Systemic sclerosis therapy reference (2026)

Systemic sclerosis (SSc) therapy in 2026 organises around organ-specific manifestations plus emerging disease-modifying approaches.

Raynaud phenomenon and digital ulcers: calcium channel blockers (nifedipine, amlodipine), PDE5 inhibitors (sildenafil, tadalafil), iloprost in severe cases, bosentan for prevention of new digital ulcers in selected patients.

Skin involvement: methotrexate, mycophenolate, sometimes intravenous immunoglobulin or rituximab in severe diffuse skin disease.

Interstitial lung disease (SSc-ILD): tocilizumab carries SSc-ILD approval. Nintedanib has SSc-ILD approval as antifibrotic therapy. Mycophenolate is widely used; cyclophosphamide is an alternative for severe disease. Combination strategies (tocilizumab plus nintedanib, or mycophenolate plus nintedanib) are increasingly used.

Pulmonary hypertension associated with SSc: PAH-specific therapy applies (covered in earlier rounds).

Gastrointestinal involvement: proton pump inhibitor for reflux, prokinetics for dysmotility, antibiotics for small intestinal bacterial overgrowth.

Renal involvement (scleroderma renal crisis): ACE inhibitor (captopril traditionally) is the foundation, often combined with broader supportive care.

Severe refractory disease: hematopoietic stem cell transplant in selected patients.

Emerging disease-modifying tier: anifrolumab in late-stage scleroderma trials, novel B-cell-targeted programs, anti-fibroblast and autotaxin pathway programs in late-stage trials.

The diagnostic-pathway and care-pathway question matters. Multidisciplinary scleroderma clinics (rheumatology with pulmonology with cardiology with gastroenterology with dermatology) deliver the most comprehensive care.