Biomedical subjects
Publications and source records attributed to D L Goldenberg.
Fibromyalgia and chronic fatigue syndrome have similar clinical and demographic features. We found that most patients with chronic fatigue syndrome have a tender point examination similar to patients with fibromyalgia. Similar pathophysiologic mechanisms are also being explored in each syndrome, including a potential role for viral induced immune dysfunction.
Most previous psychologic and psychiatric studies of patients with fibromyalgia have utilized instruments that do not control for pain and therefore may be falsely interpreted as indicative of increased depression, hysteria, or hypochondriasis. Future studies must utilize psychiatric techniques that take into account a coexistent medical condition and such evaluation should include patients with varying levels of severity of fibromyalgia symptoms and utilization of health care.
The therapeutic role of medications in fibromyalgia is reviewed. The tricyclics, amitriptyline and cyclobenzaprine, have been the most extensively evaluated, and in controlled studies have proven to be more effective than placebo or NSAIDs. Their mode of action is not known, but their effect may relate to a number of potential mechanisms. However, neither the tricyclics nor any other medication has provided long-term, clinically meaningful improvement in the majority of patients.
The treatment of fibromyalgia syndrome is complex because there is no real evidence that inflammation or immune abnormalities are present. This article reviews the possible pathophysiologic changes in fibromyalgia, and presents several possible treatment modalities.
The rationale behind the use of tricyclic medications in the treatment of fibromyalgia is reviewed. Controlled therapeutic trials have demonstrated significant improvement with these agents. However, important and sustained clinical improvement occurs in the minority of patients.
We studied tenderness at 75 unilateral anatomic locations in 10 fibromyalgia patients and 10 normal control subjects to determine which sites best identified patients with fibromyalgia. Using a dolorimeter, the mean amount of pressure required to elicit tenderness was significantly lower in patients than in controls at 19 sites (P less than 0.001). Of the previously proposed tender points, only 2 were included in those 19 best discriminating points. Fifteen of the 19 best discriminating points were clustered in regions around the anterior shoulder, anterior chest, posterior scapula, and medial knee. The 19 sites that we have identified best separate patients with fibromyalgia from controls, although the discriminating power of these sites in other chronic pain syndromes will require further study. Examination of specific regions may be more useful clinically than the exact anatomic sites within these regions.
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.
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Our study examines the rheumatology knowledge and skills of trainees in internal medicine and family practice residency programs. Site visits were made to 15 programs in the eastern half of the United States. Eighty-one trainees participated in the study, 53 in internal medicine and 28 in family practice. Each completed a 50-item rheumatology quiz and performed a clinical assessment of a trained patient evaluator. Trainees in internal medicine had quiz and clinical assessment scores of 52.4% and 72.9%, respectively, while scores for family practice trainees were 43.4% and 61.6% (p less than 0.004 for both). Regression analysis showed that having had a rheumatology elective had a significant effect on knowledge and skills. Trainees in family practice programs were 3 times less likely than internal medicine trainees to have taken a rheumatology elective. Family practice trainee scores in our study were comparable to scores previously documented in 4th year medical students. These results confirm the importance of a specific rheumatology experience for the development of rheumatology knowledge and skills in internal medicine and family practice trainees, and suggest that the rheumatology content of these training programs needs to be enhanced.
Research in regard to fibromyalgia has greatly increased during the last 5 years. Initially, investigators concentrated on clinical descriptions and diagnostic criteria. Early pathophysiologic aspects studied included sleep disturbances and psychiatric aspects of the syndrome. More recently, studies have focused on peripheral tissue abnormalities, including sophisticated studies of abnormal muscle metabolism, immunologic and neurotransmitter abnormalities. Future suggested research directions are reviewed.
Recent reports have not emphasized the presence of paresthesias in fibromyalgia syndrome. In our retrospective review of 161 patients with fibromyalgia we found that 84% complained of numbness or tingling at initial evaluation. Most had either bilateral upper and lower extremity or bilateral upper extremity paresthesias. None had concurrent diseases commonly associated with peripheral neuropathy. Thirty-six patients with paresthesias had electromyograms performed before the diagnosis of fibromyalgia and 32 were normal. At a second assessment performed at a mean of 25 months from time of diagnosis, 56 of these 57 patients reported current paresthesias. Paresthesias are common in fibromyalgia and may mimic a neurologic disorder, although objective abnormalities are rare. Judicious use of neurodiagnostic tests are therefore indicated in the clinical setting of fibromyalgia.
Fifty patients with primary fibromyalgia who had been followed in an academic rheumatology practice frequently reported symptoms thought to be typical of "chronic Epstein-Barr virus infection," but not of fibromyalgia: recurrent sore throat (54%), recurrent rash (47%), chronic cough (40%), recurrent adenopathy (33%), and recurrent low-grade fevers (28%). In 55% of the patients, illness had begun suddenly, with what seemed to be a viral syndrome. Antibody titers to Epstein-Barr virus in the patients with fibromyalgia, however, were not significantly different from those in age- and sex-matched "healthy" and "unhealthy" control subjects.
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.
Sixty-two patients with fibromyalgia were randomly assigned to receive 25 mg of amitriptyline at night, 500 mg of naproxen twice daily, both amitriptyline and naproxen, or placebo in a 6-week, double-blind trial. Amitriptyline was associated with significant improvement in all outcome parameters, including patient and physician global assessments, patient pain, sleep difficulties, fatigue on awakening, and tender point score. Patients taking the combined naproxen-amitriptyline regimen experienced minor, but not significant, improvement in pain when compared with patients who took amitriptyline alone. Amitriptyline, or amitriptyline and naproxen, is an effective therapeutic regimen for patients with fibromyalgia.
The natural history of fibromyalgia was studied in 39 treated patients. All patients were surveyed by interviews conducted in 1983 (at an average of 1.3 years after diagnosis), in 1984, and again in 1985. Throughout the survey period, more than 60% of patients had moderate to severe continuing symptoms, and almost all took medications regularly to control symptoms. Younger patients (P = 0.02), those with less severe symptoms at the initial survey (P = 0.005), and those with isolated Raynaud's phenomenon (P = 0.04) were more likely to be doing well 2 years later, although symptom remission was usually transitory.
One hundred eighteen consecutive patients with fibromyalgia were evaluated prospectively. Immunoglobulin deposits at the dermal-epidermal junction were found in only 4 of 36 patients. Twelve patients (14%) had at least one positive antinuclear antibody (ANA) test. Eight patients (7%) had at least one low C3. Thirty-five patients (30%) has a history of Raynaud's phenomenon and 22 (18%) had sicca symptoms, defined as symptomatic dry eyes and mouth and a positive Schirmer test. The 35 patients with Raynaud's phenomenon had a significantly higher prevalence of sicca symptoms, positive ANA or low C3 compared to the 83 patients who did not have Raynaud's phenomenon. Thus, a subset of patients with fibromyalgia may have features suggestive of a systemic connective tissue disorder.
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The Medical Research Education Subcommittee of the American Rheumatism Association surveyed a random selection of large and small programs in internal medicine and family practice residency programs in order to evaluate their rheumatology training. Formal rheumatology training is offered in 90% of these residency programs, but many available positions are not being filled. A full-time staff rheumatologist was present at 69% of large internal medicine programs, 32% of small internal medicine programs, and 11% of family practice programs. The methods of rheumatology training are similar in most programs, although small internal medicine programs and family practice programs more often utilize physicians' offices or outside medical centers for the rheumatology elective training. A majority of the directors of these residency programs thought that many basic skills and techniques were not taught adequately and that the training of their rheumatology residents was not equal to that of residents in cardiology or gastroenterology.