Systemic Sclerosis Treatment
Systemic sclerosis requires an organ-specific treatment approach targeting each affected system, with the most recent EULAR guidelines (2017) providing comprehensive evidence-based recommendations for managing vascular, pulmonary, skin, renal, and gastrointestinal complications. 1
Treatment Framework by Organ System
Raynaud's Phenomenon and Digital Vasculopathy
- Dihydropyridine-type calcium channel blockers (oral nifedipine) are first-line therapy for Raynaud's phenomenon 2
- PDE-5 inhibitors should be considered for both SSc-related Raynaud's phenomenon and digital ulcers 1, 2
- Fluoxetine may be used as an alternative treatment option for SSc-related Raynaud's phenomenon 1, 2
- Intravenous iloprost should be considered for severe Raynaud's phenomenon that fails oral therapy 2
Pulmonary Arterial Hypertension (PAH)
Treatment options include multiple drug classes with strong evidence 1, 2:
- Endothelin receptor antagonists
- Prostacyclin analogues
- PDE-5 inhibitors
- Riociguat (newly added in 2017 update) 1
Interstitial Lung Disease (ILD)
Mycophenolate mofetil, tocilizumab, and rituximab are recommended as first-line immunosuppressive therapies for SSc-ILD 3:
- Cyclophosphamide is recommended for skin involvement, quality of life, and function with moderate strength of evidence 2
- Immunosuppressive therapy should target both skin and lung fibrosis 4
- Antifibrotic therapy plays an adjunctive role 3
Skin Disease
For active, potentially disfiguring or disabling forms: methotrexate combined with systemic corticosteroids is first-line therapy 2:
- Cyclophosphamide shows efficacy for skin involvement 2
- Other immunosuppressive agents (azathioprine, mycophenolate mofetil, ciclosporine A) have shown efficacy in selected manifestations, though evidence is from uncontrolled studies 2
Critical caveat: Cyclosporine may decrease renal function and induce hypertension, requiring careful monitoring 2
Rapidly Progressive Disease
Hematopoietic stem cell transplantation should be considered in selected patients with rapidly progressive SSc affecting skin and/or lung 1, 2:
- This represents a major addition to the 2017 guidelines 1
- Reserved for carefully selected patients with aggressive disease 3
Scleroderma Renal Crisis
- ACE inhibitors are the standard of care (though specific recommendations are referenced in the guidelines) 1
- Early recognition and aggressive treatment are critical for mortality reduction 4
Gastrointestinal Involvement
Aggressive treatment with proton pump inhibitors as first-line therapy for gastroesophageal reflux 5:
- Prokinetic agents for GI motility disorders 1, 2, 5
- Rotating antibiotics for small intestinal bacterial overgrowth 5
- Close monitoring for malnutrition, which is the leading cause of mortality from GI involvement 5
- Enteral or parenteral nutrition may be required 5
Critical Management Principles
Referral and Monitoring
Patients with systemic sclerosis should be referred to a specialized center due to disease heterogeneity, diagnostic complexity, and the wide array of treatment options 2:
- Regular clinical assessment using standardized tools is essential to monitor disease activity and treatment response 2
- Close monitoring for medication side effects, particularly with methotrexate (nausea, headache, transient hepatotoxicity) 2
Treatment Withdrawal
- Methotrexate or alternative disease-modifying drugs should be withdrawn once the patient is in remission and off steroids for at least 1 year 2
Important Caveats
Truly disease-modifying medications for systemic sclerosis in terms of mortality are lacking, and treatment efficacy is often only modest to moderate 2:
- The disease presents significant morbidity and mortality despite recent advances 6
- Some patients do not respond to treatment and deteriorate even with adequate therapy, representing difficult-to-treat cases 6
- Early combination therapy with vasodilators, immunosuppressive and antifibrotic drugs should be started from disease onset to successfully downregulate progression 7