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The rapid onset and potentially fatal outcome in the absence of managed treatment prevent its study. Up today, there are still no known biomarkers that allow an unequivocal diagnosis. Therefore, the aim of this study was to explore metabolic changes in patients suffering anaphylactic reactions depending on the trigger (food and\/or drug) and severity (moderate and severe) in a real\u2010life set\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighteen episodes of anaphylaxis, one per patient, were analysed. Sera were collected during the acute phase (T1), the recovery phase (T2) and around 2\u20133\u00a0months after the anaphylactic reaction (T0: basal state). Reactions were classified following an exhaustive allergological evaluation for severity and trigger. Sera samples were analysed using untargeted metabolomics combining liquid chromatography coupled to mass spectrometry (LC\u2010MS) and proton nuclear magnetic resonance spectroscopy (<jats:sup>1<\/jats:sup>H\u2010NMR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>\u2018Food T1 <jats:italic>vs<\/jats:italic> T2\u2019 and \u2018moderate T1 <jats:italic>vs<\/jats:italic> T2\u2019 anaphylaxis comparisons showed clear metabolic patterns during the onset of an anaphylactic reaction, which differed from those induced by drugs, food\u00a0+\u00a0drug or severe anaphylaxis. Moreover, the model of food anaphylaxis was able to distinguish the well\u2010characterized IgE (antibiotics) from non\u2010IgE\u2010mediated anaphylaxis (nonsteroidal anti\u2010inflammatory drugs), suggesting a differential metabolic pathway associated with the mechanism of action. Metabolic differences between \u2018moderate <jats:italic>vs<\/jats:italic> severe\u2019 at the acute phase T1 and at basal state T0 were studied. Among the altered metabolites, glucose, lipids, cortisol, betaine and oleamide were observed altered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of this exploratory study provide the first evidence that different anaphylactic triggers or severity induce differential metabolic changes along time or at specific time\u2010point, respectively. Besides, the basal status T0\u00a0might identify high\u2010risk patients, thus opening new ways to understand, diagnose and treat anaphylaxis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13991","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T17:33:33Z","timestamp":1627320813000},"page":"1295-1309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers"],"prefix":"10.1111","volume":"51","author":[{"given":"Carolina","family":"Perales\u2010Chorda","sequence":"first","affiliation":[{"name":"Allergy Department of Hospital Universitari i Polit\u00e8cnic La Fe Valencia 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