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?

Question

Accepted Answer

D. Prednisolone. ## 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.

Answer

A. Azathioprine

Answer

B. Infliximab

Answer

C. Methotrexate

Explanation

Sarcoidosis: First-Line Immunosuppression

Pathophysiology of Sarcoidosis

First-Line Agent: Corticosteroids

Dosing & Duration

Indications for Treatment

Second-Line & Steroid-Sparing Agents

Monitoring During Therapy

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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