Gout Treatment Dosage Affects Risk for

Hypersensitivity Syndrome
News Author: Janis C. Kelly
CME Author: Dsire Lie, MD, MSEd
CME Released: 08/07/2012; Valid for credit through 08/07/2013

Clinical Context
According to the authors, allopurinol hypersensitivity syndrome (AHS) is a rare but
potentially fatal adverse event. It is characterized by rash (eg, Stevens-Johnson syndrome or
toxic epidermal necrolysis), eosinophilia, leukocytosis, fever, hepatitis, and renal failure. The
mortality is as high as 27%, there is no cure, and supportive therapy is the main treatment.
Dosing guidelines based on creatinine clearance have been proposed, as dosages of more than
300 mg/day may be associated with AHS, especially in patients with renal impairment. The
relationship between the allopurinol starting dose and AHS is unknown.
This is a retrospective case-control study of patients with gout who developed AHS between
1998 and 2010 to determine the relationship of the starting dose of allopurinol to the
occurrence of AHS.

Study Synopsis and Perspective

Allopurinol hypersensitivity syndrome (AHS), a rare but potentially fatal adverse reaction in
patients beginning allopurinol therapy for gout, might be largely avoided by keying the
starting dose to kidney function and slowly increasing it to therapeutic levels once tolerance
is certain, according to a retrospective case-control study.
AHS, which is characterized by devastating rash, such as Stevens-Johnson syndrome or toxic
epidermal necrolysis, as well as by eosinophilia, leukocytosis, fever, hepatitis, and renal
failure, is associated with mortality rates as high as 27% and can be treated only by early
diagnosis, prompt allopurinol withdrawal, and supportive care, according to the study,
performed by Lisa K. Stamp, MBChB, PhD, FRACP, from the University of Otago,
Christchurch, New Zealand, and colleagues and published online July 27 and in the August
print issue of Arthritis & Rheumatism.
Women, older patients, those with renal impairment, those receiving diuretics, and those who
are just beginning allopurinol are at greatest risk.
Dr. Stamp's group began the study because of reports that patients receiving "full-dose"
allopurinol (300 mg/day) with renal impairment were at risk for AHS and that such patients
have reduced excretion of oxypurinol, the active metabolite of allopurinol. Current dosing
guidelines do not address starting dose vs maintenance dose issues, and the aim of the study
was "to determine the relationship of the starting dose and the dose of allopurinol at the time
of the reaction to the occurrence of AHS in patients with gout."