What is the management approach for a patient with systemic sclerosis?

Management of Systemic Sclerosis

Mycophenolate mofetil is the first-line treatment for progressive skin fibrosis and interstitial lung disease in systemic sclerosis, with tocilizumab and nintedanib serving as critical additions for specific manifestations. 1, 2

Initial Risk Stratification and Organ Assessment

Classify disease subtype immediately:

• Limited cutaneous SSc: skin involvement distal to elbows/knees only 2
• Diffuse cutaneous SSc: proximal and/or truncal skin involvement, which carries higher risk for rapid progression and internal organ involvement 2

Obtain autoantibody profile to predict organ involvement: 2

• Anti-topoisomerase I (Scl-70): high risk for interstitial lung disease 3
• Anti-centromere: associated with limited disease and pulmonary arterial hypertension risk 2
• Anti-RNA polymerase III: significantly elevated risk for scleroderma renal crisis and malignancy 3, 4

Quantify skin involvement using modified Rodnan skin score at 17 anatomical sites to identify high-risk patients and guide treatment intensity. 2, 4

Mandatory Baseline Organ Screening

Pulmonary assessment (perform in all patients): 2, 3

• Chest radiography, pulmonary function tests with DLCO, and high-resolution CT 3
• Decreased DLCO mandates further evaluation for pulmonary arterial hypertension 3

Cardiovascular screening: 3

• Echocardiography for pulmonary arterial hypertension screening 2
• Institute regular blood pressure monitoring, particularly with anti-RNA polymerase III antibodies (high scleroderma renal crisis risk) 3

Gastrointestinal evaluation: 3, 4

• Assess for gastroesophageal reflux (present in ~90% of patients) 4
• Screen for malnutrition, which is the primary cause of mortality from gastrointestinal involvement 4

Treatment Algorithm by Disease Manifestation

Skin Fibrosis and Early Diffuse Disease

First-line therapy: Mycophenolate mofetil for progressive skin and lung involvement in early diffuse cutaneous SSc. 1, 2, 4

Second-line options: 1, 2

• Methotrexate for less severe skin involvement and musculoskeletal disease 2
• Rituximab for severe and refractory systemic manifestations 1, 2
• Tocilizumab (162 mg subcutaneously weekly) is now FDA-approved and EULAR-recommended for SSc-associated interstitial lung disease 1, 5

Critical timing consideration: Inflammation is potentially reversible if treated early, but transforms into irreversible fibrosis with permanent organ damage if treatment is delayed. 3

Interstitial Lung Disease (SSc-ILD)

First-line: Mycophenolate mofetil 1, 2, 4

Add nintedanib if ILD is fibrotic and progressing despite immunosuppression. 1, 2

Tocilizumab 162 mg subcutaneously weekly is FDA-approved for SSc-ILD and represents a novel biologic option. 1, 5

Pulmonary Arterial Hypertension

Initiate combination therapy immediately with phosphodiesterase-5 inhibitor PLUS endothelin receptor antagonist. 2, 3, 4

Add prostacyclin analogue if inadequate response to initial combination therapy. 2

Scleroderma Renal Crisis

Start high-dose ACE inhibitors immediately upon detection of elevated blood pressure or rising creatinine. 3

Critical pitfall: Risk of renal crisis increases significantly with glucocorticoid doses ≥15 mg/day—avoid high-dose steroids. 4

Raynaud's Phenomenon

First-line: Dihydropyridine calcium channel blockers 2, 3, 4

Gastrointestinal Manifestations

Treat gastroesophageal reflux aggressively with proton pump inhibitors as first-line therapy. 3, 4

Musculoskeletal Involvement

Methotrexate for arthritis and less severe skin involvement 2

Dose Modifications and Monitoring

For tocilizumab (when used for SSc-ILD): 5

• Dose: 162 mg subcutaneously once weekly 5
• Interrupt dosing for elevated liver enzymes, neutropenia, or thrombocytopenia 5
• Monitor: ALT/AST, neutrophil count, platelet count, lipid parameters 5

Laboratory monitoring for all immunosuppressive therapy: 1, 2

• Baseline and periodic liver enzymes, complete blood count
• Interrupt or reduce dosing for significant laboratory abnormalities 5

Critical Clinical Pitfalls to Avoid

Screen systematically for malignancy, particularly in older patients with rapidly progressive disease, weight loss, and anti-RNA polymerase III antibodies. 3

Ensure all vaccinations (pneumococcal, influenza, COVID-19) are current BEFORE starting immunosuppressive therapy. 3

Evaluate and treat depression and osteoporosis, as these comorbidities are frequent and impact outcomes. 3

Avoid glucocorticoid doses ≥15 mg/day due to significantly increased scleroderma renal crisis risk. 4

Multidisciplinary Coordination and Ongoing Monitoring

Rheumatology leads treatment with mandatory coordination across pulmonology, cardiology, nephrology, gastroenterology, and physical/occupational therapy. 2

Annual screening protocol: 2

• Pulmonary function tests and echocardiography for ILD and PAH surveillance
• Regular disease activity assessment with therapeutic adjustment 2

Consider patient education and self-management support to improve hand function, orofacial outcomes, quality of life, and ability to perform daily activities. 4

Refer immediately to specialized scleroderma center for confirmation and treatment initiation, as early immunosuppressive intervention can prevent irreversible organ damage. 3