Dermatology MCQ - Inflammatory Dermatoses - Systemic sclerosis management

A 62-year-old woman with a 10-year history of limited cutaneous systemic sclerosis (anti-centromere positive) presents with progressive dyspnea on exertion and fatigue. An echocardiogram shows an elevated right ventricular systolic pressure of 65 mmHg with a normal left ventricular ejection fraction. Right heart catheterization confirms pre-capillary pulmonary arterial hypertension. Which of the following is the most appropriate first-line pharmacologic therapy for this complication?

A. High-dose oral prednisone
B. An endothelin receptor antagonist (e.g., bosentan)
C. Mycophenolate mofetil
D. Nifedipine
E. D-penicillamine

Correct Answer: B. An endothelin receptor antagonist (e.g., bosentan)

Explanation

Pulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc), particularly in the limited cutaneous subset. Its management requires specific PAH-directed therapies that target the underlying pathogenic pathways of pulmonary vascular proliferation and constriction.

• PAH-Specific Therapy: The three main pathways targeted by modern PAH therapy are the endothelin, nitric oxide, and prostacyclin pathways. Endothelin receptor antagonists (ERAs), such as bosentan, ambrisentan, and macitentan, are a cornerstone of treatment. They work by blocking the potent vasoconstrictor and proliferative effects of endothelin-1. Other first-line options for SSc-PAH can also include phosphodiesterase-5 inhibitors (e.g., sildenafil) or a soluble guanylate cyclase stimulator (riociguat).

Why other options are incorrect

• A. High-dose oral prednisone: Corticosteroids have a limited role in SSc and are generally avoided as they can precipitate scleroderma renal crisis. They are not effective for treating the pathobiology of PAH and may cause significant harm.

• C. Mycophenolate mofetil: This is a first-line immunosuppressive agent for treating systemic sclerosis-associated interstitial lung disease (SSc-ILD). While some patients may have both ILD and PAH, the right heart catheterization confirmed pre-capillary PAH, and mycophenolate is not a primary treatment for the pulmonary vascular component.

• D. Nifedipine: This is a calcium channel blocker used for the treatment of severe Raynaud's phenomenon. It is only used for PAH after a positive acute vasoreactivity test is confirmed during right heart catheterization, which is rare in patients with SSc-PAH. It is not a first-line therapy for this population.

• E. D-penicillamine: This was historically used in an attempt to modify skin fibrosis in SSc, but it has fallen out of favor due to lack of proven efficacy and significant toxicity. It has no role in the management of PAH.

Key Associations for Systemic Sclerosis Management

• Disease-Modifying vs. Organ-Specific Therapy: Management of SSc is primarily organ-specific, as no therapy has been proven to be broadly disease-modifying for all manifestations.

• Raynaud's Phenomenon & Digital Ulcers:

  • First-line: Calcium channel blockers (e.g., nifedipine).

  • Refractory/Severe: Phosphodiesterase-5 inhibitors (sildenafil), intravenous iloprost (a prostacyclin analog), and endothelin receptor antagonists.

• Skin Fibrosis (in Diffuse Cutaneous SSc): Methotrexate can be used for early skin disease. Mycophenolate mofetil is also widely used and has a better side-effect profile for long-term use.

• Interstitial Lung Disease (SSc-ILD): This is a major cause of death, especially in diffuse disease. First-line treatment is mycophenolate mofetil or cyclophosphamide. Nintedanib, an antifibrotic tyrosine kinase inhibitor, is approved to slow the rate of decline in pulmonary function.

• Scleroderma Renal Crisis (SRC): A medical emergency characterized by malignant hypertension and acute kidney injury.

  • Prophylaxis: Avoid high-dose corticosteroids.

  • Treatment: Prompt, aggressive control of blood pressure with ACE inhibitors (e.g., captopril) is the cornerstone of therapy, even in the face of rising creatinine.

• Gastrointestinal: Proton pump inhibitors for GERD, prokinetic agents for dysmotility, and alternating antibiotics for bacterial overgrowth.

• Prognosis: Prognosis is highly variable and depends on the extent and progression of major organ involvement (ILD, PAH, SRC). Early diagnosis and proactive screening for organ complications are essential for improving outcomes.