Treatment Options for Scleroderma
Scleroderma treatment should follow an organ-specific approach targeting affected systems, with methotrexate combined with systemic corticosteroids as first-line therapy for active, potentially disfiguring or disabling forms of the disease. 1
Types of Scleroderma and Treatment Approach
Systemic Sclerosis (SSc)
SSc is a complex systemic autoimmune disorder affecting multiple organ systems. Treatment must address specific organ involvement:
Raynaud's Phenomenon and Digital Vasculopathy
- Dihydropyridine-type calcium channel blockers (oral nifedipine) are first-line therapy 1
- PDE-5 inhibitors should be considered for SSc-related Raynaud's phenomenon and digital ulcers 1
- Intravenous iloprost for severe Raynaud's phenomenon that fails to respond to oral therapy 1
- Fluoxetine may be used as an alternative treatment option 1
Pulmonary Arterial Hypertension (PAH)
- Treatment options include endothelin receptor antagonists, prostacyclin analogues, PDE-5 inhibitors, and riociguat 1
Skin and Lung Involvement
- For rapidly progressive SSc with skin/lung involvement, hematopoietic stem cell transplantation may be considered in selected patients 1
- Cyclophosphamide has shown efficacy for skin involvement, quality of life, and function in two RCTs 2
- Methotrexate is recommended for skin involvement 1
Gastrointestinal Involvement
- Prokinetic agents are beneficial for GI motility disorders 1
Localized Scleroderma (Morphea)
Morphea is confined to the skin and/or subcutaneous tissues:
Assessment
- Standardized assessment using the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) is recommended 1, 3
- Classification based on subtype, extent, and depth should guide treatment decisions 1
Treatment Algorithm
- For limited, superficial lesions (circumscribed morphea): Topical treatments are generally sufficient 1, 3
- Medium-dose UVA1 therapy is effective in improving skin softness and reducing thickness 1, 3
- For linear, deep, generalized, or pansclerotic morphea: Methotrexate (15 mg/m²/week, oral or subcutaneous) combined with systemic corticosteroids during the initial inflammatory phase 1, 3
- For MTX-refractory or MTX-intolerant patients: Mycophenolate mofetil (500-1000 mg/m²) as second-line therapy 3
Special Considerations
Immunosuppressive Therapies
- Uncontrolled and retrospectively controlled studies with immunosuppressive regimens (azathioprine, mycophenolate mofetil, ciclosporine A) have reported efficacy in selected manifestations of SSc 2
- Caution is necessary when using cyclosporine as it may decrease renal function and induce hypertension 2
Other Treatments
- NSAIDs are generally not more harmful in SSc than in the general population, but formal evidence is lacking 2
- Drugs that improve calcinosis are currently lacking 2
- D-penicillamine and colchicine have been disappointing in clinical practice despite anecdotal evidence 4
Monitoring and Follow-up
- Regular clinical assessment using standardized tools is essential to monitor disease activity and response to treatment 1
- Close monitoring for medication side effects, particularly with MTX which may cause nausea, headache, and transient hepatotoxicity 1
- MTX or alternative disease-modifying drugs should be withdrawn once the patient is in remission and off steroids for at least 1 year 1
Common Pitfalls
- Inadequate treatment duration is a common pitfall; treatment should be continued for sufficient time to prevent relapse 3
- Underestimating the importance of treating skin disease aggressively can lead to significant physical and psychological morbidity 3
- Medications that are truly disease-modifying for SSc in terms of mortality are lacking, and the efficacy of treatments is often only modest to moderate 2
Referral Considerations
- In view of the heterogeneity of SSc, the complexity of diagnostic evaluation, and the wide array of available treatment options, patients with SSc should be referred to a specialized center 2