Faculty Bibliography

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.

Topical drug delivery may be the optimal route for the treatment of localized musculoskeletal disorders because higher drug concentrations can be achieved at the sites of clinical significance. The rationale for the use of topical salicylates and other nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of soft-tissue rheumatic complaints and osteoarthritis is reviewed. Topical capsaicin offers another potentially beneficial therapy for the treatment of osteoarthritis of selected joints. Although there are extensive, uncontrolled experiences with DMSO that suggests its effectiveness in the treatment of musculoskeletal disorders, controlled trials yield conflicting results. The basis for the use of physical modalities such as phonophoresis and iontophoresis to improve topical drug efficacy is summarized.

The role of trace metallic elements (copper, selenium, zinc, gold) in chronic inflammatory states is of great interest because many of them are co-factors in metabolic processes involving articular tissues and immune system function. Deficiencies of several of these have been documented in patients with rheumatoid arthritis. Other than for the clinically approved gold compounds, there exists only inconsistent evidence for a therapeutic role of trace metallic elements in the management of rheumatoid arthritis.

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.