Dapsone induced hemolysis in a patient with ANCA associated glomerulonephritis and normal G6PD level and implications for clinical practice: case report and review of the literature

Abstract

Dapsone is a commonly used second line drug for prophylaxis of pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients. Oxidant hemolysis, caused by dapsone’s metabolite hydroxylamine, is a common side effect, and screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency is recommended before the drug is started in order to prevent potential hemolytic reactions. We report a case of dapsone induced hemolytic anemia in a patient with ANCA associated glomerulonephritis and normal G6PD level. Her anemia improved after cessation of therapy with dapsone. We review the literature of dapsone induced hemolysis in patients who have normal G6PD level and discuss potential pathways leading to hemolytic anemia and its implications for clinical practice.

Evaluation of quantitative biosensor for glucose-6-phosphate dehydrogenase activity detection

“…However, the quantitative G-6-PD enzymatic activity assay (SGT) measured by spectrophotometric and automated UV enzymatic methods remains the reference method [5, 16, 25, 27]. The threshold of G-6-PD activity has also been used as criteria for malarial drug execution [7, 8, 11–13]. The WHO recommended that patients having less than 30% G-6-PD enzymatic activity and 70% normal activity should be excluded from primaquine and tafenoquine treatment [14, 22].…”

“…Lack of awareness concerning G-6-PD deficiency in newborns could cause extreme hyperbilirubinemia, bilirubin neurotoxicity, kernicterus and, eventually, mental retardation [8, 10]. Accordingly, the World Health Organization (WHO) has recommended screening for G-6-PD deficiency in newborns to promote early diagnosis and prevent unwanted outcomes in a timely manner [8, 10–13]. Moreover, individuals suffering from severe G-6-PD deficiency with residual activity less than 30% and 70% should be excluded from primaquine and tafenoquine administration, respectively [14, 15].…”

The medication for pneumocystis pneumonia with glucose-6-phosphate dehydrogenase deficiency patients

“…The Enzyme activity detection is a routine test for G6PD deficiency, but molecular analysis of female heterozygotes may be required. We found a Greek woman whose G6PD enzyme activity was detected to decrease and developed severe acute hemolysis following initiation of dapsone therapy ( Lee and Geetha, 2015 ). A multicenter randomized controlled study of thousands of people showed signs of hemolysis in almost all G6PD deficient children receiving sulfoxide, with normal erythrocyte morphology before treatment and a significant decrease in haemoglobin after treatment ( Pamba et al, 2012 ).…”

Dapsone-Associated Hemolytic Anemia in Renal Transplant Recipients With Normal Glucose-6-Phosphate-Dehydrogenase Levels

“…23 Concurrent therapy with these drugs may lead to elevated dapsone-hydroxylamine levels. 4,19 Finally, unrecognized mutations in hexose monophosphate shunt or glutathione metabolism may lead to glutathione depletion and subsequent hemolysis. 4,18 Methemoglobinemia, another side effect of dapsone, is also increasingly reported in renal transplant recipients.…”

“…Dapsone-induced hemolytic anemia with normal G6PD levels has been reported in diverse populations: leprosy patients 16,17 ; human immunodeficiency virus-infected patients 7 ; immunocompromised patients 4 ; and hematopoietic stem cell transplant recipients. 18 It is less common in SOTRs.…”