A 38-year-old man with lepromatous leprosy on anti-leprosy therapy for 3 months presents with acute onset fever, painful nodules on extensor surfaces, and neuritis. Histology shows neutrophilic infiltrate with immune complex deposition. All of the following are features of Type 2 lepra reaction (Erythema Nodosum Leprosum) EXCEPT:

Explanation

## Type 2 Lepra Reaction (Erythema Nodosum Leprosum) — Immunopathology ### Mechanism & Timing **Key Point:** Type 2 lepra reaction (ENL) is mediated by **Type III hypersensitivity** (immune complex deposition), NOT Type IV delayed-type hypersensitivity. **High-Yield:** ENL occurs in patients with **high bacillary loads** (LL and BL forms), typically **within the first year of treatment** (often 3–6 months), when immune complexes form as bacilli are killed and antigens are released. ### Pathophysiology 1. **Immune Complex Formation**: As anti-leprosy drugs kill bacilli, mycobacterial antigens are released 2. **Circulating Immune Complexes**: These form with IgG and IgM antibodies in antigen excess 3. **Deposition**: Complexes deposit in skin, nerves, eyes, testes, and kidneys 4. **Complement Activation**: Leads to neutrophilic infiltration and tissue damage ### Clinical Features of ENL | Feature | Details | |---------|----------| | **Skin** | Painful nodules (often on extensor surfaces), erythematous plaques | | **Systemic** | Fever, malaise, weight loss | | **Neuritis** | Painful neuritis (different from Type 1 reaction) | | **Ocular** | Iritis, episcleritis | | **Testicular** | Orchitis, testicular pain | | **Renal** | Glomerulonephritis (rare but serious) | ### Type 1 vs Type 2 Lepra Reactions | Feature | Type 1 (Reversal Reaction) | Type 2 (ENL) | |---------|---------------------------|---------------| | **Hypersensitivity** | Type IV (delayed) | Type III (immune complex) | | **Leprosy Forms** | BT, BL, BB, BF | LL, BL | | **Timing** | Anytime during treatment | Usually first year | | **Lesion Type** | Existing lesions inflame | New painful nodules | | **Histology** | Epithelioid granulomas | Neutrophilic infiltrate | | **Antigen** | M. leprae antigens | Circulating immune complexes | **Warning:** Do NOT confuse Type 1 and Type 2 reactions — they have opposite immunological mechanisms and occur in different leprosy forms. ### Why Option 4 is Incorrect Type 2 ENL is **NOT** caused by delayed-type hypersensitivity (Type IV). That is the mechanism of **Type 1 lepra reaction** (reversal reaction). ENL is specifically a Type III immune complex–mediated reaction. **Clinical Pearl:** Patients with ENL respond to **thalidomide** (inhibits TNF-α production) or **corticosteroids**, not to increased anti-leprosy drugs alone — this clinical response confirms the immune complex mechanism.