Predictors and outcomes of scleroderma renal crisis: The High-Dose Versus Low-Dose D-Penicillamine in early diffuse systemic sclerosis trial

Objective. The reported frequency of scleroderma M01-R renal crisis (SRC) in diffuse systemic sclerosis (SSc; scleroderma) is 15-20%. Early use of angiotensin-converting enzyme (ACE) inhibitors has markedly improved outcome. The present analysis reexamines the prognostic factors for and outcome of SRC in a prospective cohort of patients with early diffuse SSc. Methods. We retrospectively evaluated the cohort of SSc patients who participated in the High-Dose Versus Low-Dose D-Penicillamine in Early Diffuse SSc trial. Patients with diffuse cutaneous scleroderma were enrolled if their disease duration was <18 months. Because the trial failed to show a difference between treatment groups, the data were pooled. Results. One hundred thirty-four SSc patients entered the observation period a mean ± SD of 0.8 ± 0.3 years after onset of SSc. SRC occurred in 18 patients a mean ± SD of 0.9 ± 1.1 years after entry. During a mean ± SD 4.0 ± 1.1 years of followup after entry, 9 of the 18 patients died (mean ± SD 0.6 ± 0.9 years after SRC onset). Baseline characteristics that predicted SRC included a modified Rodnan skin thickness score of ≥20 (P < 0.01), enlarged cardiac silhouette on radiograph (P = 0.04), large joint contractures (wrist, elbow, knee) (P = 0.008), and prednisone use at entry (P = 0.01). Baseline characteristics that did not predict SRC included age, sex, race, Health Assessment Questionnaire score, fist closure, handspread, lung involvement, muscle weakness, erythrocyte sedimentation rate, and platelet count. In 5 of 10 subjects for whom at least 2 sequential skin scores were available, skin scores increased significantly (P = 0.012) in the 6 months before onset of SRC. Conclusion. SRC occurred in 13% of patients soon (mean 11 months) after entry into the cohort. Predictors of SRC identified in this study included higher than average skin score, prednisone use at study entry, large joint contractures, and heart enlargement. Our data suggest, however, that low-dose prednisone alone was not associated with the onset of SRC, except in the appropriate clinical setting. Although ACE inhibitors and dialysis are now readily available, SRC continues to be associated with poor survival (in this study, 50% of patients with SRC died).