What is the initial treatment for scleroderma?

Initial Treatment for Scleroderma

Methotrexate (15 mg/m²/week) is recommended as first-line therapy for extensive or disfiguring forms of scleroderma, particularly for skin manifestations in early diffuse cutaneous systemic sclerosis (dcSSc). 1

Treatment Algorithm Based on Disease Subtype

For Diffuse Cutaneous Systemic Sclerosis (dcSSc):

1. First-line options:

   • Mycophenolate mofetil (MMF) (500-1000 mg/m²): Most commonly used first-line drug for skin manifestations, especially beneficial when interstitial lung disease (ILD) is present 2, 1
   • Methotrexate (15 mg/week initially, can be increased to 25 mg/week): Shown in RCTs to improve skin scores compared to placebo 2

2. For rapidly progressive early dcSSc:

   • Consider autologous hematopoietic stem cell transplantation for patients with high mortality risk, such as those with very high skin scores or moderate skin involvement with worsening ILD 2, 1

3. Alternative/second-line options:

   • Cyclophosphamide: Effective for both skin and lung involvement, but has higher toxicity profile 2, 1
   • Rituximab: For refractory cases 2, 1
   • Tocilizumab: Particularly if inflammatory markers are elevated 2

For Localized Scleroderma (Morphea):

1. Limited lesions:

   • Topical corticosteroids 1
   • UVA1 phototherapy for circumscribed lesions 1

2. Extensive lesions:

   • Methotrexate (15 mg/m²/week) 1

Organ-Specific Treatment

Interstitial Lung Disease:

• First-line: Mycophenolate mofetil 2, 1
• For severe cases: Cyclophosphamide 2, 1
• For progressive fibrotic ILD: Add nintedanib 2, 1

Raynaud's Phenomenon:

• First-line: Calcium channel blockers (dihydropyridines, especially nifedipine) 2, 1
• Second-line: Phosphodiesterase-5 inhibitors or IV iloprost 2, 1

Gastrointestinal Involvement:

• For GERD: Proton pump inhibitors 1
• For motility disorders: Prokinetic agents 1
• For bacterial overgrowth: Rotating antibiotics 1

Pulmonary Arterial Hypertension:

• Initial therapy: Combined phosphodiesterase-5 inhibitors and endothelin receptor antagonists 2, 1
• Add if necessary: Prostacyclin analogs 2, 1

Scleroderma Renal Crisis:

• Immediate treatment: High-dose ACE inhibitors 1
• Caution: Avoid corticosteroids as they are associated with higher risk of renal crisis 2

Important Considerations

• Early intervention is crucial: Treatment should be initiated promptly after diagnosis to prevent irreversible organ damage and improve mortality outcomes
• Monitoring: Regular evaluation of pulmonary function, HRCT of chest, and echocardiography is essential, especially during the first 3 years of disease 1
• Duration of treatment: For methotrexate, treatment should continue for at least 12 months after achieving acceptable clinical improvement 1
• Caution with steroids: Four retrospective studies suggest that steroids are associated with a higher risk of scleroderma renal crisis. Patients on steroids should be carefully monitored for blood pressure and renal function 2

Treatment Efficacy Evidence

• Methotrexate has shown improvement in skin scores in two RCTs, with the larger study showing a between-group difference of approximately 5 points in modified Rodnan skin score (mRSS) compared to placebo 2
• Mycophenolate mofetil has demonstrated significant improvement in mRSS at 12 months compared to historical controls (-7.59 vs -2.47 with D-penicillamine, p<0.001) 3
• Cyclophosphamide has been studied in 11 RCTs and showed a 3-point improvement in mRSS compared to placebo in the Scleroderma Lung Study I 2

The treatment approach should be tailored based on disease subtype, extent of organ involvement, and disease activity, with early aggressive intervention for patients with poor prognostic factors to improve long-term outcomes and reduce mortality.