title: An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing.
abstract: OBJECTIVE
  This study was conducted to evaluate the usefulness of human leukocyte antigen (HLA) typing in preventing allopurinol-induced severe cutaneous adverse reactions (SCARs) through the application of an allopurinol tolerance induction protocol or prescription of other alternative medications in high-risk patients.
  
  
  METHODS
  HLA typing was performed in patients with chronic renal insufficiency who needed allopurinol. HLA-B*58:01-negative patients were prescribed the usual dose of allopurinol. For HLA-B*58:01-positive patients, administration of either allopurinol based on a 28-day tolerance induction protocol or alternative medications was initiated. Hypersensitivity reactions were surveyed for 90 days and compared with the result of a previous retrospective cohort study.
  
  
  RESULTS
  Among a total of 401 study subjects, no SCARs were noted in HLA-B*58:01-positive patients with application of the tolerance induction protocol (n = 30) or alternative medications (n = 16), nor were any SCARs observed in HLA-B*58:01-negative patients who started allopurinol at the usual dose (n = 355). Compared with the previous retrospective cohort study, a significant reduction in SCARs was observed in HLA-B*58:01-positive patients (0 vs. 18%; P = 0.002).
  
  
  CONCLUSIONS
  This study shows the usefulness of HLA-B*58:01 screening in identifying patients at high risk for the development of allopurinol-induced SCARs and suggests that application of a tolerance induction protocol or alternative medications could be an effective strategy to prevent allopurinol-induced SCARs in HLA-B*58:01-positive patients.
authors: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.|Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
authors: Jae-Woo
authors: JW
authors: Jung
authors: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Dong-Ki
authors: http://orcid.org/0000-0002-2317-4201
authors: DK
authors: Kim
authors: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Heung-Woo
authors: HW
authors: Park
authors: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Kook-Hwan
authors: KH
authors: Oh
authors: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Kwon-Wook
authors: KW
authors: Joo
authors: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Yon-Su
authors: YS
authors: Kim
authors: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Curie
authors: C
authors: Ahn
authors: Hallym Institute for Genome Application, Hallym University College of Medicine, Anyang, Korea.
authors: Kyung Wha
authors: KW
authors: Lee
authors: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Sang-Heon
authors: SH
authors: Cho
authors: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Kyung-Up
authors: KU
authors: Min
authors: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Hye-Ryun
authors: HR
authors: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000493:Allopurinol / Q000008:administration & dosage / Q000009:adverse effects*; D003888:Desensitization, Immunologic; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006649:Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007108:Immune Tolerance; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D015235:HLA-B Antigens; D006649:Histocompatibility Antigens; D000493:Allopurinol
references: Am J Med. 1984 Jan;76(1):47-56
references: 6691361
references: Pharmacogenet Genomics. 2011 May;21(5):303-7
references: 21301380
references: Curr Opin Rheumatol. 2002 May;14(3):281-6
references: 11981327
references: J Invest Dermatol. 1994 Jun;102(6):28S-30S
references: 8006430
references: Br Med J (Clin Res Ed). 1985 Jun 29;290(6486):1969-70
references: 3924329
references: Epilepsia. 2014 Apr;55(4):496-506
references: 24597466
references: Tissue Antigens. 1996 Jun;47(6):538-46
references: 8813743
references: Nature. 2004 Apr 1;428(6982):486
references: 15057820
references: Nucleic Acids Res. 1988 Feb 11;16(3):1215
references: 3344216
references: N Engl J Med. 2005 Dec 8;353(23):2450-61
references: 16339094
references: Curr Opin Allergy Clin Immunol. 2005 Aug;5(4):309-16
references: 15985812
references: Arthritis Rheum. 2012 Aug;64(8):2529-36
references: 22488501
references: Curr Rheumatol Rep. 2001 Feb;3(1):29-35
references: 11177768
references: N Engl J Med. 2011 Mar 24;364(12):1126-33
references: 21428768
references: Arthritis Rheum. 1986 Jan;29(1):82-7
references: 3947418
references: Arthritis Rheum. 2001 Jan;44(1):231-8
references: 11212165
references: N Engl J Med. 2008 Feb 7;358(6):568-79
references: 18256392
references: Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4134-9
references: 15743917
references: Ann Rheum Dis. 2006 Oct;65(10):1312-24
references: 16707532
references: Sci China Life Sci. 2013 Feb;56(2):119-24
references: 23393027
references: Clin Exp Allergy. 2013 Nov;43(11):1246-55
references: 24152157
references: Neth J Med. 1998 Mar;52(3):107-10
references: 9599967
references: JAMA. 2014 Jun 4;311(21):2231-2
references: 24893093
references: Nephrol Dial Transplant. 2011 Nov;26(11):3567-72
references: 21393610
references: Lancet. 2002 Mar 2;359(9308):727-32
references: 11888582
references: J Invest Dermatol. 2002 Apr;118(4):728-33
references: 11918724
references: Pharmacogenomics. 2006 Sep;7(6):813-8
references: 16981842
references: Curr Opin Allergy Clin Immunol. 2006 Aug;6(4):271-7
references: 16825867
references: Drug Saf. 1997 Dec;17(6):374-89
references: 9429837
references: J Invest Dermatol. 2008 Jan;128(1):35-44
references: 17805350
references: Pharmacogenet Genomics. 2009 Sep;19(9):704-9
references: 19696695
references: Tissue Antigens. 2005 May;65(5):437-47
references: 15853898
references: Lancet. 2000 Oct 7;356(9237):1255-9
references: 11072960
references: N Engl J Med. 1994 Nov 10;331(19):1272-85
references: 7794310