{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:33:04Z","timestamp":1782300784422,"version":"3.54.5"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Allergy"],"abstract":"<jats:p>Idiopathic anaphylaxis (IA) is a severe allergic reaction without identifiable external triggers, presenting significant challenges in diagnosis and management. However, growing evidence suggests that many cases classified as idiopathic may actually be driven by cofactors such as exercise, hormonal fluctuations, medications, or hidden allergens. This mini-review explores the evolving understanding of IA, highlighting the role of these cofactors in triggering or amplifying anaphylactic reactions. It emphasizes how advances in diagnostic tools, including component-resolved diagnostics, are helping to identify previously undetected allergens, leading to more accurate diagnoses and reducing the prevalence of true idiopathic cases. As our knowledge of anaphylaxis and its underlying mechanisms deepens, the need for comprehensive evaluations that account for cofactor involvement becomes increasingly clear. Continued research in this area is essential to improve patient outcomes and better manage this complex condition.<\/jats:p>","DOI":"10.3389\/falgy.2024.1468945","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T05:10:34Z","timestamp":1729228234000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["When allergies have no name: is idiopathic anaphylaxis driven by co-factors?"],"prefix":"10.3389","volume":"5","author":[{"given":"Shuayb","family":"Elkhalifa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haggar","family":"Elbashir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abuzakouk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.iac.2021.09.010","article-title":"Anaphylaxis: epidemiology and differential diagnosis","volume":"42","author":"Motosue","year":"2022","journal-title":"Immunol Allergy Clin North Am"},{"key":"B2","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1111\/all.15032","article-title":"EAACI guidelines: anaphylaxis (2021 update)","volume":"77","author":"Muraro","year":"2022","journal-title":"Allergy"},{"key":"B3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s11882-021-00988-y","article-title":"Idiopathic anaphylaxis: a perplexing diagnostic challenge for allergists","volume":"21","author":"Gulen","year":"2021","journal-title":"Curr Allergy Asthma Rep"},{"key":"B4","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1365-2222.1978.tb03227.x","article-title":"Evaluation of severe (anaphylactic) reactions","volume":"8","author":"Bacal","year":"1978","journal-title":"Clin Allergy"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1182\/blood-2006-06-028100","article-title":"Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with \u201cidiopathic\u201d anaphylaxis","volume":"110","author":"Akin","year":"2007","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.15036\/arerugi.70.1211","article-title":"World allergy organization anaphylaxis guidance 2020","volume":"70","author":"Cardona","year":"2021","journal-title":"Arerugi"},{"key":"B7","doi-asserted-by":"publisher","first-page":"481","DOI":"10.2500\/aap.2021.42.210081","article-title":"Idiopathic anaphylaxis: diagnosis and management","volume":"42","author":"Burrows","year":"2021","journal-title":"Allergy Asthma Proc"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1111\/all.12272","article-title":"The epidemiology of anaphylaxis in Europe: a systematic review","volume":"68","author":"Panesar","year":"2013","journal-title":"Allergy"},{"key":"B9","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.jaci.2013.08.016","article-title":"Anaphylaxis in America: the prevalence and characteristics of anaphylaxis in the United States","volume":"133","author":"Wood","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1001\/archinte.1995.00430080119014","article-title":"Idiopathic anaphylaxis. 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