Dapsone-induced agranulocytosis-possible involvement of low-activity N-acetyltransferase 2

Fundam Clin Pharmacol. 2017 Oct;31(5):580-586. doi: 10.1111/fcp.12287. Epub 2017 Apr 26.

Abstract

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.

Keywords: NAT2 *5/*6; adverse drug reactions; agranulocytosis; dapsone; glucose-6-phosphate dehydrogenase.

Publication types

  • Case Reports

MeSH terms

  • Agranulocytosis / chemically induced*
  • Agranulocytosis / diagnosis
  • Agranulocytosis / enzymology*
  • Anti-Infective Agents / adverse effects*
  • Arylamine N-Acetyltransferase / metabolism*
  • Dapsone / adverse effects*
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Humans
  • Male
  • Middle Aged

Substances

  • Anti-Infective Agents
  • Dapsone
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human