutorial

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Private body consciousness, anxiety and pain symptom reports of chronic pain patients.

An information processing model of pain symptom perception and reporting predicts that individuals prone to high levels of attentional self-focus and negative affect will report more pain than individuals low in these characteristics. Past research on college student and medical patient samples has shown that individuals high in private body consciousness (PBC), or attentional self-focus and who report higher levels of anxiety report more pain symptoms than counterparts low in PBC and anxiety. The present study examined effects of PBC and anxiety on pain reports of individuals suffering chronic pain (N = 144). Pain patients suffering chronic headache, low back pain, rheumatoid arthritis and fibromyalgia were included in the sample. A non-pain control sample (N = 31) was also studied to examine potential differences between controls and pain patients. Results indicated that pain patients reporting high levels of PBC reported more pain, although the effects of anxiety on pain reports among pain patients was not significant. Controls did not differ from pain patients on PBC, nor did the 4 groups of pain patients differ on PBC, suggesting PBC is a dispositional variable. Implications for the importance of attentional self-focus in pain symptom reporting are discussed.

Ferguson RJ, Ahles TA Department of Psychiatry, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. robert.j.ferguson@dartmouth.edu Behav Res Ther 1998 May;36(5):527-35

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A protocol-contract for opioid use in patients with chronic pain not due to malignancy.

The legal, psychosocial, and medical factors that we believe have contributed to the success of our protocol- contract in prescribing opioids to patients with chronic pain not due to malignancy are outlined. These factors may be applicable to the treatment of a variety of chronic nonmalignant pain syndromes such as postherpetic neuralgia or human immunodeficiency virus/acquired immunodeficiency syndrome. The intended target audience of this paper is the physician (primary care, chronic pain specialist) who is involved in prescribing opioids for the treatment of chronic, nonmalignant pain.

Kirkpatrick AF, Derasari M, Kovacs PL, Lamb BD, Miller R, Reading A Department of Anesthesiology, University of South Florida College of Medicine, Tampa 336124799, USA. J Clin Anesth 1998 Aug;10(5):435-43

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Protocol for verifying expertise in locating fibromyalgia tender points.

OBJECTIVE: To develop a protocol for determining when an individual is adequately trained to locate the tender points relative to fibromyalgia in an exam.

METHODS: The error distance for each tender point was established by polling individuals with experience in conducting tender point exams. Bayesian statistical methods were employed to form a protocol for determining an individual's proficiency in locating the tender points. A predictive distribution was utilized to find the probability of remaining trained at locating tender points. Also, the probability of classifying at least 11 tender points as tender (mild) under different "locating" criteria and different number of points that are truly tender was computed.

RESULTS: Critical values indicating the number of tender points needed in the qualification process for various standards of reliability--80%, 85%, and 90%--are presented. To be certified after 3 subjects have been examined in the 80%, 85%, and 90% criteria, one has to correctly identify 48, 50, and 52, respectively, out of the 54 possible tender points.

CONCLUSION: We believe that at least 3 subjects should be examined before certification is granted using any of the 3 criteria--80%, 85%, and 90%. In our example, when using the 85% criterion, the qualification process required 7 subjects to certify an individual.

McIntosh MJ, Hewett JE, Buckelew SP, Conway RR, Rossy LA Department of Psychology, University of Missouri, Columbia 65211, USA. Arthritis Care Res 1998 Jun;11(3):210-6 [Medline record in process]

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Psychological and behavioral approaches to pain management for patients with rheumatic disease.

This article reviews the efficacy of the psychological and behavioral pain management interventions that have been evaluated among adult patients with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM). Using published criteria for empirically validated interventions, it is concluded that cognitive-behavioral therapies and the Arthritis Self- Management Program represent well-established treatments for pain among patients with RA and OA.

These interventions involve education, training in relaxation and other coping skills, and rehearsal of these skills in patients' home and work environments. There currently are no psychological or behavioral interventions for pain among FM patients that can be considered as well-established treatments.

Future intervention research should use clinically meaningful change measures in addition to conventional tests of statistical significance, attend to the pain management needs of children, and assess whether outcomes produced in university-based treatment centers generalize to those in local treatment settings.

Bradley LA, Alberts KR Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, USA. larry.bradley@ccc.uab.edu Rheum Dis Clin North Am 1998 Feb;25(1):215-32, viii Publication Types: Review; Review, tutorial

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Psychological and psychiatric aspects of fibromyalgia syndrome.

Fibromyalgia patients hardly suffer from major psychiatric illnesses. Most often, persistent somatoform pain disorder (ICD-10) and dysthymia are identified by psychiatric assessment. Features of "pain proneness" can also be found regularly, which can explain the elevated levels of stress observed in FMS. Repeated traumatic experiences during childhood and as adults can be discovered in many cases, which helps to understand some of the difficulties met in psychotherapy with FMS patients. Modified psychotherapy techniques are recommended using pain-centered behavioral methods initially, and progressing only later to an insight orientated approach.

Keel P Psychiatrische Universitatspoliklinik Zweigstelle, Basel, Switzerland. Z Rheumatol 1998;57 Suppl 2:97-100 [Medline record in process]

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Psychosocial factors and the fibromyalgia syndrome.

Psychosocial distress and psychological abnormality occurs frequently in fibromyalgia patients. Patterns of decreased levels of education, and increased rates of divorce, obesity, and smoking have been noted in clinical and epidemiological studies. Links to physical and sexual abuse have been noted as well. Major depression as well as increased rates of depression, anxiety, and somatization are also commonly found in fibromyalgia.

Wolfe F, Hawley DJ Arthritis Research Center, University of Kansas School of Medicine, Wichita, USA. fwolfe@southwind.net Z Rheumatol 1998;57 Suppl 2:88-91 [Medline record in process]

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Psychosocial vulnerability and maintaining forces related to fibromyalgia. In-depth interviews with twenty-two female patients.

The aim of this qualitative study was to describe, from the perspective of 22 women (aged 22-60 years) with fibromyalgia, their experiences and beliefs of the pain and its origin and how the pain affects family and social life. Open-ended interviews were analysed via a method influenced by grounded theory. Seven descriptive categories were grounded in the data, forming two higher-order concepts: psychosocial vulnerability and maintaining forces. The first of these core concepts, psychosocial vulnerability, comprises the categories: traumatic life history, over- compensatory perseverance, pessimistic life view, and unsatisfying work situation. In the interviews, there are abundant examples of early loss, high degree of responsibility early in life, and social problems with feelings of helplessness and hoplessness later in life. The second core concept, maintaining forces, consists of the categories professional care, pain benefits and family support, which seem to contribute to the persistence of pain. Our results indicate intrapsychic and psychosocial dimensions, which support the hypothesis that individuals with insecure attachment styles are overrepresented among patients with chronic pain.

Hallberg LR, Carlsson SG Department of Psychology, Goteborg University, Sweden. Lillemor.Hallberg@psy.gu.se Scand J Caring Sci 1998;12(2):95-103 [Medline record in process]

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Quantitative rheumatology: a survey of outcome measurement procedures in routine rheumatology outpatient practice in Canada.

OBJECTIVE: To assess the extent to which quantitative clinical measurement is performed by rheumatologists in the longitudinal followup of patients with rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and fibromyalgia (FM) in routine outpatient practice in Canada.

METHODS: A cross sectional postal survey was conducted using an 18 item self-administered questionnaire sent to Canadian Rheumatology Association members.

RESULTS: Rheumatologists (response rate 85%) were more likely to longitudinally follow patients with RA and AS than those with OA or FM. There was a high degree of variability in the methods used to monitor patients longitudinally. Many measures used in clinical research were used infrequently in routine clinical practice. In general, the major health status measures surveyed were not used in clinical monitoring. There was a high level of agreement (>80%) that the characteristics required of an outcome measure for use in clinical practice should include simplicity, brevity, ease of scoring, reliability, validity, and sensitivity to change.

CONCLUSION: The majority of Canadian rheumatologists perform outcome measurement during the longitudinal followup of their outpatients with RA, AS, OA, and FM. However, the process lacks standardization. High performance health status measures, developed for clinical research, have not been widely adopted in rheumatology practices. There is agreement on the characteristics required by Canadian rheumatologists for measurement procedures used in routine clinical care. Quantitative measurement in clinical practice using standardized procedures is an attainable, but as yet, unrealized opportunity.

Bellamy N, Kaloni S, Pope J, Coulter K, Campbell J Department of Medicine, University of Western Ontario, London, Canada. J Rheumatol 1998 May;25(5):852-8

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A randomized, double-blind, placebo-controlled study of growth hormone in the treatment of fibromyalgia.

PURPOSE: The cause of fibromyalgia (FM) is not known. Low levels of insulin-like growth factor 1 (IGF-1), a surrogate marker for low growth hormone (GH) secretion, occur in about one third of patients who have many clinical features of growth hormone deficiency, such as diminished energy, dysphoria, impaired cognition, poor general health, reduced exercise capacity, muscle weakness, and cold intolerance. To determine whether suboptimal growth hormone production could be relevant to the symptomatology of fibromyalgia, we assessed the clinical effects of treatment with growth hormone.

METHODS: Fifty women with fibromyalgia and low IGF-1 levels were enrolled in a randomized, placebo- controlled, double-blind study of 9 months' duration. They gave themselves daily subcutaneous injections of growth hormone or placebo. Two outcome measures--the Fibromyalgia Impact Questionnaire and the number of fibromyalgia tender points-were evaluated at 3-monthly intervals by a blinded investigator. An unblinded investigator reviewed the IGF-1 results monthly and adjusted the growth hormone dose to achieve an IGF-1 level of about 250 ng/mL.

RESULTS: Daily growth hormone injections resulted in a prompt and sustained increase in IGF1 levels. The treatment (n=22) group showed a significant improvement over the placebo group (n=23) at 9 months in both the Fibromyalgia Impact Questionnaire score (P <0.04) and the tender point score (P <0.03). Fifteen subjects in the growth hormone group and 6 subjects in the control group experienced a global improvement (P <0.02). There was a delayed response to therapy, with most patients experiencing improvement at the 6-month mark. After discontinuing growth hormone, patients experienced a worsening of symptoms. Carpal tunnel symptoms were more prevalent in the growth hormone group (7 versus 1); no other adverse events were more common in this group.

CONCLUSIONS: Women with fibromyalgia and low IGF-1 levels experienced an improvement in their overall symptomatology and number of tender points after 9 months of daily growth hormone therapy. This suggests that a secondary growth hormone deficiency may be responsible for some of the symptoms of fibromyalgia.

Bennett RM, Clark SC, Walczyk J Department of Medicine, Oregon Health Sciences University, Portland 97201, USA. Am J Med 1998 Mar;104(3):227-31 Publication Types: Clinical trial; Randomized controlled trial

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A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder.

OBJECTIVE: To study the usefulness of moclobemide and amitriptyline in the treatment of fibromyalgia (FM) in females without psychiatric disorder.

METHODS: In the present four centre, 12 week study, 130 female FM patients not suffering from psychiatric disorders were randomized to receive amitriptyline (AMI; 25 37.5 mg), moclobemide (MOCLO; 450-600 mg) or identical placebo.

RESULTS: Seventy-four, 54 and 49 per cent of patients on AMI, MOCLO and placebo, respectively, were judged as responders. The patients on AMI also managed best regarding the respective improvements during the trial in general health, pain, sleep quality and quantity, and fatigue on visual analogue scales (VAS), the areas of the Nottingham Health Profile (NHP), as

well as in the three Sheehan's functional disability scales. In the within-group comparisons, MOCLO also improved pain assessed both on VAS and on the NHP pain dimension, but the improvement was invalidated by the poor success of the drug with regard to sleep. The tolerabilities of all three drugs were comparable.

CONCLUSION: The study indicates that MOCLO may not be helpful in FM patients free from clinically meaningful psychiatric problems.

Hannonen P, Malminiemi K, Yli-Kerttula U, Isomeri R, Roponen P Department of Medicine, Central Hospital, Jyvaskyla, Finland. Br J Rheumatol 1998 Dec;37(12):1279-86 [Medline record in process]

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A randomised double-blind 16-week study of ritanserin in fibromyalgia syndrome: clinical outcome and analysis of autoantibodies to serotonin, gangliosides and phospholipids.

The aim of the study was to evaluate in a double-blind manner the effect of the long-acting 5- hydroxytryptamine 2 (5-HT2)-receptor blocker Ritanserin on clinical symptoms in patients with fibromyalgia syndrome (FM) and on production of antibodies to serotonin, gangliosides and phospholipids, recently shown to have a high incidence in this disease. Fifty-one female patients with typical FM were included in the 16-week study: 24 received Ritanserin and 27 received a placebo. Antibodies to 5-HT, gangliosides (Gm1) and phospholipids (thromboplastin) were determined by enzyme-linked immunosorbent assay at day 0 and at the end of week 16. The psychological and physical status, including tender points, of the patients was evaluated at day 0 and at the end of weeks 4 and 16. At the end of the study, there was an improvement (p < 0.05) in feeling refreshed in the morning in the Ritanserin- treated group and headache was also significantly improved compared with the placebo group. There was no difference in pain, fatigue, sleep, morning stiffness, anxiety and tender point counts in the Ritanserin and placebo groups. Fifty-one per cent of the 51 patients had at least one of the three antibodies to 5-HT, Gm1 and phospholipids. The incidence and activity of these antibodies were not influenced by Ritanserin or placebo. The observation that Ritanserin has only a small effect on clinical symptoms indicates that disturbances in serotonin metabolism or uptake may be only one factor in the pathogenesis of the disease. The high incidence of a defined autoantibody pattern in FM could again be confirmed in this study. However, it remains speculative whether immunological reactions are, indeed, involved.

Olin R, Klein R, Berg PA Department of Infectious Diseases, Huddinge Hospital, Karolska Institute, Stockholm, Sweden. Clin Rheumatol 1998;17(2):89-94 Publication Types: Clinical trial; Randomized controlled trial

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Referral and diagnosis of common rheumatic diseases by primary care physicians.

OBJECTIVE: To describe primary care patterns of referral and diagnoses of patients with rheumatic diseases referred to rheumatologists.

METHODS: The medical records of all consecutive patients referred in 1994 by >300 primary care physicians to two rheumatologists at an academic centre were reviewed. The referring physician diagnosis was compared with the rheumatologist's diagnosis. Sensitivity, specificity and predictive values of primary care diagnoses were estimated using the rheumatologist diagnosis as the 'gold standard'.

SETTING: University-based rheumatology out-patient clinic.

RESULTS: Over half of the patients referred had a rheumatologist diagnosis of soft-tissue rheumatism or a spinal pain syndrome. Three hundred and forty-seven patients (49%) had a primary care diagnosis of a defined rheumatic disease. Of these, 142 (41%) of the primary care diagnoses were subsequently modified by the rheumatologist. The highest agreement between primary care physician and rheumatologist was observed for crystal-induced arthritis (kappa = 0.86), and the lowest agreement for polymyalgia rheumatica (kappa = 0.39) and systemic lupus (kappa = 0.46). Sensitivity was lowest for a primary care diagnosis of fibromyalgia (48%) and highest for ankylosing spondylitis (94%). Positive predictive values were generally low, in particular for systemic lupus erythematosus (33%) and polymyalgia rheumatica (30%).

CONCLUSION: Most patients referred to an academic rheumatology centre had soft-tissue rheumatism or other pain syndromes. In general, diagnostic agreement between rheumatologists and primary care physicians was low. Increased emphasis on musculoskeletal disorders should be encouraged in medical education to increase the efficiency of rheumatology referrals.

Gamez-Nava JI, Gonzalez-Lopez L, Davis P, Suarez-Almazor ME Department of Public Health Sciences, Faculty of Medicine and Oral Health Sciences, University of Alberta, Edmonton, Canada. Br J Rheumatol 1998 Nov;37(11):1215-9 [Medline record in process]

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The relationship between temporomandibular disorders and stress-associated syndromes.

OBJECTIVES: The purpose of this study was to determine the comorbidity of temporomandibular disorders and other stress-associated conditions in patients with chronic fatigue syndrome and fibromyalgia.

STUDY DESIGN: Of 92 patients who fulfilled the criteria for chronic fatigue syndrome or fibromyalgia (or both), 39 (42%) reported a prior diagnosis of temporomandibular disorder. Further questionnaires were sent to the members of this group, and 30 patients responded.

RESULTS: Of the original 92 patients, of whom 42% reported temporomandibular disorders, 46% had histories of irritable bowel syndrome, 42% of premenstrual syndrome, and 19% of interstitial cystitis. Of the patients with temporomandibular disorders, the great majority reported an onset of generalized symptoms befor the onset of facial pain. Despite this, 75% had been treated exclusively for temporomandibular disorders, usually with bite splints.

CONCLUSIONS: Patients appearing for treatment with chronic facial pain show a high comorbidity with other stress-associated syndromes. The clinical overlap between these conditions may reflect a shared underlying pathophysiologic basis involving dysregulation of the hypothalamic-pituitary-adrenal stress hormone axis in predisposed individuals. A multidisciplinary clinical approach to temporomandibular disorders would improve diagnosis and treatment outcomes for this group of patients.

Korszun A, Papadopoulos E, Demitrack M, Engleberg C, Crofford L Department of Psychiatry and School of Dentistry, University of Michigan, Ann Arbor 481090840, USA. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998 Oct;86(4):416-20 [Medline record in process]

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A research-based guideline for appropriate use of transdermal fentanyl to treat chronic pain.

PURPOSE/OBJECTIVES: To describe a research utilization project intended to develop, implement, and evaluate a research-based guideline for the use of transdermal fentanyl.

DATA SOURCES: The guideline was based on existing literature, clinical expert knowledge, manufacturer recommendations, and cost considerations. Principles of guideline development and evaluation were based on recommendations from the Agency for Health Care Policy and Research.

DATA SYNTHESIS: A comparison of data from baseline to six months after guideline implementation revealed improvements in all criteria. Most of the improvements were maintained at 18 months postguideline implementation.

CONCLUSIONS: The guideline improved the appropriate use of transdermal fentanyl. Ongoing education and monitoring is necessary to maintain change in practice.

IMPLICATIONS FOR NURSING PRACTICE: The cost-effective use of expensive technology is a concern in the area of health care. Nurses need to promote the appropriate use of painmanagement techniques to provide quality care for patients with chronic pain. Guidelines will help nurses to support the use of higher-cost medications in this subpopulation of patients.

Wakefield B, Johnson JA, Kron-Chalupa J, Paulsen L Department of Veterans Affairs Medical Center, Iowa City, USA. Oncol Nurs Forum 1998 Oct;25(9):1505-13

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Rheumatic findings in Gulf War veterans.

BACKGROUND: Rheumatic symptoms were commonly described among soldiers who served in previous wars.

OBJECTIVE: To describe the frequency of rheumatology consultations, along with the diagnoses, and abnormal results on serologic testing in Gulf War veterans evaluated for Gulf War syndrome.

METHODS: The medical records of the first 250 consecutive Gulf War veterans referred to the comprehensive clinical evaluation program at Wilford Hall Air Force Medical Center and Brooke Army Medical Center, San Antonio, Tex, were reviewed for demographic characteristics and frequency of subspecialty consultations. A retrospective review of rheumatic diagnoses and the frequency of abnormal serologic test results was recorded.

RESULTS: Of the 250 Gulf War veterans evaluated in the comprehensive clinical evaluation program, 139 (56%) were referred for rheumatology consultation, which was the most common elective subspecialty referral.

Of the patients evaluated, 82 (59%) had soft tissue syndromes, 19 (14%) had rheumatic disease, and 38 (27%) had no rheumatic disease.

The most common soft tissue syndromes were patellofemoral syndrome (33 patients [25%]), mechanical low back pain (23 patients [18%]), and fibromyalgia (22 patients [17%]).

Of the 19 patients with rheumatic disease, 10 had osteoarthritis, 2 had rheumatoid arthritis, 2 had gout, and 1 each had systemic lupus erythematosus, Behcet disease, parvovirus arthritis, psoriatic arthritis, and hypothyroid arthropathy.

Abnormal serologic test results were common among the Gulf War patients regardless of the presence or absence of rheumatic disease.

CONCLUSIONS: The rheumatic manifestations in Gulf War veterans are similar to symptoms and diagnoses described in previous wars and are not unique to active duty soldiers. Overall, the results of serologic screening were poor predictors of the presence of rheumatic disease.

Grady EP, Carpenter MT, Koenig CD, Older SA, Battafarano DF Rheumatology Service, Wilford Hall Medical Center, San Antonio, Texas, USA. Arch Intern Med 1998 Feb 23;158(4):367-371

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Rheumatologic disorders in women.

This article reviews common rheumatic diseases that most frequently occur in women including fibromyalgia, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus and the antiphospholipid antibody syndrome. Many of these women are of child bearing potential and special considerations concerning pregnancy often arise.

Rheumatic conditions that frequently affect older women such as osteoarthritis and polymyalgia rheumatica are discussed as well. Osteoporosis, which has emerged as a significant women's health issue, is also reviewed.

Belilos E, Carsons S Department of Medicine, Winthrop-University Hospital, Mineola, New York, USA. Med Clin North Am 1998 Jan;82(1):77-101

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Risk of connective tissue disease and related disorders among women with breast implants: a nation- wide retrospective cohort study in Sweden.

OBJECTIVE: To examine the relation between connective tissue disease and related conditions and breast implants. DESIGN: Retrospective cohort study of all women in the Swedish national inpatient registry who underwent breast augmentation surgery with artificial implants during 1964-93, compared with women who underwent breast reduction surgery during the same period.

SETTING: Sweden.

SUBJECTS: 7442 women with implants for cosmetic reasons or for reconstruction after breast cancer surgery and 3353 women with breast reduction surgery.

MAIN OUTCOME MEASURES: Subsequent hospitalisation for definite connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, and Sjogren's syndrome) or related disorders.

RESULTS: 29 women with implants were hospitalised for definite connective tissue disease compared with 25.5 expected based on general population rates (standardised hospitalisation ratio 1.1 (95% confidence interval 0.8 to 1.6)). There were no diagnoses of systemic sclerosis, and no significant excess in risk for polymyalgia rheumatica, fibromyalgia, and several related disorders. Among women who underwent breast reduction surgery, 14 were hospitalised for definite connective tissue disease compared with 10.5 expected (standardised hospitalisation ratio 1.3 (0.7 to 2.2)). Compared with the breast reduction group, women with breast implants showed a slight reduction for all definite connective tissue disease (relative risk 0.8 (95% confidence interval 0.5 to 1.4)).

CONCLUSIONS: This large nationwide cohort study shows no evidence of association between breast implants and connective tissue disease.

Nyren O, Yin L, Josefsson S, McLaughlin JK, Blot WJ, Engqvist M, Hakelius L, Boice JD Jr, Adami HO Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden. Olof.Nyren@mep.ki.se BMJ 1998 Feb 7;316(7129):417-422

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The role of anxiety and depression in fatigue and patterns of pain among subgroups of fibromyalgia patients.

This study explored the relationship of anxiety and depression with two major symptoms of fibromyalgia, pain and fatigue, among fibromyalgia patients (N = 322). Due to collinearity between anxiety and depression scores, extreme groups were defined according to high versus low anxiety and depression scores. Two-thirds of the initial sample were excluded by this approach, which permitted a two by two factorial split-plot ANOVA for the assessment of main effects and the interaction of anxiety and depression upon pain and fatigue. Results stated independent, additive, effects of anxiety and depression upon levels of pain and fatigue, whereas interaction between anxiety and depression failed to significantly explain symptom differences among the participants. Correlational analyses indicated widespread pain among the low anxiety subgroups. In contrast, widespread pain was not indicated among anxious patients with low scores on depression. The findings support the hypothesis that (1) anxiety and depression are independently associated with severity of pain symptoms in fibromyalgia, and that (2) patients with high anxiety and low depression may communicate to the medical doctor in ways that involve a risk of diagnosing fibromyalgia when the criterion of widespread pain is not supported. These conclusions were confirmed by results from ANCOVAs that permitted more extensive control of collinearity among variables.

Kurtze N, Gundersen KT, Svebak S North-Troendelag Research Institute, Steinkjer, Norway. nk@ntforsk.no. Br J Med Psychol 1998 Jun;71 ( Pt 2):185-94

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Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones.

To study the hormonal perturbations in FMS patients we injected sixteen FMS patients and seventeen controls a cocktail of the hypothalamic releasing hormones: Corticotropin-releasing hormone (CRH), Thyrotropin-releasing hormone (TRH), Growth hormone-releasing hormone (GHRH), and Luteinizing hormone-releasing hormone (LHRH) and observed the hormonal secretion pattern of the pituitary together with the hormones of the peripheral endocrine glands. We found in FMS patients elevated basal values of ACTH and cortisol, lowered basal values of insulin-like growth factor I (IGF-I) and of triiodothyronine (T3), elevated basal values of follicle- stimulating hormone (FSH) and lowered basal values of estrogen. Following injection of the four releasing-hormones, we found in FMS patients an augmented response of ACTH, a blunted response of TSH, while the prolactin response was exaggerated. The effects of LHRH stimulation were investigated in six FMS patients and six controls and disclosed a significantly blunted response of LH in FMS. We explain the deviations of hormonal secretion in FMS patients as being caused by chronic stress, which, after being perceived and processed by the central nervous system (CNS), activates hypothalamic CRH neurons. CRH, on the one hand, activates the pituitary-adrenal axis, but also stimulates at the hypothalamic level somatostatin secretion which, in turn, causes inhibition of GH and TSH at the pituitary level. The suppression of gonadal function may also be attributed to elevated CRH by its ability to inhibit hypothalamic LHRH release, although it could act also directly on the ovary by inhibiting FSH-stimulated estrogen production. We conclude that the observed pattern of hormonal deviations in FMS patients is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily evoked by activated CRH neurons.

Riedel W, Layka H, Neeck G Klinik fur Rheumatologie am Klinikum, Justus-Liebig-Universitat Giessen, Bad Nauheim, Germany. Z Rheumatol 1998;57 Suppl 2:81-7 [Medline record in process]

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Selenium status in fibromyalgia.

Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown etiology. The serum concentration of selenium (Se) was measured in 68 consecutive patients (nine male, mean age: 47 years; 59 female, mean age 49 years) with FM. The age- and sex-matched control group included 97 female healthy blood donors (mean age 46 years). The method is based on high-

performance liquid chromatography (HPLC) involving detection of the fluorescent diaminonaphthalene (DAN) derivate of selenite. There was a statistical significant difference (P < 0.05) in serum Se between control (median 77 microg/l; range: 50-118 microg/l) and patients (median 71 microg/l; range: 39-154 microg/l) groups in the region of Tubingen, Germany.

Reinhard P, Schweinsberg F, Wernet D, Kotter I Chemisches Labor, Abteilung Allgemeine Hygiene und Umwelthygiene, Hygiene-Institut, Universitat Tubingen, Germany. Toxicol Lett 1998 Aug;96-97(###):177-80 [Medline record in process]

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Self-management of fibromyalgia: the role of formal coping skills training and physical exercise training programs.

There has been growing interest in the use of formal self-management training programs for people with fibromyalgia (FM). In these programs, health care professionals serve as trainers and provide education about FM and guided instruction in specific self-management strategies. A review of the literature on formal self-management training programs for FM suggests that they can be divided into groups: 1) those emphasizing training in coping skills (e.g., relaxation, activity pacing, and problem-solving techniques), and 2) those emphasizing training in physical exercise (e.g., cardiovascular fitness, strength, and endurance training). In this article, we review studies that have tested the efficacy of both types of programs. In addition, we identify key individual and contextual variables that are related to outcome and highlight future directions in the research and development of self- management programs.

Sandstrom MJ, Keefe FJ Duke University Medical Center, Durham, North Carolina 27710, USA. Arthritis Care Res 1998 Dec;11(6):432-47 [Medline record in process]

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Self-reported bodily pain in schoolchildren.

It has been suggested that musculoskeletal symptoms develop from early age and can be regarded as a lifespan phenomenon. The study of childhood pain might provide a better understanding of the origin of chronic pain in adults. In a study of 569 schoolchildren, aged 10- 15 years, in a local community close to Oslo, 75% reported that they usually experience bodily pain. Girls reported more pain than boys. 25% of those reporting pain experience symptoms several days a week. Knee symptoms and back pain were most frequently reported. Thirty-seven % of the girls reported headache, only 20% of the boys. Girls also reported more neck and shoulder pain than boys. The oldest respondents reported symptoms from more body parts.

Symptoms from several body parts were more frequent among girls. Thirty-eight % of the respondents reported that it sometimes is hard to concentrate because of the pain, and 26% reported that they sometimes have to use medication. The consequences of pain increased with increasing age and increasing number of body parts affected. The results are consistent with findings in the adult population.

Smedbraten BK, Natvig B, Rutle O, Bruusgaard D The Ullensaker Study Group, Jessheim, Norway. Scand J Rheumatol 1998;27(4):273-6

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Self-reported depression, familial history of depression and fibromyalgia (FM), and psychological distress in patients with FM.

The prevalence of FM in the general population is estimated at 2%. FM is among the three most common diagnoses in ambulatory adult rheumatology practice. To study the degree of depression, the familial history of depression and FM, as well as the psychological distress in our FM population, we mailed a standardized questionnaire to 304 FM patients. The response rate was 33%. We found BDI scores higher than 21 in 27% of the patients indicating clinical relevant depression. The patients had high levels of global distress measured with the SCL-90-R as well as elevated scores in the subscales. Twenty three percent had a familial history of depression, 46% a familial history of FM, and 46% had been diagnosed with depression in the past.

Offenbaecher M, Glatzeder K, Ackenheil M Department of Physical Medicine and Rehabilitation, University Hospital Munich, Germany. M.Offenbaecher@Irz.uni- muenchen.de Z Rheumatol 1998;57 Suppl 2:94-6 [Medline record in process]

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Serum neopterin and somatization in women with chemical intolerance, depressives, and normals.

The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is a feature of several controversial polysymptomatic conditions that overlap symptomatically with depression and somatization, i.e., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and Persian Gulf syndrome. These syndromes can involve many somatic symptoms consistent with possible inflammation. Immunological or neurogenic triggering might account for such inflammation. Serum neopterin, which has an inverse relationship with l-tryptophan availability, may offer a marker of inflammation and macrophage/monocyte activation. This study compared middle-aged women with CI (who had high levels of affective

distress; n = 14), depressives without CI (n = 10), and normals (n = 11). Groups did not differ in 4 p.m. resting levels of serum neopterin. However, the CI alone had strong positive correlations between neopterin and all of the scales measuring somatization. These preliminary findings suggest the need for additional research on biological correlates of 'unexplained' multiple somatic symptoms in subtypes of apparent somatizing disorders.

Bell IR, Patarca R, Baldwin CM, Klimas NG, Schwartz GE, Hardin EE Department of Psychiatry, Psychology, Family and Community Medicine, University of Arizona Health Sciences Center, and the Department of Psychiatry, Tucson Veterans Affairs Medical Center, Tucson, Ariz., USA. Neuropsychobiology 1998;38(1):13-8

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Serum nucleotide pyrophosphohydrolase activity; elevated levels in osteoarthritis, calcium pyrophosphate cyrstal deposition disease, scleroderma, and fibromyalgia.

OBJECTIVE: Quantification of serum nucleotide pyrophosphohydrolase (NTPPHase) activity in healthy subjects and in patients with various rheumatic diseases or with quad/hemiplegia, hemodialysis, or renal transplant.

METHODS: Colorimetric assay of enzyme activity in serum.

RESULTS: Serum NTPPHase activity in 85 healthy subjects was independent of age or sex and was highly reproducible in each individual. The biologic and methodologic coefficients of variation were nearly identical.

Elevated enzyme levels were found in sera from patients with osteoarthritis/spondylosis, calcium pyrophosphate dihydrate (CPPD) crystal deposition, scleroderma, fibromyalgia, or hemodialysis.

Renal transplant patients receiving cyclosporine had the highest enzyme activity of any group, whereas transplant patients not taking this drug had normal levels. Histograms of values in all groups showed a normal distribution.

CONCLUSION: Serum NTPPHase activity levels were significantly elevated in patients with degenerative arthritis whether or not CPPD crystals were present, in patients with either scleroderma or fibromyalgia, and in patients receiving hemodialysis therapy or taking cyclosporine.

Cardenal A, Masuda I, Ono W, Haas AL, Ryan LM, Trotter D, McCarty DJ Department of Medicine, Arthritis Institute, Medical College of Wisconsin, Milwaukee 53226, USA. J Rheumatol 1998 Nov;25(11):2175-80 [Medline record in process]

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Sexual and physical abuse in women with fibromyalgia: association with outpatient health care utilization and pain medication usage.

OBJECTIVE: To evaluate the relationship between sexual and/or physical abuse and health care usage in patients with fibromyalgia (FM) and identify variables that may influence this relationship.

METHODS: We assessed history of sexual/physical abuse, health care utilization, and medication usage, as well as related variables in 75 women with FM using standardized questionnaires, structured interviews, and laboratory pain perception tasks.

RESULTS: Fifty-seven percent of FM patients reported a history of sexual/physical abuse. Compared to non- abused patients, abused patients reported significantly greater utilization of outpatient health care services for problems other than FM and greater use of medications for pain (P < or = 0.025). Consistent with our expectations, abused patients also were characterized by significantly greater pain, fatigue, functional disability, and stress, as well as by a tendency to label dolorimeter stimuli as painful regardless of their intensities (P < or = 0.05). Additional analyses suggested that the high frequency of sexual/physical abuse in our patients was associated primarily with seeking health care for chronic pain rather than the FM syndrome itself or genetic factors.

CONCLUSION: There is an association in FM patients between sexual/physical abuse and increased use of outpatient health care services and medications for pain. This association may be influenced by clinical symptoms, functional disability, psychiatric disorders, stress, and abnormal pain perception. The relationships among these variables should be further tested in prospective, population-based studies.

Alexander RW, Bradley LA, Alarcon GS, Triana-Alexander M, Aaron LA, Alberts KR, Martin MY, Stewart KE Department of Psychology (Medical Psychology Program), University of Alabama at Birmingham 35294, USA. Arthritis Care Res 1998 Apr;11(2):102-15 [Medline record in process]

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Silicone breast implants and autoimmune disease.

In 1992, the Food and Drug Administration requested a voluntary moratorium on the scale and implantation of silicone-gel-filled breast implants because of growing concern over the lack of scientific and clinical data supporting their safety and effectiveness.

Breast implants had been reported to cause serious local complications, and new questions about breast implants and increased risk for autoimmune disease, including the rare but sometimes fatal connective tissue disease scleroderma, were also raised.

Since that time, clinical studies have focused on the adjuvant effect of silicone and of potential autoantibody production. Epidemiologic studies have ruled out a large increased risk for connective tissue disease overall in women with breast implants, but samples were too small to rule out an increase in rare connective tissue diseases.

Nor were studies properly designed to address whether an atypical syndrome might develop in women with breast implants. Meta-analyses of these studies cannot remedy their underlying methodologic weaknesses.

While the question of whether rare connective tissue disease is associated with breast implants may never be answered definitively, recent progress in identifying new syndromes such as fibromyalgia and chronic fatigue syndrome may provide an insight into methodology for evaluating the existence of a silicone-related syndrome in women with breast implants.

Brown SL, Langone JJ, Brinton LA J Am Med Womens Assoc 1998;53(1):21-24

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Skeletal muscle abnormalities in patients with fibromyalgia.

Widespread muscle pain and tender points are the most common complaints of fibromyalgia patients, and the underlying mechanisms responsible for these symptoms have been studied intensively during the past decade. It has been suggested that fatigue and pain may lead to decreased levels of physical activity in many patients. The resulting deconditioned state may itself contribute to muscle abnormalities. Associated symptoms such as disturbed sleep, anxiety, depression, or irritable bowel also may have a negative impact on muscle function and level of daily activities. The important interactions between the central nervous and musculoskeletal systems may involve another element, the neuroendocrine stress-response system. This review will consider both the current state of knowledge and also future studies which might be designed to answer more effectively the outstanding questions regarding the underlying pathogenesis of fibromyalgia.

Olsen NJ, Park JH Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. nancy.olsen@mcmail.vanderbilt.edu Am J Med Sci 1998 Jun;315(6):351-8 Publication Types: Review; Review, tutorial [back to top of page]

Sleep in fibromyalgia patients: subjective and objective findings.

Fibromyalgia (FM) patients report early morning awakenings, awakening feeling tired or unrefreshed, insomnia, as well as mood and cognitive disturbances; they may also experience primary sleep disorders including sleep apnea. Longitudinal studies have demonstrated the chronic nature of these disturbances in patients with FM. A distinct relationship exists between poor sleep quality and pain intensity. Polysomnographic findings during sleep in these patients include an alpha frequency rhythm, termed alpha-delta sleep anomaly, which is also seen in normal controls during stage 4 sleep deprivation; deep pain induced during sleep in normal controls also causes this anomaly. Sleep architecture is altered in FM patients showing an increase in stage 1, a reduction in delta sleep, and an increased number of arousals. Before prescribing pharmacologic compounds aimed at modifying sleep, adequate pain control and sleep habits should be achieved; tricyclic antidepressants, trazadone, zopiclone, and selective serotonin reuptake inhibitors, however, may be required. More research is needed to elucidate the cellular and molecular mechanisms involved in the sleep disturbances occurring in patients with FM.

Harding SM Sleep/Wake Disorders Center, University of Alabama at Birmingham, 35294, USA. harding@pulm.dom.uab.edu Am J Med Sci 1998 Jun;315(6):367-76 Publication Types: Review; Review, tutorial

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Social context of pain in children with Juvenile Primary Fibromyalgia Syndrome: parental pain history and family environment.

OBJECTIVE: The purpose of this study was to describe parental pain history and the family environment as it relates to the functional status of children with Juvenile Primary Fibromyalgia Syndrome (JPFS).

DESIGN AND OUTCOME MEASURES: Twenty-nine parents of children with JPFS completed a pain history questionnaire, Von Korff Chronic Pain Grading system, and the Family Environment Scale (FES). Twenty-one adolescents with JPFS completed the FES, the Visual Analogue Scale for Pain, the modified Fibromyalgia Impact Questionnaire for Children, the Arthritis Impact Measurement Scales, and the Symptom Checklist-90-Revised. Correlational analyses were performed.

RESULTS: Parents of children with JPFS reported multiple chronic pain conditions, including but not limited to fibromyalgia. Parental pain history and the family environment correlated with the health status of adolescents with JPFS. Children with JPFS perceived the family environment as significantly more cohesive than did their parents. Greater incongruence between parent and child responses on the FES positively correlated with greater impairment.

CONCLUSIONS: These results suggest that family environment and parental pain history may be related to how children cope with JPFS. Behavioral interventions targeting the family may improve the long-term functional status of children with JPFS.

Schanberg LE, Keefe FJ, Lefebvre JC, Kredich DW, Gil KM Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. Clin J Pain 1998 Jun;14(2):107-15

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Soft tissue problems associated with rheumatic disease.

Rheumatic disease and associated soft tissue problems encompass a large number of syndromes and account for a high percentage of visits to primary care practitioners. This article describes the symptoms, causes, and treatments for five of the problems most commonly encountered: bursitis, tendinitis, carpal tunnel syndrome, myofascial pain syndrome, and fibromyalgia.

Effective management requires a structured history, physical examination, and definitive diagnosis that distinguishes the soft tissue problem from a joint problem and an inflammatory syndrome from a noninflammatory syndrome. The overriding principle is self-management of treatments that focuses on relief of pain, maintenance of function, and avoidance of factors that cause recurrence or exacerbation of the problem.

Medications, physical therapies, biomechanical aids, and exercise strategies, along with cognitive-behavioral techniques for the more chronic problems, are all known to decrease symptoms and to assist patients in returning to normal functioning.

Burckhardt CS, Jones KD, Clark SR School of Nursing, Oregon Health Sciences University in Portland 97201, USA. Lippincotts Prim Care Pract 1998 Jan;2(1):20-29

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Soft tissue problems in older adults.

This article describes common soft tissue problems encountered in older adults, including fibromyalgia, selected bursitis/tendinitis syndromes, nerve entrapment syndromes, and miscellaneous topics such as Dupuytren's contractures, trigger fingers, palmar fasciitis, and reflex-sympathetic dystrophy. Clinical presentations, diagnosis, and treatment are emphasized. These are conditions that are frequently encountered but are generally diagnosed as arthritis or normal age-related problems. This article will hopefully enlighten the reader in distinguishing between these conditions.

Holland NW, Gonzalez EB Division of Rheumatology, Emory University School of Medicine, Atlanta Veterans Affairs Medical Center, Decatur, Georgia 30033, USA. Clin Geriatr Med 1998 Aug;14(3):601-11 Publication Types: Review; Review, tutorial

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Somatized depression as a subgroup of fibromyalgia syndrome.

An increase of depressive symptoms in fibromyalgia patients has been noted in a number of studies. The etiologic significance of this finding remains, however, controversial. We suggest that a subgroup of patients with this symptom combination may be pragmatically classified as suffering from somatized depression.

Clinical indicators such as a family history of depressive disorders, circadian disturbances, pronounced loss of appetite or libido, and chronic psychosocial stressors should be assessed and, if present, prompt the initiation of psychiatric evaluation and treatment including pharmaco- and psychotherapeutic modalities. Other psychiatric diseases arising in the differential diagnosis of fibromyalgia are discussed.

Meyer-Lindenberg A, Gallhofer B Unit on PET, Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, MD 20892-1365, USA. meyera@intra.nimh.nih.gov Z Rheumatol 1998;57 Suppl 2:92-3 [Medline record in process]

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Tramadol in the fibromyalgia syndrome: a controlled clinical trial versus placebo.

This study assessed the analgesic action of tramadol compared with placebo in patients suffering from fibromyalgia syndrome. Twelve patients (11 females, one male) were treated according to a double-blind crossover experimental design. Each patient, after signing informed consent, was randomly allocated to either tramadol (100 mg ampul in 100 ml given intravenously in 15 min doses) or placebo for a single dose treatment. At the second visit, patients crossed over to the other drug for a further single dose treatment. There was a wash-out period of 1 week. Nine patients completed the study, while in three cases (two tramadol, one placebo) the study was discontinued due to the onset of side effects. The assessment of efficacy, carried out at the baseline and 15 min and 2 hours after administration of each dose, involved the use of a visual analog scale (VAS 100 mm) for spontaneous pain and pressure dolorimetry (kg/cm2) at 12 "symptomatic" tender points and nine "control" tender points for fibromyalgic pain. During the first treatment cycle effective control of spontaneous pain was achieved with tramadol, which determined a reduction of 20.6% while with the placebo spontaneous pain increased by 19.8%. With pressure dolorimetry there were no clinically important differences observed after either active treatment or placebo. The contrasting results found in the present study could be a stimulus for the organization of new projects, which may lead to the identification of an optimal therapeutic approach for fibromyalgic patients, also using tramadol for long periods.

Biasi G, Manca S, Manganelli S, Marcolongo R Institute of Rheumatology, University of Siena, Polyclinic Le Scotte, Italy. Int J Clin Pharmacol Res 1998;18(1):13-9 Publication Types: Clinical trial; Randomized controlled trial

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[Treatment of fibromyalgia].

The paper reports the results of therapy of 23 patients with fibromyalgia (FM). Tetracyclic antidepressant lerivon, was administered to group 1, nonsteroid antiinflammatory (NSAI) preparation nurofen to group 2 and phototherapy (exposure to bright white light) was used in group 3. Clinical effect in the form of a decrease of both the intensivity of algesic syndrome and autonomic manifestations as well as improvement of night sleep were clearly seen in group 1. Manifestations of both anxious and depressive disorders were less pronounced. Treatment by Nurofen resulted in slight decrease of intensivity of pains but didn't lead to pronounced alterations of emotional sphere. Administration of either Lerivon or Nurofen promoted the increase of pain thresholds (according to the data of nociceptive flexory reflex). The data obtained testified the necessity of complex therapy of FM patients including administration of antidepressants and analgetic drugs of NSAI group. Dynamic polysomnographic examination of patients from group 3 revealed the increase of total sleep duration, decrease of the time of falling asleep, the latent period of the phase of the fast sleep, activated movement index, intensivity of movements and the time of being awake in the sleep. The conclusion was made that it was worth while to use phototherapy as alternative, nonmedicine method of phothotherapy.

Tabeeva GR, Levin IaI, Korotkova SB, Khanunov IG Zh Nevrol Psikhiatr Im S S Korsakova 1998;98(4):40-3. Russian.

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Tuberculous spondylitis as a cause of inflammatory spinal pain: a report of 4 cases.

Patients are said to have inflammatory spinal pain if they fulfill at presentation 4 of the following 5 criteria: duration of spinal discomfort for at least 3 months, spinal morning stiffness, age less than 40, insidious onset of symptoms, and no relief from pain with rest, but improvement with exercise.

Inflammatory spinal pain is typical of the spondylarthropathies. Only in a minority of the cases it is found in other rheumatic disorders such as rheumatoid arthritis, fibromyalgia or infectious spondyilitis. Tuberculous spondylitis is rarely mentioned as a possible cause of inflammatory spinal pain.

We describe 4 patients with tuberculous spondylitis seen over a 3-year period who met the clinical criteria for inflammatory spinal pain at presentation. We conclude that inflammatory spinal pain may be a presenting feature, albeit rare, of tuberculous spondylitis. Awareness of this finding should help facilitate the proper diagnosis and the institution of appropriate therapy.

Cantini F, Salvarani C, Olivieri I, Niccoli L, Padula A, Bellandi F, Palchetti R Unita Reumatologica, II Divisione di Medicina Interna, Ospedale di Prato, Italy. Clin Exp Rheumatol 1998 May-Jun;16(3):305-8

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The use of opioid drugs in management of chronic orofacial pain.

The use of opioid analgesics for the management of patients with chronic pain is controversial. However, randomized and double-blind clinical trials have shown that in select groups of patients with chronic pain, the daily administration of oral opioids decreases pain levels and improves quality of life.

This article provides a review of the most recent basic and clinical research supporting the rationale for the use of opioids in a select group of patients with chronic orofacial pain. Critical to the employment of this technique are proper patient evaluation and use of comprehensive management strategies.

This management scheme should be reserved for patients with chronic pain that is refractory to most nonopioid therapy. The primary reason for the clinician's reluctance to initiate long-term opioid therapy for their patients with chronic pain is the potential risk of developing opioid tolerance, dependence, or addiction.

In contrast to these beliefs, studies have shown a nonexistent to low risk of opioid dependence or addiction behavior with administration of scheduled oral opioids in chronic pain patients. It is

essential that potential patients for this type of therapy have been carefully screened and have not had a history of drug addiction.

The criteria to be evaluated when considering opioid therapy for chronic orofacial pain control include 1) inadequate pain diminution from prior nonopioid therapy, 2) negative history of substance abuse, 3) definitive determination that the pain being treated is of physiologic rather than psychologic origin, 4) a willingness to adhere to an "opioid contract" between the doctor and patient, 5) compliance with a scheduled, rather than "as needed" or "breakthrough," administration of an oral opioid, and 6) close clinical follow-up to evaluate pain relief, return to daily activities, and titration of drug levels.

If these criteria are followed, administration of oral opioids may be a successful means of decreasing the patient's debilitating chronic pain to tolerable levels, enabling an improvement in the quality of life and return to function.

Swift JQ, Roszkowski MT Division of Oral and Maxillofacial Surgery, University of Minnesota School of Dentistry, Minneapolis 55455, USA. J Oral Maxillofac Surg 1998 Sep;56(9):1081-5

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Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia.

Park JH, Phothimat P, Oates CT, Hernanz-Schulman M, Olsen NJ Department of Radiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2681, USA. Arthritis Rheum 1998 Mar;41(3):406-413

OBJECTIVE: To investigate the metabolic and functional status of muscles of fibromyalgia (FM) patients, using P-31 magnetic resonance spectroscopy (MRS).

METHODS: Twelve patients with FM and 11 healthy subjects were studied. Clinical status was assessed by questionnaire. Biochemical status of muscle was evaluated with P-31 MRS by determining concentrations of inorganic phosphate (Pi), phosphocreatine (PCr), ATP, and phosphodiesters during rest and exercise. Functional status was evaluated from the PCr/Pi ratio, phosphorylation potential (PP), and total oxidative capacity (Vmax).

RESULTS: Patients with FM reported greater difficulty in performing activities of daily living as well as increased pain, fatigue, and weakness compared with controls. MRS measurements showed that patients had significantly lower than normal PCr and ATP levels (P < 0.004) and PCr/Pi ratios (P < 0.04) in the quadriceps muscles during rest. Values for PP and Vmax also were significantly reduced during rest and exercise.

CONCLUSION: P-31 MRS provides objective evidence for metabolic abnormalities consistent with weakness and fatigue in patients with FM. Noninvasive P-31 MRS may be useful in assessing clinical status and evaluating the effectiveness of treatment regimens in FM.

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Utilization and predictive value of laboratory tests in patients referred to rheumatologists by primary care physicians.

OBJECTIVE: Antinuclear antibodies (ANA), rheumatoid factors (RF), and erythrocyte sedimentation rate (ESR) are among the most frequently requested tests in the diagnosis and investigation of connective tissue diseases (CTD). We evaluate the utilization patterns and predictive value of these tests in patients referred to rheumatologists by primary care physicians.

METHODS: We reviewed the records of all new patients referred by primary care physicians in 1994 to 2 rheumatologists practicing at the University of Alberta. Data extracted from the records included diagnostic tests requested by referring primary care physicians, signs and symptoms at the initial rheumatology consult, and followup diagnoses.

RESULTS: Seven hundred eleven new patients had been referred by over 300 primary care physicians: RF had been requested in 25%, ANA in 21%, and ESR in 29%. One hundred nine (15%) of the 711 patients had a CTD, 45 (6%) had rheumatoid arthritis (RA), and 8 (1%) systemic lupus erythematosus (SLE). The predictive values of positive tests for the diagnosis of CTD were low: 49% for RF, 29% for ANA, and 35% for ESR. For RA, the positive predictive values were 44% for RF, 8% for ANA, 17% for ESR; for SLE, 2, 12, and 3%, respectively. Diffuse musculoskeletal pain and fatigue were significantly associated with test utilization, although most patients with these symptoms had fibromyalgia or localized soft tissue rheumatism.

CONCLUSION: Primary care physicians frequently requested autoantibodies in patients referred to rheumatologists. Most tests were negative, and were often requested in patients without CTD, resulting in low positive predictive values and questionable clinical utility. These findings suggest inappropriate overuse and lack of understanding of the use of autoantibody tests in diagnosing rheumatic diseases. A decrease in inappropriate use could be achieved by emphasizing that fatigue and diffuse musculoskeletal pain are not indicative of CTD in the absence of other features such as joint swelling, typical rash, or organ involvement.

Suarez-Almazor ME, Gonzalez-Lopez L, Gamez-Nava JI, Belseck E, Kendall CJ, Davis P Healthcare Quality and Outcomes Research Centre, the Department of Public Health Sciences, University of Alberta, Edmonton, Canada. Maria.Suarez-Almazor@ualberta.ca J Rheumatol 1998 Oct;25(10):1980-5 [Medline record in process]

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Validation of questionnaire-based response criteria of treatment efficacy in the fibromyalgia syndrome.

OBJECTIVE: To compare the validity of self-reported questionnaires as response criteria of treatment efficacy in patients with fibromyalgia syndrome.

METHOD: At the beginning of the treatment period, 70 fibromyalgia patients, randomly allocated to electro- acupuncture or placebo, underwent a clinical evaluation by rheumatologists and answered 1) a generic quality of life questionnaire--the Psychological General Well-Being Index (PGWB), 2) a specific function and symptom questionnaire, and 3) a pain questionnaire-- the Regional Pain Score (RPS). The same evaluation was repeated at the end of the treatment period. Severity of the condition was assessed by a composite outcome score, a combination of different clinical outcome measures forming a clinical severity index. The variations between these questionnaire scores before and after treatment and the variations between the clinical severity indices estimated by clinicians were used as measures of the treatment impact. The first rationale for the validation was a positive correlation between clinical and questionnaire score changes. Another rationale for validation of the new instruments was the ability to identify the different treatment interventions.

RESULTS: The correlation between the clinical severity index and the RPS was good (r = 0.62). Moreover, the RPS demonstrated a good discriminant power in detecting patients with effective treatment: it showed a specificity of 74% and a sensitivity of 75%. The PGWB correlated less well with the clinical score and was less discriminant. The specific function and symptom questionnaire showed little additional validity.

CONCLUSIONS: Outcomes of syndrome severity such as pain and subjective well-being, as measured by self- reported questionnaires, can be valid instruments to evaluate treatment efficacy in short-term clinical trials. In the current study, the RPS proved to be particularly useful to assess the widespread tenderness of fibromyalgia and demonstrated high discriminative power.

Finckh A, Morabia A, Deluze C, Vischer T Department of Internal Medicine, University of Geneva, Switzerland. Arthritis Care Res 1998 Apr;11(2):116-23 [Medline record in process]

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[What is a disease]?

The concept of disease is more complex than it may seem. Disease is both a natural category and a social construction. Medical anthropology distinguishes between three realities under the

different words defining "disease": the biological abnormalities (disease), the subjective experience of altered physical state (illness), and the process of socialization of pathological episodes (sickness).

The constructivist perspective of the sociology of science shows that scientific knowledge reflects cultural beliefs and social values. A diagnosis is "constructed" in the interaction of patients and physicians, and of their respective representations of disease, in a given historical and social contex. The example of fibromyalgia has been chosen to illustrate this social construction of diagnostic categories.

Cathebras P Service de medecine interne, hopital Nord, CHU de Saint-Etienne, France. Rev Med Interne 1997;18(10):809-13 [Article in French]

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What use are fibromyalgia control points?

OBJECTIVE: To investigate the relationship between control points and symptom and distress severity in fibromyalgia (FM).

METHODS: Eighty-four new patients with FM seen at an outpatient rheumatology center from December 1994 through August 1996 underwent tender point and dolorimetry examinations at 18 active and 4 control sites. All completed the assessment scales for fatigue, sleep disturbance, anxiety, depression, global severity, pain, and functional disability, and a composite measure of distress constructed from scores of sleep disturbance, fatigue, anxiety, depression, and global severity -- the Rheumatology Distress Index (RDI).

RESULTS: Control point positivity was common in FM (63.1%) and was associated with somewhat more severe FM symptoms and general distress, yielding an increase in the RDI of 9.2 units or 0.55 standard deviation units. There was no evidence of particularly worse disease in patients with high counts of control tender points, and increasing numbers of tender points beyond the first positive control point were generally not associated with, or were only weakly associated with, increasing symptom severity. Many patients with positive control points had only mild levels of symptom severity. Finally, we found no clusters of patients with very severe symptoms associated with control points, or with dolorimetry scores, or with ratios of dolorimetry scores from different body regions of varying pain thresholds.

CONCLUSION: Positive control points are a common feature (63%) in FM, and appear to be a marker for a generally low pain threshold rather than a disproportionate increase in severe symptoms or distress. Control point positivity should not be used to disqualify a diagnosis of FM. Control point measurements do not add much to FM diagnosis or assessment and, perhaps, should be abandoned. At the least, they should be designated "high threshold" points rather than

control points. Dolorimetry is considerably less useful in FM assessment than the manual tender point examination.

Wolfe F Arthritis Research Center and University of Kansas School of Medicine, Wichita 67214, USA. fwolfe@southwind.net J Rheumatol 1998 Mar;25(3):546-50

YEAR 1995 Abstracts

31P NMR spectroscopy and electromyography during exercise and recovery in patients with fibromyalgia.

OBJECTIVE. To investigate whether patients with fibromyalgia (FM) have normal motor unit recruitment in relation to muscle metabolism during exhausting exercise and recovery, and whether the reduced voluntary muscle force normally seen is related to a smaller muscle size.

METHODS. Female patients with FM and sedentary controls were examined using simultaneous 31P nuclear magnetic resonance spectroscopy (NMR) and surface electromyography (SEMG) during exhaustive static exercise of the anterior tibial muscle and during recovery. The maximum voluntary contraction force was estimated, and the maximum cross sectional muscle area was evaluated using 1H NMR imaging. The sedentary controls were matched to patients for sex, age and, as far as possible, daily physical activity levels.

RESULTS. Patients with FM had reduced maximum voluntary contraction force in relation to the sedentary controls, despite having similar muscle size. In general the myoelectrical-metabolic relation during exercise and recovery was normal in patients with FM.

CONCLUSION. The less extreme changes in motor unit recruitment and metabolism during exhaustive exercise indicated a lower exercise tolerance that could be connected with the lower physical activity levels.

Vestergaard-Poulsen P, Thomsen C, Norregaard J, Bulow P, Sinkjaer T, Henriksen O Danish Research Center of Magnetic Resonance, Hvidovre Hospital, University of Copenhagen, Denmark. J Rheumatol 1995 Aug;22(8):1544-1551

Aspects of fibromyalgia in the general population: sex, pain threshold, and fibromyalgia symptoms.

OBJECTIVE. To investigate relationships between sex, pain threshold and fibromyalgia (FM) symptoms in the general population.

METHODS. Data were obtained from a randomized populations survey of 3,006 persons in Wichita, KS and a subsample of 391 who completed a detailed interview and had an examination. Tender point counts, dolorimetry scores, clinical and psychological variables were measured.

RESULTS. Dolorimetry scores were 2.04 kg/cm (1.42-2.66) lower in women than men, and women were almost 10 times more likely to have 11 tender points [OR 9.6 (2.00-46.3)] than men. Women are also more likely to have FM symptoms than men: "Pain all over," [OR 3.94 (1.34-11.38)], sleep disturbance [OR 3.06 (1.45-6.46)], fatigue [OR 4.52 (2.03-10.09)], and irritable bowel syndrome [OR 5.23 (1.83-14.96)]. Tender point counts are more correlated with FM symptoms than dolorimetry scores.

CONCLUSION. Symptoms of FM are correlated with pain threshold in the general population, but tender point counts correlate better than dolorimetry. These 2 measures of pain threshold assay different but overlapping factors. Pain threshold is lower in women; and women have more FM symptoms. Decreased pain threshold correlates with all of the symptoms of FM, even in those who do not meet criteria for the syndrome. This suggests that decreased pain threshold, as measured by the tender point counts, is an intrinsically important aspect of patient distress, regardless of the extent and kind of concomitant disease; and that much can be learned about patients by employing this examination.

Wolfe F, Ross K, Anderson J, Russell IJ Arthritis Research and Clinical Centers (St. Francis Research Institute, Wichita, KS 67214. J Rheumatol 1995 Jan;22(1):151-6 Country of Publication: CANADA

An association of fibromyalgia with primary Sjogren's syndrome: a prospective study of 72 patients.

OBJECTIVE. Fibromyalgia patients often describe the presence of dry eyes and dry mouth. Conversely there is an increasing recognition that many patients with Sjogren's syndrome (SS) have fibromyalgia (FM). We decided to investigate this association.

METHODS. Seventy-two patients with FM were screened with a Schirmer's test. All patients with an abnormal test had a minor salivary gland biopsy.

RESULTS. Thirty-eight percent (n = 28) had a Schirmer's test of < 15 mm wetting at 5 minutes, however sicca symptoms were noted in only 19% of patients. Salivary gland biopsy in these 28 patients showed a focus score of > or = 1 in 5; a positive antinuclear antibody test (ANA) was found in 4, a positive rheumatoid factor in 3 and anti- SSA SSB antibodies in 2. Another 8 patients had abnormal salivary gland lymphocytic foci, but there were < 50 cells or the density was < 1 focus/4 mm2; all 8 of these patients had a positive ANA. None of these patients have developed systemic features of SS over a 6 year period of followup.

CONCLUSION. There is a subgroup of patients presenting with FM who, on further testing, have findings consistent with primary SS. The prevalence of this association was 6.9% for probable SS and 11% for possible SS. These figures are probably an overestimation due to tertiary center referral bias. The etiologic and management implications of these observations are unclear.

Bonafede RP, Downey DC, Bennett RM Department of Medicine and School of Dentistry, Oregon Health Sciences University, Portland. J Rheumatol 1995 Jan;22(1):133-6

Capillary Structure and Mitochondrial Volume Density in the Trapezius Muscle of Chronic Trapezius Myalgia, Fibromyalgia and Healthy Subjects

Objectives: To better understand some of the possible pathophysiological mechanisms of chronic muscle pain.

Methods: Muscle biopsies were obtained from myalgic areas in the trapezius muscle of female patients suffering from either chronic trapezius myalgia or fibromyalgia and from corresponding areas in healthy, symptom-free subjects. Electron microscopy and morphometric analysis were used to determine mean myofibrillar mitochondrial density and the capillary structure.

Results: The mitochondrial fraction was higher in the patients with chronic trapezius myalgia than in those with fibromyalgia or in the healthy subjects. The mean volume density of mitochondria in the trapezius muscle fibers, however, was lower than that previously reported for human female limb muscle in all three groups. This indicates that the trapezius muscle in general has a lower capacity to tolerate endurance work than limb muscles. The morphometric analysis of the capillary structure revealed that the area and thickness of the endothelium was significantly larger in the fibromyalgia group than in the patients with chronic myalgia and in the healthy subjects. Capillaries with structural changes in the endothelium were more frequent in the fibromyalgia group of patients than in the other two groups; the differences in frequency, however, were not significant.

Conclusions: It is proposed that the higher mitochondria fraction in chronic trapezius myalgia might be a result of an insufficient capillarization of the fibers in these patients. The capillary changes in the fibromyalgic group might be secondary to disturbances in muscle microcirculation causing localized hypoxia/ischemia. Thus, the present result might indicate differences in the pathophysiology of chronic myalgia and fibromyalgia.

Rolf Lindman D.D.S., Ph.D., Mats Hagberg M.D., Ph.D., Ann Bengtsson M.D., Ph.D., Karl G. Henriksson M.D., Ph.D., Lars-Eric Thornell M.D., Ph.D.Rolf Lindman, DDS, Ph.D. Department of Orthodontics, Torkelbergsgatan 11, S-581 85 Linköbing, Sweden. Address correspondence to: Professor Lars-Eric Thornell, Department of Anatomy, Umeå University, S-901 87 Umeå, Sweden. Journal of Musculoskeletal Pain 1995;3(3):5-6

**Cerebral dysfunction in fibromyalgia: evidence from regional cerebral blood flow measurements, otoneurological tests and cerebrospinal fluid analysis.

Measurements of regional cerebral blood flow (rCBF), analysis of cerebrospinal fluid, auditory brain stem responses (ABR) and oculomotor tests were performed in 19 patients with fibromyalgia. The results from the rCBF measurements showed a normal flow level with slight but significant focal flow decreases in dorsolateral frontal cortical areas of both hemispheres. The ABR results showed signs of dysfunction at least at the brain stem level and the oculomotor tests showed high frequency of pathology. The cerebrospinal fluid analysis showed discrete changes in the cell differential count. Possible explanations for the involvement of the central nervous system in fibromyalgia are discussed.

Johansson G; Risberg J; Rosenhall U; Orndahl G; Svennerholm L; Nyström S; Department of Rehabilitation Medicine, Sahlgren Hospital, Göteborg, Sweden. Acta Psychiatr Scand 1995;91(2):86-94

[Clinical aspects and neurologic expert assessment in sequelae of whiplash injury to the cervical spine].

Whiplash injury to the cervical spine and its possible long-term sequelae, the late (or chronic) whiplash syndrome, are analysed based on a clearly defined accident mechanism and an initial battery of investigations to exclude lesions other than those affecting the soft tissue of the neck region (i.e. the consequences of strain and sprain). Predictors are discussed that may point to a delayed and complicated recovery, with development of a complex array of symptoms.

The pattern of this symptomatology, as reviewed on the basis of different neuropsychological investigations, appears inhomogeneous. Comparison with other non-traumatic conditions, such as the chronic fatigue syndrome, the fibromyalgia syndrome and chronic daily headache, as well as with chronic disturbances of cervical origin, reveals striking similarities. In cases of litigation, these circumstances require careful assessment of the patient's previous history and an extensive differential diagnosis. Whiplash injury to the cervical spine rarely results in disability and, if so, is only minor.

Jenzer G Nervenarzt 1995 Oct;66(10):730-735 [Article in German]

Clinical features of systemic lupus erythematosus.

Major findings in the understanding of the epidemiology of systemic lupus erythematosus and in the description and understanding of its presentation and course in individual organ systems are reviewed. The role of serologic tests as correlates of disease activity remains controversial. No consensus has been reached on the association of either corticosteroid dose or of antiphospholipid antibodies with avascular necrosis of bone. Multiple rare presentations of cutaneous lupus have been reviewed during the past year. The role of hormones in the activity of lupus and the use of hormonal agents in the treatment of lupus are rapidly expanding and contentious areas of research. Cognitive function deficit continues to be an area of great interest, with studies differing on whether psychiatric disorders or organic lupus (or both) are responsible. Finally, fatigue and the potential role of fibromyalgia as an explanation for "lupus fatigue," are of major interest.

Petri M Division of Molecular and Clinical Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Curr Opin Rheumatol 1995 Sep;7(5):395-401

Clustering of sleep electroencephalographic patterns in patients with the fibromyalgia syndrome.

Several electroencephalographic (EEG) abnormalities have been observed during sleep in patients suffering from the fibromyalgia syndrome (FMS). In this study, 12 patients with fibromyalgia and 14 control subjects had two polysomnographic recordings obtained at home. Data from the second night were subjected to blinded manual scoring as well as signal processing using linked or 'step-wise clustering for pattern recognition. In this procedure, a common learning set was generated using the spectral information in three 2 min EEG samples from each of the sleep stages selected from five patients with FMS and five controls. In this way, 17 characteristic EEG classes were defined. All 2 s EEG segments from the whole night from all subjects were then assigned to one of these classes. Five of the classes (dominated by 0.5-4.5 Hz activity) were more frequent in the control group, whereas three other classes (dominated by 8- 11 Hz activity) were prevalent in the patient group. This trend was consistent in all sleep stages, although most striking in non-rapid eye movement (NREM) sleep. The predominance of these classes in the patient group may correspond to the alpha-EEG sleep anomaly previously reported in subjects with FMS. More importantly, as the EEG power in the lowest frequency range (prevalent in controls) probably is a marker for restorative sleep, the findings may reflect important aspects of sleep disturbances n subjects suffering from FMS, thereby contributing to some of the daytime symptoms in these patients.

Drewes AM, Gade K, Nielsen KD, Bjerregard K, Taagholt SJ, Svendsen L Department of Rheumatology, Aalborg Hospital, Denmark. Br J Rheumatol 1995 Dec;34(12):1151-1156

Common rheumatologic diseases in elderly patients.

OBJECTIVE: To review common rheumatologic disorders that affect elderly patients and emphasize the unique diagnostic and therapeutic challenges inherent in the management of rheumatologic diseases in this age-group.

DESIGN: We summarize our approach to treatment and management of specific rheumatologic problems in geriatric patients and discuss pertinent studies from the literature.

RESULTS: Among the spectrum of rheumatologic disorders frequently encountered in the elderly population are polymyalgia rheumatica, fibromyalgia, giant cell arteritis, crystalline arthropathies (gout and pseudogout), and degenerative joint disease.

The initial manifestations of these rheumatologic diseases in elderly patients may differ from the typical findings in younger patients. Geriatric patients may have nonspecific complaints, a decline in physical function, or even confusion.

Because of physiologic changes associated with aging and a decrease in functional reserves, elderly patients are susceptible to adverse effects of pharmacologic therapy (including nonsteroidal anti-inflammatory medications, corticosteroids, narcotic analgesics, allopurinol, and colchicine). Clinicians should be alert for such problems as hepatotoxicity and occult gastrointestinal blood loss.

Comorbid conditions such as cardiovascular disease and cognitive impairment may complicate management strategies and may limit the goals of both surgical intervention and rehabilitation programs in elderly patients.

CONCLUSION: Rheumatologic disorders in geriatric patients pose special challenges to primary-care physicians. In the selection of optimal pharmacologic and nonpharmacologic therapeutic modalities, clinicians should focus on maintaining or improving the patient's quality of life and level of independent function.

Michet CJ Jr, Evans JM, Fleming KC, O'Duffy JD, Jurisson ML, Hunder GG Division of Rheumatology and Internal Medicine, Mayo Clinic Scottsdale, Arizona, USA. Mayo Clin Proc 1995 Dec;70(12):1205-1214

Concentration and memory deficits in patients with fibromyalgia syndrome.

OBJECTIVES: A frequent complaint among patients with Fibromyalgia Syndrome (FS) is poor memory and concentration. Despite these complaints, there have been no studies investigating these neuropsychological features. The present study was designed to assess whether these specific cognitive deficits exist in those with FS.

CONCLUSIONS: These results suggest that FS patients suffer from mild memory and sustained concentration deficits. Interestingly, subjective ratings of sleep qualilty were unrelated to these cognitive deficits. Implications of these results for multidisciplinary treatment programs are discussed.

Nielson-WR, Grace-GM, Hopkins-M, Berg-M. J-Musculoskeletal Pain. 1995 Nov;3(1):123.

The courts, expert witnesses and fibromyalgia.

Fibromyalgia, a condition that sometimes causes disagreement among physicians, has also been debated in several court cases that highlight the role of physicians as expert witnesses. Lawyer Karen Capen says physicians who provide expert opinion in court should be aware that there are specific requirements regarding their qualifications. In an Alberta court case, a judge discounted evidence provided by a rheumatologist who ran a clinic that treated fibromyalgia patients because of his "personal and perhaps financial interest in perpetuating the existence of this condition." The judge ruled that "this particular disorder is often found in individuals who will not or cannot cope with everyday stresses of life and convert this inability into acceptable physical symptoms to avoid dealing with reality."

Capen K Can Med Assoc J 1995 Jul ;153(2):206-8 Country of Publication: CANADA

A database for fibromyalgia.

FMS is a complex condition mainly characterized by the presence of chronic pain. The nature of this complaint thus demands assessment in a hierarchal fashion of the various components of the pain system ranging from the nociceptor through to complex central pain-processing mechanisms. The condition is common and represents the most important defined chronic pain syndrome. Elucidation of the mechanisms and better management of FMS will result in improved knowledge of a whole range of related chronic pain syndromes. The database in FMS is necessarily large but does need to be focused according to the need of the person constructing the database and the need of the individual with FMS. As our understanding of FMS evolves, better ways of assessing the various dimensions of the problem will be devised. Perhaps the challenge we face is to bring all the parts together. In doing so, we may find there is a single essential component that links all the clinical features together, which correlates well with severity, disability and outcome, which is amenable to treatment programs, and which is measurable. The search for the soul of the "elephant" of FMS continues.

Littlejohn GO Rheumatology Department, Monash Medical Centre, Clayton, Victoria, Australia. Rheum Dis Clin North Am 1995;21(2):527-57 Number of References: 112

Determination of observer-rated alpha activity during sleep.

Patients suffering from chronic fatigue syndrome (CFS) have been described as having alpha intrusion into sleep. In a separate study of the relationship between depression and CFS, we investigated the sleep of CFS patients. We could not detect any observable alpha anomaly in our group of CFS patients. It is possible that there is a subgroup of CFS patients in whom no alpha anomaly is present. However, the sleep electroencephalogram (EEG) montage used in our study was different to that employed by previous researchers. This paper investigates the influence of electrode derivations on the outcome of observable alpha ratings. We compared simultaneous recordings of sleep EEG using three commonly employed montages. Our results indicate that use of the mastoid reference (montage 1) results in the highest observer-related alpha. This may suggest that data regarding alpha intrusion should always be collected using montage 1. However, there is a possibility that the mastoid electrode is not electrically silent and is contaminating the data of the referenced channels. The implications of these findings are discussed in relation to the validity of alpha intrusion measurement of CFS and fibromyalgia.

Flanigan MJ, Morehouse RL, Shapiro CM Department of Psychiatry, University of Toronto, Ontario, Canada. Sleep 1995 Oct;18(8):702-6

[The diagnosis and treatment of fibromyalgia] Health ResponseAbility Systems

Fibromyalgia syndrome (FMS) affects predominantly females and is characterised by widespread musculoskeletal pain, fatigue, insomnia, nonrefreshing sleep, diffuse stiffness and other organic and psychic signs and symptoms. Diagnosis is essentially based on the 1990 American College of Rheumatology Classificative Criteria, but if, in some cases, they are not completely fulfilled, diagnosis is not excluded in a particular patient.

The causes of the enhanced pain perception and of all the other clinical characteristics are unknown. Both the central hypothesis (sleep disturbance; psychological affection; hypothalamus-hypophysis-adrenal axis disorder; neuromediators disregulation; etc.) and the peripheral theory (anatomical and/or functional muscle disturbance) try to explain FMS etiopathogenesis.

Tricycles antidepressants (i.e. amitriptilin) and some muscle relaxants (i.e. ciclobenzaprine) have demonstrated some beneficial effect contrary to the classic antirheumatic drugs (NSAID; corticosteroids; etc.). Physical exercise, multidisciplinary support (behavioural therapy, physical agents; etc.) and patient education are some of the other approaches which contribute to the correct management of FMS.

Branco JC Unidade de Reumatologia, Hospital de Egas Moniz, Lisboa.

Acta Med Port 1995 Apr;8(4):233-8 Number of References: 78 Country of Publication: PORTUGAL Language of Article: Por

Diagnostic associations with hypermobility in rheumatology patients.

Although we have considerable knowledge of the demographic characteristics of hypermobile individuals in population studies, we have little understanding of the implications of hypermobility. In this rheumatology clinic- based study we assessed the prevalence, diagnostic associations and clinical features of hypermobility in consecutive newly referred patients. Hypermobility was identified in 50 of 378 patients (13.2%). The most common clinical diagnosis in the hypermobile patients, compared with controls (those without hypermobility), was soft tissue rheumatism observed in 67% vs 25% (P<0.001).

Fibromyalgia syndrome was the common specific rheumatological diagnosis in 30% vs 8% (P<0.001) and inflammatory arthritis the least common diagnosis in 4% vs 32% (P<0.001) of hypermobile versus non- hypermobile patients, respectively. Hypermobile patients complained of previous pain, including widespread or multiple localized sites of pain and spinal pain. Although clinic-based studies may not accurately reflect disease patterns as seen in the population, these results suggest an association between hypermobility and soft tissue rheumatic complaints and should be useful to the clinical rheumatologist.

Hudson N, Starr MR, Esdaile JM, Fitzcharles MA Rheumatic Disease Unit, McGill University, Montreal, Quebec, Canada. Br J Rheumatol 1995 Dec;34(12):1157-1161

Drug Related Lupus Misdiagnosed as Fibromyalgia: Case Report

Background: Drug-related lupus [DRL] especially with hydralazine has been known for 40 years. Signs and symptoms of DRL may be readily mistaken for other disorders such as fibromyalgia. The purpose of the case presentation is to review the pathophysiology and similarities between DRL and fibromyalgia in addition to emphasize the importance of accurate diagnosis in physiatric practice.

Findings: This is a case of a 57-year-old hypertensive woman on hydralazine for nine years who developed multiple complaints including bilateral chest pain, cough, shortness of breath, joint pain at knees and ankles, muscle pain in thighs and calf, swelling of hands and feet, intermittent skin lesions, depression and anxiety. She was referred to a physiatrist with the mistaken diagnosis of fibromyalgia. The patient's signs and symptoms were not diagnostic of DRL but were suspicious of something other than fibromyalgia. An immunological work-up showed suggestion of DRL and hydralazine was discontinued.

Conclusion: Drug-related lupus may be misdiagnosed especially as fibromyalgia. Careful evaluation should lead to accurate diagnosis.

Kanakadurga R. Poduri, MD, is Assistant Professor and Charles J. Gibson, MD, is Professor, Department of Orthopaedics, Division of Rehabilitation Medicine, Strong Memorial Hospital, University of Rochester, Medical Center, Rochester, NY. Address correspondence to: Kanakadurga R. Poduri, MD, Box 664, Strong Memorial Hospital, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642.

This paper was presented at the 53rd Annual Assembly of the American Academy of Physical Medicine and Rehabilitation, Washington, DC, October 28, 1991. Submitted: December 12,1994. Revision accepted: February 14, 1995.

Journal of Musculoskeletal Pain, Vol. 3(4) 1995 Kanakadurga R. Poduri, Charles J. Gibson, "Drug Related Lupus Misdiagnosed as Fibromyalgia: Case Report " Journal of Musculoskeletal Pain, vol. 3, no. 4, 1995, 71-72.

Effects of intravenous morphine, lidocaine, and ketamine.

Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Pain intensity, muscle strength, static muscle endurance, pressure pain threshold, and pain tolerance at tender points and control points were assessed in 31 patients with fibromyalgia (FM), before and after intravenous administration of morphine (9 patients), lidocaine (11 patients), and ketamine (11 patients). The three different studies were double-blind and placebo-controlled. The patients were classified as placebo-responders, responders (decrease in pain intensity by > 50%) and non-responders.

The morphine test did not show any significant changes. The lidocaine test showed a pain decrease during and after the infusion. The ketamine test showed a significant reduction in pain intensity during and after the test period. Tenderness at tender points decreased and endurance increased significantly, while muscle strength remained unchanged. The present results support the hypothesis that the NMDA receptors are involved in pain mechanisms in fibromyalgia. These findings also suggest that central sensitization is present in FM and that tender points represent secondary hyperalgesia.

Sorensen J, Bengtsson A, Backman E, Henriksson KG, Bengtsson M Department of Anesthesiology, University Hospital, Linkoping, Sweden. Scand J Rheumatol 1995;24(6):360-5

The epidemiology of drug treatment failure in rheumatoid arthritis.

The length of time that patients remain on anti-rheumatic therapy is an important measure of the effectiveness of that therapy since length of time on therapy is a composite measure that accounts for sustained, positive therapeutic benefit as well as negative therapeutic benefit (e.g. adverse reactions, unacceptable costs and loss of efficacy), and accounts for noise (noncompliance, psychological factors, misunderstanding, etc.). Effectiveness is a measure of how well a drug does work, while efficacy, the measure used in randomized controlled trials, means that a drug can work; however, efficacy may or may not translate to usefulness in the clinic. To understand drug effectiveness we reviewed studies of 5809 patients receiving various SMARDs. The average median time on drug ranged from 1.10 to 2.27 years, excluding methotrexate, with shortest survival times falling to sulfasalazine (1.10) and auranofin (1.16), intermediate times to hydroxychloroquine (1.59), penicillamine (1.42), IM gold (1.40), and the longest time to azathioprine (2.27). Overall, excluding methotrexate, the average median survival time was 1.41 for 3998 patients. Median time on drug was 3.3 times greater for all other drugs combined, averaging 4.61 years. Expressed in terms of '5-year survival,' an average of 55.7% of patients remained on methotrexate 5 years after it was started. Better results noted here for methotrexate stand in contradistinction to short-term randomized controlled trials which find most SMARDs to be equal in efficacy. Other factors that may influence drug survival time include age, age, education level, psychological status, presence of fibromyalgia, rank order of SMARD administration, disease severity or corticosteroid administration. Studies can provide more information if they also measure clinical variables as well as time on drug, providing area-under-the-curve measurements.

Wolfe F University of Kansas School of Medicine, Arthritis Research and Clinical Centers, Emporia 67214, USA. Baillieres Clin Rheumatol 1995 Nov;9(4):619-632

[Fibromyalgia].

Fibromyalgia, also called (primary) fibromyalgia syndrome or fibrositis (syndrome), is a chronic soft tissue pain syndrome characterized by the presence of widespread musculosceletal aching, tender points at characteristic sites, fatigue, and poor sleep. The etiology of this common and painful condition is incompletely understood, non- restorative sleep, which has been correlated with an electroencephalic abnormality called alpha-delta sleep (intrusion of alpha rhythms in the non-REM sleep EEG), may be important. Several observations suggest that serotonin is likely to mediate both pain and non-REM sleep, and serotonin deficiency in the brain has been suggested to be of pathogenetic significance in fibromyalgia syndrome. A lower than normal threshold for pain can often be observed. The newly proposed criteria for the classification of fibromyalgia syndrome (widespread pain in combination with tender points at 11 or more of 18 specific tender point sites) are important for the differential diagnosis and to compare results in international studies.

Siegmeth W, Geringer EM Ludwig Boltzmann-Forschungsstelle fur Epidemiologie rheumatischer Erkrankungen, Baden.

Wien Med Wochenschr 1995;145(14):320-325 [Article in German]

Fibromyalgia.

The article details the history, concept, definition and assessment of the still enigmatic condition of 'fibrositis' or, as it has more recently been called, 'fibromyalgia'. The concept and diagnosis became popular, especially in North America, in the 1970s, after the seminal publications of Hugh Smythe (1972) and Smythe and Moldofsky (1977). It is noticeable that there does not appear to be an early case report as there is for instance for gout, rheumatoid arthritis or certain vasculitides. This may be one reason why we still lack a commonly shared clinical image of the 'typical' case. After Smythe and coworkers, operational definitions and classification criteria were given by Yunus et al, Lautenschlager et al (both in 1989) and Wolfe et al in 1990. The latter received the endorsement of the American College of Rheumatology and are now the most widely used. They identify fibromyalgia as a musculoskeletal disorder with spontaneous widespread pain and exaggerated tenderness as prominent and distinctive features. The other two criteria sets refer to a different concept of fibromyalgia as a 'functional' or 'dysfunctional' disorder. These and other nosological differences pose problems for clinical as well as epidemiological research. They may be of minor importance if it is accepted that any present definition is arbitrary and that a wide range of possible elements are more relevant to research than a uniform concept of a disease called fibromyalgia.

Raspe H, Croft P Institute for Social Medicine, Medical University at Lubeck, Germany. Baillieres Clin Rheumatol 1995 Aug;9(3):599-614

Fibromyalgia. A neuro-immuno-endocrinologic syndrome?

Fibromyalgia is an enigmatic long-lasting polysymptomatic disease which has been thought to be caused by peripheral muscle dysfunction or psychological factors. Based on a clinical evaluation of a large series of in-patients and a review of international findings, the article advances the hypothesis of irreversible disturbances of the neuroimmunoendocrinological system as the main cause of this disease. The therapeutic consequences of this hypothesis are discussed.

Olin R Riksforsakringsverkets sjukhus, Tranas. Lakartidningen 1995 Feb 22;92(8):755-8, 761-3 Number of References: 66

Fibromyalgia and disability. Report of the Moss International Working Group on medicolegal aspects of chronic widespread musculoskeletal pain complaints and fibromyalgia

The present article is the result of a working group conference held in Moss, Norway, in June 1993, financed by the Royal Norwegian Ministry of Health and Social Affairs. Its purpose was to review and focus upon problems and needs related to the medico-legal aspects of fibromyalgia and chronic widespread musculoskeletal complaints: thus to define directions for future work on issues which have generally not been addressed within the medical community.

Our report describes specific problems in this area in regard to definition, evaluation and recommendation, and in currently available work and disability statistics. We have recommended international efforts to establish research programs through organizations such as the International Social Security Association and the World Health Organization.

While our recommendations call for research into medico-legal interactions, causes and pathogenic mechanisms, prevention and treatment are also key and relevant concerns in the medico-legal setting.

Wolfe F, Aarflot T, Bruusgaard D, Henriksson KG, Littlejohn G, Moldofsky H, Raspe H, Vaery H Dept. of Internal Medicine, University of Kansas School of Medicine,/Arthritis Research and Clinical Centers, Wichita, USA. Scand J Rheumatol 1995;24(2):112-8

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

Two important studies in which nuclear magnetic resonance spectroscopy was used convincingly demonstrated that muscle is not the primary pathologic factor in fibromyalgia. There were further studies reporting that fibromyalgia- chronic fatigue syndrome may follow well treated Lyme disease or mimic Lyme disease. The longest therapeutic trial to date in fibromyalgia demonstrated an initial modest effect of tricyclic medications, but at 6 months that efficacy was no longer evident.

Investigation in both fibromyalgia and chronic fatigue syndrome now focuses on the central nervous system. The use of new technology, eg, neurohormonal assays and imaging such as single-photon emission computed tomography scan, may be important in understanding these elusive conditions.

Goldenberg DL Newton-Wellesley and Tufts University School of Medicine, Massachusetts, USA. Curr Opin Rheumatol 1995;7(2):127-35 Number of References: 88

**Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels.

OBJECTIVE. To determine if regional cerebral blood flow (rCBF) in the left and right hemithalami or the left and right heads of the caudate nucleus is abnormal in women with fibromyalgia (FM).

METHODS. Resting-state rCBF in the hemithalami and left and right heads of the caudate nucleus of 10 untreated women with FM and 7 normal control women was measured by single-photon-emission computed tomography. Pain threshold levels at tender and control points also were assessed in both the women with FM and the controls.

RESULTS. The rCBF in the left and right hemithalami and the left and right heads of the caudate nucleus was significantly lower in women with FM than in normal controls (P = 0.01, P = 0.003, P = 0.01, and P = 0.02, respectively). Compared with controls, the women with FM also were characterized by significantly lower cortical rCBF (P = 0.001) and lower pain threshold levels at both tender points (P = 0.0001) and control points (P = 0.0001).

CONCLUSION. The findings of low rCBF and generalized low pain thresholds support the hypothesis that abnormal pain perception in women with FM may result from a functional abnormality within the central nervous system.

Mountz JM, Bradley LA, Modell JG, Alexander RW, Triana-Alexander M, Aaron LA, Stewart KE, Alarcon GS, Mountz JD Department of Radiology, University of Alabama Medical Center, Birmingham 35233, USA. Arthritis Rheum 1995 Jul;38(7):926-938

Fibromyalgia is common in a postpoliomyelitis clinic.

OBJECTIVE: To determine prospectively the occurrence and clinical characteristics of fibromyalgia in patients serially presenting to a postpolio clinic. Fibromyalgia may mimic some of the symptoms of postpoliomyelitis syndrome, a disorder characterized by new weakness, fatigue, and pain decades after paralytic poliomyelitis.

DESIGN: Case series.

SETTING: A university-affiliated hospital clinic.

PATIENTS: One hundred five patients were evaluated with a standardized history and physical examination during an 18-month period. Ten patients were excluded because of the absence of past paralytic poliomyelitis.

INTERVENTIONS: Patients with fibromyalgia were treated with low-dose, nighttime amitriptyline hydrochloride or other conservative measures.

MAIN OUTCOME MEASURES: Patients with fibromyalgia had diffuse pain and 11 or more of 18 specific tender points on examination (American College of Rheumatology criteria, 1990). Patients with borderline fibromyalgia had muscle pain and five to 10 tender points on physical examination.

RESULTS: Ten (10.5%) of 95 postpolio patients met the criteria for fibromyalgia, and another 10 patients had borderline fibromyalgia. All patients with fibromyalgia complained of new weakness, fatigue, and pain. Patients with fibromyalgia were more likely than patients without fibromyalgia to be female (80% vs 40%, P < .04) and to complain of generalized fatigue (100% vs 71%, P = .057), but were not distinguishable in terms of age at presentation to clinic, age at polio, length of time since polio, physical activity, weakness at polio, motor strength scores on examination, and the presence of new weakness, muscle fatigue, or joint pain. Approximately 50% of patients in both the fibromyalgia and borderline fibromyalgia groups responded to low-dose, nighttime amitriptyline therapy.

CONCLUSIONS:

(1)
Fibromyalgia occurs frequently in a postpolio clinic.

(2)
Fibromyalgia can mimic some symptoms of postpoliomyelitis syndrome.

(3)
Fibromyalgia in postpolio patients can respond to specific treatment.

Trojan DA, Cashman NR Department of Neurology, Montreal Neurological Institute and Hospital, McGill University, Quebec. Arch Neurol 1995 Jun;52(6):620-624

**Fibromyalgia: more than just a musculoskeletal disease.

Fibromyalgia is a common condition characterized by diffuse musculoskeletal pain and fatigue. The syndrome is defined by the presence of musculoskeletal tender points on physical examination. Additionally, persons with this syndrome have a high incidence of headaches, ocular and vestibular complaints, paresthesias, esophageal dysmotility, "allergic" symptoms, irritable bowel syndrome, genitourinary symptoms and affective disorders. Recent research has revealed a number of objective biochemical, hormonal and neurotransmitter abnormalities associated with fibromyalgia, making it a clearly identifiable condition. These abnormalities may clarify our understanding of the pathogenesis and treatment of fibromyalgia.

Clauw DJ Georgetown University School of Medicine, Washington, D.C., USA. Am Fam Physician 1995;52(3):843-51, 853-4 Number of References: 33

Fibromyalgia syndrome and psychiatric disorder.

Fibromyalgia syndrome (FMS) is characterised by generalised aches, pains, tender points, stiffness and fatigue, yet, despite increasing recognition of this syndrome as a clinical entity, its aetiology remains obscure. There is now increasing evidence that FMS represents a distinct rheumatic disorder and should not be regarded as a somatic illness secondary to psychiatric disorder.

Dunne FJ, Dunne CA Warley Hospital, Brentwood. Br J Hosp Med 1995 Sep 6;54(5):194-197

Webmaster's Note: What a pompous ELK ass! (ELK = Extremely Lacking Knowledge) Fibromyalgia syndrome and myofascial pain syndrome. Do they exist?

"It is in the healing business that the temptations of junk science are the strongest and the controls against it the weakest." Despite their subjective nature, these syndromes (particularly MPS) have little reliability and validity, and advocates paint them as "objective." Despite a legacy of poor-quality science, enthusiasts continue to cite small, methodologically flawed studies purporting to show biologic variables for these syndromes. Despite a wealth of traditional pain research, disciples continue to ignore the placebo effect, demonstrating a therapeutic hubris despite studies showing a dismal natural history for FS.

In reviewing the literature on MPS and FS, F.M.R. Walshe's sage words come to mind that the advocates of these syndromes are "better armed with technique than with judgment." A sympathic observer might claim that labeling patients with monikers of nondiseases such as FS and MPS may not be such a bad thing. After all, there is still a stigma for psychiatric disease in our society, and even telling a sufferer that this plays only a partial role may put that patient on the defensive. Labeling may have iatrogenic consequences, however, particularly in the setting of the work place.

Furthermore, review of a typical support group newsletter gives ipso facto proof of this noxious potential. The author of a flyer stuffed inside the newsletter complains that getting social security and disability benefits for "the invisible disability" can be "an uphill battle. But don't loose (sic) hope." Apparently the "seriousness of the condition" is not appreciated by the medical community at large, and "clinician bias may well be the largest threat," according to Boston epidemiologist Dr. John Mason.

Sufferers are urged to trek to their local medical library and pull four particular articles claiming FS patients have more "stress," "daily hassles," and difficulty working compared with arthritis patients. If articles can't be located, patients are told to ask their lawyers for help. Although "Chronic Fatigue Syndrome" and FS are not considered by everyone to be the same malady, the "National Institute of Health (sic) has lumped these two conditions together. This could work in

your favor." (A U.S. political advocacy packet is available for $8, but a list of U.S. senators with Washington, DC addresses is freely provided.)

These persons see themselves as victims worthy of a star appearance on the Oprah Winfrey show. A sense of bitterness emerges; one literally bed-bound Texas homemaker writes in Parents magazine that "Some doctors may give up and tell you that you are a hypochondriac." (ABSTRACT TRUNCATED AT 400 WORDS)

Bohr TW Department of Neurology, Loma Linda University School of Medicine, California, USA. Neurol Clin 1995 ;13(2):365-84 Number of References: 97

Webmaster's Note: Thank You, Dr. Bennett! Literature Review of "Fibromyalgia Syndrome and Myofascial Pain Syndrome. Do They Exist?:"

By Robert Bennett, M.D. Oregon Health Sciences University, Portland, Oregon, U.S.A.

Summary

Dr. Bohr states "It is in the healing business that the temptations of junk science are the strongest and the controls against it the weakest. Despite their subjective nature, these syndromes have little reliability and validity. Despite a legacy of poor quality science, enthusiasts continue to cite small, methodologically flawed studies reporting to show biological variables for these syndromes." Dr. Bohr apparently views fibromyalgia as a manifestation of hypochondriasis of somatization and says "After all, there is a still a stigma for psychiatric diseases in our society, and even telling a sufferer that this plays only a partial role may put the patient on the defense."

Comments

Dr. Bohr does not believe the multiplicity of fibromyalgia symptoms are due to a discrete pathophysiological entity, and neither do I. However, we agree on little else. Dr. Bohr's article was in an issue of Neurological Clinics devoted to "Malingering and Conversion reactions." The article is full of contradictions and illogic. When Dr. Bohr has seen a few thousand fibromyalgia patients and conducted some controlled studies to substantiate his theorizing, he will have more credibility.

Fibromyalgia: the commonest cause of widespread pain.

FM affects approximately six million Americans, four million are women. It is a chronic muscle pain syndrome with poorly understood associations with many other conditions. Although there

is no distinctive pathophysiological basis for the syndrome, these patients are readily recognized by their history of widespread body pain and multiple tender-point areas.

Failure to recognize these patients results in much frustration, both in the physician and in the patient, and often results in unnecessary investigations. Treatment of FM patients has to be individualistic and demands a holistic approach; this requires time, empathy, and interaction with other specialists. Providing effective treatment to these patients is a true test of a physician's skill.

Bennett RM Department of Medicine, Oregon Health Sciences University, Portland 97201, USA. Compr Ther 1995 ;21(6):269-75 Number of References: 16

Fibromyalgia: what help can nurses give?

Fibromyalgia is a common cause of pain, discomfort and disability. In this article, the author describes the symptoms and possible aetiology. The article also highlights how nurses can enhance patients' quality of life by helping them to cope with pain, establish sleep patterns, take exercise, manage stress, improve concentration and memory, and fight isolation.

Ryan S Nurs Stand 1995 Jun 7;9(37):25-28

Fitness Characteristics of Female Patients with Fibromyalgia

Objectives: To characterize the fitness status of female fibromyalgia syndrome [FS] patients through comparison of performances in fitness testing between FS patients and matched healthy controls [HC]; examination of the reproducibility of fitness testing in FS patients; and analysis of the effect of [former] sports participation on fitness testing in FS patients

Methods: Eighty-seven FS patients [mean: 44.5 yrs of age, 12.5 yrs of disease duration] and 52 matched HCs from clerical personnel [44 yrs of age] participated in the study. Twelve fitness tests were selected to evaluate cardiorespiratory endurance, muscular strength and endurance, flexibility, coordination [skills] and body composition.

Results: The peak workload achieved in an incremental bicycle ergometer test was significantly lower [30 W, 19%] in FS patients than in HCs. The peak heart rate was also significantly lower [15 b/min, 11%] in FS patients, but the perceived exertion rate was higher [0.7 units, 4%]. These findings indicate that FS patients perceived the peak workload achieved as their maximum although the maximal aerobic power was not yet attained as suggested by the submaximal heart rate. At the same submaximal work [50 W] the heart rate in the FS patients was also lower [5 b/

min, 4%], but the perceived exertion rate higher [1.4 units, 12%]. The performances in the strength, flexibility and skill tests were poor [P

Conclusions: FS patients may avoid potentially beneficial physical exercise because of the muscle soreness it provokes. Therefore, it may be incorrect to attribute their poor performance in fitness testing entirely to poor fitness.

Frans T. J. Verstappen M.D. Ph.D., H. Marijke S. van Santen-Hoeufft M.D., Sander van Sloun MSc., Paulien H. Bolwijn MSc., Sjef van der Linden M.D. Ph.D. Address correspondence to: Frans T. J. Verstappen, Institute of Movement Sciences, University of Limburg, P.O. Box 616, 6200 M.D. Maastricht, The Netherlands. Journal of Musculoskeletal Pain 1995, vol. 3, no. 3, 45-6.

The frequency of transition of chronic low back pain to fibromyalgia.

In a retrospective study, the outcome of the chronic low back pain syndrome was investigated in a group of 53 patients. Average time since the diagnosis was established was 18 years. 25% of the patients--all female but one-- developed fibromyalgia. The criteria of Yunus and Wolfe, modified by Muller and Lautenschlager, were applied to establish the diagnosis of fibromyalgia.

In 60% of the patients chronic low back pain persisted at the time of final examination, while 8 patients were asymptomatic.

Predictive parameters for the chance of getting fibromyalgia were sex and postural disorders such as scoliosis. Other radiological findings, for example degenerative changes of the spine, did not coincide with the group of patients who developed fibromyalgia. The predictive value of pain localisation, number of tender points, presence and severity of functional and vegetative symptoms, and the psychosocial situation is uncertain and should be investigated in further long term prospective studies.

Lapossy E •Maleitzke R •Hrycaj P •Mennet W •Muller W Hochrheininstitut fur Rheumaforschung und Rheumapravention, Bad Sackingen, Germany. Scand J Rheumatol 1995;24(1):29-33

Health promotion and clinical dialogue.

Clinical medicine would gain from a discussion of the significance of health promotion. Some central concepts are discussed: the diagnostic process; disease prevention vs. health promotion; the practical importance of the understanding of the difference between the 2 concepts health and absence-of-disease. The concept of health catches the intra-personal level, the undisrupted self, whereas absence of disease concerns the proper functioning of the organism, the human biology.

By means of comparing 2 diagnoses, multiple sclerosis (MS) and fibromyalgia syndrome (FS), it is argued that there are diagnoses of at least 2 distinct kinds. The diagnosis of MS is similar to a scientific discovery, whereas the diagnosis of FS is constructed more like criminal law. Consequently, diagnosis-based disease prevention and health promotion have to comply with a wide range of reality. Finally, clinical dialogue is pointed out as a method that successfully combines diagnostic, preventive and promotive efforts, as well as clinical care and cure.

Hellstrom OW Department of Health and Society, Linkoping University, Sweden. Patient Educ Couns 1995;25(3):247-56 Special Journal List: Nursing Journal

High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders.

The fibromyalgia syndrome (FMS) is one of the most frequent rheumatic disorders showing a wide spectrum of different symptoms. An association with the chronic fatigue syndrome (CFS) has been discussed. Recently, a defined autoantibody pattern consisting of antibodies to serotonin (5-hydroxytryptamine, 5-HT), gangliosides and phospholipids was found in about 70% of the patients with FMS. We were therefore interested in seeing whether patients with CFS express similar humoral immunoreactivity. Sera from 42 CFS patients were analysed by ELISA for these antibodies, and the results were compared with those previously observed in 100 FMS patients. 73% of the FMS and 62% of the CFS patients had antibodies to serotonin, and 71% or 43% to gangliosides, respectively. Antibodies to phospholipids could be detected in 54% of the FMS and 38% of the CFS patients. 49% of FMS and 17% of the CFS patients had all three antibodies in parallel, 70% and 55%, respectively had at least two of these antibody types. 21% of FMS and 29% of CFS patients were completely negative for these antibodies. Antibodies to 5- HT were closely related with FMS/CFS while antibodies to gangliosides and phospholipids could also be detected in other disorders. The observation that family members of CFS and FMS patients also had these antibodies represents an argument in favour of a genetic predisposition. These data support the concept that FMS and CFS may belong to the same clinical entity and may manifest themselves as 'psycho-neuro-endocrinological autoimmune diseases'.

Klein R, Berg PA Department of Internal Medicine, University of Tubingen, Germany. Eur J Med Res 1995 Oct 16;1(1):21-26

HLA typing in women with breast implants.

Since the 1970s, anecdotal reports have described a relatively small number of women who received silicone gel breast implants and later developed either a recognized rheumatologic disease or unexplained symptoms suggestive of an autoimmune disorder. The study reported

here examined whether there is any association between the symptoms seen in implant patients and HLA molecules. One-hundred and ninety-nine subjects were evaluated by HLA typing: symptomatic patients with implants (group I, n = 77), asymptomatic women with implants (group II, n = 37), healthy female volunteers without implants (group III, n = 54), and fibromyalgia patients without implants (group IV, n = 31). A statistically significant 68 percent of group I were positive for HLA-DR53, compared with 35 percent of group II and 52 percent of group III. The fibromyalgia patients were strikingly similar to group I women in terms of HLA- DR molecules, with 65 percent of group IV being positive for DR53. Group I also had a statistically significant increased frequency of HLA-DQ2. Asymptomatic women with implants (group II) had an increased frequency of DR1 and DQ1. In addition, 42 percent of symptomatic patients with implants formed autoantibodies to their own B cells; of these, 81 percent were DR53-positive. Although frequencies of capsular contracture and implant rupture were not significantly different in the two groups with implants, there were statistically significant associations in group I between contractures and ruptures and the presence of DR53 and B- cell autoantibodies. These data suggest that symptomatic patients with implants share important genetic characteristics (primarily HLA-DR53 positivity) that differentiate them from their asymptomatic counterparts. DR53 may be a marker of women who are predisposed by their HLA genotype to develop symptoms following exposure to silicone gel breast implants.

Young VL, Nemecek JR, Schwartz BD, Phelan DL, Schorr MW Department of Medicine, Washington University School of Medicine, St. Louis, Mo, USA. Plast Reconstr Surg 1995 Dec;96(7):1497-1519

Identification of patient subsets among those presumptively diagnosed with, referred, and/or followed up for systemic lupus erythematosus at a large tertiary care center.

Calvo-Alen J, Bastian HM, Straaton KV, Burgard SL, Mikhail IS, Alarcon GS The University of Alabama at Birmingham 35294, USA. Arthritis Rheum 1995 Oct;38(10):1475-1484

OBJECTIVE. To identify different subsets of patients from a large tertiary care center who were presumptively referred for and/or diagnosed with systemic lupus erythematosus (SLE) (or followed up).

METHODS. All patients who were referred, followed up, and/or diagnosed with SLE at our center, who had disease duration of < or = 5 years, and who resided in Alabama, were identified and their charts reviewed and abstracted.

RESULTS. Abstracted data were reviewed by 3 rheumatologists, and patients were assigned to 1 of 3 categories: 1) SLE by the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) criteria, 2) clinical SLE but not meeting 4 of the ACR criteria, or 3) fibromyalgia-like manifestations with antinuclear antibody (ANA) positivity. There were 90 patients in the first group (criteria), 22 in the second group (clinical), and 37 in the third group (fibromyalgia-like). Patients in all 3 groups were predominantly women. Only 5% of the

fibromyalgia-like group were African-American, compared with 55-65% for the other 2 groups. Organ system involvement occurred with comparable frequency in the first 2 groups, but mucocutaneous and hematologic abnormalities were more frequent in the criteria group; in contrast, the patients with fibromyalgia-like symptoms primarily presented with arthralgias/myalgias, fatigue, depression, and sleep disturbances, as well as mucocutaneous manifestations.

CONCLUSION. When the ACR criteria for SLE are used to determine eligibility for lupus studies, a group of patients with clinically unequivocal SLE are excluded. A group of patients with fibromyalgia-like manifestations, who test positive for ANA and differ clinically and sociodemographically from the patients in the other 2 groups, very likely do not belong within the spectrum of SLE.

Increased pressure pain sensibility in fibromyalgia patients is located deep to the skin but not restricted to muscle tissue.

This study was aimed at comparing pressure pain sensibility in different tissues in fibromyalgia patients. Pressure pain thresholds (PPTs) were assessed in 16 fibromyalgia (FM) patients bilaterally at the bony part of epicondylus lateralis humeri, at the belly of m. extensor carpi ulnaris and at m. brachioradialis where the radial nerve branches pass underneath. Following a double-blind design, either a local anesthetic cream (EMLA) or a control cream was applied to the skin and PPTs were reassessed. The site with underlying nerve had a lower PPT than the bony site (P < 0.001) and the 'pure' muscle site (P < 0.001), respectively. These relations remained unaltered by skin hypoesthesia. The PPTs over the bony and the 'pure' muscle sites did not differ. Application of EMLA, compared to control cream, did not change PPTs over any area examined. The results demonstrated that pressure-induced pain sensibility in FM patients is not most pronounced in muscle tissue and does not depend on increased skin sensibility.

Kosek E, Ekholm J, Hansson P Department of Rehabilitation Medicine, Karolinska Hospital/Institute, Stockholm, Sweden. Pain 1995 Dec;63(3):335-339

Information processing in primary fibromyalgia, major depression and healthy controls.

OBJECTIVE. To assess the information processing capabilities in 25 patients with primary fibromyalgia (FM) by comparing them with 22 patients with major depression and 18 healthy controls.

METHODS. A broad range of tasks related to various subcomponents of information processing were included.

RESULTS. Our results indicated that patients with primary FM in general share with depressives a nonspecific deficit in information processing capacity. However, our data showed that cognitive dysfunction reflecting a presumed compromise of the right hemisphere is present in major depression, but not in primary FM.

CONCLUSION. This finding would suggest that primary FM and depression are probably different conditions.

Sletvold-H; Stiles-TC; Landro-NI. J-Rheumatol. 1995 Jan; 22(1): 137-42.

Interrelationships of Biochemical Parameters in Classification of Fibromyalgia Syndrome and Healthy Normal Controls

Objective. To determine if a combination of biochemical variables [e.g., plasma amino acids and catecholamines] would better classify patients with fibromyalgia syndrome [FMS] and pain-free normal controls than a single variable alone.

Methods. Plasma amino acids and catecholamines as well as urinary catecholamines were analyzed in 29 patients with FMS and 30 painfree normal controls who were clinically and psychologically evaluated. Discriminant analysis was used to select a number of biochemical variables which in combination would best classify the study subjects.

Results. A combination of 7 variables [plasma histidine, methionine, tryptophan, norepinephrine, isoleucine and leucine, and urinary dopamine] provided the optimum sensitivity of 86% and specificity of 77%, with an accuracy of 81%. Pain, fatigue, poor sleep and number of tender points, but not anxiety, depression or mental stress, significantly [P

Conclusion. A combination of biochemical variables better classifies patients with FMS and normal painfree controls than a single variable alone. The interrelationships of these variables may be important in the biophysiological mechanisms of FMS. Further studies are indicated.

Muhammad B. Yunus, MD, is Professor of Medicine, Section of Rheumatology, Jean C. Aldag, PhD, is Associate Professor of Preventive Medicine in Medicine, John W. Dailey, PhD, is Professor of Pharmacology, and Phillip C. Jobe, PhD, is Professor of Pharmacology and Chair, Department of Basic Sciences, all at the University of Illinois College of Medicine at Peoria, Peoria, IL. Address correspondence to: Dr. M. B. Yunus, Department of Medicine, UI-COM-P, Box 1649, Peoria, IL 61656. Journal of Musculoskeletal Pain, vol. 3, no. 4, 1995, 15-16.

Literature Review: Prevalence in Characteristics of Fibromyalgia in the General Population

by Robert M. Bennett M.D., FRCP

Summary

A random sample of 3,006 subjects in Wichita, Kansas were given a mailed or telephone questionnaire regarding

pain characteristics. Patients with current widespread pain that had been present for at least six months were asked to undergo a brief physical examination and a further interview. Subjects had a tender point and dolorimetry examination and completed the symptom checklist 90, revised SCLR-90-R, and the AIMS Scales for anxiety and depression. In all, 392 persons were examined. The overall prevalence of fibromyalgia was 2%, with 3.4% in women and 0.5% in men. Interestingly, the syndrome increased with age, approximately 7% of women between ages 60 and 79 had FM. Of particular interest was that the population prevalence of widespread pain increased progressively from ages 18-69 and then declined over the next two decades. In the 6069 decade, its prevalence was 23%. In contrast, local pain increased progressively from age 18 and did not show any dip in the latter decades. By age 80 nearly 30% of subjects reported local musculoskeletal pain.

Comments

It is no surprise to most rheumatologists that fibromyalgia is at least as common as rheumatoid arthritis. However, the observation made here that fibromyalgia is not primarily a disorder of young women, and is most common in the ages of 50 and above, breaks new ground. Another intriguing observation is the peaking of fibromyalgia prevalence in the seventh decade.

Likewise, widespread pain [not fulfilling fibromyalgia criteria] had a similar sex and chronological profile at a much higher prevalence at 23%. It is quite probable that some of these patients had fibromyalgia but are excluded by the current criteria.

It is hypothesized that there is a relationship between fibromyalgia and chronic pain, aging, and musculoskeletal deterioration, in terms of persistent nociceptive input leading to widespread hyperalgesia by the process of central sensitization. This paper indicates that the ACR criteria for fibromyalgia can be applied in epidemiological studies. I suspect that in the future these criteria will be shown to lack adequate sensitivity in this setting.

Robert M. Bennett, M.D., FRCP, is Professor of Medicine, Chairman, Division of Arthritis and Rheumatic Diseases, Department of Medicine [L 329 A], Oregon Health Sciences University, Portland, OR 97201. Journal of Musculoskeletal Pain, vol. 3, no. 3,p. 089-90

Living with continuous muscular pain--patient perspectives. Part I: Encounters and consequences.

The purpose of the present study was to focus on the patient perspectives of living with chronic muscular pain, and to identify factors that can explain and give further understanding of how the condition influences everyday life. Forty women with fibromyalgia, living in two different cultural, health care and social security settings, Sweden and the USA, were interviewed, using a semi-structured format. Three preliminary typologies are suggested for further studies: Encounters, Consequences, and Strategies.

The study is presented in two articles: Part I: Encounters and consequences, Part II: Strategies for daily life. This first article shows that the contradiction between the patients' perception of illness and the lack of objective findings is stressful. The women feel rejected, misunderstood, and disbelieved, which prevents them from dealing with their situation constructively. Long investigation periods provoke anxiety, and confirmation of the diagnosis is a relief.

Daily routines are disrupted, conflicts between life roles lead to additional stress and the women experience loss of ability to perform valued activities, lack of physical fitness and loss of future opportunities. Patients need early and adequate information and the consequences of the condition must be acknowledged and taken into consideration if secondary economic and psychosocial consequences are to be minimized.

Henriksson CM Scand J Caring Sci 1995;9(2):67-76 Journal List: Nursing Journal

Living with continuous muscular pain--patient perspectives. Part II: Strategies for daily life.

This second article of the study Living with Continuous Muscular Pain is Part II: Strategies for Daily Life. The primary purpose was to explore, analyse and describe how women with fibromyalgia, living in two different cultural, health care and social security settings, managed their everyday life in spite of the limitations imposed by the condition.

Data were collected through qualitative semi-structured interviews with 40 women, 20 living in the USA and 20 in Sweden. The different strategies used by the women were identified and a preliminary typology of strategies is proposed as a base for further and more specific studies. The results support earlier findings, though the qualitative approach adds knowledge regarding the women's own perception, interpretation and experiences of how to deal with the problems that arose.

The findings in the two national groups were very similar, but differences in the medicolegal compensation systems influenced the women's opportunities to reduce working hours. Changes of habits, roles and lifestyle, as well as ergonomic considerations were required.

These changes take time and require continued support from the environment and the health care

providers. Further insight into the consequences of the condition is necessary for the planning of successful treatment and support programs.

Henriksson CM Scand J Caring Sci 1995;9(2):77-86 Special Journal List: Nursing Journal

Localized fibromyalgia in a child.

A 14-year-old male was investigated because of a limp and a localized sharp pain in the right lumber paravertebral region radiating to the lower abdomen and the medial aspect of the thigh, which started following forced physical activity. With the diagnosis of fibromyalgia the patient received two perifacetal injections of local anaesthetics with steroids followed by transcutaneous electrical nerve stimulation (TENS). Following the injections, pain intensity dropped dramatically, disability was reduced and muscle swelling resolved. The possible association of symptoms to sport activity raises the question of sport-induced fibromyalgia, and the excellent response to treatment may suggest a facet joint irritation as possible aetiology.

Bassan H, Niv D, Jourgenson U, Wientroub S, Spirer Z Department of Pediatrics, Dana Children's Hospital, Tel-Aviv, Israel. Paediatr Anaesth 1995;5(4):263-265

Metaphorical pain language among fibromyalgia patients.

Fourteen women with fibromyalgia described their pain experiences using words indicating a model of pain that presented pain as an aggressive physical deformation and a torture-like experience. Metaphorical expressions were used which was seen as a means for enabling the patients to disclose tacit knowledge. The pain experience was narrated as being steady and without any distinct bodily location. Only causes explaining the present aggravation of the pain and treatment leading to a temporary relief were related.

Soderberg S Norberg A Scand J Caring Sci 1995;9(1):55-9 Special Journal List: Nursing Journal

Methodological issues of patient utility measurement. Experience from two clinical trials.

This article explores various methodological issues of patient utility measurement in two randomized controlled clinical trials involving 85 patients with fibromyalgia and 144 with ankylosing spondylitis. In both trials one baseline and two follow-up measurements of the patients' preferences for their own health state and several hypothetical states were performed using the rating scale and the standard gamble methods. It was confirmed that standard gamble scores are consistently higher than rating scale scores for both the experienced and the hypothetical states. The 3-month test-retest reliability for hypothetical states measured by intraclass correlation coefficients ranged from 0.24 to 0.33 for the rating scale and from 0.43 to

0.70 for the standard gamble. Although the reproducibility is not high, the group mean scores are fairly stable over time. Mean standard gamble scores tend to differ depending on the way the measurements are undertaken. Utilities elicited with chained gambles were significantly higher than utilities elicited with basic reference gambles. At the individual level some inconsistent responses occurred. However, more than 70% of these fell within the bounds of the measurement error, which ranged from 0.11 to 0.13 on the standard gamble (0-1 scale) and from 8 to 10 on the rating scale (0-100 scale). The large number of negative utilities for the severe hypothetical state, which was used as an anchor point in the chained gambles, and the magnitude of these negative utilities (down to -19) calls for intensified research efforts to handle these responses in utility calculations.

Rutten-van Molken MP, Bakker CH, van Doorslaer EK, van der Linden S Department of Health Economics, University of Limburg, Maastricht, The Netherlands. Med Care 1995 Sep;33(9):922-937

**A model to assess severity and impact of fibromyalgia.

OBJECTIVE: To establish a model for the detection of specific factors associated with the severity of symptoms and the impact of fibromyalgia (FM).

METHODS: We evaluated 332 consecutive new patients with FM for factors that may be associated with disease severity, assessed by patient global assessment, and function, evaluated by the Fibromyalgia Impact Questionnaire (FIQ). Fifteen potential explanatory factors were evaluated in a multiple linear regression model on data taken from an extensive group of standardized instruments.

RESULTS: Of the 15 factors, pain levels, self-assessed inability to work, psychological distress, pending litigation, helplessness, level of education, and coping ability had a significant association with patients' global assessment and with scores on the total FIQ as well as on the activities of daily living subcomponent of the FIQ.

CONCLUSION: Disease related factors such as pain and psychological factors such as work status, helplessness, education, and coping ability had an independent and significant relationship to FM symptom severity and function.

Goldenberg DL, Mossey CJ, Schmid CH Department of Medicine, Newton-Wellesley Hospital, Boston, MA, USA. J Rheumatol 1995 Dec;22(12):2313-2318

Muscle strength, voluntary activation and cross-sectional muscle area in patients with fibromyalgia.

The objectives were to determine whether the low muscle strength in fibromyalgia is due to lack of exertion and to determine the relation between strength and muscle area. Secondarily we examined the voluntary muscle strength of the different muscles of the leg. The twitch interpolation technique was used to estimate the degree of central activation and the 'true' quadriceps muscle strength. Muscle cross-sectional area was determined with magnetic resonance imaging (MRI). The estimated 'true' muscle strength was 91 Nm (S.D. = 34 Nm) in 15 fibromyalgia patients compared with 125 Nm (28 Nm) in 14 healthy controls (P fibromyalgia patients compared with 2.11 Nm/ cm2 (0.39 Nm/cm2) in the controls (P fibromyalgia patients.

Nrregaard J •Bulow PM •Vestergaard-Poulsen P •Thomsen C •Danneskiold-Same B Department of Rheumatology, Frederiksberg Hospital, Copenhagen, Denmark. Br J Rheumatol 1995;34(10):925-31

Nocturnal motor activity in fibromyalgia patients with poor sleep quality.

Nocturnal motor activity was examined in long-term rehabilitation patients complaining of poor sleep and having fibromyalgia syndrome (N = 24) or other musculoskeletal disorders (N = 60) and compared with that in 91 healthy controls drawn from a random community sample.

Self-reports on sleep complaints and habits were collected. The frequency of nocturnal body movements, the 'apnoea' index and ratio of 'quiet sleep' to total time in bed were measured using the Static Charge Sensitive Bed (SCSB) (BioMatt).

As a group, patients with fibromyalgia syndrome did not differ from patients with other musculoskeletal disorders or from healthy controls in their nocturnal motor activity. The 'apnoea' index was a little higher in the fibromyalgia group than in the healthy control group but did not differ from that of the group of other musculoskeletal patients.

Further multivariate analyses adjusted for age, BMI, medication and 'apnoea' index did not support the assumption that an increased nocturnal motor activity characterizes patients with fibromyalgia syndrome.

J Psychosom Res, Yr. 1995 Jan, Vol. 39, P. 85-91

[Non-steroidal antirheumatic ointments in the treatment of primary periarticular and intramuscular fibrositis].

The author presents his experience assembled in a short-term (two-week) therapeutic trial with Mobilisin ointment, which contains flufenamic acid, in 50 patients with primary localized

periarticular and muscular fibrositis. The preparation was used locally three times per day-2-3 cm of ointment pressed from a tube. The patients were given a form in which they recorded every night the effect classified in four grades from the best to zero effect. In 49 the tolerance of the ointment was very good. In 45 patients a therapeutic effect was achieved (90%), comprising 21 (42%) where the effect was excellent, in 24 it was good or satisfactory (48%) and only in 5 patients no effect was recorded or the patents' statement was vague. In the first group of 21 patients 16 were able to abandon analgetic and anti-inflammatory treatment with non-steroid antirheumatics. Patients with the muscular form of fibrositis practically agreed in favour of the ointment. Gels according to these patients tissues. The authors remind that according to their experience gels, incl. Mobilisin, are suited for periarticular forms of fibrositis. It is also useful to rub the ointment in micro-massage to achieve a greater initial hyperaemia and better resorption. Mobilisin ointment may prove useful also in other disciplines, in particular orthopaedics, surgery, traumatology, neurology, rehabilitation and sports medicine.

Vachtenheim J Revmatologicka ordinace polikliniky Jihlava. Vnitr Lek 1995 Sep;41(9):609-612 [Article in Czech]

P450 Metabolism in Fibromyalgia

Objectives: To determine if the perceived high incidence of hypersensitivity to various substances in fibromyalgia, including medications, is due to abnormal P450 xenobiotic Metabolism.

Methods: The metabolism via two genetically polymorphic P450 pathways was determined for 33 fibromyalgia patients, and matched controls.

Results: There was no statistical difference between the genotypic frequency of the CYP2D6 gene or phenotypic expression of CYP2C19 between patients and controls.

Conclusion: Xenobiotic metabolism by the two pathways studied is normal in fibromyalgia. Although other P450 pathways could conceivably be abnormal in fibromyalgia, we speculate that such hypersensitivity to multiple substances in these conditions is unlikely to be due to abnormal metabolism, and postulate instead that these symptoms are mediated by neural mechanisms.

Daniel J. Clauw, MD, is Assistant Professor of Medicine, Division of Rheumatology, Immunology, and Allergy, Jan Hewett, RN, Division of Clinical Pharmacology, Carolyn A. Blank, BS, Division of Rheumatology, Immunology, and Allergy, Paul Katz, MD, is Professor and Vice-Chairman of Medicine, Division of Rheumatology, Immunology, and Allergy, and David A. Flockhart, MD, PhD, Division of Clinical Pharmacology, all at the Georgetown University Medical Center, Washington, DC. Address correspondences to: Daniel J. Clauw, MD, Georgetown University Medical Center, 3800 Reservoir Road NW, Washington, DC 20007.

Journal of Musculoskeletal Pain, vol. 3, no. 4, 1995, 25-26.

Pain and fatigue induced by exercise in fibromyalgia patients and sedentary healthy subjects.

OBJECTIVE. To examine whether general feelings of fatigue, exercise-induced pain in the extremities, and exertion were different in female patients with fibromyalgia syndrome (FS) compared with sedentary healthy women.

METHODS. Thirty-seven FS patients and 20 healthy subjects were studied. Cardiovascular fitness was assessed by Aastrand's indirect, submaximal method. The period of repetitive dynamic muscle contractions and sustained static muscle contraction were measured. General feelings of fatigue before exercise and exercise-induced extremity pain were assessed by visual analogue scales. Exercise-induced exertion was recorded by Borg's Rating Scale of Perceived Exertion.

RESULTS. No significant group difference in cardiovascular fitness was found (p = 0.8). In the FS patients general fatigue was

(median 95% confidence interval) 69 (59 - 75) versus 32 (22 - 47) for the healthy controls (p < 0.0001). At the moment of interrupting the bicycle test, the perceived exertion score was 17 (16 - 18) among patients versus 13 (13 - 15) among controls (p < 0.0001). Compared with the controls, high exercise-induced extremity pain was found after sustained static and repetitive dynamic muscle contractions in the FS patients (p < 0.004), and 24 hours later the patients' pain intensities had not returned to pre-exercise values (p < 0.01).

CONCLUSION. High general fatigue, exercise-induced extremity pain, exertion and 24 hours post-exercise extremity pain in FS patients compared with healthy controls could not be explained by any group difference in cardiovascular fitness.

Mengshoel AM; V*llestad NK; F*rre O Oslo Sanitetsforening Rheumatism Hospital, Norway. Clin Exp Rheumatol Vol. 13 no. 4 pp. 477-82 1995

Pain coping mechanisms in fibromyalgia: relationship to pain and functional outcomes.

OBJECTIVE. To evaluate the factor structure of the Coping Strategies Questionnaire (CSQ) in patients with fibromyalgia (FM) and to compare the factors derived from this measure, along with the active and passive pain coping scales of the Pain Management Inventory (PMI) in predicting pain, depression, quality of well being (QWB), and pain behavior concurrently and over time.

METHODS. One hundred twenty-two patients with FM were recruited from medical clinics, the community, and support groups. Eligible patients completed a battery of self-report measures of pain and psychosocial functioning at baseline assessment before random assignment to a clinical trial. A subset of 69 patients who completed the clinical trial were readministered the same battery 3 mo later. Data were analyzed within the baseline period, and from the baseline period to posttreatment to evaluate the predictive effects of coping strategies on clinical outcomes.

RESULTS. Principal components analysis of the CSQ revealed Coping Attempts (CA) and Pain Control and Rational Thinking (PCRT) factors, which have been found in other patient populations with chronic pain. Hierarchical multiple regression analyses revealed that high active coping and low PCRT contributed to higher concurrent pain, while low active coping and high passive coping were related to greater concurrent depression and pain behavior, respectively. Controlling for baseline scores on criterion measures, longitudinal multiple regression analyses demonstrated that high active coping and low PCRT scores contributed to greater pain, greater depression, and lower QWB at posttreatment, while low PCRT alone predicted greater pain behavior.

CONCLUSION. The results show the import of the pain coping construct in FM and highlight the negative contribution of low perceived control over pain and high active coping to a range of pain outcomes. The findings on low perceived control converge with data on other chronic pain populations, while the role of active coping appears to be detrimental in FM, in contrast to its positive effects in patients with rheumatoid arthritis.

Nicassio PM, Schoenfeld-Smith K, Radojevic V, Schuman C California School of Professional Psychology, San Diego 92121, USA. J Rheumatol 1995 Aug;22(8):1552-1558

The pathogenesis of chronic pain and fatigue syndromes, with special reference to fibromyalgia

Syndromes characterized by chronic pain and fatigue have been described in the medical literature for centuries. Fibromyalgia is the term currently used to describe this symptom complex, and considerable research has been performed in the last decade to delineate the epidemiology, pathophysiology, and genesis of this entity.

Although fibromyalgia is defined by its musculoskeletal features, it is clear that there are a large number of non- musculoskeletal symptoms, such that we now understand that there is considerable overlap with allied conditions such as the chronic fatigue syndrome, migraine and tension headaches, irritable bowel syndrome, and affective disorders.

This article will review our current state of knowledge regarding fibromyalgia and these allied conditions, and present a unifying hypothesis that describes both the pathophysiology of symptoms and the genesis of these disorders.

Clauw DJ Georgetown University Medical Center, Washington, DC 20007, USA. Med Hypotheses 1995 May;44(5):369-78 Number of References: 83

[Patient education--a contribution to improvement of long-term management of patients with rheumatism].

Patient education has been recognized as an important tool in the therapy and the rehabilitation of patients with chronic rheumatic diseases. An increasing body of literature refers to favorable effects of patient education. Patient education improves coping with disease, reduces pain and depression and decreases arthritic "helplessness". Therefore, patient education should be a part of the comprehensive care for the rheumatic patient. The patient education group (Arbeitskreis Patientenschulung) of the German Society of Rheumatology (Deutsche Gesellschaft fur Rheumatologie) has been initiated to develop a general concept of patient education in rheumatology and to elaborate various patient education programs. The patient education program for rheumatoid arthritis is described as a model for further patient education programs. It consists of six group sessions (modules). The program is conducted by an interdisciplinary team. A group leader is in charge of the program. Train-the-trainer courses should improve the quality of the program. Currently, the patient education group develops education programs for patients with systemic lupus erythematodes and related collagen diseases, spondyarthritis patients, patients with fibromyalgia and rheumatic children and their parents.

Langer HE Rheinisches Rheumazentrum St. Elisabeth-Hospital, Meerbusch. Z Rheumatol 1995 Jul;54(4):207-212 [Article in German]

Patient utilities in fibromyalgia and the association with other outcome measures.

OBJECTIVE. To compare in patients with fibromyalgia (FM) utilities derived by rating scale and standard gamble methods; to gain insight into construct validity by relating utility values to other outcome measures; to assess the sensitivity to change of utilities.

METHODS. A total of 73 patients with FM were randomized into one of 3 groups: low impact fitness training, biofeedback, or controls. At baseline and after 6 mo the Maastricht Utility Measurement Questionnaire was applied. By means of both the rating scale and standard gamble method patients were asked to value their own health status. Construct validity of patient utility measurements was evaluated by Spearman correlation and multiple regression of baseline values with pain, stiffness, patient's global assessment, Sickness Impact Profile (SIP), modified Health Assessment Questionnaire and Arthritis Impact Measurement Scale (AIMS). Sensitivity to change was assessed against changes in these outcomes.

RESULTS. Rating scale utilities correlated significantly (p < 0.05) with patient's global assessment (rs = 0.53), pain (rs = -0.47), SIP (rs = -0.43), and with 9 of 11 dimensions of the AIMS (rs ranging from 0.23 to 0.62). Standard gamble utilities correlated significantly with mobility, pain, and arthritis impact of the AIMS scale (rs from 0.22 to 0.36) and with pain by visual analog scale (rs = -0.24) and patient's global assessment (rs = 0.32). Multiple regression analysis showed that patient's global assessment explained 41% (rating scale) and 10% (standard gamble) of total variance in baseline utilities. Also, 16% of the variance in change in rating scale utility values was explained by changes in patient's global assessment. In contrast, variance of changes in standard gamble utility values was not explained significantly by changes in other disease outcomes. 0.05) with patient's global assessment (rs = 0.53), pain (rs = -0.47), SIP (rs = -0.43), and with 9 of 11 dimensions of the AIMS (rs ranging from 0.23 to 0.62). Standard gamble utilities correlated significantly with mobility, pain, and arthritis impact of the AIMS scale (rs from 0.22 to 0.36) and with pain by visual analog scale (rs = -0.24) and patient's global assessment (rs = 0.32). Multiple regression analysis showed that patient's global assessment explained 41% (rating scale) and 10% (standard gamble) of total variance in baseline utilities. Also, 16% of the variance in change in rating scale utility values was explained by changes in patient's global assessment. In contrast, variance of changes in standard gamble utility values was not explained significantly by changes in other disease outcomes.

CONCLUSION. Rating scale utilities correlated more strongly with disease outcome measures than standard gamble utilities. Also, construct validity for the rating scale was better than for the standard gamble. In FM, utility measurement is sensitive to the method chosen to elicit patient priorities.

Bakker C Rutten M van Santen-Hoeufft M Bolwijn P van Doorslaer E Bennett K van der Linden S Department of Internal Medicine, University of Limburg, Maastricht, The Netherlands. J Rheumatol 1995;22(8):1536-43

Phenobarbital-induced fibromyalgia as the cause of bilateral shoulder pain.

A female swimming instructor was seen with chronic bilateral shoulder pain and loss of range of motion. Intensive physical therapy significantly improved the range of motion but did not alleviate the pain. Osteopathic manipulative treatment produced no further improvement in pain or function. Results of laboratory tests were all within normal limits. Four months after the initial consultation, the patient, who was taking medication for tonic/clonic seizures, recalled that her symptoms began after her anticonvulsant medication was switched from hydantoin sodium to phenobarbital. Therefore, phenobarbital-induced fibromyalgia was diagnosed. In 4 months, pain had completely disappeared. The authors discuss several theories regarding the cause of fibromyalgia and the mechanism of action of phenobarbital, including its relationship to sleep disturbance, a probable contributor to pain and dysfunction in the patient described.

Goldman SI, Krings MS

Total Rehabilitation and Athletic Conditioning Center, Botsford General Hospital, Farmington Hills, Mich, USA. J Am Osteopath Assoc 1995 Aug;95(8):487-490

Postcardiac injury rheumatism.

The incidence, clinical comparison, laboratory features, therapeutic choices with outcomes of early and late postcardiac injury rheumatism (PIR) were studied prospectively. Out of the 249 patients who survived cardiac surgery, 20 (8%) and 22 (9%) patients had early and late PIR respectively. Earlier onset (within two weeks of surgery), milder articular involvement, absence of constitutional features and laboratory abnormalities and good response to analgesics were characteristics of early PIR. In contrast, late PIR which occurred between the third and fourteenth week after surgery was associated with more marked articular involvement along with systemic and laboratory abnormalities and required longer analgesic therapy, steroid support or prolonged physiotherapy in different combinations. We conclude that two distinct rheumatic syndromes with different clinical dimensions and therapeutic options can occur after cardiac surgery.

Mukhopadhyay P, Chakraborty S, Mukherjee S Dept. of Thoracic and Cardiovascular Surgery, Medicine College, Calcutta. J Assoc Physicians India 1995 Jun;43(6):388-390

The prevalence and characteristics of fibromyalgia in the general population.

OBJECTIVE. To determine the prevalence and characteristics of fibromyalgia in the general population.

METHODS. A random sample of 3,006 persons in Wichita, KS, were characterized according to the presence of no pain, non-widespread pain, and widespread pain. A subsample of 391 persons, including 193 with widespread pain, were examined and interviewed in detail.

RESULTS. The prevalence of fibromyalgia was 2.0% (95% confidence interval [95% CI] 1.4, 2.7) for both sexes, 3.4% (95% CI 2.3, 4.6) for women, and 0.5% (95% CI 0.0, 1.0) for men. The prevalence of the syndrome increased with age, with highest values attained between 60 and 79 years (> 7.0% in women). Demographic, psychological, dolorimetry, and symptom factors were associated with fibromyalgia.

CONCLUSION. Fibromyalgia is common in the population, and occurs often in older persons. Characteristic features of fibromyalgia--pain threshold and symptoms--are similar in community and clinic populations, but overall severity, pain, and functional disability are more severe in the clinic population.

Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L University of Kansas School of Medicine-Wichita. Arthritis Rheum 1995;38(1):19-28

Prevalence and treatment outcome of primary and secondary fibromyalgia in patients with spinal pain.

STUDY DESIGN. This was a prospective cohort study.

OBJECTIVES. To determine the prevalence of primary and secondary fibromylagia and response to therapy in patients with spinal pain over a 12-month period.

SUMMARY OF BACKGROUND DATA. Fibromyalgia is a syndrome characterized by generalized pain and widespread tenderness on palpation in specific areas of the musculoskeletal system, including the cervical and lumbosacral spine. Primary fibromyalgia is idiopathic, whereas secondary fibromyalgia occurs in association with underlying disorders such as ankylosing spondylitis, trauma, or surgery. The frequency of fibromyalgia in patients with spinal pain has not been determined.

METHODS. One-hundred-twenty-five consecutive patients referred to a rheumatologist in a spine center for evaluation of back pain over a 4-month period were evaluated for fibromyalgia. Diagnosis at the time of referral and referring physician were recorded. Fifteen patients, six with primary fibromyalgia and nine with secondary fibromyalgia, were identified and followed for 12 months. Standardized therapy was offered to all patients with fibromyalgia. Patients with secondary fibromyalgia also received therapy for their underlying condition.

RESULTS. At 12 months, the six patients with primary fibromyalgia had an improvement in symptoms. The treatment outcome for the nine patients with secondary fibromyalgia was less successful.

CONCLUSIONS. Fibromyalgia is a disorder that occurs in a small proportion of patients with back pain. Fibromyalgia is not frequently recognized by referring physicians. In the authors' limited experience, patients with primary fibromyalgia appear to improve with conservative care. They have been less successful with those diagnosed as having secondary fibromyalgia.

Borenstein D Division of Rheumatology, George Washington University Medical Center, Washington, D.C., USA. Spine 1995;20(7):796-800

Problem elicitation to assess patient priorities in ankylosing spondylitis and fibromyalgia.

OBJECTIVE. To elicit patient priorities as outcome measures in ankylosing spondylitis (AS) and fibromyalgia (FM); to relate these measures to other outcomes; to assess construct validity and sensitivity to change of the problem elicitation technique (PET) questionnaire.

METHODS. One hundred thirty-four patients with AS were randomly allocated to weekly sessions of group physical therapy or daily exercises at home, whereas 73 patients with FM were randomized into one of 3 groups (low impact fitness, biofeedback, controls). The PET questionnaire was applied by trained interviewers at baseline and at 6 (FM) and 9 (AS) month followup. A PET score was calculated at each assessment. Construct validity of the PET was assessed by correlation and multiple regression of baseline values with other disease outcomes (pain, stiffness, patient's global assessment, Sickness Impact Profile (SIP), Health Assessment Questionnaire (HAQ), Arthritis Impact Measurement Scale (AIMS), patient utilities). Sensitivity to change of PET was assessed against changes in these outcomes and by comparing the efficiency of the PET with other outcomes.

RESULTS. Patients with FM identified more problems (mean 6.8) than patients with AS (mean 4.4). Moreover, more patients with AS than with FM were unable to identify any problem at baseline (10% compared to 1%). The PET score improved from 14.9 to 11.3 (p = 0.0001) in patients with AS but did not change from 21.8 to 21.1 (p = 0.24) in patients with FM. Construct validity testing of the PET score showed statistically significant (p < 0.05) correlations with AIMS, utilities, SIP, HAQ, pain, stiffness, and patient's global health in both groups of patients (r varying from 0.22 to 0.66). By multiple regression pain explained 29% of the variance in PET scores among patients with AS. In FM patient global assessment accounted for 39% of total variance of PET scores, whereas pain explained another 15%. Changes in PET scores correlated significantly (p < 0.05) with changes in AIMS, utilities, pain, stiffness, and patient global health in both AS and FM (r varying from 0.22 to 0.51). Some 6% of the variance in changes in PET scores was explained by changes in pain in patients with AS and 35% by changes in pain and subjective health in patients with FM. Assessment of sensitivity to change revealed that efficiency of the PET score was 0.6 in patients with AS and 0.09 in those with FM. Compared to other outcomes this was reasonable in patients with AS but low in those with FM.

CONCLUSION. Obtaining patient priorities was generally feasible. In both groups of patients construct validity of the PET questionnaire was satisfactory. The PET was much more sensitive to change in patients with AS than in patients with FM.

Bakker C, van der Linden S, van Santen-Hoeufft M, Bolwijn P, Hidding A Department of Internal Medicine, University of Limburg, Maastricht, The Netherlands. J Rheumatol 1995 Jul;22(7):1304-1310

Psychological aspects of Brazilian women with fibromyalgia

In order to determine the occurrence of psychological disturbances the authors studied 47 women who fulfilled the American College of Rheumatology Criteria for the classification of

fibromyalgia and 25 random selected control patients without chronic muscle pain, all of whom live in Sorocaba, SP, Brazil.

Personality disturbances were observable in 63.8% of the patients and 8.0% of the control group (p 0.05); depression in 80.0% of the fibromyalgia group and 12.0% of the controls (p 0.05) and anxiety in 63.8% of the patients and 16.0% of the controls (p 0.05).

The Hamilton test mean scores showed higher values for depression and anxiety among the fibromyalgia patients when compared to the control group. A significant association between fibromyalgia and depression, anxiety and personality disturbances was studied and recorded.

Martinez JE Ferraz MB Fontana AM Atra E Escola Paulista de Medicina, Pontificia Universidade Catolica de Sao Paulo, Brazil. J Psychosom Res 1995 Feb;39(2):167-174

The relationship between headaches and sleep disturbances.

The relationship between headaches and sleep disturbances is complex and difficult to analyze. Both symptoms may have causal relations, or may be associated in the same patient with mutual reinforcements. We studied 25 patients presenting with morning or nocturnal headaches. Standard headache diagnosis and polysomnography were performed. After polysomnography, the diagnoses were reevaluated. The main headache entities were cluster, chronic paroxysmal hemicrania, migraine, tension, combined headache, and chronic substance abuse headache. For each group, headache, sleep data, and changes in diagnosis are discussed. The diagnosis was changed in 13 patients; the final diagnoses were periodic movements of sleep, fibromyalgia syndrome, and obstructive sleep apnea. The diagnoses of cluster headache and chronic paroxysmal hemicrania were not modified by polysomnography. The migraine and tension headache groups had a relative male preponderance, and the diagnosis was changed in approximately half of the patients. This was also observed in combined headaches. Patients who had chronic substance abuse headaches had mainly insomnia, which in some cases, was relieved by stopping medication. Data were also analyzed in terms of simple models linking headache and sleep disturbances. Such an approach allowed the identification of several modes of mutual interaction. In summary, morning or nocturnal headaches are frequent indicators of a sleep disturbance and their presence might justify polysomnography, and the use of simple clinical models may be useful for understanding the complex relationship between headache and sleep.

Paiva T, Batista A, Martins P, Martins A EEG and Sleep Laboratory, Centro de Estudos Egas Moniz, Neurology, Hospital Santa Maria, Lisboa, Portugal. Headache 1995 Nov;35(10):590-596

Reliability and Reproducibility of Fibromyalgic Tenderness, Measurement by Electronic and Mechanical Dolorimeters

Objectives: To compare an electronic dolorimeter to a mechanical dolorimeter in the measurement of fibromyalgic tenderness, and to determine which factors contribute to variation in the measurement of tenderness.

Methods: Seventy-two adult female patients satisfying 1990 classification criteria for fibromyalgia were examined at 6 fibromyalgic tender points by 4 examiners using 2 electronic dolorimeters and 2 x 9 kg Chatillon mechanical dolorimeters. The order of examination and the assignment of instruments to examiners was randomized according to a Graeco-Latin square design. Analysis of variance and of components of variation was performed on the total dolorimetry score for each patient.

Results: Virtually identical mean dolorimetry scores were obtained with the 2 Chatillon dolorimeters. Scores with the 2 electronic dolorimeters differed significantly from each other and from the mechanical dolorimeter scores. Other significant sources of variation in tenderness were examination sequence and interobserver variation. Measurements with the mechanical dolorimeters demonstrated high reliability coefficients [80-85%]. Electronic dolorimeter data showed fair to good reliability [65-72%].

Conclusions: Measurements of fibromyalgic tenderness with the mechanical dolorimeter are highly reproducible; measurements with the electronic dolorimeter show lesser, but still good, reliability. Further studies with the electronic dolorimeter are feasible.

Michael Puttick, MD, FRCPC, is a Fellow, Division of Rheumatology, Michael Schulzer, PhD, is Professor, Department of Statistics and Medicine, Alice Klinkhoff, MD, FRCPC, is Clinical Assistant Professor, Division of Rheumatology, Barry Koehler, MD, FRCPC, is Clinical Associate Professor, Karen Rangno, RN, The Arthritis Centre, and Andrew Chalmers, MD, FRCPC, is Associate Professor, Division of Rheumatology, University of British Columbia and The Arthritis Society, BC and Yukon Division. Address correspondence to: Dr. Andrew Chalmers, 895 W. 10th Avenue, Vancouver, BC, V5Z 1L7, Canada. Journal of Musculoskeletal Pain, 1995; 3(4):3-4

Selection of measures suitable for evaluating change in fibromyalgia clinical trials.

OBJECTIVE: To use growth curve model methods to investigate which of 46 variables associated with fibromyalgia (FM) clinical trials are potentially useful in measuring change.

METHODS: For each of the 46 variables the reliability of change and corresponding standard error were estimated. Data were from a randomized clinical trial designed to compare the effectiveness of biofeedback/ relaxation, exercise, and a combined program for the treatment of FM. There was also a control group.

RESULTS: The reliabilities of change for the outcome variables Myalgic Score, Tenderpoint Count, and Tenderpoint Index, as well as the variable, number of words chosen from the McGill Pain Questionnaire were quite acceptable for both the 18 and 58 week time periods. There were 9 other variables that had reliabilities of change in the acceptable range.

CONCLUSION: Thirteen of 46 variables considered had desirable reliabilities of change by the methods used. The 3 variables often used as measures of disease activity as well as one pain variable were among the 13. Data from this study produced no acceptable reliabilities of change for the 33 other variables. For these variables, further evaluation is required.

Hewett JE, Buckelew SP, Johnson JC, Shaw SE, Huyser B, Fu YZ Department of Statistics, Physical Medicine and Rehabilitation, University of J Rheumatol 1995 Dec;22(12):2307-2312

Self-efficacy, pain, and physical activity among fibromyalgia subjects

PURPOSE. The purpose of this study was to examine the effects of self-efficacy on self-report pain and physical activities among subjects with fibromyalgia (FM). In addition, descriptive statistics of the Arthritis Impact Measurement Scale (AIMS), a measure developed for use with arthritis patients, were reported.

METHODS. Seventy-nine subjects with FM, as classified by the American College of Rheumatology (ACR) criteria, completed the Visual Analogue Scale for Pain, the AIMS, and the Arthritis Self-Efficacy Scale. A myalgic score was obtained during a tender point evaluation. Hierarchical multiple regression analyses were used to assess the effect of self-efficacy on self-report pain and physical activities measures after controlling for demographic variables (age, education, and symptom duration), disease severity (myalgic scores), and psychological distress (negative affect from the AIMS).

RESULTS. Higher self-efficacy was associated with less pain and less impairment on the physical activities measure after controlling for demographic and disease severity measures.

CONCLUSIONS. This study underscores the unique importance of self-efficacy in understanding pain and physical activities impairment.

Buckelew SPSEJEJB Arthritis Care Res 1995;8(1):43-50 Journal List: Nursing Journal

The semeiology of arthritis: discriminating between patients on the basis of their symptoms.

OBJECTIVES--To examine the intended meaning of words used by patients to describe arthritic symptoms, and to distinguish between different patient groups on the basis of these words.

METHODS--A Joint Symptom Questionnaire, developed to resemble the McGill Pain Questionnaire, was given to health professionals (n = 50) and patients with rheumatoid arthritis (RA) (n = 100), fibromyalgia (FM) (n = 50), ankylosing spondylitis (AS) (n = 50), and osteoarthritis (OA) (n = 50). Respondents were invited to define each word by selecting an appropriate heading. Comparison of patient groups was based on the selection of words they chose to describe their joint symptoms.

RESULTS--Between health professionals and patients there were no semantic differences in the words given. Patients with FM chose more words to describe their symptoms than the other patient groups (RA median nine words; AS nine words; OA 10 words; FM 12 words). Using receiver operating characteristic curves, a clear distinction between patients with RA, FM, and AS was found, but patients with RA were not readily separated from patients with OA.

CONCLUSIONS--There appears to be no semeiological confusion between health professionals and patients regarding arthritic symptoms. However, the spectrum of words chosen by patients to describe the feelings in their joints permits a separation between patients with RA, AS, and FM. Using this questionnaire, patients with RA and OA are symptomatically similar.

Helliwell PS Rheumatology and Rehabilitation Research Unit, Research School of Medicine, Leeds, United Kingdom. Ann Rheum Dis 1995 Nov;54(11):924-926

Silicone breast implant--associated musculoskeletal manifestations.

Three hundred consecutive women with silicone breast implants (SBI), referred to the arthritis clinic with a variety of musculoskeletal complaints, were evaluated for the presence of underlying connective tissue disease. A complete history and physical examination were performed, as well as laboratory testing for C-reactive protein, rheumatoid factor; and autoantibody determination by indirect immunofluorescence and immunodiffusion. The group mean age was 44.4 years (range 25-69), the mean time from initial implant surgery to appearance of symptoms was 6.8 years (range: 6m-19y) and 83.3% of women studied had clinical manifestations highly suggestive of an underlying connective tissue disorder. Fifty-four percent met criteria for fibromyalgia and/or chronic fatigue syndrome, distinct connective tissue diseases was detected in 11%, undifferentiated connective tissue disease or human adjuvant disease was found in 10.6%, and a variety of disorders such as angioneurotic oedema, frozen shoulder, multiple sclerosis-like syndrome were present. Several other miscellaneous conditions including recurrent unexplained low grade fever, hair loss, skin rash, sicca symptoms, Raynaud's phenomenon, carpal tunnel syndrome, memory loss, headaches, chest pain, and shortness of breath were also seen accompanying specific and non-specific conditions. Seventy percent of patients who underwent explanation of the implants reported improvement of their systemic symptomatology. A significant proportion of SBI patients referred for rheumatic evaluation have clinical manifestations highly suggestive of an underlying connective tissue disease. Furthermore, improvement of their symptomatology follows explanation of the implants in over half of the patients.

Cuellar ML, Gluck O, Molina JF, Gutierrez S, Garcia C, Espinoza R Department of Medicine, LSU Medical Center at New Orleans, USA. Clin Rheumatol 1995 Nov;14(6):667-672

The skinache syndrome.

Chronic pain of unknown aetiology, and characterized by cutaneous trigger points, has been coined the skinache syndrome. The treatment of the skinache syndrome was evaluated in 94 patients by two independent methods 2 years after treatment. After one subcutaneous injection of lidocaine 68% of the patients were cured. The pain recurred in 27 patients having suffered for an average of 2 years. Surgical removal of the cutaneous trigger points cured 77% of the latter patients. The odds ratio of success of surgical treatment versus all other treatments combined was 101.3. The skinache syndrome requires a precise clinical investigation. Even when the origin of the pain in tendons, muscle and adipose tissue is excluded, the skinache syndrome remains a common, debilitating disorder. In contrast to fibromyalgia, the skinache syndrome has a simple and effective cure.

Bassoe CF Promed Institute, Bergen, Norway. J R Soc Med 1995 Oct;88(10):565-569

[Sleep apnea and fibromyalgia: the absence of correlation does not indicate an exclusive central hypothesis]

Fibromyalgia (FM) is a chronic painful syndrome characterized by widespread aching and points of tenderness, changed perception of pain and reduced brain serotonin. Abnormal EEG patterns have been reported in this condition.

A study of FM occurrence in subjects with sleep abnormalities demonstrated by polysom- nography was performed. Fifty patients (group 1:29 with sleep apnea and group 2:21 with poor sleep without sleep apnea) and 31 control subjects (without any sleep abnormal- ties) were submitted to the same clinical research of FM (ACR criteria). There was one 1 FM in group 1 (3.4%), one FM in group 2 (4.7%), and one FM in control group (3.2%).

Sleep abnormalities and particularly sleep apnea are not significantly associated with FM. Other pathophysiological factors than central mechanisms are probably involved in the pathogenesis of FM.

Plantamura A, Steinbauer J, Eisinger J Service de rhumatologie, hopital Georges-Clemenceau, centre hospitalier Toulon-La Seyne, La Garde, France. Rev Med Interne 1995;16(9):662-5 Language of Article: Fre

[Sleep disorders in chronic pain and generalized tendomyopathy].

Patients with a chronic pain syndrome often suffer from sleep disturbance. As both symptoms are frequent in the fibromyalgia syndrome, these patients in particular have been examined in this regard. No clear polysomnographic evaluation of the subjectively experienced sleep disturbance in these patients has been done so far. Therefore, we recorded the sleep EEG of 13 patients with a fibromyalgia syndrome in order to objectively characterize their sleep. Furthermore, we were interested in the relationship between the sleep alterations and pain intensity. In a subsequent placebo-controlled study based on pathophysiological considerations, we attempted to beneficially influence the sleep disturbance and the pain syndrome with the 5- HT2-receptor antagonist ketanserine, as this system has been proved to play a major role in the regulation of both sleep and pain. The results of our studies in patients with fibromyalgia show that the alteration of sleep is mainly characterized by a disturbance of sleep continuity associated with the experience of pain intensity. The application of 5-HT-receptor-antagonists may be a new strategy for the common treatment of sleep disturbance and the pain syndrome which needs to be evaluated in further studies. Duration of the patients' illness seems to be a predictive value in relation to intensity of the symptoms and the therapeutic outcome.

Hemmeter U, Kocher R, Ladewig D, Hatzinger M, Seifritz E, Lauer CJ, Holsboer-Trachsler E Psychiatrische Universitatsklinik Basel. Schweiz Med Wochenschr 1995 Dec 9;125(49):2391-2397 [Article in German]

Sleep electroencephalography and the clinical response to amitriptyline in patients with fibromyalgia.

OBJECTIVE. To determine the prevalence and clinical correlations of an anomaly consisting of electroencephalographic (EEG) waves within the alpha frequency band during non-rapid eye movement (NREM) sleep in patients with fibromyalgia, and to evaluate the alpha NREM sleep anomaly as a predictor of response to amitriptyline.

METHODS. Twenty-two patients with fibromyalgia were studied in a 2-month, double-blind, crossover trial of amitriptyline (25 mg/day) versus placebo. Nocturnal EEGs were conducted on 2 consecutive nights at baseline and at the end of each 2-month treatment period.

RESULTS. Six patients (27%) had a clinical response to amitriptyline, while none responded to placebo (P = 0.02). Treatment with amitriptyline or placebo did not result in any changes in the alpha ratings during NREM sleep. Only 8 patients (36%) exhibited the alpha NREM sleep anomaly at baseline. Those patients reported more sleep difficulty, but otherwise were clinically indistinguishable from those without this EEG sleep anomaly. Lower baseline alpha NREM sleep ratings were seen in responders to amitriptyline than in nonresponders, but these differences did not reach statistical significance.

CONCLUSION. The alpha NREM sleep anomaly is present in only a small proportion of patients with fibromyalgia. It does not correlate with disease severity nor is it affected by treatment with amitriptyline. A larger sample size will be needed to adequately assess the value of this sleep anomaly in predicting the response to amitriptyline.

Carette S, Oakson G, Guimont C, Steriade M Laval University, Sainte-Foy, Quebec, Canada. Arthritis Rheum 1995 Sep;38(9):1211-1217

Sleep intensity in fibromyalgia: focus on the microstructure of the sleep process.

Alpha electroencephalography (EEG) predominance has been described during sleep in patients suffering from the fibromyalgia syndrome (FMS). However, EEG power density in the lower frequency bands probably better reflects the restorative functions of sleep. This study was conducted to describe the energy in all frequency bands in the sleep EEG. Ambulatory sleep recordings were performed on 12 women with FMS and 14 control women. Epochs were classified according to standard criteria. Moreover, all 2-s segments (n = 287,355) of the EEG in non-rapid-eye-movement (NREM) 2-4 sleep were subjected to frequency analysis using autoregressive modelling. Frequency bands were: delta (0.5-3.5 Hz), theta (3.5-8 Hz), alpha (8- 12 Hz), sigma (12-14.5 Hz) and beta (14.5-25 Hz). In patients with FMS, there was a predominance of EEG power in the higher frequency bands [two-way analysis of variance (ANOVA), alpha: P = 0.043; sigma: P = 0.004] at the expense of the lower frequencies (ANOVA, delta: P = 0.005; theta: P = 0.008). The same trends were obtained for the individual sleep cycles. The calculations of total delta power in the time domain showed an exponentially declining curve in healthy subjects, but a flatter decline in FMS. The decreased power in the low-frequency range might reflect a disorder in homoeostatic and circadian mechanisms during sleep and may contribute to daytime symptoms in patients with fibromyalgia.

Drewes AM, Nielsen KD, Taagholt SJ, Bjerregard K, Svendsen L, Gade J Department of Rheumatology, Aalborg Hospital, Denmark. Br J Rheumatol 1995 Jul;34(7):629-635

Somatomedin-C and Procollagen Aminoterminal Peptide in Fibromyalgia

Objective: We wanted to examine serum Somatomedin-C [Sm-C] and procollagen aminoterminal peptide [PIIINP] in patients with fibromyalgia.

Methods: Serum Sm-C level in 15 fibromyalgia patients was compared to levels from 15 controls, matched with respect to age and physical activity. Serum Sm-C and PIIINP were examined in 43 other patients to allow comparisons with reference values and correlations with clinical symptoms.

Results: We found no difference in Sm-C levels among 15 patients compared to the control group. Similarly, the Sm-C values of 43 patients were not lower than the control group, indeed 41 of the values were inside the 955b reference interval. Sm-C was significantly correlated to age but not to any of the clinical symptom scores. PIIINP was 12% lower [P

Conclusions: Abnormalities of neuroendocrine parameters in fibromyalgia should be interpreted with care due to confounders like physical activity level.

Jesper Nørregaard, MD, Per Martin Bülow, MD, Helge Volkman, MD, Department of Rheumatology, Jesper Mehlsen, MD, Department of Clinical Physiology, and Bente Danneskiold Samsøe, MD, PhD, Department of Rheumatology, all at the Frederiksberg Hospital, Copenhagen, Denmark. Address correspondence to: Jesper Nørregaard, MD, Bomlærkevej 14, DK-2970 Hørsholm, Denmark. Supported by funds from H. Lundbeck A/S, the OAK foundation, and Bodil Petersens foundation. Journal of Musculoskeletal Pain, vol. 3, no. 4, 1995, 33-34.

Struggling to maintain balance: a study of women living with fibromyalgia.

Thirty-six women with fibromyalgia (FM) were asked to describe how they live with their FM. Data were analysed using the constant comparative method. The goal was understanding the process of living with FM through theory development. The women described living with FM as struggling to maintain balance; this involves recalling perceived normality, searching for a diagnosis, finding out and moving on (transcending the illness). Several women relinquished the struggle because of situations that may or may not be under their control (e.g. depression and feeling imprisoned by treatment). Over time the illness moves from being a primary life focus to being part of the backdrop of the lives of women with FM.

Schaefer KM Department of Nursing and Health, Allentown College of St Francis de Sales, Center Valley, Pennsylvania 18034-9568. J Adv Nurs 1995 ;21(1):95-102

Tender points/fibromyalgia vs. trigger points/myofascial pain syndrome: a need for clarity in terminology and differential diagnosis.

OBJECTIVE: This study reviews the clinical distinctions between fibromyalgia (FM) and myofascial pain syndrome (MPS), which represent two separate and distinct soft-tissue syndromes. The major aim of this article is to clarify the terminology associated with these syndromes and clearly define the parameters of differential diagnosis and treatment.

DATA SOURCES: Pertinent articles in the chiropractic and medical literature are reviewed with an emphasis on the literature published from 1985-1994.

STUDY SELECTION: Studies were selected that emphasized differential diagnosis of FM and MPS, as well as individual articles on either FM or MPS.

DATA SYNTHESIS: The literature on fibromyalgia and myofascial pain syndromes has grown considerably since 1985. It is now clear that there are several important differences between FM and MPS. The most important criteria for differential diagnosis are the presence of tender points (TrPs) and widespread, nonspecific, soft tissue pain in FM, compared with regional and characteristic referred pain patterns with discrete muscular trigger points (TrPs) and taut bands of skeletal muscle in MPS. The etiology of TrPs is still unknown and it is uncertain which specific soft tissues are tender in FM patients. Myofascial TrPs are found within a taut band of skeletal muscle and have a characteristic "nodular" texture upon palpation. TrPs are thought to develop after trauma, overuse or prolonged spasm of muscles. Local treatment applied to TrPs is ineffective, yet specific treatment of TrPs is often dramatically effective.

CONCLUSION: FM and MPS are two different clinical conditions that require different treatment plans. FM is a systemic disease process, apparently caused by dysfunction of the limbic system and/or neuroendocrine axis. It often requires a multidisciplinary treatment approach including psychotherapy, low dose antidepressant medication and a moderate exercise program. MPS is a condition that arises from the referred pain and muscle dysfunction caused by TrPs, which often respond to manual treatment methods such as ischemic compression and various specific stretching techniques. Both of these conditions are seen routinely in chiropractic offices; therefore, it is important for field practitioners to understand these distinctions.

Schneider-MJ SOURCE (BIBLIOGRAPHIC CITATION) J-Manipulative-Physiol-Ther. 1995; 18(6): 398-406

Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study.

OBJECTIVE. To study the efficacy and safety of Super Malic, a proprietary tablet containing malic acid (200 mg) and magnesium (50 mg), in treatment of primary fibromyalgia syndrome (FM).

METHODS. Twenty-four sequential patients with primary FM were randomized to a fixed dose (3 tablets bid), placebo controlled, 4-week/course, pilot trial followed by a 6-month, open label,

dose escalation (up to 6 tablets bid) trial. A 2-week, medication free, washout period was required before receiving treatment, between blinded courses, and again before starting open label treatment. The 3 primary outcome variables were measures of pain and tenderness but functional and psychological measures were also assessed.

RESULTS. No clear treatment effect attributable to Super Malic was seen in the blinded, fixed low dose trial. With dose escalation and a longer duration of treatment in the open label trial, significant reductions in the severity of all 3 primary pain/ tenderness measures were obtained without limiting risks.

CONCLUSIONS. These data suggest that Super Malic is safe and may be beneficial in the treatment of patients with FM. Future placebo-controlled studies should utilize up to 6 tablets of Super Malic bid and continue therapy for at least 2 months.

Russell IJ, Michalek JE, Flechas JD, Abraham GE Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874, USA. J Rheumatol 1995;22(5):953-8

Treatment of "resistant" fibromyalgia.

Long-term outcome for the majority of patients with fibromyalgia is sufficiently disappointing so that most patients can be considered to have "resistant" disease. Among published treatments, education, active exercise, and nighttime antidepressant medications perform best.

Patients eligible for treatment include those with primarily regional symptoms, wide-spread pain without 11 or fewer tender points, or "typical patients" as defined by the American College of Rheumatology criteria.

Factors important in the process of prognosis of the syndrome should be identified and addressed in an integrated therapeutic program in order to positively influence outcome.

Wilke WS Cleveland Clinic Foundation, Ohio, USA. Rheum Dis Clin North Am 1995 Feb;21(1):247-60 Number of References: 75

[Use of antidepressants in sleep disorders: practical considerations].

There is a general tendency to restrict the notion of sleep disorders to insomnia and consequently to limit treatment to the prescription of hypnotics. However, it is very often of benefit to prescribe psychotropic agents, in particular antidepressants, not only in insomnia but also in certain cases of hypersomnia, parasomnia and dysomnia associated with organic diseases. In

some conditions, however, antidepressants may either induce or aggravate sleep disorders. This is the case with a number of psychostimulants that occasionally induce insomnia. It is also true of the tricyclic antidepressants, which may worsen or even induce a restlessleg syndrome that is often associated with periodic movement syndrome. On the other hand, the antidepressants may play a therapeutic role in certain sleep disorders : - depression-related insomnia is of course the << primary >> indication for antidepressants. Furthermore, certain antidepressants exhibit a sedative action resulting in a hypnogenic-type effect which appears well before the antidepressant effect; - the other types of insomnia may also often be treated with antidepressants : not acute reactional insomnia, against which hypnotics are remarkably effective, but chronic insomnia. In addition, all antidepressants may eventually correct depressive hypersomnia, but in these cases, it is evidently preferable to prescribe non-sedative drugs. Although some tricyclic antidepressants have been proposed for use in hypersomnia due to sleep apnea, their therapeutic interest is minor compared with mechanical and surgical treatment. In contrast, antidepressants play an important role in the treatment of narcolepsy, particularly for the correction of attacks of cataplexy. Antidepressants have also been used for some time in the treatment of parasomnia related to slow deep sleep (night terrors and sleepwalking), but the antidepressants may also be used in enuresis and in parasomnia related to REM sleep : nightmares, sleep paralysis, behavioral problems associated with REM sleep. Antidepressant (mainly serotoninergic drugs) are often used in the treatment of fibrolitis syndrome. Finally, antidepressants (particularly the serotoninergic antidepressants) play an important role in the drug treatment of fibromyalgia.

Touchon J Service de neurologie B, Hopital Arnaud de Villeneuve, Montpellier. Encephale 1995 Dec;21 (7):41-7 [Article in French]

The use of topical 4% lidocaine in spheno-palatine ganglion blocks for the treatment of chronic muscle pain syndromes: a randomized, controlled trial.

To assess the efficacy of 4% topical lidocaine in spheno-palatine blocks, a randomized controlled trial was carried out on patients with chronic muscle pain syndromes. Sixty-one patients (42 with fibromyalgia (FM) and 19 with myofascial pain syndrome (MPS)) completed the trial. Outcome measures included pain intensity, a daily pain diary, headache frequency, sensitivity to pressure using a dolorimeter, anxiety, depression, and sleep quality. Patients were randomized to receive either 4% lidocaine or sterile water (placebo) 6 times over a 3-week period. Both subjects and investigators were blind to treatment allocation. The results showed that 4% lidocaine had no superiority over placebo in any of the outcome measures. Twenty-one subjects (35%) showed a decrease in pain which was greater than 30% of their baseline value. Of these 21 subjects, 10 received lidocaine and 11 received placebo. These data suggest that, in this population, 4% lidocaine is no better than placebo in the treatment of chronic muscle pain.

Scudds RA, Janzen V, Delaney G, Heck C, McCain GA, Russell AL, Teasell RW, Varkey G, Woodbury MG Faculties of Applied Health Sciences, University of Western Ontario, London, Canada. Pain 1995 Jul;62(1):69-77

Work disability evaluation and the fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a common and costly cause of work disability. Patients with FMS, nevertheless, encounter considerable difficulties in their assessment of claims for disability payments. Factors that contribute to FMS as an important cause of disability are its high prevalence, the patients' perception of severe discomfort, and poor function.

Disability evaluation in FMS is controversial for several reasons including lack of acceptance of the diagnosis, concurrent psychological abnormalities, difficulties in objectifying disability, deficiencies in instruments of evaluation, the uncertain efficacy of treatment, and physician attitudes.

Third parties appear to have inappropriate expectations of the physician's role in determining disability. We suggest that the process of disability evaluation be improved by more objective assessments and by the inclusion of other health professionals in assessing disability and necessary retraining.

Further research is needed to develop better instruments for measuring disability, to assess the long-term effects of various treatments, and to clarify the contributions of the work place and of compensation in causing or aggravating FMS.

White KP; Harth M; Teasell RW Department of Medicine, University Hospital, University of Western Ontario, Canada. Semin Arthritis Rheum 1995;24(6):371-81