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Br J Dermatol. 2016 Nov;175(5):994-1002. doi: 10.1111/bjd.14701. Epub 2016 Aug 29.

In vitro test to confirm diagnosis of allopurinol-induced severe cutaneous adverse reactions.

Author information

  • 1Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Allergy and Clinical Immunology Research Group, Chulalongkorn University, Bangkok, Thailand. jettanong.k@chula.ac.th.
  • 2King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. jettanong.k@chula.ac.th.
  • 3Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Allergy and Clinical Immunology Research Group, Chulalongkorn University, Bangkok, Thailand.
  • 4King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
  • 5Division of Dermatology, Department of Medicine, Faculty of Medicine, Allergy and Clinical Immunology Research Group, Chulalongkorn University, Bangkok, Thailand.
  • 6Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
  • 7Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • 8Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • 9Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
  • 10Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
  • 11Division of Dermatology, Department of Medicine, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
  • 12Dermatological Division, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand.
  • 13Division of Dermatology, Department of Medicine, Phramongkutklao Hospital, Phramongkutklao College of Medicine, Bangkok, Thailand.

Abstract

BACKGROUND:

Allopurinol is a frequent cause of severe cutaneous adverse reactions (SCARs), such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The reactions can potentially be fatal. As drug rechallenge in patients with a history of drug-induced SCARs is contraindicated, in vitro testing may have a diagnostic role as a confirmation test.

OBJECTIVES:

To study the diagnostic value of interferon (IFN)-γ enzyme-linked immunospot (ELISpot) assay as a confirmatory test in patients with a history of allopurinol-induced SCARs.

METHODS:

Peripheral blood mononuclear cells (PBMCs) from 24 patients with a history of allopurinol-induced SCAR (13 DRESS, 11 SJS/TEN) and 21 control subjects were incubated with allopurinol or oxypurinol in the presence or absence of antiprogrammed death ligand 1 antibody (anti-PD-L1). The numbers of IFN-γ-releasing cells after stimulation in each group were subsequently measured with ELISpot.

RESULTS:

The numbers of IFN-γ-releasing cells in allopurinol-allergic subjects were significantly higher than in control subjects when stimulating PBMCs with oxypurinol 100 μg mL-1 , especially when adding anti-PD-L1 supplementation. According to the receiver operating characteristic curve results, the optimal discriminatory power of IFN-γ ELISpot in confirming diagnosis of allopurinol-induced SCARs can be obtained using 16 spot-forming cells per 106 PBMCs as a cut-off value upon oxypurinol/anti-PD-L1 stimulation (79·2% sensitivity and 95·2% specificity).

CONCLUSIONS:

The measurement of oxypurinol/anti-PD-L1-inducing IFN-γ-releasing cells yields a high diagnostic value in distinguishing between allopurinol-allergic and control subjects. This technique is beneficial in confirming diagnosis of allopurinol-induced SCARs in patients whose reaction develops while taking multiple drugs.

PMID:
27106261
DOI:
10.1111/bjd.14701
[PubMed - in process]
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