During a leprosy control programme in Odisha, a field worker screens 500 patients with confirmed leprosy. Which is the most common adverse effect encountered with dapsone therapy in this cohort?

Explanation

## Dapsone Adverse Effects: Frequency & Mechanism **Key Point:** Hemolytic anemia is the most common and clinically significant adverse effect of dapsone, occurring in 5–10% of patients on standard antileprosy regimens and in up to 25% of those with G6PD deficiency. ### Mechanism of Dapsone-Induced Hemolysis 1. **Oxidative stress:** Dapsone and its metabolite (dapsone hydroxylamine) generate reactive oxygen species (ROS). 2. **RBC vulnerability:** RBCs lack nuclei and cannot synthesize new antioxidant enzymes; they depend on existing catalase and glutathione peroxidase. 3. **G6PD interaction:** Patients with G6PD deficiency are at dramatically higher risk (25–30% incidence vs. 5–10% in normal individuals). 4. **Hemoglobin denaturation:** Oxidative stress denatures hemoglobin, forming Heinz bodies, leading to intravascular and extravascular hemolysis. ### Frequency of Dapsone Adverse Effects | Adverse Effect | Incidence | Severity | Monitoring | |---|---|---|---| | **Hemolytic anemia** | **5–10% (up to 25% in G6PD)** | **Mild to moderate** | **Baseline & 3-monthly Hb** | | Methemoglobinemia | 1–5% | Usually asymptomatic | Pulse oximetry | | Peripheral neuropathy | <1% | Rare, dose-dependent | Clinical exam | | Hepatotoxicity | <1% | Rare | LFTs at baseline | | Photosensitivity | <1% | Rare | Counseling | **High-Yield:** Hemolytic anemia with dapsone is *dose-dependent* and *reversible*—it resolves within weeks of stopping the drug. This distinguishes it from irreversible toxicities. **Clinical Pearl:** Always check **G6PD status** before starting dapsone in endemic populations (Africa, Mediterranean, Southeast Asia, India). In G6PD-deficient individuals, consider alternative regimens (e.g., ofloxacin + minocycline + clofazimine). **Warning:** Do not confuse dapsone-induced hemolytic anemia with sulfone syndrome (a rare, severe hypersensitivity reaction with fever, rash, hepatosplenomegaly, and lymphadenopathy occurring 2–8 weeks after initiation). Sulfone syndrome is much rarer but more serious. **Mnemonic:** **DAPSONE = DAP-Sone-Oxidative-Necrosis-Erythrocytes** — hemolysis via oxidative stress on red cells.