Dapsone-induced agranulocytosis-possible involvement of low-activity N-acetyltransferase 2.
Dapsone-induced agranulocytosis is a rare but potentially fatal adverse drug reaction (ADR). A 45-year-old male Caucasian patient developed agranulocytosis caused by dapsone (diamino-diphenyl sulfone), which he was prescribed for leukocytoclastic vasculitis. Patient's treatment consisted of termination of dapsone, antibiotic therapy, and granulocyte colony-stimulating factor leading to prompt improvement of symptoms and normalization of laboratory blood values. Diagnostic evaluation revealed methemoglobinemia and excluded glucose-6-phosphate dehydrogenase deficiency. Pharmacogenetics testing showed that he was a carrier of NAT2 *5/*6 genotype, predisposing to low activity of the N-acetyltransferase 2 enzyme. This was the first and only ADR to dapsone reported in Croatia. In total, there have been 73 ADR to dapsone recorded worldwide, including only four cases of agranulocytosis.
Clinical Unit of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital Centre Sisters of Charity, Vinogradska cesta, 10 000, Zagreb, Croatia.
Ines
http://orcid.org/0000-0001-9351-9669
I
Potočnjak
University of Zagreb School of Medicine, Šalata 3, 10 000, Zagreb, Croatia.|Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, Kišpatićeva 12, 10 000, Zagreb, Croatia.
Robert
R
Likić
University of Zagreb School of Medicine, Šalata 3, 10 000, Zagreb, Croatia.|Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, Kišpatićeva 12, 10 000, Zagreb, Croatia.
Iveta
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Šimić
Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, Kišpatićeva 12, 10 000, Zagreb, Croatia.
Danica
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Juričić Nahal
Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, Kišpatićeva 12, 10 000, Zagreb, Croatia.
Ivana
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Čegec
University of Zagreb School of Medicine, Šalata 3, 10 000, Zagreb, Croatia.|Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Kišpatićeva 12, 10 000, Zagreb, Croatia.
Lana
L
Ganoci
University of Zagreb School of Medicine, Šalata 3, 10 000, Zagreb, Croatia.|Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Kišpatićeva 12, 10 000, Zagreb, Croatia.
Nada
N
Božina
D000380:Agranulocytosis / Q000139:chemically induced* / Q000175:diagnosis / Q000201:enzymology*; D000890:Anti-Infective Agents / Q000009:adverse effects*; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D003622:Dapsone / Q000009:adverse effects*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged
D000890:Anti-Infective Agents; D003622:Dapsone; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human
NAT2 *5/*6; adverse drug reactions; agranulocytosis; dapsone; glucose-6-phosphate dehydrogenase