A subset of fibromyalgia patients have findings suggestive of chronic inflammatory demyelinating polyneuropathy and appear to respond to IVIg.

OBJECTIVES: The aetiopathogenesis of the fibromyalgia syndrome (FMS) remains unknown. Recent reports, however, suggest that a subgroup of FMS subjects has an immune-mediated disease. Therefore, our primary objective was to study FMS subjects for evidence of an immune-mediated demyelinating polyneuropathy. Our secondary objective was to determine the effects of treating these FMS subjects with the immune modulator, intravenous immunoglobulin (IVIg). METHODS: Fifty-eight FMS subjects, 26 rheumatic non-FMS subjects and 52 non-rheumatic non-FMS subjects were studied. Subjective measures of paraesthesias, weakness, stocking hypaesthesia, pain, fatigue and stiffness were made. Objective measures of tenderness, proximal muscle strength and electrodiagnostic (EDX) evidence of polyneuropathy and demyelination were also made. Eleven other FMS subjects underwent sural nerve biopsy. RESULTS: Paraesthesias, subjective weakness and stocking hypaesthesia were more common in FMS than in rheumatic non-FMS (P < or = 0.0001). Proximal muscle strength was less in FMS than in rheumatic non-FMS (P < or = 0.0001). EDX demonstrated a distal demyelinating polyneuropathy, suggestive of chronic inflammatory demyelinating polyneuropathy (CIDP), in 33% of FMS subjects. No rheumatic non-FMS subject had polyneuropathy (P = 0.005), or demyelination (P = 0.05). Fifteen FMS/CIDP subjects were subsequently treated with IVIg (400 mg/kg each day for 5 days). Pain (P = 0.01), tenderness (P = 0.001) and strength (P = 0.04) improved significantly. Fatigue and stiffness trended towards improvement. CONCLUSIONS: A significant subset of FMS subjects have clinical and EDX findings suggestive of CIDP. IVIg treatment shows promise in treating this subset. These observations have implications for better understanding and treating some FMS patients.

Immunofluorescent studies of skin in primary fibrositis syndrome.

Primary fibrositis syndrome is a painful musculoskeletal disorder of unknown cause. Although numerous hypotheses have been proposed to explain its clinical features, few studies have demonstrated a reproducible tissue abnormality in this condition. Recently, five reports of cutaneous immunoreactant deposition in primary fibrositis syndrome have become available and form the basis of this review. Four of these reports have described immunoglobulin G deposition at the dermal-epidermal junction of sun-exposed skin with a prevalence ranging from 12 to 76 percent. One study reported immunoglobulin M deposition in the dermal vasculature of patients with primary fibrositis syndrome. The reasons for the lack of uniformity in reported prevalence rates and types of skin immunofluorescence in primary fibrositis syndrome are unknown but are assumed to be due to differences in patient populations and immunofluorescence techniques between reporting centers. These factors are discussed in detail and speculations as to the significance of these skin findings are expressed, particularly with respect to the concept of enhanced vascular permeability in these patients.

Is there an immunologic component to the fibrositis syndrome?

PFS is an enigmatic disorder whose etiology remains largely unknown. Its clinical spectrum probably encompasses a heterogeneous group of patients displaying multifactorial symptomatology. Recent evaluation of PFS patients, on both a clinical and laboratory basis, suggests that there is a subpopulation of these patients who exhibit a low grade connective tissue disorder. This group of patients exhibit many of the clinical features expected with rheumatic diseases such as SLE and Sjögren's syndrome. They can be distinguished on a clinical basis from other PFS patients and from patients with the CEBV syndrome. Their disease may be disablingly painful and resistant to many therapeutic modalities. Results of newer information reviewed here suggests that these patients may have EVP on the basis of a peripheral, low grade, quasi-inflammatory process that may have a neurologic and an immune dysregulatory component. The implications of such a mechanism of injury are profound and potentially impact on the treatment of this group of patients.

New concepts in primary fibrositis syndrome.

PFS is a painful rheumatologic disorder that may be detected by the wary clinician attuned to the presence of seven or more tender points. This common disorder may be seen at any age, including childhood, and may be associated with secondary symptoms of depression and other affective disorders. It may also be associated with findings of disturbed sleep, hearing and vestibular abnormalities, and profound complaints of fatigue. The vagueness of this latter complaint means that PFS must be distinguished from the newly described CEBV syndrome. Although the etiology of PFS remains unknown, recent investigations suggest that these patients may suffer a disorder with a central nervous system component as well as a subtle peripheral tissue lesion. Newer PFS studies demonstrate tissue changes that may be consistent with altered microvascular permeability and blood flow, tissue hypoxia, and chronic muscle spasm. An immunologic abnormality, or even a previously undescribed connective tissue disease, may be important as a pathogenic factor in some PFS patients.

A controlled and blinded study of immunoreactant deposition at the dermal-epidermal junction of patients with primary fibrositis syndrome.

The prevalence of immunoreactant deposition at the dermal-epidermal junction (DEJ) in clinically normal, sun exposed skin was assessed by direct immunofluorescence (IF) in 36 patients with primary fibrositis syndrome (PFS) and 12 clinically healthy control subjects. A granular or homogeneous deposition of IgG was seen at the DEJ in 52.8% (19/36) of patients with PFS and in 16.7% (2/12) of controls. The difference in IgG deposition between patients with PFS and controls was statistically significant (p = 0.030). Patients with PFS and controls did not demonstrate significant IF staining for IgA, IgM, or C3. Albumin deposition at the DEJ appeared to parallel IgG deposition in patients with PFS and control subjects who were positive for this immunoglobulin. No relationship was noted between IgG deposition and demographic or clinical characteristics of these patients' disease. These data suggest that IgG and albumin deposition at the DEJ is frequent in PFS and that further study of this skin phenomenon is warranted.

Work and disability status of persons with fibromyalgia.

OBJECTIVE: To determine the prevalence and determinants of self-reported work disability in persons with fibromyalgia (FM). METHODS: A longitudinal, multicenter survey of 1604 patients with FM from 6 centers with diverse socioeconomic characteristics was begun in 1988. Assessments were by self-report questionnaire and telephone contact, and included work and disability events that occurred before and after 1988. Comparative analyses were performed on the entire data set and, separately, on the Wichita data set. RESULTS: More than 16% of patients reported receiving US Social Security disability (SSD) payments (highest center rate 35.7%; lowest center rate 6.3%) compared to 2.2% of the US population (US Social Security Administration data) and 28.9% of patients with rheumatoid arthritis seen at the Wichita outpatient rheumatology clinic. Overall, 26.5% reported receiving at least one form of disability payment when SSD and other sources of disability payments were considered. In Wichita, less than 25% of SSD awards were made specifically for FM, but after 1988 that figure increased to 46.4%. Work disability was greatest at the San Antonio and Los Angeles centers. Multivariate predictors (correlates) included pain, Health Assessment Questionnaire disability, and unmarried status. In addition, more than 70% of patients reporting being disabled did receive disability payments. On the other hand, 64% reported being able to work all or most days, and more than 70% were employed or were homemakers. CONCLUSION: Although most patients (64%) report being able to work, we found high rates of self-reported work disability awards among persons with FM followed in 6 rheumatology centers. But we also found great variability among centers as to awards and as to self-reported work ability. Center differences in work disability might reflect clinic referral patterns, physician beliefs, or socioeconomic status.

A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia.

OBJECTIVE: To study, for the first time, service utilization and costs in fibromyalgia, a prevalent syndrome associated with high levels of pain, functional disability, and emotional distress. METHODS: Five hundred thirty-eight fibromyalgia patients from 6 rheumatology centers were enrolled in a 7-year prospective study of fibromyalgia outcome. Patients were assessed every 6 months with validated, mailed questionnaires which included questions regarding fibromyalgia symptoms and severity, utilization of services, and work disability. RESULTS: Fibromyalgia patients averaged almost 10 outpatient medical visits per year, and when nontraditional treatments were considered, this number increased to approximately 1 visit per month. Patients were hospitalized at a rate of 1 hospitalization every 3 years. In each 6-month study period, patients used a mean of 2.7 fibromyalgia-related drugs. Costs increased over the course of the study. The mean yearly per-patient cost in 1996 dollars was $2,274. However, results were skewed by high utilizers, and many patients used few services and had limited costs. Total costs and utilization were independently associated with the number of self-reported comorbid or associated conditions, functional disability, and global disease severity. Compared with patients with other rheumatic disorders, those with fibromyalgia were more likely to have lifetime surgical interventions, including back or neck surgery, appendectomy, carpal tunnel surgery, gynecologic surgery, abdominal surgery, and tonsillectomy, and were more likely than other rheumatic disease patients to report comorbid or associated conditions. Almost 50% of hospitalizations occurring during the study were related to fibromyalgia-associated symptoms. CONCLUSION: The average yearly cost for service utilization among fibromyalgia patients is $2,274. Fibromyalgia patients have high lifetime and current rates of utilization of all types of medical services. They report more symptoms and comorbid or associated conditions than patients with other rheumatic conditions, and symptom reporting is linked to service utilization and, to a lesser extent, functional disability and global disease severity.

Health status and disease severity in fibromyalgia: results of a six-center longitudinal study.

OBJECTIVE: To determine the intermediate and long-term outcomes of fibromyalgia in patients seen in rheumatology centers in which there is special interest in the syndrome. METHODS: We conducted a longitudinal outcome study by mailed comprehensive Health Assessment Questionnaire administered every 6 months to 538 patients, from 6 rheumatology centers, whose median duration of disease at first assessment was 7.8 years. The final assessment took place after 7 years. In addition, there was study followup on 85 patients who had attended the Wichita center for > 10 years. RESULTS: Although functional disability worsened slightly and health satisfaction improved slightly, measures of pain, global severity, fatigue, sleep disturbance, anxiety, depression, and health status were markedly abnormal at study initiation and were essentially unchanged over the study period. Correlations between first and last assessment values were as high as r = 0.82. For some variables, abnormalities were 3 times greater at one center compared with another. CONCLUSION: Patients with established fibromyalgia, seen in rheumatology centers in which there a special interest in the disease and followed up for as long as 7 years, have markedly abnormal scores for pain, functional disability, fatigue, sleep disturbance, and psychological status, and these values do not change substantially over time. Half the patients are dissatisfied with their health, and 59% rate their health as fair or poor. There are marked differences in disease severity among the various centers, but < 14% of the variance in outcomes can be explained by demographic or center factors. Values at the first assessment are predictive of final values.