Management of Dapsone-Induced Methemoglobinemia without Methylene Blue in Leprosy: A Case Report

Aye Mya Theingi Win , Nyunt Thein

Case Summary

Dapsone, an integral drug in multidrug therapy (MDT) for leprosy, is associated with oxidative hemolysis and methemoglobinemia, particularly in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, clinically significant methemoglobinemia may occur even in G6PD-normal patients. We report a case of a 38-year-old man with tuberculoid leprosy who developed symptomatic dapsone-induced methemoglobinemia manifesting with hypoxia and jaundice. As methylene blue was unavailable, he was managed successfully with high-dose intravenous vitamin C followed by oral vitamin C, with gradual reduction in methemoglobin levels and clinical improvement. This case highlights the importance of recognizing dapsone-induced methemoglobinemia in leprosy and the role of vitamin C as an effective alternative therapy.

Keywords: Leprosy, Dapsone, Methemoglobinemia, Vitamin C

Case Report

A 38-year-old man presented with a maculopapular rash over the left side of his face. Skin biopsy confirmed tuberculoid leprosy, and World Health Organization multidrug therapy (MDT) for multibacillary leprosy was initiated, including dapsone, rifampicin, and clofazimine. Before starting MDT treatment, his G6PD level was checked and it was normal ( i,e 12 U/g Hb ). Two months later, he presented with fever, jaundice, and shortness of breath. On admission, his oxygen saturation was 86% on room air. Physical examination did not reveal cyanosis or respiratory findings. Laboratory investigations showed: hemoglobin 10 g/dL Hct 34%, MCV 110 fL, retic count 2.6%, WBC 7.8 × 10⁹/L, platelets 360 × 10⁹/L, serum bilirubin 6.5 mg/dL, with normal ALT, AST, creatinine, and renal function. Recheck G6PD activity was again normal. Inflammatory markers showed CRP 31 mg/L and procalcitonin 0.2 ng/mL. LDH was high 285 U/L, blood for malaria parasite and dengue serology and NS1Ag were negative. Hepatitis B, C and HIV status were non-reactive. Chest radiograph and abdominal ultrasonography were normal. Since he had low SPO2 not responded to O2 therapy but no obvious respiratory signs with normal CXR, dapsone induced methemoglobinemia was suspected and arterial blood gas analysis was proceeded. And the result turned out perfectly normal PaO2 and PaCO2 level. Then, the methemoglobin level was checked at occupational health laboratory which revealed 15%. Finally, diagnosis of dapsone-induced methemoglobinemia and hemolysis was made. As methylene blue was not available, the patient was treated with intravenous vitamin C (ascorbic acid) 1g every 8 hours for 4 days, followed by oral vitamin C 1 g three times daily together with supplementary O2 therapy. Recheck methemoglobin levels (one week after treatment) decreased to 5% with resolution of symptoms. He was planned to give vitamin C orally until his methemoglobin level return back to normal i,e <1%. Dapsone was discontinued, and a dapsone-sparing regimen was planned for continuation of leprosy treatment.

Fig. 1: Photo of patient before skin biopsy and MBT treatment

Fig 2: Photo of patient during MBT treatment

Discussion

Dapsone is a sulfone antibiotic widely used in the treatment of leprosy, dermatitis herpetiformis, and Pneumocystis jirovecii prophylaxis 1. A major adverse effect is oxidative stress leading to hemolysis and methemoglobinemia, especially in G6PD-deficient individuals ². Methemoglobinemia occurs when hemoglobin iron is oxidized from the ferrous (Fe²⁺) to ferric (Fe³⁺) state, impairing oxygen delivery and leading to tissue hypoxia 3. Clinically, patients may present with cyanosis, hypoxemia unresponsive to oxygen, fatigue, and in severe cases, arrhythmias and seizures⁴. Our patient developed symptomatic methemoglobinemia despite having normal G6PD levels, consistent with prior reports that idiosyncratic reactions can occur in G6PD-normal individuals⁵. The treatment of choice for symptomatic methemoglobinemia is intravenous methylene blue, which reduces methemoglobin via the NADPH-methemoglobin reductase pathway ⁶. However, methylene blue may not always be available in resource-limited settings, and is contraindicated in G6PD deficiency due to risk of hemolysis ⁷. Vitamin C (ascorbic acid) acts as a reducing agent that can non-enzymatically convert methemoglobin to hemoglobin, though it is less potent and slower than methylene blue ⁸. In our case, intravenous vitamin C resulted in a significant reduction in methemoglobin levels from 15% to 5% with clinical improvement, highlighting its role as an effective alternative when methylene blue is unavailable. Previous case reports also support high-dose vitamin C as a safe adjunct or substitute treatment ⁹.

Conclusion

This case emphasizes the need for vigilance for dapsone-induced methemoglobinemia in patients on MDT for leprosy, even in those with normal G6PD levels. In settings where methylene blue is unavailable, high-dose vitamin C offers a safe and effective alternative. Early recognition and prompt management are essential to prevent morbidity.

References

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Author Information

Aye Mya Theingi Win
Senior Consultant physician, Tropical and Infectious Diseases Department, Yangon General Hospital

Nyunt Thein
Senior Consultant physician, Former Head of Department of Medicine, Emeritus Professor of Medicine, University of Medicine (1), Yangon