Analysis of HLA-B allelic variation and interferon-gamma ELISpot responses in patients with severe cutaneous adverse reactions associated with drugs

Publication date: Available online 22 May 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Jettanong Klaewsongkram, Chonlaphat Sukasem, Pattarawat Thantiworasit, Nithikan Suthumchai, Pawinee Rerknimitr, Papapit Tuchinda, Leena Chularojanamontri, Yuttana Srinoulprasert, Ticha Rerkpattanapipat, Kumutnart Chanprapaph, Wareeporn Disphanurat, Panlop Chakkavittumrong, Napatra Tovanabutra, Chutika Srisuttiyakorn
BackgroundThe prevention and confirmation of drug-induced severe cutaneous adverse reactions (SCARs) are difficult.ObjectiveTo determine the benefit of HLA-B allele pre-screening and the measurement of drug-specific interferon-gamma (IFN-γ) releasing cells in the prevention and identification of the culprit drug in SCAR patients.MethodsA total of 160 SCAR patients were recruited from six 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 SCAR patients were also measured.ResultsThe drugs commonly responsible for SCARs were anticonvulsants, allopurinol, beta-lactams, anti-tuberculosis 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% (53/116) of patients with SCARs caused by five 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.ConclusionsHLA-B pre-screening 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.