Allopurinol hypersensitivity: investigating the cause and minimizing the risk

Nat Rev Rheumatol. 2016 Apr;12(4):235-42. doi: 10.1038/nrrheum.2015.132. Epub 2015 Sep 29.


Allopurinol is the most commonly prescribed urate-lowering therapy for the management of gout. Serious adverse reactions associated with allopurinol, while rare, are feared owing to the high mortality. Such reactions can manifest as a rash combined with eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Risk factors for allopurinol-related severe adverse reactions include the recent introduction of allopurinol, the presence of the HLA-B(*)58:01 allele, and factors that influence the drug concentration. The interactions between allopurinol, its metabolite, oxypurinol, and T cells have been studied, and evidence exists that the presence of the HLA-B(*)58:01 allele and a high concentration of oxypurinol function synergistically to increase the number of potentially immunogenic-peptide-oxypurinol-HLA-B(*)58:01 complexes on the cell surface, thereby increasing the risk of T-cell sensitization and a subsequent adverse reaction. This Review will discuss the above issues and place this in the clinical context of reducing the risk of serious adverse reactions.

Publication types

  • Review

MeSH terms

  • Allopurinol / administration & dosage
  • Allopurinol / adverse effects*
  • Allopurinol / immunology
  • Drug Hypersensitivity / etiology*
  • Drug Hypersensitivity / genetics
  • Drug Hypersensitivity / prevention & control
  • Drug Hypersensitivity Syndrome / diagnosis
  • Drug Hypersensitivity Syndrome / etiology
  • Drug Hypersensitivity Syndrome / genetics
  • Drug Hypersensitivity Syndrome / therapy
  • Genetic Testing
  • Gout / drug therapy
  • HLA-B Antigens / physiology
  • Kidney / drug effects
  • Oxypurinol / blood
  • Skin / drug effects
  • Skin / immunology
  • T-Lymphocytes / immunology


  • HLA-B Antigens
  • Allopurinol
  • Oxypurinol