Fibromyalgia syndrome a decade later: what have we learned?

Despite substantial interest and investigation during the past 10 years, fibromyalgia continues to provoke many controversies. The major issues discussed in this review include the diagnostic utility of fibromyalgia, psychiatric and central nervous system factors, therapy and outcome, and compensation and disability. It is important to recognize the psychosocial factors that distinguish patients with fibromyalgia from persons in the community who meet criteria for the syndrome but who do not seek medical care. Such factors may be among the most important in long-term treatment.

Circadian rhythms of women with fibromyalgia.

Fibromyalgia syndrome is a chronic and debilitating disorder characterized by widespread nonarticular musculoskeletal pain whose etiology is unknown. Many of the symptoms of this syndrome, including difficulty sleeping, fatigue, malaise, myalgias, gastrointestinal complaints, and decreased cognitive function, are similar to those observed in individuals whose circadian pacemaker is abnormally aligned with their sleep-wake schedule or with local environmental time. Abnormalities in melatonin and cortisol, two hormones whose secretion is strongly influenced by the circadian pacemaker, have been reported in women with fibromyalgia. We studied the circadian rhythms of 10 women with fibromyalgia and 12 control healthy women. The protocol controlled factors known to affect markers of the circadian system, including light levels, posture, sleep-wake state, meals, and activity. The timing of the events in the protocol were calculated relative to the habitual sleep-wake schedule of each individual subject. Under these conditions, we found no significant difference between the women with fibromyalgia and control women in the circadian amplitude or phase of rhythms of melatonin, cortisol, and core body temperature. The average circadian phases expressed in hours posthabitual bedtime for women with and without fibromyalgia were 3:43 +/- 0:19 and 3:46 +/- 0:13, respectively, for melatonin; 10:13 +/- 0:23 and 10:32 +/- 0:20, respectively for cortisol; and 5:19 +/- 0:19 and 4:57 +/- 0:33, respectively, for core body temperature phases. Both groups of women had similar circadian rhythms in self-reported alertness. Although pain and stiffness were significantly increased in women with fibromyalgia compared with healthy women, there were no circadian rhythms in either parameter. We suggest that abnormalities in circadian rhythmicity are not a primary cause of fibromyalgia or its symptoms.

Fibromyalgia and major affective disorder: a controlled phenomenology and family history study.

Fibromyalgia is a form of nonarticular rheumatism characterized by diffuse musculoskeletal pain. To investigate the relationship between fibromyalgia and major affective disorder, the authors evaluated 31 patients with fibromyalgia and 14 patients with rheumatoid arthritis for rates of current or past major affective disorder and family history of major affective disorder. Both the rate of major affective disorder and the familial prevalence of major affective disorder were significantly higher in the fibromyalgia patients than the rheumatoid arthritis patients. The results suggest that fibromyalgia may be related to major affective disorder.

Synovial membrane histopathology in the differential diagnosis of rheumatoid arthritis, gout, pseudogout, systemic lupus erythematosus, infectious arthritis and degenerative joint disease.

The synovial membrane histologic sections from patients with six common rheumatic diseases were reviewed without knowledge of the clinical diagnosis. After histopathologic evaluation, the synovial membrane characteristics were grouped according to the patient's clinical diagnosis, and included 29 patients with rheumatoid arthritis, 13 with systemic lupus erythematosus, 17 with degenerative joint disease, 10 with acute bacterial arthritis, 8 with gout, and 13 with pseudogout. The only specific characteristics identified were bacteria (infectious arthritis), crystals (gout, pseudogout), and lymphoid follicles (rheumatoid arthritis). Nevertheless, other characteristic features of differential diagnostic utility were recognized, including the intensity and nature of synovial lining cell hyperplasia and of leukocyte infiltration. Light microscopic histopathologic changes in the common rheumatic diseases are not specific, but are of diagnostic utility. Complete and exhaustive review of each pathologic synovial membrane characteristic provides more justification for the routine use of synovial membrane biopsy as an adjunct to arthrocentesis in the evaluation of common rheumatic diseases.

Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms.

Forty-nine patients with disseminated gonococcal infection (DGI) hospitalized at Boston City and University Hospitals over a 7-year period were studied. Patients with clinical manifestations of DGI and with cervical, urethral, rectal, pharyngeal, synovial or blood cultures positive for Neisseria gonorrhoeae were separated into two groups based on the presence or absence of suppurative arthritis. There were 19 cases of suppurative arthritis (Group II) and 30 cases with only tenosynovitis, skin lesions, or both (Group I). Blood cultures were positive only in Group I patients (43%) and synovial fluid cultures only in Group II patients (47%). Polyarthralgia was the most common initial symptom in both groups of patients. Twenty-six Group I patients had tenosynovitis (87%), while only 4 Group II patients (21%) had tenosynovitis (p less than 0.001). The knee was the most commonly involved suppurated joint. Twenty-seven Group I patients (90%) had skin lesions compared to 8 Group II patients (42%) (p less than 0.001). Some of these lesions progressed on treatment; some patients were unaware of their lesions. Genitourinary symptoms were unusual in both groups of patients. Eleven women (33%) were menstruating or were pregnant at the onset of DGI. Thirteen patients had histories suggestive of previous gonococcal infections; one had recurrent DGI. This patient and one other were found to have complement abnormalities. There were no cases of endocarditis or meningitis. Four patients had unexplained liver function abnormalities. All patients recovered uneventfully. Strains isolated from disseminated sites were predominantly of the transparent phenotype (90%). Many strains (58%) required arginine, hypoxanthine and uracil for growth. They were also more susceptible to penicillin than reported strains that cause pelvic inflammatory disease. Most strains were of a single outer membrane protein coagglutination serogroup, WI (85%). These characteristics did not vary between the Group I and Group II isolates. The two groups of strains, however, did vary in their complement-dependent bactericidal reactivity to normal human sera. Eighteen of 24 Group I strains (75%) versus 9 of 19 Group II strains (47%) resisted killing by all normal human sera tested (p less than .05). Likewise, convalescent sera from Group II patients were able to kill their infecting strains more often than did sera from Group I patients (70% vs 17%) (p less than 0.01). Thus, variations in the clinical expression of disease in patients with DGI may be explained, in part, by differences in certain phenotypic and immunologic features of infecting strains.

Psychologic studies in fibrositis.

During the past five years, there have been a number of controlled reports regarding the possible association of fibrositis with psychologic disorders. The results of these studies are quite different, which is not surprising in view of the differences in patient populations and study instruments used. We gave the Diagnostic Interview Schedule to 82 patients with fibrositis and to control subjects, and we found an association of depression with fibrositis. Depression was also more common in first-degree relatives of patients with fibrositis. However, in most instances, the depression antedated fibrositis by more than one year, indicating a possible psychobiologic association, rather than a casual one.

Acute infectious arthritis. A review of patients with nongonococcal joint infections (with emphasis on therapy and prognosis).

The clinical course of 59 patients with acute nongonococcal septic arthritis has been reviewed with special emphasis on the changing bacterial spectrum in recent years. The results of treatment were dependent on various factors, including the specific microbial agent and host defenses. Treatment should include parenteral antibiotics and drainage with needle aspiration, except in hips which should be surgically drained. Successful therapy requires rapid initiation of treatment and ongoing assessment of adequacy of response.

Acquired immunodeficiency syndrome-associated arthritis.

A subacute, oligoarthritic syndrome developed in four patients with human immunodeficiency virus (HIV) infection. Three had true acquired immunodeficiency syndrome (AIDS) and all had lymphocyte abnormalities. The arthritis was characterized by extreme pain and disability in three patients and moderate pain in one. Knees and ankles were affected. Symptoms developed over a one- to six-week interval; response to treatment was rapid, especially to intra-articular corticosteroids. Despite the clinical severity of the arthritis, synovial fluids were non-inflammatory and biopsy specimens revealed only mild chronic synovitis. A definite etiology could not be established. None of the patients had recognized infections predisposing to reactive arthritis, and the three patients who underwent tissue typing were HLA-B27-negative. A viral infection, including HIV, is a possible cause. In distinction to these four patients, arthritides with clearly established etiologies developed during this same time period in four other HIV-infected patients.

Comorbidity of fibromyalgia with medical and psychiatric disorders.

PURPOSE: Patients with fibromyalgia have been reported to display high rates of several concomitant medical and psychiatric disorders, including migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. To test further these and other possible associations, we assessed the personal and family histories of a broad range of medical and psychiatric disorders in patients with fibromyalgia. PATIENTS AND METHODS: Subjects were 33 women (mean age 42.1 years) who each met American College of Rheumatology criteria for fibromyalgia and presented to a rheumatologist at a tertiary referral center. They received the Structured Clinical Interview for DSM-III-R (SCID); a supplemental interview, in SCID format, for other medical and psychiatric disorders, including migraine, irritable bowel syndrome, and chronic fatigue syndrome; and an interview for family history of medical and psychiatric disorders. RESULTS: Patients with fibromyalgia displayed high lifetime rates of migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. They also exhibited high rates of familial major mood disorder. CONCLUSIONS: The finding that migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder are frequently comorbid with fibromyalgia is consistent with the hypothesis that these various disorders may share a common physiologic abnormality.

Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome.

PURPOSE: To perform a detailed comparison of the hypothalamic-pituitary-adrenal axis and the sympathoadrenal system in women with and without fibromyalgia. SUBJECTS AND METHODS: Fifteen premenopausal women who met the 1990 American College of Rheumatology criteria for the diagnosis of fibromyalgia and 13 healthy, premenopausal women were enrolled. We measured baseline 24-hour urinary free cortisol levels and evening and morning adrenocorticotropic hormone (ACTH) and cortisol levels, performed stepped hypoglycemic hyperinsulinemic clamp studies in which serum glucose levels were decreased from 5.0 to 2.2 mmol/L, and compared the effects of infusions of placebo and ACTH. RESULTS: Women with fibromyalgia had normal 24-hour urinary free cortisol levels and normal diurnal patterns of ACTH and cortisol. There was a significant, approximately 30%, reduction in the ACTH and epinephrine responses to hypoglycemia in women with fibromyalgia compared with controls. Prolactin, norepinephrine, cortisol, and dehydroepiandrosterone responses to hypoglycemia were similar in the two study groups. In subjects with fibromyalgia, the epinephrine response to hypoglycemia correlated (P = 0.01) inversely with overall health status as measured by the fibromyalgia impact questionnaire. Graded ACTH infusion revealed similar increases in cortisol in women with fibromyalgia and healthy controls. CONCLUSIONS: Patients with fibromyalgia have an impaired ability to activate the hypothalamic-pituitary portion of the hypothalamic-pituitary-adrenal axis as well as the sympathoadrenal system, leading to reduced ACTH and epinephrine responses to hypoglycemia.