Low N-acetylating capacity in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.
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.
Dietrich
A
A
Department of Dermatology, University of Freiburg, Germany.
Kawakubo
Y
Y
Rzany
B
B
Mockenhaupt
M
M
Simon
J C
JC
Schöpf
E
E
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*
D001191:Arylamine N-Acetyltransferase