## Dapsone and G6PD Deficiency **Key Point:** Dapsone is absolutely contraindicated in G6PD-deficient patients because it oxidizes hemoglobin and precipitates hemolytic anemia in individuals lacking adequate antioxidant defense. ### Mechanism of Hemolysis 1. **Oxidative Stress Generation:** Dapsone and its metabolites (particularly dapsone hydroxylamine) generate reactive oxygen species (ROS) and oxidative stress within red blood cells. 2. **G6PD Deficiency Impact:** G6PD catalyzes the first step of the pentose phosphate pathway, producing NADPH — the primary reducing agent that maintains glutathione in its reduced form (GSH). 3. **Hemoglobin Denaturation:** Without adequate GSH, hemoglobin cannot be protected from oxidative damage, leading to Heinz body formation and hemolysis. ### Clinical Manifestations - Acute hemolytic anemia (jaundice, dark urine, pallor) - Hemoglobinuria - Reticulocytosis on blood smear - Elevated indirect bilirubin and LDH - Reduced haptoglobin **Warning:** Even asymptomatic G6PD carriers can develop severe hemolysis with dapsone; screening is mandatory before initiating therapy. ### Screening Protocol - **Baseline:** G6PD enzyme assay or rapid fluorescent spot test (FST) - **Timing:** Perform before starting dapsone, especially in populations with high G6PD prevalence (African, Mediterranean, Asian descent) - **Result:** If deficient or variant → use alternative antileprotic (rifampicin + clofazimine ± minocycline) **High-Yield:** Dapsone is the ONLY first-line antileprotic with this absolute contraindication. Rifampicin, clofazimine, and minocycline are safe in G6PD deficiency. ### Other Adverse Effects of Dapsone (G6PD-Independent) - Methemoglobinemia (dose-dependent, reversible) - Agranulocytosis (rare but serious) - Stevens-Johnson syndrome / Toxic epidermal necrolysis - Peripheral neuropathy - Hepatotoxicity [cite:KD Tripathi 8e Ch 49]
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