What is the recommended treatment for a patient with scleroderma?

Treatment of Scleroderma

Treatment for scleroderma must be organ-specific and manifestation-directed, with immediate ACE inhibitor therapy for renal crisis, cyclophosphamide for interstitial lung disease with severe involvement, calcium channel blockers for Raynaud's phenomenon, and methotrexate with corticosteroids for active localized disease. 1, 2

Systemic Sclerosis (SSc) - Organ-Based Treatment Algorithm

Scleroderma Renal Crisis (SRC)

• Immediately initiate high-dose ACE inhibitors at the first sign of blood pressure elevation or renal dysfunction - this is life-saving therapy with 1-year survival improving from 15% without treatment to 76% with ACE inhibitors 1
• Continue ACE inhibitors long-term as kidney function may continue to improve over months 1
• Critical pitfall: Do NOT use ACE inhibitors prophylactically - published evidence does not support preventive use and may paradoxically worsen outcomes 1

Interstitial Lung Disease (ILD)

• Cyclophosphamide is indicated for patients with FVC <70% predicted OR extensive HRCT involvement (≥50% of any lung zone with reticular infiltrates) OR modified Rodnan skin score ≥23 1
• Treatment effect is substantial in severe disease: 9.81% FVC improvement at 18 months (p<0.001) versus no benefit in mild disease 1
• Patients with baseline FVC <70% show 6.8% improvement at 18 months (p<0.006), while those with FVC >70% show minimal benefit 1
• Alternative regimen: IV cyclophosphamide 600 mg/m²/month for 6 months followed by azathioprine 2.5 mg/kg/day 1

Raynaud's Phenomenon and Digital Ulcers

• First-line: Dihydropyridine calcium channel blockers (oral nifedipine) with Level 1a evidence 3, 2
• Second-line: PDE-5 inhibitors as alternative or adjunctive therapy with Level 1a evidence 3, 2
• For severe/refractory cases: IV iloprost after oral therapy failure, particularly when associated with digital ulcers 3, 2
• Fluoxetine may be considered as an alternative option 2

Rapidly Progressive Disease

• Hematopoietic stem cell transplantation (HSCT) should be considered for rapidly progressive SSc at risk of organ failure, but only in specialized centers with expertise 1, 2
• This carries significant treatment-related mortality risk and requires careful benefit-to-risk assessment by experts 1
• Reserved for patients with early diffuse disease, modified Rodnan skin score ≥15, and internal organ involvement 1

Gastrointestinal Manifestations

• Prokinetic drugs are recommended for SSc-related GI motility disorders 1, 2

Skin Disease

• For diffuse cutaneous disease with vascular manifestations, consider methotrexate, mycophenolate mofetil, or rituximab with Level 1a-1b evidence 3, 2
• Cyclophosphamide also benefits skin involvement, quality of life, and function 2

Localized Scleroderma (Morphea)

Limited Superficial Disease (Circumscribed Morphea)

• Topical treatments are generally sufficient 2
• Medium-dose UVA1 therapy improves skin softness and reduces thickness 2

Active Linear, Deep, Generalized, or Pansclerotic Morphea

• First-line: Methotrexate 15 mg/m²/week (oral or subcutaneous) combined with systemic corticosteroids during the initial inflammatory phase 2
• This is the standard of care for potentially disfiguring or disabling forms 2
• Withdraw MTX or alternative disease-modifying drugs once in remission and off steroids for at least 1 year 2
• Monitor for MTX side effects including nausea, headache, and transient hepatotoxicity 2

Assessment and Monitoring

• Use standardized Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) to evaluate disease activity and damage 2
• Classification based on subtype, extent, and depth guides treatment decisions 2

Critical Management Principles

Referral Pathways

• All patients require rheumatology referral as the primary specialist to coordinate multidisciplinary care 4
• Immediate pulmonology referral for suspected ILD, especially with anti-topoisomerase I (Scl-70) antibodies 4
• Urgent nephrology referral for any blood pressure elevation or renal dysfunction 4
• Baseline cardiology evaluation for cardiac involvement and pulmonary arterial hypertension screening 4
• Gastroenterology for GI manifestations 4
• Physical and occupational therapy to maintain function and range of motion 4

Important Pitfalls to Avoid

• Avoid glucocorticoids in early diffuse cutaneous SSc due to increased scleroderma renal crisis risk 4
• Do not use ACE inhibitors prophylactically to prevent renal crisis 1
• Cyclosporine requires caution as it may decrease renal function and induce hypertension 2
• Historical agents like D-penicillamine and colchicine have been disappointing despite anecdotal evidence 5

Disease Heterogeneity Considerations

The strength of evidence varies significantly: while ACE inhibitors for renal crisis show dramatic mortality benefit despite lack of RCTs, cyclophosphamide for ILD shows only modest benefits in selected populations 1. No single therapy is disease-modifying for overall SSc mortality, making organ-specific targeting essential 2, 6. Treatment must be initiated early before irreversible organ damage occurs to improve both quality of life and survival 6.