J Klaewsongkram1,2, P Thantiworasit3, N Suthumchai3, P Rerknimitr4,5, C Sukasem6, P Tuchinda7, L Chularojanamontri7, Y Srinoulprasert8, T Rerkpattanapipat9, K Chanprapaph10, W Disphanurat11, P Chakkavittumrong11, N Tovanabutra12, C Srisuttiyakorn13. 1. Division 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. 2. King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. jettanong.k@chula.ac.th. 3. Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Allergy and Clinical Immunology Research Group, Chulalongkorn University, Bangkok, Thailand. 4. King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. 5. Division of Dermatology, Department of Medicine, Faculty of Medicine, Allergy and Clinical Immunology Research Group, Chulalongkorn University, Bangkok, Thailand. 6. Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 7. Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 8. Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 9. Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 10. Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 11. Division of Dermatology, Department of Medicine, Faculty of Medicine, Thammasat University, Pathumthani, Thailand. 12. Dermatological Division, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand. 13. Division 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.
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.
Authors: Hyun Jung Jin; Dong Yoon Kang; Young Hee Nam; Young Min Ye; Young Il Koh; Gyu Young Hur; Sae Hoon Kim; Min Suk Yang; Sujeong Kim; Yi Yeong Jeong; Min Hye Kim; Jeong Hee Choi; Hye Ryun Kang; Eun Jung Jo; Hye Kyung Park Journal: Allergy Asthma Immunol Res Date: 2021-03 Impact factor: 5.764