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

Management of Limited Systemic Sclerosis

Limited cutaneous systemic sclerosis (lcSSc) requires organ-based surveillance and targeted treatment of specific manifestations, as there is currently no proven disease-modifying therapy for early lcSSc itself. 1

Key Management Principles

The management approach differs fundamentally from diffuse cutaneous SSc because:

• Appropriate treatment for patients with early limited cutaneous SSc is unknown, and further research is needed 1
• Treatment focuses on organ-specific complications rather than disease modification 1
• Nearly all patients require management of Raynaud's phenomenon and screening for internal organ involvement 1

Organ-Based Management Algorithm

1. Raynaud's Phenomenon (Present in Nearly All Patients)

First-line therapy:

• Dihydropyridine calcium channel blockers (especially nifedipine) should be used as first-line therapy 1
• Nifedipine reduces the frequency and severity of ischemic attacks with a weighted mean difference of -10.21 attacks over 2 weeks 1

Second-line therapy:

• Phosphodiesterase-5 inhibitors (sildenafil, tadalafil) should be added in patients with severe Raynaud's or those who do not satisfactorily respond to calcium channel blockers 1
• PDE-5 inhibitors provide moderate improvement in frequency (-0.49 attacks/day), severity (-0.46 points), and duration (-14.62 minutes/day) 1

Third-line therapy:

• Intravenous iloprost should be considered for severe, refractory cases 1

2. Digital Ulcers

Prevention strategy:

• Start with calcium channel blockers, then add PDE-5 inhibitors 1, 2
• Bosentan can reduce the development of new digital ulcers, especially in patients with multiple (≥4) digital ulcers at baseline 1
• Bosentan is particularly indicated for patients who have multiple digital ulcers despite treatment with calcium channel blockers, PDE-5 inhibitors, and iloprost 1

Active ulcer treatment:

• Intravenous iloprost (0.5-2 ng/kg/min for 3-5 consecutive days) should be considered for healing active digital ulcers 1

3. Interstitial Lung Disease (ILD) Screening and Management

Screening protocol:

• All patients should undergo baseline pulmonary function tests (PFTs) and high-resolution CT of the lungs 1
• ILD is clinically meaningful in 12% of patients with lcSSc 1
• Patients with anti-topoisomerase 1 (anti-Scl-70) antibodies are at particularly high risk regardless of disease subset 1

Treatment if ILD develops:

• Mycophenolate mofetil has surpassed cyclophosphamide as the initial treatment for SSc-interstitial lung disease 1
• If ILD is fibrotic and progressing, nintedanib (and possibly pirfenidone) can be added as anti-fibrotic therapy 1
• Rituximab or tocilizumab may be considered as second-line agents 1, 3

4. Pulmonary Arterial Hypertension (PAH) Screening and Management

Screening:

• Serial PFTs to monitor for disproportionate decline in DLCO (diffusing capacity) 1
• Echocardiography and right heart catheterization when PAH is suspected 1

Treatment:

• Initial combination therapy with phosphodiesterase-5 inhibitors and endothelin receptor antagonists should be considered 1
• If necessary, add a prostacyclin analogue 1
• Continuous intravenous epoprostenol improves exercise capacity and hemodynamic measures in severe SSc-PAH 1

5. Gastrointestinal Manifestations (Affects ~90% of Patients)

Gastroesophageal reflux disease:

• Proton pump inhibitors should be used for prevention of gastro-oesophageal reflux, esophageal ulcers and strictures 1
• Exceed maximum recommended PPI dose if required (supported by >50% of experts) 2

Motility disturbances:

• Prokinetic drugs should be used for symptomatic motility disturbances (dysphagia, early satiety, bloating, pseudo-obstruction) 1

Bacterial overgrowth:

• Rotating antibiotics may be useful when malabsorption is caused by bacterial overgrowth 1

6. Scleroderma Renal Crisis (SRC) - Critical Complication

Treatment:

• ACE inhibitors should be used immediately in the treatment of SRC 1
• ACE inhibitors improve 1-year survival to 76% and 5-year survival to 66% compared to 15% and 10% without treatment 1

Critical caveat:

• Corticosteroids are associated with higher risk of SRC; patients on steroids should be carefully monitored for blood pressure and renal function 1
• Avoid high-dose corticosteroids (≥15 mg/day prednisone), which increase SRC risk 4-fold 4

Monitoring Schedule

Regular assessments should include:

• Blood pressure monitoring (home monitoring if high-risk features present) 4
• Pulmonary function tests every 3-6 months 3
• Skin examination for digital ulcers and assessment for tendon friction rubs 4
• Renal function monitoring, especially if on corticosteroids 1
• Periodic echocardiography to screen for PAH 1

Critical Pitfalls to Avoid

• Do not use high-dose corticosteroids (≥15 mg/day) as they quadruple the risk of scleroderma renal crisis 4
• Do not delay ACE inhibitor initiation if renal crisis develops; sudden drug withdrawal of epoprostenol can be life-threatening 1
• Do not assume stable disease means no monitoring is needed; ILD progression can occur at any disease duration 1
• Hormonal contraceptives may not be reliable if co-administered with bosentan due to cytochrome P450 interference 1
• Monitor for liver toxicity with bosentan and other endothelin receptor antagonists 1

Non-Pharmacological Management

• Patient education and support for physical exercise should be offered 1
• Smoking cessation and avoidance of cold exposure are important 1
• Hand and mouth exercises are important in SSc 1