A 32-year-old man from rural Maharashtra presents with a 3-month history of productive cough, fever, and weight loss. Chest X-ray shows cavitary lesions in the right upper lobe. Sputum smear microscopy is positive for acid-fast bacilli. He is started on standard first-line antitubercular therapy (RIPE: rifampicin, isoniazid, pyrazinamide, ethambutol). After 2 weeks of therapy, he develops acute onset painful red nodules on the shins and fever. What is the most likely adverse effect?

Explanation

## Clinical Presentation Analysis The patient presents with: - Cavitary pulmonary TB (confirmed by smear microscopy) - Acute onset painful red nodules on shins (erythema nodosum) - Fever occurring 2 weeks into treatment ## Erythema Nodosum in TB Treatment **Key Point:** Erythema nodosum is a Type III hypersensitivity reaction (immune complex-mediated) that occurs in TB patients, typically during the first 2–8 weeks of antitubercular therapy. **Clinical Pearl:** It represents an exaggerated host immune response to tuberculous antigens being released as bacilli die during treatment — this is part of the immune reconstitution inflammatory syndrome (IRIS) spectrum in TB. ### Characteristic Features of Erythema Nodosum | Feature | Details | |---------|----------| | **Timing** | 2–8 weeks into ATT (early phase) | | **Lesions** | Painful, tender, red nodules on anterior shins | | **Associated Symptoms** | Fever, arthralgia (especially ankles/knees) | | **Pathophysiology** | Type III hypersensitivity (immune complex deposition) | | **Prognosis** | Self-limiting; resolves with continued ATT | | **Management** | NSAIDs, continue ATT, rarely systemic corticosteroids | **High-Yield:** Erythema nodosum in TB is **NOT** an indication to stop antitubercular drugs — it is a sign of immune activation and usually resolves spontaneously with continued therapy. ## Why This Is IRIS IRIS occurs when the immune system begins to recover during ATT and mounts an exaggerated inflammatory response to TB antigens. Erythema nodosum is one of the classical manifestations of TB-IRIS. **Mnemonic: IRIS Manifestations in TB — "FELINE"** - **F**ever - **E**rythema nodosum - **L**ymph node enlargement (paradoxical) - **I**ncreased infiltrates on CXR (paradoxical worsening) - **N**eurological (TB meningitis worsening) - **E**xacerbation of existing lesions [cite:Harrison 21e Ch 205]