BackgroundEarly recognition of perioperative anaphylaxis, a life-threatening, usually immunoglobulin E [IgE]-mediated, immediate hypersensitivity, is essential, but bedside diagnosis is not always straightforward as clinical presentation may vary. ObjectivesTo describe early characteristics of perioperative immediate hypersensitivity (POH), with a special attention on cutaneous phenotypes, and identify risk factors for IgE-mediated allergy. MethodsWe retrospectively analyzed data from adults with suspected POH who were investigated in two academic medical centers. Multivariable logistic regression was conducted to evaluate associations between patient, clinical, and paraclinical characteristics and IgE-mediated allergy. ResultsOut of 145 patients enrolled, 99 (68.3%) and 46 (31.7%) were respectively categorized in the IgE-mediated allergy and non-allergy groups. Cutaneous vasoconstriction phenotype (pallor, piloerection, thelerethism, sweating ± cyanosis) occurring within minutes (or even one minute) of drug-exposure, was strongly associated with IgE-mediated allergy (adjusted odds ratio [aOR]: 28.02, 95% confidence interval [CI]: 4.41-305.18). IgE-mediated allergy was always life-threatening in this setting. Other early factors associated with allergy were low end-tidal carbon dioxide (ETco2) ≤25mmHg (aOR: 5.45, 95%CI: 2.39-26.45), low mean arterial pressure (MAP) ≤60mmHg (aOR: 3.82, 95%CI: 1.28-17.31), and early cutaneous vasodilation (erythema, urticaria and/or angioedema) (aOR: 2.78, 95%CI: 0.73-20.54). Late cutaneous vasodilation following restoration of hemodynamics corroborated the diagnosis of allergy (aOR: 23.67, 95%CI: 4.94-205.09). The best-fit model including three readily available variables (cutaneous phenotype involving the three modalities [reference lack of cutaneous signs], low MAP and low ETco2) had an AUC of 0.91. ConclusionsCutaneous vasoconstriction phenotype is associated with the strongest risk of life-threatening allergy and may thus be regarded as pathognomonic of perioperative IgE-mediated anaphylaxis.