Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel.
BACKGROUND
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions.


OBJECTIVE
We sought to update knowledge on the causes of SJS or TEN with a focus on the rate of allopurinol-associated cases and to identify risk factors for allopurinol-associated SJS or TEN.


METHODS
We conducted a multinational case-control study.


RESULTS
In all, 379 patients with severe cutaneous adverse reactions validated as SJS or TEN and 1505 matched hospitalized control subjects were enrolled. Allopurinol was the drug most frequently associated with SJS or TEN, with 66 exposed patients (17.4%) and 28 exposed control subjects (1.9%) (adjusted odds ratio = 18, 95% confidence interval: 11-32). Allopurinol use was greater than in a previous case-control European study. Daily doses equal to or greater than 200 mg were associated with a higher risk (adjusted odds ratio = 36, 95% confidence interval: 17-76) than lower doses (adjusted odds ratio = 3.0, 95% confidence interval: 1.1-8.4). The risk was restricted to short-term use (<or=8 weeks). The use of comedications did not increase the risk.


CONCLUSIONS
Nonsystematic recording of the indications for allopurinol use was a limitation.


CONCLUSIONS
Results of this multinational study (EuroSCAR) revealed that allopurinol is the drug most commonly associated with SJS or TEN. The incidence of allopurinol-associated SJS or TEN has increased possibly because of increased use and dosages of this drug.
Halevy
Sima
S
Department of Dermatology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel. halevy@bgu.ac.il
Ghislain
Pierre-Dominique
PD
Mockenhaupt
Maja
M
Fagot
Jean-Paul
JP
Bouwes Bavinck
Jan Nico
JN
Sidoroff
Alexis
A
Naldi
Luigi
L
Dunant
Ariane
A
Viboud
Cecile
C
Roujeau
Jean-Claude
JC
D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D003710:Demography; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005060:Europe / Q000453:epidemiology; D005260:Female; D006074:Gout Suppressants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D007557:Israel / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology*
D006074:Gout Suppressants; D000493:Allopurinol