Jettanong Klaewsongkram1, Chonlaphat Sukasem2, Pattarawat Thantiworasit3, Nithikan Suthumchai3, Pawinee Rerknimitr4, Papapit Tuchinda5, Leena Chularojanamontri5, Yuttana Srinoulprasert6, Ticha Rerkpattanapipat7, Kumutnart Chanprapaph8, Wareeporn Disphanurat9, Panlop Chakkavittumrong9, Napatra Tovanabutra10, Chutika Srisuttiyakorn11. 1. Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, The Skin and Allergy Research Unit, Chulalongkorn University, Bangkok, Thailand; King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. Electronic address: Jettanong.K@chula.ac.th. 2. Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 3. Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, The Skin and Allergy Research Unit, Chulalongkorn University, Bangkok, Thailand. 4. King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Division of Dermatology, Department of Medicine, Faculty of Medicine, The Skin and Allergy Research Unit, Chulalongkorn University, Bangkok, Thailand. 5. Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 6. Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 7. Allergy Immunology and Rheumatology Division, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 8. Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 9. Division of Dermatology, Department of Medicine, Faculty of Medicine, Thammasat University, Pathumthani, Thailand. 10. Dermatologic Division, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand. 11. Division of Dermatology, Department of Medicine, Phramongkutklao Hospital, Phramongkutklao College of Medicine, Bangkok, Thailand.
Abstract
BACKGROUND: The prevention and confirmation of drug-induced severe cutaneous adverse reactions (SCARs) are difficult. OBJECTIVE: To determine the benefit of HLA-B allele prescreening and the measurement of drug-specific IFN-γ-releasing cells in the prevention and identification of the culprit drug in patients with SCARs. METHODS: A total of 160 patients with SCARs were recruited from 6 university hospitals in Thailand over a 3-year period. HLA-B alleles were genotypically analyzed. The frequencies of drug-specific IFN-γ-releasing cells in patients with SCARs were also measured. RESULTS: The drugs commonly responsible for SCARs were anticonvulsants, allopurinol, beta-lactams, antituberculosis agents, and sulfonamides. If culprit drugs had been withheld in patients carrying known HLA-B alleles at risk, it would have prevented 21.2% of SCAR cases, mainly allopurinol- and carbamazepine-related SCARs. Culprit drug-specific IFN-γ-releasing cells could be identified in 45.7% (53 of 116) of patients with SCARs caused by 5 major drug groups, particularly in patients diagnosed with drug reactions with eosinophilia and systemic symptoms (DRESS) (50.0%), followed by Stevens-Johnson syndrome/toxic epidermal necrolysis (46.0%), and acute generalized exanthematous pustulosis (31.3%). According to our study, high frequencies of drug-specific IFN-γ-releasing cells were significantly demonstrated in patients who suffered from DRESS phenotype, having anticonvulsants or the drugs belonging to the "probable" category based on the Naranjo algorithm scale, as the culprit drugs. CONCLUSIONS: HLA-B prescreening would succeed in preventing only a minority of SCAR victims. Drug-specific IFN-γ-releasing cells are detectable in almost half of patients. Better strategies are required for better SCAR prevention and culprit drug confirmation.
BACKGROUND: The prevention and confirmation of drug-induced severe cutaneous adverse reactions (SCARs) are difficult. OBJECTIVE: To determine the benefit of HLA-B allele prescreening and the measurement of drug-specific IFN-γ-releasing cells in the prevention and identification of the culprit drug in patients with SCARs. METHODS: A total of 160 patients with SCARs were recruited from 6 university hospitals in Thailand over a 3-year period. HLA-B alleles were genotypically analyzed. The frequencies of drug-specific IFN-γ-releasing cells in patients with SCARs were also measured. RESULTS: The drugs commonly responsible for SCARs were anticonvulsants, allopurinol, beta-lactams, antituberculosis agents, and sulfonamides. If culprit drugs had been withheld in patients carrying known HLA-B alleles at risk, it would have prevented 21.2% of SCAR cases, mainly allopurinol- and carbamazepine-related SCARs. Culprit drug-specific IFN-γ-releasing cells could be identified in 45.7% (53 of 116) of patients with SCARs caused by 5 major drug groups, particularly in patients diagnosed with drug reactions with eosinophilia and systemic symptoms (DRESS) (50.0%), followed by Stevens-Johnson syndrome/toxic epidermal necrolysis (46.0%), and acute generalized exanthematous pustulosis (31.3%). According to our study, high frequencies of drug-specific IFN-γ-releasing cells were significantly demonstrated in patients who suffered from DRESS phenotype, having anticonvulsants or the drugs belonging to the "probable" category based on the Naranjo algorithm scale, as the culprit drugs. CONCLUSIONS:HLA-B prescreening would succeed in preventing only a minority of SCAR victims. Drug-specific IFN-γ-releasing cells are detectable in almost half of patients. Better strategies are required for better SCAR prevention and culprit drug confirmation.
Authors: Fiona James; Michelle S Y Goh; Effie Mouhtouris; Sara Vogrin; Kyra Y L Chua; Natasha E Holmes; Andrew Awad; Ana-Maria Copaescu; Joseph F De Luca; Celia Zubrinich; Douglas Gin; Heather Cleland; Abby Douglas; Johannes S Kern; Constance H Katelaris; Francis Thien; Sara Barnes; James Yun; Winnie Tong; William B Smith; Andrew Carr; Tara Anderson; Amy Legg; Jack Bourke; Laura K Mackay; Ar Kar Aung; Elizabeth J Phillips; Jason Trubiano Journal: BMJ Open Date: 2022-08-17 Impact factor: 3.006