Allopurinol hypersensitivity syndrome

Clinical bottom line

Cutaneous rash and fever were the most common clinical findings. Patients with reported allopurinol hypersensitivity syndrome were mostly middle-aged men with hypertension and/or renal failure, receiving excessive doses of allopurinol primarily for asymptomatic hyperuricaemia.

The standard criteria for allopurinol hypersensitivity syndrome (AHS) are:

1 A clear history of exposure to allopurinol

2 A clinical picture of either -

At least two of the following criteria:

worsening renal function

acute hepatocellular injury

a rash, including toxic epidermal necrolysis, erythema multiforme or a diffuse macropapular or exfoliative dermatitis

Or one of the above plus at least one of the following:

fever

eosinophilia

leukocytosis

3 Lack of exposure to another drug that may cause a similar clinical picture.

Reference

F Arellano, JA Sacristn. Allopurinol hypersensitivity syndrome: a review. Annals of Pharmacotherapy 1993 27: 337-343.

Review

The review was an extensive computer search of English, French, german and Spanish literature up to the end of 1990 for cases of AHS from which patient, treatment and clinical data were extracted.

Results

There were 101 cases, 68 of whom were men. There were 27 deaths.

The age range was 25-89 years with a mean of about 58 years. Many patients had chronic illnesses including hypertension, chronic renal failure (both in about half), diabetes and congestive heart failure (in about a fifth). Concomitant medicines were commonly diuretics (61 cases), with thiazide diuretics in 38 cases.

Doses of allopurinol were in the range of 100 mg to 400 mg, with the most common dose of 300 mg. The most frequent indication was asymptomatic hyperuricaemia (76 cases) and established or suspected gout (20 cases). The onset of AHS ranged from 1 to 728 days after starting therapy, with an average of 47 days.

Signs and symptoms were as shown in Table 1, with skin rash, fever, renal failure and AST elevation being the most common.

Table 1: Signs and symptoms of AHS

Sign or symptom

Number

Percent

Skin rash

94/101

93

Fever

58/61

95

Renal failure

57/68

84

AST elevation

44/50

88

Eosinophilia

46/77

60

Leukocytosis

33/82

40

Comment

This is a useful review and discussion on AHS, limited to being now over a decade old. Though there are 101 cases of AHS in the literature several hundreds of millions of allopurinol doses are used annually, and though it is not possible to give an absolute risk, it does appear to be rare.

Moreover, that risk may also be partly avoidable, in that three-quarters of these cases were taking allopurinol for asymptomatic hyperuricaemia.