Objective: To describe a group of patients with systemic sclerosis (SSc) and diffuse cutaneous (dc) involvement with isolated pulmonary hypertension (IPHT) and to compare them to 2 other SSc patient groups, i.e., one with limited cutaneous (lc) involvement with IPHT and another with dcSSc without IPHT.
Methods: The Pittsburgh Scleroderma Databank was screened to identify appropriate patients. SSc specific serum autoantibodies were determined using published methods. Chi-squared tests and Kaplan-Meier survival analysis were performed.
Results: During the period 1975-92, 60 of 580 (10%) consecutive new patients with lcSSc and 14 of 677 (2%) with dcSSc have developed IPHT (p < 0.0001). The patients with IPHT did not differ from their parent dc or lc groups by age, race, sex, or cutaneous manifestations. All 14 patients with dcSSc IPHT had minimal or no pulmonary interstitial fibrosis on chest radiograph. The 12 tested had a striking reduction in DLCO (mean 50% of predicted normal), similar to results for patients with lcSSc with IPHT. Of note, 5 of these 14 patients had survived "scleroderma renal crisis" 1.3 to 10.7 (mean 5.5) years before onset of IPHT. Six of 13 (46%) patients with dcSSc with IPHT were positive for serum anti-U3RNP antibody by immunoprecipitation, and one had the typical nucleolar staining pattern of anti-U3RNP, but was not tested for U3RNP by immunoprecipitation. In contrast, only 13 (6%) of the 244 patients with dcSSc without IPHT (p < 0.0001) had anti-U3RNP antibody. Survival from the first reported symptom consistent with pulmonary hypertension (usually dyspnea on exertion) was uniformly poor in both IPHT groups, with the vast majority of patients dying during the first 2 years.
Conclusion: Patients with SSc with dc involvement can develop severe, fatal isolated pulmonary arterial hypertension. This complication occurs disproportionately more often in patients with serum anti-U3RNP antibody.