Faculty Bibliography

Autoantibodies to the insulin receptor have been demonstrated to antagonize the physiologic actions of insulin, most often resulting in hyperglycemia unresponsive to massive doses of insulin (type B insulin resistance). Patients with these anti-insulin receptor antibodies typically have a coexistent autoimmune disorder, most commonly systemic lupus erythematosus (SLE) or undifferentiated autoimmune syndromes. Attempting to determine the prevalence and significance of anti-insulin receptor antibodies, sera from consecutive patients with SLE and early undifferentiated connective tissue disease (UCTD) were tested for the presence of anti-insulin receptor antibodies by radio-immuno assay. Thirty-eight patients participated in the study. Twenty-six had SLE and 12 had UCTD. One patient with SLE (2.6%) was positive for anti-insulin receptor antibodies. None of the patients demonstrated evidence of insulin resistance, hypoglycemia, ovarian hyperandrogenism, or acanthosis nigricans, findings commonly linked with the presence of anti-insulin receptor antibodies. The results presented here indicate that the incidence of anti-insulin receptor antibodies in patients with SLE or UCTD, without associated history of altered glucose metabolism, is quite low. Because in most cases the disturbance of glucose metabolism dominates the clinical picture at presentation and the associated systemic autoimmune syndrome presents either simultaneously with or subsequent to the diagnosis of diabetes, the measurement of anti-insulin receptor antibodies should be reserved for patients with indications of disordered glucose homeostasis.

PURPOSE: Although aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) exert inhibitory effects on platelets in vitro and in vivo, there are insufficient data to substantiate the use of NSAIDs alone as antiplatelet drugs in patients already taking aspirin. We therefore sought to determine whether aspirin, added to NSAID therapy, further suppresses platelet function. SUBJECTS AND METHODS: We enrolled 25 healthy adult volunteers who were administered ketoprofen (extended-release capsules, 200 mg daily) for 1 week, followed by ketoprofen (200 mg daily) and aspirin (325 mg daily) or ketoprofen (200 mg daily) alone during the second week. Platelet aggregation, stimulated by epinephrine and arachidonic acid, and cyclooxygenase activity, measured by thromboxane B(2), were measured at baseline, on day 8, and on day 15. RESULTS: On day 8, all subjects demonstrated abnormal platelet aggregation (>50% inhibition), which persisted at day 15 in both the aspirin and no aspirin groups. One week of ketoprofen treatment reduced thromboxane B(2) levels by 84% in the aspirin group and by 85% in the no aspirin group (P = 0.8), without any further inhibition measured on day 15. CONCLUSION: Extended-release ketoprofen significantly inhibited platelet aggregation and thromboxane B(2) production in healthy volunteers. Addition of aspirin had no additional effect. Trials are warranted to determine whether these in vitro effects result in clinical antiplatelet activity in patients who require chronic treatment with NSAIDs, thereby avoiding the toxicity of NSAID/aspirin combination therapy.

OBJECTIVE: To increase awareness of giant cell myocarditis (GCM), its pathogenesis, and treatment. METHODS: Review of relevant publications from the English-language literature. RESULTS: GCM is a rare, frequently fatal inflammatory disorder of cardiac muscle of unknown origin, characterized by widespread degeneration and necrosis of myocardial fibers.Congestive heart failure and ventricular tachycardia are common clinical manifestations. GCM occurs primarily in previously healthy adults, although it is frequently associated with various systemic diseases, primarily of autoimmune causes. The inflammatory infiltrate is characterized by the presence of multinucleated giant cells and is distinct from cardiac sarcoidosis. Animal models of GCM are similar to models of other autoimmune disorders such as rheumatoid arthritis. The prognosis, which is poor despite partial responsiveness to immunosuppressive medications, is improved with cardiac transplantation. CONCLUSIONS: The clinical and immunopathogenetic similarities with classical rheumatologic diseases, the differential diagnosis with sarcoidosis and other inflammatory conditions, and the use of standard immunosuppressive medications make GCM a disease process that should be added to the rheumatologist's expertise.

The use of complementary or alternative therapies by patients with rheumatic diseases is widespread and under-reported by patient to physician. The most commonly used forms of therapy are herbal/nutrient supplements, chiropractic, homeopathy, and acupuncture. The use of these therapies for treatment of rheumatic disease is not substantiated by review of the available medical literature. Furthermore, these therapies are expensive and potentially toxic. Incorporation of these treatments into the therapeutic armamentarium of the rheumatologist cannot be recommended until they are shown to be effective, safe, and affordable.

A 33-year-old woman with longstanding rheumatoid arthritis and Sjogren's syndrome developed type B insulin resistance (diabetes mellitus due to anti-insulin receptor antibodies) simultaneous with the evolution of her rheumatic disease to mixed connective tissue disease. Cyclosporine therapy induced a remission of receptor antibody mediated insulin resistance and controlled clinical manifestations of her systemic lupus erythematosus and dermatomyositis, but had no effect on the sclerodermatous features of her illness.

Multicentric reticulohistiocytosis (MR) is a rare disease in which an infiltration of histiocytic cells causes destructive polyarthritis and characteristic cutaneous lesions. It predominantly affects women between the ages of 40 and 50 years. Effective treatment has not been well established. We describe a case diagnosed in a 6-year-old girl. This is the youngest patient with MR reported to date.

Three women with breast carcinoma were treated with combination chemotherapy, including cyclophosphamide, 5-fluorouracil, and methotrexate, after mastectomy. Within two months of termination of chemotherapy, all 3 patients developed florid synovitis. Two patients had prior clinical manifestations consistent with rheumatoid arthritis; one patient had no antecedent history of arthritis. We suggest that this presentation may represent exacerbation of mild or subclinical rheumatoid arthritis as a consequence of withdrawal of methotrexate therapy.