title: Racial disparities in the risk of Stevens-Johnson Syndrome and toxic epidermal necrolysis as urate-lowering drug adverse events in the United States.
abstract: HLA-B*5801 allele carriage (a strong determinant of allopurinol hypersensitivity syndrome) varies substantially among races, which may lead to racial disparities in the risk of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) in the context of urate-lowering drug adverse events (ULDAEs). We examined this hypothesis in a large, racially diverse, and generalizable setting.
  
  
  
  Using a database representative of US hospitalizations (2009-2013), we investigated the racial distribution of hospitalized SJS/TEN (principal discharge diagnosis) as ULDAEs (ICD-9-CM Classification of External Causes). Our reference groups included the US Census population, US allopurinol users, and ULDAE hospitalizations without SJS/TEN.
  
  
  
  We identified 606 cases hospitalized for SJS/TEN as ULDAEs (mean age = 68 years; 44% male), among which there was an overrepresentation of Asians (27%) and Blacks (26%), and an underrepresentation of Whites (29%) and Hispanics (% too-low-to-report), compared with the US Census population (5%, 12%, 67%, and 15%, respectively). The hospitalization rate ratios for SJS/TEN among Asians, Blacks, and Whites were 11.9, 5.0, and 1.0 (referent), respectively. These associations persisted using other national referents. According to the NHANES 2009-2012, allopurinol constituted 96.8% of urate-lowering drug use, followed by probenecid (2.1%).
  
  
  
  These national data indicate that Asians and Blacks have a substantially higher risk of SJS/TEN as ULDAEs than Whites (or Hispanics), correlating well with corresponding frequencies of HLA-B*5801 in the US population (i.e., 7.4%, 4%, 1%, and 1%, respectively). Given its market dominance and established association with SJS/TEN, our findings support the use of vigilance in these minorities when considering allopurinol.
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Bulfinch 165, Boston, MA 02114.
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.affiliation: Arthritis Research Canada, Vancouver, British Columbia, Canada; Department of Experimental Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sharan K
authors.initials: SK
authors.lastname: Rai
authors.affiliation: Division of Rheumatology, Allergy and Immunology, VAMC/UCSD, La Jolla, CA.
authors.forename: Robert
authors.initials: R
authors.lastname: Terkeltaub
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA; Division of Rheumatology, Immunology and Allergy, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA.
authors.forename: Seoyoung C
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Mariano E
authors.initials: ME
authors.lastname: Menendez
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Bulfinch 165, Boston, MA 02114. Electronic address: hchoi@partners.org.
authors.forename: Hyon K
authors.initials: HK
authors.lastname: Choi
mesh_terms: D000368:Aged; D000493:Allopurinol / Q000009:adverse effects* / Q000627:therapeutic use; D016208:Databases, Factual; D005260:Female; D006074:Gout Suppressants / Q000009:adverse effects* / Q000627:therapeutic use; D006760:Hospitalization; D006801:Humans; D008297:Male; D044469:Racial Groups; D018570:Risk Assessment; D013262:Stevens-Johnson Syndrome / Q000209:etiology*; D014481:United States
chemical_list: D006074:Gout Suppressants; D000493:Allopurinol
keywords: Allopurinol; Gout; Race; Stevens–Johnson Syndrome; Toxic epidermal necrolysis; Urate-lowering therapy