title: Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions.
abstract: The article reviews the immunopathogenesis and risk factors related to allopurinol-induced severe cutaneous adverse reactions (SCARs).
  
  
  
  For years, allopurinol remains one of the leading cause for SCARs worldwide. The pathogenesis of allopurinol-induced SCARs have been discovered in recent years. HLA-B58 : 01 has been found to be strongly associated with allopurinol-SCARs with functional interactions between allopurinol/its metabolite-oxypurinol and the T-cell receptor (TCR). However, the genetic strength of HLA-B58 : 01 may vary among different ethnic populations. In addition to HLA-B58 : 01, specific T cells with preferential TCR clonotypes, which have no cross-reactivity with new xanthine oxidase inhibitors structurally different from allopurinol, are found to play a crucial role for allopurinol-induced SCARs. Furthermore, other nongenetic factors such as renal impairment are also found to be an important factor resulting in allopurinol-induced SCARs of greater severity and poorer prognosis.
  
  
  
  There are multiple risk factors for allopurinol-induced SCARs, including genetic and nongenetic factors. Activation of specific T cells with preferential TCR and its functional interaction of HLA-B58 : 01 molecule and allopurinol/oxypurinol are involved in the immune mechanism of allopurinol-induced SCAR. Patients with allopurinol-induced SCARs with renal impairment have significantly higher risk of mortality. A structurally different new generation xanthine oxidase inhibitor can provide a safer alternative for patients intolerant to allopurinol.
authors.affiliation: aDepartment of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Taipei, Linkou, and KeelungbChang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung UniversitycCollege of Medicine, Chang Gung University, TaoyuandWhole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Chuang-Wei
authors.initials: CW
authors.lastname: Wang
authors.forename: Ro-Lan
authors.initials: RL
authors.lastname: Dao
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Chung
mesh_terms: D000485:Allergens / Q000276:immunology* / Q000627:therapeutic use; D000493:Allopurinol / Q000276:immunology* / Q000627:therapeutic use; D000818:Animals; D004342:Drug Hypersensitivity / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000276:immunology* / Q000627:therapeutic use; D005006:Ethnicity; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012307:Risk Factors; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D000485:Allergens; D004791:Enzyme Inhibitors; D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; D011948:Receptors, Antigen, T-Cell; D000493:Allopurinol; D014969:Xanthine Oxidase