Faculty Bibliography

BACKGROUND: There is concern that exogenous female hormones may worsen disease activity in women with systemic lupus erythematosus (SLE). OBJECTIVE: To evaluate the effect of hormone replacement therapy (HRT) on disease activity in postmenopausal women with SLE. DESIGN: Randomized, double-blind, placebo-controlled noninferiority trial conducted from March 1996 to June 2002. SETTING: 16 university-affiliated rheumatology clinics or practices in 11 U.S. states. PATIENTS: 351 menopausal patients (mean age, 50 years) with inactive (81.5%) or stable-active (18.5%) SLE. Interventions: 12 months of treatment with active drug (0.625 mg of conjugated estrogen daily, plus 5 mg of medroxyprogesterone for 12 days per month) or placebo. The 12-month follow-up rate was 82% for the HRT group and 87% for the placebo group. MEASUREMENTS: The primary end point was occurrence of a severe flare as defined by Safety of Estrogens in Lupus Erythematosus, National Assessment-Systemic Lupus Erythematosus Disease Activity Index composite. RESULTS: Severe flare was rare in both treatment groups: The 12-month severe flare rate was 0.081 for the HRT group and 0.049 for the placebo group, yielding an estimated difference of 0.033 (P = 0.23). The upper limit of the 1-sided 95% CI for the treatment difference was 0.078, within the prespecified margin of 9% for noninferiority. Mild to moderate flares were significantly increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person-year for placebo (relative risk, 1.34; P = 0.01). The probability of any type of flare by 12 months was 0.64 for the HRT group and 0.51 for the placebo group (P = 0.01). In the HRT group, there were 1 death, 1 stroke, 2 cases of deep venous thrombosis, and 1 case of thrombosis in an arteriovenous graft; in the placebo group, 1 patient developed deep venous thrombosis. LIMITATIONS: Findings are not generalizable to women with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis. CONCLUSIONS: Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. Most of these flares are mild to moderate. The benefits of HRT can be balanced against the risk for flare because HRT did not significantly increase the risk for severe flare compared with placebo

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine. Agents that neutralize TNF-alpha are effective in the treatment of disorders such as rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), spondyloarthropathies, and inflammatory bowel disease. TNF-alpha antagonist therapy has been associated with the development of antinuclear antibodies (ANA) and double-stranded DNA (dsDNA) antibodies, as well as the infrequent development of systemic lupus erythematosus (SLE)-like disease. We describe the first case of biopsy-confirmed proliferative lupus nephritis and leukocytoclastic vasculitis in a patient treated with etanercept for JRA

Aplastic anemia is a rare but serious complication of systemic lupus erythematosus (SLE) with an often dramatic and unanticipated onset. The peripheral destruction of formed blood elements, which frequently accompanies the syndrome, may obscure or delay the diagnosis of bone marrow suppression, and the number of published cases may be an underestimate of the actual incidence of the disease. Furthermore, the disease course may differ significantly from other forms of acquired aplastic anemia and seems to carry a more favorable prognosis once effectively diagnosed and treated. In addition, aplastic anemia may precede other manifestations of SLE. Therefore, the possibility of bone marrow aplasia should be excluded in all SLE patients with severe pancytopenia, and conversely, the diagnosis of SLE should be explored in cases of aplastic anemia. Two patients with aplastic anemia in SLE, one with aplastic anemia preceding the onset of SLE, are described along with 15 cases reviewed from the English language literature. The presentation, prognosis, treatment, and pathogenesis of aplastic anemia complicating SLE are discussed. Recognition that cytopenias, especially pancytopenia, may occur on the basis of inhibited myelopoesis rather than peripheral destruction as either a harbinger of SLE or as a manifestation of disease flare is important. This knowledge will prompt the astute clinician to obtain screening antinuclear antibodies in the setting of otherwise unexplained bone marrow acellularity or, given the prognosis of SLE associated aplastic anemia, give early consideration to more aggressive immunosuppression

OBJECTIVE: In flares of systemic lupus erythematosus (SLE), endothelial cells (EC; activated by immune stimuli) are potential participants in the inflammatory processes that contribute to tissue damage. Accordingly, elevated levels of circulating endothelial cells (CEC) may be a marker for vascular injury. This study was undertaken to examine the possibility that stimulated EC are found in the circulation in patients with active SLE. METHODS: The study cohort included 38 patients with SLE and 16 healthy controls. Immunostaining was performed on mononuclear isolates, using mouse P1H12 (endothelial-specific antibody) and rabbit antinitrotyrosine (a 'footprint' of a reactive form of nitric oxide [peroxynitritel). RESULTS: Levels of CEC were significantly higher in patients with active SLE compared with those in healthy controls (mean +/- SEM 32+/-7/ml versus 5+/-2/ml; P = 0.0028) and were correlated positively with plasma C3a in these patients (r = 0.81, P = 0.0008). Furthermore, CEC from these patients expressed an activated phenotype, as indicated by staining for nitrotyrosine. CONCLUSION: Elevated levels of CEC observed in patients with active SLE may represent a marker of endothelial injury. The activated phenotype of these cells suggests that they may be capable of further potentiating vascular injury by the production of inflammatory and prothrombotic mediators and engaging in heterotypic aggregation with neutrophils or platelets