{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:32Z","timestamp":1787026592791,"version":"build-2736575974"},"reference-count":207,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017657","name":"Fondation de l'H\u00f4pital G\u00e9n\u00e9ral de Montr\u00e9al","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017657","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Delayed drug T-cell immune-mediated hypersensitivity reactions have a large clinical heterogeneity varying from mild maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and severe skin necrosis and blistering as seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Given the knowledge gaps related to the immunopathogenesis of these conditions, the absence of validated diagnostic tools and the significant associated morbidity and mortality, patients with SCARs often have limited drug choices. We performed a comprehensive review aiming to evaluate\n                    <jats:italic>in vivo<\/jats:italic>\n                    diagnostic tools such as delayed intradermal skin and patch testing and\n                    <jats:italic>ex vivo\/in vitro<\/jats:italic>\n                    research assays such as the lymphocyte transformation test (LTT) and the enzyme-linked ImmunoSpot (ELISpot) assay. We searched through\n                    <jats:italic>PubMed<\/jats:italic>\n                    using the terms \u201cdrug allergy,\u201d \u201c\n                    <jats:italic>in vivo<\/jats:italic>\n                    \u201d and \u201c\n                    <jats:italic>ex vivo<\/jats:italic>\n                    \u201d for original papers in the last 10 years. A detailed meticulous approach adapted to the various clinical phenotypes is recommended for the diagnostic and management of delayed drug hypersensitivity reactions. This review highlights the current diagnostic tools for the delayed drug hypersensitivity phenotypes.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2022.923991","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:42:28Z","timestamp":1665621748000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Tools to improve the diagnosis and management of T-cell mediated adverse drug reactions"],"prefix":"10.3389","volume":"9","author":[{"given":"Ana Maria","family":"Copaescu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Ben-Shoshan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Trubiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1111\/all.13765","article-title":"Immune pathomechanism and classification of drug hypersensitivity.","volume":"74","author":"Pichler","year":"2019","journal-title":"Allergy."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/j.jaip.2016.04.026","article-title":"A comparative analysis between antibiotic\u2013 and nonantibiotic-associated delayed cutaneous adverse drug reactions.","volume":"4","author":"Trubiano","year":"2016","journal-title":"J Allergy Clin Immunol Pract."},{"key":"B3","doi-asserted-by":"publisher","first-page":"474","DOI":"10.2500\/aap.2019.40.4275","article-title":"Drug allergy.","volume":"40","author":"Greenberger","year":"2019","journal-title":"Allergy Asthma Proc."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2020.104953","article-title":"In vitro identification of drugs inducing systemic hypersensitivity reactions known in vivo to be associated with specific HLA genotypes.","volume":"68","author":"Iulini","year":"2020","journal-title":"Toxicol In Vitro."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1002\/jat.3272","article-title":"Allopurinol induces innate immune responses through mitogen-activated protein kinase signaling pathways in HL-60 cells.","volume":"36","author":"Nakajima","year":"2016","journal-title":"J Appl Toxicol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.anai.2014.06.019","article-title":"Multinational experience with hypersensitivity drug reactions in Latin America.","volume":"113","author":"Jares","year":"2014","journal-title":"Ann Allergy Asthma Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.jaip.2017.02.013","article-title":"Severe cutaneous adverse drug reactions in pediatric patients: a multicenter study.","volume":"5","author":"Dibek Misirlioglu","year":"2017","journal-title":"J Allergy Clin Immunol Pract."},{"key":"B8","doi-asserted-by":"publisher","first-page":"152","DOI":"10.5152\/TurkPediatriArs.2016.3836","article-title":"Evaluation of the patients diagnosed with Stevens Johnson syndrome and toxic epidermal necrolysis: a single center experience.","volume":"51","author":"Cekic","year":"2016","journal-title":"Turk Pediatri Ars."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1016\/j.jaad.2020.03.081","article-title":"Drug reaction with eosinophilia and systemic symptoms (DRESS) in the pediatric population: a systematic review of the literature.","volume":"83","author":"Kim","year":"2020","journal-title":"J Am Acad Dermatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.jaip.2017.01.025","article-title":"Severe delayed cutaneous and systemic reactions to drugs: a global perspective on the science and art of current practice.","volume":"5","author":"Peter","year":"2017","journal-title":"J Allergy Clin Immunol Pract."},{"key":"B11","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1111\/pai.13485","article-title":"Skin eruptions in children: drug hypersensitivity vs viral exanthema.","volume":"32","author":"Tsabouri","year":"2021","journal-title":"Pediatr Allergy Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3358","DOI":"10.1001\/jama.256.24.3358","article-title":"Drug-induced cutaneous reactions. 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