What are the treatment options for scleroderma?

Treatment of Scleroderma

For localized scleroderma (morphea), treat active, potentially disfiguring or disabling forms with methotrexate 15 mg/m²/week combined with systemic corticosteroids during the initial inflammatory phase; for systemic sclerosis, use an organ-specific approach targeting Raynaud's phenomenon with calcium channel blockers, managing skin/lung involvement with immunosuppression, and aggressively treating gastrointestinal complications with proton pump inhibitors. 1

Classification-Based Treatment Approach

The treatment strategy fundamentally differs based on whether the patient has localized scleroderma (morphea) or systemic sclerosis (SSc), requiring initial classification by subtype, extent, and depth of involvement 1, 2.

Localized Scleroderma (Morphea) Treatment Algorithm

Assessment and Monitoring:

• Use the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) to evaluate disease activity and damage before initiating therapy 1, 2
• Perform skin biopsy from the most active sclerotic area when diagnostic uncertainty exists or atypical features are present 2

Treatment by Disease Extent:

Limited, Superficial Lesions (Circumscribed Morphea):

• Topical treatments are sufficient as these lesions are primarily of cosmetic concern 2
• Topical imiquimod decreases skin thickening by upregulating interferons that inhibit collagen production 2
• Medium-dose UVA1 therapy effectively improves skin softness and reduces thickness 1, 2

Linear, Deep, Generalized, or Pansclerotic Morphea:

• First-line therapy: Methotrexate 15 mg/m²/week (oral or subcutaneous) combined with systemic corticosteroids during the initial inflammatory phase 1, 2
• Maintain methotrexate for at least 12 months after achieving clinical improvement before tapering 2
• Monitor for methotrexate side effects including nausea, headache, and transient hepatotoxicity 1, 2
• Second-line therapy: Mycophenolate mofetil 500-1000 mg/m² for methotrexate-refractory or methotrexate-intolerant patients 2
• Biologics (TNF or IL-6 inhibitors) may be considered for severe recalcitrant morphea 2
• Withdraw disease-modifying drugs once the patient achieves remission and has been off steroids for at least 1 year 1, 2

Systemic Sclerosis (SSc) Treatment by Organ System

The American College of Rheumatology emphasizes that truly disease-modifying medications for systemic sclerosis mortality are lacking, and treatment efficacy is often only modest to moderate, necessitating referral to specialized centers 1.

Raynaud's Phenomenon:

• First-line: Dihydropyridine-type calcium channel blockers (oral nifedipine) as recommended by the European League Against Rheumatism 1
• Phosphodiesterase-5 (PDE-5) inhibitors for SSc-related Raynaud's phenomenon and digital ulcers 1
• Intravenous iloprost for severe Raynaud's phenomenon failing oral therapy 1
• Fluoxetine as an alternative treatment option 1

Skin and Lung Involvement:

• Cyclophosphamide for skin involvement, quality of life, and function with moderate strength of evidence 1
• Azathioprine, mycophenolate mofetil, and ciclosporine A have shown efficacy in selected manifestations, though based on uncontrolled and retrospectively controlled studies 1
• Exercise caution with cyclosporine as it may decrease renal function and induce hypertension 1
• Hematopoietic stem cell transplantation may be considered for rapidly progressive SSc with skin and/or lung involvement in selected patients 1

Pulmonary Arterial Hypertension (PAH):

• Treatment options include endothelin receptor antagonists, prostacyclin analogues, PDE-5 inhibitors, and riociguat 1

Gastrointestinal Involvement:

• Treat gastroesophageal reflux aggressively with proton pump inhibitors as first-line therapy 3
• Prokinetic agents for GI motility disorders 1, 3
• Address small intestinal bacterial overgrowth with rotating antibiotics 3
• Monitor closely for malnutrition, which is the leading cause of mortality attributed to GI involvement and may require enteral or parenteral nutrition 3
• Watch for signs of mechanical or pseudo-obstruction, which can be life-threatening in multi-organ involvement 3

Critical Pitfalls to Avoid

Inadequate Treatment Duration:

• Continuing treatment for sufficient time is essential to prevent relapse, particularly with morphea where treatment should extend at least 12 months after clinical improvement 2

Underestimating Skin Disease Severity:

• Aggressive treatment of skin disease is crucial as it is associated with significant physical and psychological morbidity 2

Misdiagnosis:

• Distinguish morphea from lichen sclerosus, especially in extragenital sites, through skin biopsy when uncertainty exists 2

Inadequate Monitoring:

• Regular clinical assessment using standardized tools (LoSCAT for morphea) is essential to monitor disease activity and treatment response 1, 2
• Close monitoring for medication side effects, particularly methotrexate-related complications, is necessary 1, 2

Nuances in Evidence Quality

The guideline evidence strongly supports methotrexate combined with corticosteroids as first-line therapy for active morphea, with consistent recommendations from the American College of Rheumatology 1, 2. For systemic sclerosis, the evidence is more heterogeneous, with the European League Against Rheumatism providing moderate-strength evidence for cyclophosphamide 1. The lack of truly disease-modifying therapies for SSc mortality underscores the importance of organ-specific management and early referral to specialized centers 1.