What are the medical guidelines for treating systemic sclerosis?

Medical Guidelines for Treating Systemic Sclerosis

Immediate Referral and Early Intervention

Refer immediately to a specialized center upon suspicion of systemic sclerosis, particularly if early diffuse cutaneous disease or interstitial lung disease is detected, as early immunosuppressive therapy can prevent irreversible organ damage. 1, 2

The inflammation phase is potentially reversible if treated promptly, but delays result in irreversible fibrosis with permanent organ damage. 1, 2

---

Organ-Specific Treatment Approach

Raynaud's Phenomenon

• Dihydropyridine-type calcium channel blockers (e.g., oral nifedipine) are first-line therapy 3, 1, 4
• Consider phosphodiesterase-5 (PDE-5) inhibitors as second-line or for patients who fail calcium channel blockers 4
• Reserve intravenous iloprost for severe Raynaud's phenomenon unresponsive to oral therapy 4
• Fluoxetine may be used as an alternative treatment option 4

Digital Ulcers

• PDE-5 inhibitors should be considered for both prevention and treatment 4
• Approximately 50% of patients develop digital ulcers requiring specific management 1, 2

Skin Involvement (Diffuse Cutaneous Disease)

• Mycophenolate mofetil is first-line therapy for early diffuse cutaneous systemic sclerosis 1, 2
• Methotrexate combined with systemic corticosteroids is recommended for active, potentially disfiguring or disabling forms 4
• Cyclophosphamide has shown efficacy for skin involvement, quality of life, and function 4
• Assess skin involvement using the modified Rodnan skin score (0-51) to quantify disease extent and guide treatment 1, 2

Interstitial Lung Disease (ILD)

• Mycophenolate mofetil is first-line therapy for SSc-associated ILD 1, 2
• Cyclophosphamide is recommended for progressive SSc-ILD 5
• Tocilizumab and rituximab are emerging options with evidence-based support 6
• Perform high-resolution computed tomography (HRCT) for diagnosis 2, 6
• Obtain full pulmonary function tests with DLCO and ambulatory desaturation testing for disease monitoring 6

Pulmonary Arterial Hypertension (PAH)

• Initial combination therapy with PDE-5 inhibitors and endothelin receptor antagonists is recommended 1, 2
• Treatment options include endothelin receptor antagonists, prostacyclin analogues, PDE-5 inhibitors, and riociguat 4
• Screen systematically when DLCO is decreased, as this significantly increases PAH risk 1, 2
• Perform Doppler echocardiography for screening 7

Scleroderma Renal Crisis

• Initiate high-dose ACE inhibitors immediately upon diagnosis 2
• Monitor blood pressure and renal function closely, especially in patients with early diffuse cutaneous disease 1, 2
• Avoid glucocorticoids ≥15 mg/day, as this significantly increases renal crisis risk 1, 2

Gastrointestinal Involvement

• Proton pump inhibitors (PPIs) are first-line therapy for gastroesophageal reflux disease and should be prescribed aggressively 1, 2
• Reflux is present in approximately 90% of patients, with the esophagus being the most frequently affected digestive organ 1, 2
• Consider prokinetic agents for GI motility disorders 4
• Monitor closely for malnutrition, as it is the primary cause of mortality related to digestive involvement 1, 2

---

Critical Screening and Monitoring

Baseline Evaluation

• Chest radiography, pulmonary function tests, and HRCT if appropriate for ILD detection 1, 2
• DLCO measurement for PAH screening 1, 2
• Blood pressure and renal function monitoring 1, 2
• Assessment for gastroesophageal reflux 1, 2
• Modified Rodnan skin score for cutaneous involvement 1, 2

Comorbidity Screening

• Screen systematically for malignancy, particularly in elderly patients with rapidly progressive diffuse cutaneous disease 1, 2
• Evaluate for depression and osteoporosis, as these are frequent comorbidities requiring specific management 1, 2
• Ensure all vaccinations are current (pneumococcal, influenza, COVID-19) before initiating immunosuppressive therapy 1

---

Advanced Therapies for Severe Disease

Hematopoietic Stem Cell Transplantation

• Consider for rapidly progressive SSc with skin and/or lung involvement in selected patients where poor survival risk outweighs the high procedure-related mortality 4, 5

Alternative Immunosuppressive Agents

• Rituximab has shown improvement in cutaneous and lung involvement 5
• Azathioprine, ciclosporine A (with caution due to renal effects and hypertension risk) 4

---

Critical Pitfalls to Avoid

• Never delay immunosuppressive therapy in early diffuse disease or ILD—inflammation is reversible only if treated early 1, 2
• Strictly limit glucocorticoids to <15 mg/day to prevent scleroderma renal crisis 1, 2
• Do not overlook malnutrition screening in patients with GI involvement 1, 2
• Avoid cyclosporine without careful renal function and blood pressure monitoring 4
• Do not miss malignancy screening in high-risk patients (elderly, rapidly progressive disease, anti-RNA polymerase III antibodies) 2

---

Patient Education and Supportive Care

• Provide therapeutic education and self-management support to improve manual function, orofacial outcomes, quality of life, and ability to perform daily activities 1
• Implement lifestyle modifications to prevent complications such as digital ulcers and Barrett esophagus 7
• Ensure multidisciplinary care coordination given the complexity of multi-organ involvement 4, 7