The allopurinol hypersensitivity syndrome. Unnecessary morbidity and mortality

Abstract

Patients receiving allopurinol are at risk of developing the allopurinol hypersensitivity syndrome, an immunologic reaction to the drug, characterized by multiple abnormalities such as fever, rash, decreased renal function, hepatocellular injury, leukocytosis, and eosinophilia. The records of 8 patients with the allopurinol hypersensitivity syndrome evaluated at the Downstate Medical Center hospitals and an additional 72 patients described in the literature were reviewed. All were seriously ill. Three of the 8 patients at the Downstate Medical Center hospitals died as a result of allopurinol hypersensitivity; 19 of the 72 previously described patients also died from consequences of taking the drug. Only 1 of our 8 patients with allopurinol hypersensitivity was given allopurinol for an appropriate reason. Eight of the 59 previously described patients on whom there was adequate information had legitimate indications for allopurinol therapy. Severe, often fatal iatrogenic disease occurred unnecessarily in the others.

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: A twenty‐eight–day, multicenter, phase II, randomized, double‐blind, placebo‐controlled, dose‐response clinical trial examining safety and efficacy in patients with gout

“…Allopurinol is effective in reducing sUA levels, but achieving normal sUA levels may be difficult in patients with impaired renal function or in transplant recipients (2,6,9,26). An uncommon, but significant, limitation to the use of allopurinol is the risk, more common in elderly and renally impaired individuals, of reactions that may include rashes (some severe), hematologic cytopenias, hepatitis, vasculitis, and the potentially life-threatening allopurinol hypersensitivity syndrome (1,9,26,(29)(30)(31)(32)(33)(34).…”

An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing

“…SCARs include SJS, TEN, and allopurinol hypersensitivity syndrome. 8,22 SJS was defined as skin detachment across less than 10% of the body surface area, SJS/TEN was defined as detachment between 10 and 30% of the body surface area, and TEN was defined as detachment of more than 30% of the body surface area. 22 Allopurinol hypersensitivity syndrome was defined as present when patients with a clear history of exposure to allopurinol met at least two major criteria, including worsening of renal function, acute hepatocellular injury, and a generalized rash, or one of the major criteria plus at least one of the following minor criteria: fever, eosinophilia, and leukocytosis.…”

“…22 Allopurinol hypersensitivity syndrome was defined as present when patients with a clear history of exposure to allopurinol met at least two major criteria, including worsening of renal function, acute hepatocellular injury, and a generalized rash, or one of the major criteria plus at least one of the following minor criteria: fever, eosinophilia, and leukocytosis. 8 Allopurinol hypersensitivity reactions were evaluated by two board-certified allergy specialists and defined as a case of certain or probable causality based on the World Health Organization Adverse Reaction Terminology assessment. 23 …”

“…6,7 Therefore, physicians have to pay more attention to recognize and prevent the development of SCARs when they prescribe allopurinol. 8 Chronic renal insufficiency (CRI) is a well-known risk factor for allopurinolinduced SCARs and is an underlying disease that needs an allopurinol prescription for the related hyperuricemia.…”

Allopurinol dosage selection: relationships between dose and plasma oxipurinol and urate concentrations and urinary urate excretion.

“…Oxipurinol is cleared from the body through the kidneys and accordingly, the dosage of oxipurinol should be reduced in patients with renal impairment (Elion et al, 1968;Hande et al, 1984). Severe toxic reactions to allopurinol are observed uncommonly but can be fatal (Hande et al, 1984;Singer & Wallace, 1986). Exfoliative dermatitis, hepatitis and progressive renal failure are features of the toxic reaction to this drug.…”