Bernard F. Germain

Rheumatic manifestations of human immunodeficiency virus infection

PURPOSE The prevalence and characteristics of the rheumatic and extra-rheumatic manifestations of human immunodeficiency virus (HIV) infection were determined in a prospective manner. PATIENTS AND METHODS One hundred one patients with HIV infection were consecutively interviewed and examined. The prevalence of autoantibodies and their association with rheumatologic symptoms were also determined. RESULTS The musculoskeletal system was involved in 72 patients. Thirty-five patients had arthralgias, 10 had Reiters syndrome, two had psoriatic arthritis, two had myositis, and one had vasculitis. Also found were two previously unreported syndromes. The first, occurring in 10 patients, consisted of severe intermittent pain involving less than four joints, without evidence of synovitis, of short duration (two to 24 hours), and requiring therapy (ranging from nonsteroidal antiinflammatory drugs to narcotics). The second, occurring in 12 patients, consisted of arthritis (oligoarticular in six patients, monoarticular in three patients, and polyarticular in three patients) involving the lower extremities and lasting from one week to six months. The synovial fluid of five patients (three with arthritis, one with Reiters syndrome, and one with psoriatic arthritis) was sterile and inflammatory. CONCLUSION Musculoskeletal complications are common in advanced stages of HIV infection. Persons in a high-risk group for HIV infection who manifest oligoarthritis with or without any other extra-articular manifestation suggestive of Reiters syndrome or other form of spondyloarthropathy should be tested for HIV.

Misoprostol Compared with Sucralfate in the Prevention of Nonsteroidal Anti-inflammatory Drug-induced Gastric Ulcer: A Randomized, Controlled Trial

Objectives To compare the efficacy and frequency of adverse experiences of misoprostol and sucralfate in the prevention of gastric ulcers in patients receiving nonsteroidal anti-inflammatory drug (NSAID) therapy. Design A prospective, randomized, single-blind, multicenter trial. Patients Patients with osteoarthritis receiving treatment with ibuprofen, piroxicam, or naproxen and experiencing abdominal pain were eligible. Interventions Patients who were expected to receive at least 3 months of NSAID therapy and who did not have a gastric ulcer at the time of the initial screening endoscopy were randomized to receive misoprostol, 200 micrograms four times a day, or sucralfate, 1 g four times a day. A gastric ulcer was defined as a lesion of the gastric mucosa 0.3 cm or greater in diameter. Patients were followed clinically, and repeat endoscopies were performed after 4, 8, and 12 weeks. Main measurement The development of a gastric ulcer, which was regarded as a prophylaxis failure. Results Two hundred fifty-three patients were evaluable for efficacy analysis. A gastric ulcer developed in 2 of the 122 (1.6%, 95% CI, 0.3% to 6.4%) patients on misoprostol, compared with 21 of 131 patients on sucralfate (16%, CI, 10.4% to 23.7%). The difference in ulcer rates was 14.4% (CI, 10.4% to 19.5%; P less than 0.001). Conclusion In patients receiving chronic NSAID therapy for osteoarthritis, treatment with misoprostol for 3 months was associated with a significantly lower frequency of gastric ulcer formation, compared with treatment with sucralfate (P less than 0.001).

Prolactin, immunoregulation, and autoimmune diseases

Cells of the immune system synthesize prolactin and express mRNA and receptors for that hormone. Interleukin 1, interleukin 6, gamma interferon, tumor necrosis factor, platelet activator factor, and substance P participate in the release of prolactin. This hormone is involved in the pathogenesis of adjuvant arthritis and restores immunocompetence in experimental models. In vitro studies suggest that lymphocytes are an important target tissue for circulating prolactin. Prolactin antibodies inhibit lymphocyte proliferation. Prolactin is comitogenic with concanavalin A and induces interleukin 2 receptors on the surface of lymphocytes. Prolactin stimulates ornithine decarboxylase and activates protein kinase C, which are pivotal enzymes in the differentiation, proliferation, and function of lymphocytes. Cyclosporine A interferes with prolactin binding to its receptors on lymphocytes. Hyperprolactinemia has been found in patients with systemic lupus erythematosus. Fibromyalgia, rheumatoid arthritis, and low back pain patients present a hyperprolactinemic response to thyrotropin-releasing hormone. Experimental autoimmune uveitis, as well as patients with uveitis whether or not associated with spondyloarthropathies, and patients with psoriatic arthritis may respond to bromocriptine treatment. Suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine A with significantly less toxicity. Prolactin may also be a new marker of rejection in heart-transplant patients. This body of evidence may have an impact in the study of rheumatic disorders, especially connective tissue diseases. A role for prolactin in autoimmune diseases remains to be demonstrated.

Histocompatibility typing in the seronegative spondyloarthropathies: A survey

T HE FIRST association of a human disease (Hodgkin disease) and increased prevalence of a histocompatibility (HLA) antigen was described by Amiel in 1967.’ Since then, a large number of other diseases have been associated with increased or decreased frequencies of various HLA antigens.2-5 A number of different correlations have emerged; some are detectable at the population level, while some are detectable only at the haplotype level within families. The most significant and reproducible associations, however, have been reported in the seronegative group of rheumatic diseases. HLA-B27 has been shown to be a frequent genetic marker for rheumatic disease characterized by axial (spondylitis) types of arthritis. Ankylosing spondylitis (AS),“” Reiter syndrome (RS),“,‘* psoriatic spondylitis (PsS),“~‘~ and spondylitis associated with inflammatory bowel disease (IBD)15 are all characterized by significant increases in HLA-B27. Recently, we and others’6-‘9 reported a significantly increased prevalence of HLA-Bw38 in patients with peripheral psoriatic arthritis (PsA) in whom the frequency of HLA-B27 was within normal limits. Because HLA-Bw38 is a recently identified antigen, we concluded that it was useful to evaluate in other conditions characterized by seronegative peripheral arthritis. In this study of the association among HLAB27, Bw38, the DR antigens and seronegative arthritis, we evaluated clinically, radiologically, and by means of HLA typing, a large number of patients with seronegative arthritis. We confirmed the significant association of B27 and spinal involvement in the spondyloarthropathies and the association of Bw38 and DRw4 with psoriatic arthritis. Additionally, Bw38 and DRw4 were not found to be elevated in any other form of arthritis. No abnormal elevation and/or depression of a given HLA antigen was observed in patients with seronegative rheumatoid arthritis or osteoarthritis. MATERIALS AND METHODS

Reactive arthritis induced by parasitic infestation.

Arthritis developed in two patients during the course of parasite infestation with Strongyloides stercoralis and Taenia saginata, respectively. The joint involvement was polyarticular and symmetrical but seronegative and nonerosive radiologically. We found evidence of abnormal humoral immunity to the parasites, immune complexes in serum and synovial fluid, and immunoglobulin deposits in the synovia. Nonsteroidal anti-inflammatory agents proved ineffective but specific antiparasitic treatment resulted in resolution of the symptoms and immunologic abnormalities. Our findings provide further documentation of the interaction between the bodys immune system and parasites and suggest that arthritis induced by parasitic infestation may be mediated by immune complex formation in susceptible hosts.

Cholesterol embolism: A pseudovasculitic syndrome

T HE ORIGINAL description of atheromatous embolism was credited by Panum in 1862, although it has been justly noted that he only described the necropsy of the famous Danish sculptor Thorwaldsen performed two decades earlier by Dahlerup and Fenger.’ Cholesterol embolism remained a pathologic curiosity until the 1960s when its clinical similarity to a multisystern disorder was recognized. One factor that increased the awareness of the entity was Flory’s* demonstration of cholesterol crystals in small arteries of experimental animals after injection of human atheromatous material into their circulation. Despite the various descriptions in the literature, both the failure to recognize this clinical phenomena and the subsequent institution of improper therapy continue to occur and contribute to patient morbidity. Cholesterol microembolism may produce a variety of signs and symptoms resembling a multisystem disorder such as a systemic vasculitis. Laboratory abnormalities contributing to the diagnostic confusion include leukocytosis, eosinophilia, hypocomplementemia, and erythrocyte sedimentation rate (ESR) elevation. Our current series demonstrated the additional finding of antinuclear antibody (ANA) and rheumatoid factor positivity, whose presence should not automatically implicate a systemic vasculitis or connective tissue disease.

Oral methotrexate therapy for chronic rheumatoid arthritis ulcerations

Eight patients with long-standing rheumatoid arthritis and cutaneous vasculitis ulcerations resistant to conventional therapy were treated successfully with a low-dose intermittent regimen of oral methotrexate. Objective clinical response was prompt and complete resolution was observed at about 12 weeks of therapy. The drug was well tolerated. Mild gastrointestinal side effects were the most common untoward reaction. We conclude that methotrexate therapy is an effective agent for some of the extraarticular manifestations of rheumatoid arthritis including vasculitis, and further clinical evaluation should be a consideration.

Comparison of the safety and efficacy of nabumetone and aspirin in the treatment of osteoarthritis in adults

A six-month, multicenter, double-blind study compared the efficacy and safety of two therapeutic regimens in 332 patients with osteoarthritis. The patients received either 1,000 mg of nabumetone as a single bedtime dose or 900 mg of aspirin in four divided doses. At the end of the study, patients in both treatment groups showed significant improvement from baseline for all five parameters; no statistically or clinically significant differences were observed between the groups. The safety data did reveal clinically and statistically significant differences between the groups. Aspirin-treated patients experienced a greater frequency of withdrawal from the study because of adverse experiences (34 percent versus 13 percent), a greater incidence of having at least one treatment-related adverse experience (73 percent versus 52 percent), a greater percentage of patients with at least one moderate or severe treatment-related adverse experience (47 percent versus 22 percent), and a greater percentage of patients with treatment-related adverse experiences affecting the gastrointestinal system (43 percent versus 32 percent) or the inner ear (32 percent versus 10 percent). The results of this study demonstrated that nabumetone, 1,000 mg at bedtime, is as efficacious as aspirin, 900 mg four times daily, produces fewer adverse effects, and is indicated in the treatment of osteoarthritis.

Controlled evaluation of nabumetone in the treatment of active adult rheumatoid arthritis: Nabumetone versus naproxen double-blind parallel study

Nabumetone is a new nonsteroidal anti-inflammatory agent. Therapy with nabumetone 1,000 mg given at bedtime was compared with naproxen 250 mg given twice daily in a prospective double-blind study of patients with rheumatoid arthritis. Both drugs were found to be efficacious in a comparable fashion. Both drugs were well tolerated in terms of patient withdrawal rates, which were 5 and 8 percent, respectively. Gastrointestinal side effects were the most commonly encountered problem. Nabumetone holds promise as an important new therapeutic approach in arthritis.

Circulating immune complexes in the seronegative spondyloarthropathies

Abstract Circulating immune complexes (CIC) were determined in a large population of patients with seronegative spondyloarthropathies. In addition, we attempted to correlate the presence and levels of CIC with other parameters of disease activity in a serial fashion. CIC were measured using the Raji cell assay and the solid-phase Clq assay. A total of 92 patients were studied. These included 30 with ankylosing spondylitis (AS), 30 with psoriatic arthritis (PsA), 20 with Reiters syndrome, and 12 patients with Crohns arthritis (CA). Elevated levels of CIC were found in 73.3% (22 of 30) of AS patients, 60% (18 of 30) of PsA patients, 80% (16 of 20) of Reiters patients, and 67% (8 of 12) of Crohns patients studied. Both assays yielded concordant results. There was a significant correlation with disease activity, in particular arthritis, and the levels and incidence of CIC markedly declined in all groups when disease activity was under better control. Density gradient analysis of several sera revealed immune complex reactive material mainly in the 19 S region. This study suggests that CIC may play a role in the pathogenesis of some of the clinical manifestation of these conditions.