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.

The assessment of functional impairment in fibromyalgia (FM): Rasch analyses of 5 functional scales and the development of the FM Health Assessment Questionnaire.

OBJECTIVE: Functional assessment by self-report questionnaire plays an important role in most rheumatic conditions, but psychometric properties of questionnaires have not been studied in fibromyalgia (FM), particularly by Rasch analysis, which allows for examining adequacy of the questionnaire scale. To assess currently used instruments, we examined the Fibromyalgia Impact Scale (FIQ), 4 versions of the Health Assessment Questionnaire (HAQ), and the Medical Outcome Survey Short Form (SF-36). METHODS: More than 2,500 patients from 4 sites (3 US, 1 Israel) completed the FIQ. The HAQ questionnaires were completed by 1438 patients participating in the US National Data Bank for Rheumatic Diseases. Seven hundred sixty patients from Wichita, Kansas, completed the SF-36. Rasch analysis was applied separately to each of these data sets. RESULTS: The FIQ systematically underestimated functional impairment by its handling of activities not usually performed. All questionnaires had problems with non-unidimensionality and ambiguous items when applied to patients with FM. In addition, scales were found to be non-linear. Because of these findings we used the 20 item HAQ questionnaire as an item bank to develop a new questionnaire more suitable for use in FM, the fibromyalgia HAQ (FHAQ). This questionnaire fits the Rasch model well, is relevant, is linear, and has a long, well spaced scale. CONCLUSION: No available functional assessment questionnaire works well in FM. A new questionnaire, the FHAQ, was developed. It has appropriate metric properties and should function well in this condition. Since the FHAQ is a subset of the larger HAQ questionnaire, a new questionnaire is not required; only a different method of scoring is needed. Additional studies regarding sensitivity to change are required to fully validate the FHAQ.

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.

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.

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.

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.

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

The diagnosis of fibromyalgia continues to generate heated debate. The presence of multiple lifetime psychiatric diagnoses was not intrinsically related to fibromyalgia but rather to the decision of patients to seek specialty medical care. Better outcome measures in fibromyalgia were tested. Neurally mediated hypotension may be associated with chronic fatigue syndrome (CFS). Treatment of patients with fibromyalgia and CFS continues to be of limited success, although the role of multidisciplinary group intervention appears promising. Two position papers focused on the adverse aspects of the medicolegal issues in fibromyalgia and CFS.

What is the future of fibromyalgia?

This article discusses the future of fibromyalgia, including the current state of the art and potential future pathophysiologic studies. Suggestions are provided in regard to future therapeutic trials, longitudinal and outcome studies, and the role of the rheumatology community in this common disorder.

Fibromyalgia, chronic fatigue syndrome, and myofascial pain.

The prevalence of fibromyalgia in the general population was found to be 2% and increased with age. Multiple traumatic factors, including sexual and physical abuse, may be important initiating events. The most important pathophysiologic studies in fibromyalgia included evidence of altered blood flow to the brain and hypothalamic-pituitary-adrenal dysfunction. The prevalence of chronic fatigue syndrome is much less than that of fibromyalgia. Epidemiologic studies demonstrated that chronic fatigue and symptoms of fibromyalgia are distributed as continuous variables in the general population. No association between chronic fatigue and initial infections was seen in primary care practices.

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.

Bacterial arthritis.

A number of experimental models of bacterial arthritis demonstrated that immune factors, especially directed cytokines, play an important role in cartilage destruction. The most important studies in bacterial arthritis were a review of the clinical manifestations of gonococcal arthritis and two reports of the use of polymerase chain reaction to detect Neisseria gonorrhoeae DNA in synovial fluid. Polymerase chain reaction may be an important diagnostic test in culture-negative cases and may be very helpful in understanding the pathophysiology of gonococcal arthritis.

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.

Bacterial arthritis.

Acute bacterial arthritis continues to be a common occurrence, and despite improved treatment regimens, the prognosis has not improved significantly over the past 20 years. During the past year, the emergence of unique predisposing factors for bacterial arthritis, including prosthetic joints and HIV infection, were emphasized. The long-standing debate regarding optimal drainage techniques has continued with the introduction of a new drainage procedure, tidal irrigation, in the treatment of septic knees.

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

No major pathophysiologic or therapeutic findings have appeared over the past year regarding fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome, three poorly understood, controversial, and overlapping syndromes. The frequent prevalence of these disorders in association with Lyme disease and other medical and psychiatric illness was emphasized. New studies demonstrated the potential role for central nervous system activation in fibromyalgia and chronic fatigue syndrome.