What is the recommended treatment for an adult with systemic sclerosis affecting the skin, joints, and interstitial lung disease?

Treatment of Systemic Sclerosis Affecting Joints, Skin, and Lungs

First-Line Therapy: Mycophenolate Mofetil

Mycophenolate mofetil (MMF) is the preferred initial treatment for systemic sclerosis with skin, joint, and interstitial lung disease involvement. 1

• MMF addresses all three disease manifestations simultaneously: it softens skin fibrosis, modifies disease trajectory, and treats pulmonary involvement 1, 2
• The 2023 EULAR guidelines designate MMF as the novel first-line intervention with strong recommendation based on high-quality evidence 1, 2
• MMF has surpassed cyclophosphamide as the initial therapy of choice, with mean modified Rodnan skin score improvement of approximately -4.90 points 1
• Start MMF as monotherapy for both skin and lung manifestations 3

Critical Baseline Assessments Required

Before initiating therapy, obtain:

• Pulmonary function tests (PFTs) with DLCO to detect subclinical ILD and establish baseline lung function 1
• High-resolution CT (HRCT) of the chest as the primary diagnostic tool for ILD 1, 4
• Echocardiogram to screen for pulmonary arterial hypertension 1
• Blood pressure monitoring to establish baseline for scleroderma renal crisis surveillance 1

Alternative First-Line Option

• Methotrexate (≈25 mg weekly) may be used when MMF is not tolerated or when musculoskeletal disease predominates, though evidence for joint disease benefit is limited 1, 3
• Methotrexate produces approximately 5-point improvement in modified Rodnan skin score 1

Critical Steroid Avoidance

Glucocorticoids are strongly contraindicated as first-line therapy in systemic sclerosis-ILD. 5

• The 2023 ACR/CHEST guidelines provide a strong recommendation against using glucocorticoids in SSc-ILD as first-line therapy 5
• Corticosteroid monotherapy is associated with substantial long-term morbidity in fibrotic lung disease 3
• Steroids increase risk of scleroderma renal crisis, particularly in early diffuse cutaneous SSc 1, 3
• Reserve steroids only for rapidly progressive ILD with acute respiratory failure or acute exacerbation scenarios 3

Adding Antifibrotic Therapy

Nintedanib should be added when ILD remains fibrotic and progressive despite adequate MMF therapy, particularly if forced vital capacity (FVC) falls below 80% of predicted. 1, 2

• Nintedanib provides targeted antifibrotic benefit and can be combined with MMF for synergistic effect addressing both inflammatory and fibrotic components 2
• Pirfenidone is an alternative antifibrotic agent, though supporting evidence is less robust than for nintedanib 1, 3

Second-Line Biologic Options

If disease progresses on MMF or MMF is contraindicated:

• Rituximab (anti-CD20) is incorporated into 2023 EULAR recommendations as a novel option for treating skin fibrosis and SSc-ILD 1, 2, 4
• Tocilizumab (anti-IL-6) is similarly recommended by EULAR for patients who fail to achieve adequate response to MMF 1, 2, 4
• Both biologics carry conditional recommendations 1, 2

Monitoring Strategy on MMF

• Serial PFTs every 3-6 months to track forced vital capacity (FVC) 1, 3
• Repeat HRCT at defined intervals to assess fibrosis progression 1, 3
• Monitor modified Rodnan skin score at each visit to quantify skin improvement 1
• Watch for progression indicators: worsening dyspnea, declining FVC >10%, or new HRCT changes 1, 3

Autologous Hematopoietic Stem Cell Transplantation

AHSCT should be considered for patients with very high-risk features: modified Rodnan skin score >24 or moderate skin disease with worsening ILD despite conventional immunosuppression. 1, 2

• Evidence shows improved survival in early diffuse cutaneous systemic sclerosis with high skin scores or progressive ILD 1, 2
• Must be performed in specialized centers with expertise in HSCT for systemic sclerosis after rigorous multidisciplinary benefit-to-risk assessment 2

Adjunctive Management for Raynaud Phenomenon

• Dihydropyridine calcium-channel blockers (e.g., nifedipine) are first-line for Raynaud phenomenon 1
• Phosphodiesterase-5 inhibitors or intravenous iloprost when calcium-channel blockers are insufficient 1
• Bosentan reduces incidence of new digital ulcers 1

Evidence Gaps for Joint Involvement

• There is lack of high-quality evidence that corticosteroids, tocilizumab, or rituximab improve joint manifestations in systemic sclerosis 1
• Abatacept has shown mixed results: case series suggest benefit for joint disease, but phase-2 trial did not demonstrate significant differences in swollen or tender joint counts at 12 months 1

Key Clinical Pitfalls to Avoid

• Do not assume skin score improvement signifies overall disease control—ILD may progress independently and requires separate monitoring and targeted antifibrotic therapy when indicated 2
• Avoid chronic corticosteroid use; if steroids must be used, keep doses ≤15 mg/day prednisone equivalent to minimize scleroderma renal crisis risk 3
• Monitor closely in first few years after diagnosis, as risk of developing ILD is greatest early in the disease course 6