Systemic sclerosis is a complex autoimmune disease with significant morbidity and mortality, primarily due to pulmonary complications, including diffuse interstitial lung disease and pulmonary hypertension. The disease course is unpredictable due to its heterogeneous presentation. Our study aimed to form homogeneous cohorts of patients with severe visceral systemic sclerosis and assess their prognoses.

We conducted a single-centre retrospective observational study on 198 patients. These patients were clustered based on factors associated with poor disease prognosis using a bottom-up hierarchical clustering technique.

We identified four clusters in our population. Cluster 1 (n = 25) included 89% of patients with pulmonary hypertension, 64% of whom had associated interstitial lung disease. Cluster 2 (n = 11) included all patients with scleroderma renal crisis, 27% of whom developed pulmonary hypertension. Cluster 3 (n = 109) exclusively consisted of female patients, 90% of whom had a limited cutaneous form, with 62% presenting anticentromere antibodies. These patients did not exhibit severe pulmonary disease. Cluster 4 (n = 53) included patients with significant occupational exposure, 79% of whom had diffuse interstitial lung disease and 83% had anti-topoisomerase I antibodies. The survival rate was significantly lower in cluster 1 (p < 0.001).

This study characterized systemic sclerosis phenotypes, highlighting the heterogeneity in clinical presentation and disease course. The trajectory of patients within each cluster was associated with the onset of pulmonary hypertension onset, which adversely affected the prognosis.