title: Allopurinol hypersensitivity: investigating the cause and minimizing the risk.
abstract: 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.
authors.affiliation: Department of Medicine, University of Otago, Christchurch, P.O. Box 4345, Christchurch 8140, New Zealand.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Stamp
authors.affiliation: Department of Clinical Pharmacology &Toxicology, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia.
authors.forename: Richard O
authors.initials: RO
authors.lastname: Day
authors.affiliation: Department of Clinical Immunology and Allergy, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Yun
mesh_terms: D000493:Allopurinol / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D063926:Drug Hypersensitivity Syndrome / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000628:therapy; D005820:Genetic Testing; D006073:Gout / Q000188:drug therapy; D015235:HLA-B Antigens / Q000502:physiology; D007668:Kidney / Q000187:drug effects; D010117:Oxypurinol / Q000097:blood; D012867:Skin / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015235:HLA-B Antigens; D000493:Allopurinol; D010117:Oxypurinol