title: Low N-acetylating capacity in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.
abstract: Low constitutive N-acetylating capacity has been implicated as a predisposing factor for the development of adverse reactions to certain drugs. This prompted us to investigate whether the N-acetylating capacity of patients with serious cutaneous adverse reactions, i.e., Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) differed from that of healthy control subjects. N-acetylating activity was measured in hair root cells by preparing a homogenate from freshly extracted hair roots and assessing acetyl-CoA-dependent N-acetylation by RP-HPLC using 2-aminofluorene as a substrate. Samples were obtained from hospitalized patients suffering from acute SJS and TEN or from healthy controls. All patients with SJS and TEN were found to have a low N-acetylating capacity (0.85 nmol/mg/min compared to 2.21 nmol/mg/min in controls, p < 0.05). Based on these findings, a low constitutive N-acetylating capacity may be one of the predisposing factors for the development of serious cutaneous adverse reactions to drugs that require N-acetylation in these patients.
authors.affiliation: Department of Dermatology, University of Freiburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dietrich
authors.forename: Y
authors.initials: Y
authors.lastname: Kawakubo
authors.forename: B
authors.initials: B
authors.lastname: Rzany
authors.forename: M
authors.initials: M
authors.lastname: Mockenhaupt
authors.forename: J C
authors.initials: JC
authors.lastname: Simon
authors.forename: E
authors.initials: E
authors.lastname: Schöpf
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D005260:Female; D006197:Hair / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012016:Reference Values; D013262:Stevens-Johnson Syndrome / Q000150:complications* / Q000378:metabolism*
chemical_list: D001191:Arylamine N-Acetyltransferase