A 52-year-old man presents with a 6-month history of progressive dyspnea, cough, and chest pain. High-resolution CT chest shows bilateral upper lobe predominant reticulonodular opacities with hilar lymphadenopathy. Transbronchial lung biopsy confirms non-caseating granulomas. Serum ACE level and 24-hour urinary calcium are elevated. What is the drug of choice for initial management of pulmonary sarcoidosis?

Explanation

## Sarcoidosis: First-Line Immunosuppression ### Pathophysiology of Sarcoidosis Sarcoidosis is a multisystem granulomatous disorder characterized by non-caseating granulomas driven by CD4+ T-cell activation and Th1/Th17 cytokine production. Chronic inflammation in the lungs leads to progressive fibrosis if untreated. ### First-Line Agent: Corticosteroids **Key Point:** Prednisolone (or prednisone) is the gold standard first-line therapy for symptomatic pulmonary sarcoidosis and systemic manifestations (hypercalcemia, neurological involvement, cardiac arrhythmias). **High-Yield:** Corticosteroids suppress granuloma formation by: - Inhibiting TNF-α and IL-6 production by activated macrophages - Reducing T-cell proliferation and antigen presentation - Preventing progression to pulmonary fibrosis ### Dosing & Duration - **Initial dose:** 0.5–1 mg/kg/day (typically 20–40 mg/day) - **Duration:** 6–12 weeks at full dose, then gradual taper over 3–6 months - **Response:** Clinical and radiological improvement expected within 2–4 weeks ### Indications for Treatment - Symptomatic pulmonary disease (dyspnea, cough) - Extrapulmonary manifestations (hypercalcemia, uveitis, cardiac involvement, neurosarcoidosis) - Progressive radiological disease - Elevated serum ACE and hypercalciuria (as in this case) indicate systemic activity ### Second-Line & Steroid-Sparing Agents | Agent | Role | When Used | |-------|------|----------| | Methotrexate | Steroid-sparing agent | Chronic maintenance after steroid taper; steroid-resistant cases | | Azathioprine | Steroid-sparing agent | Alternative if methotrexate intolerant; slower onset | | Infliximab (TNF-α inhibitor) | Refractory disease | Steroid-resistant pulmonary sarcoidosis; neurosarcoidosis | | Hydroxychloroquine | Adjunct | Hypercalcemia, skin lesions; slower onset | **Clinical Pearl:** Methotrexate and azathioprine are NOT first-line because they have slower onset (weeks to months) and are used as steroid-sparing agents during maintenance or in steroid-resistant cases. ### Monitoring During Therapy - Serum calcium and 24-hour urinary calcium (should normalize) - Serum ACE level (may take months to normalize) - Chest X-ray (resolution of infiltrates) - Pulmonary function tests (FVC, DLCO) - Bone density (long-term steroid use) **Warning:** Do NOT start methotrexate or azathioprine as monotherapy for acute symptomatic sarcoidosis — corticosteroids are essential for rapid control of inflammation and prevention of organ damage.