Mast Cell Activation Profiles in Perioperative Immediate Hypersensitivity Reactions: A GERAP Network Study

Perioperative immediate hypersensitivity reactions (POHRs) are potentially fatal complications of anesthesia. Although tryptase is a cornerstone biomarker for mast cell activation (MCA), its diagnostic limitations call for a better understanding of the underlying mechanisms and phenotypes of POHRs to guide management. Objective: Compare the phenotypes of patients who experience POHRs based on their MCA profiles using tryptase and histamine assays.

This retrospective multicenter study included patients assessed by the GERAP Network who experienced POHRs from 2017 to 2024. Clinical characteristics and biomarker correlation were analyzed across MCA profiles. MCA profiles were determined based on the presence of MCA (peak tryptase >1.2×baseline tryptase+2 μg/L; NoMCA vs MCA) and a peak tryptase value (elevated if ≥8 μg/L; low tryptase [LT] vs high tryptase [HT]) or histamine release (elevated if ≥10 nmol/L).

MCA was recorded in 626 of the 930 patients (67%). HT-MCA and LT-NoMCA were the most frequent profiles, detected in 60% and 27% of patients, respectively. POHRs were more severe in the HT-MCA group than in the LT-NoMCA group (85% vs 43%; P<.0001). Skin test results were positive in 26% of patients in the LT-NoMCA group, and some patients exhibited histamine release only. The MCA profile differed depending on the drugs used during the perioperative period, indicating the involvement of various mechanisms.

While most reactions involving high tryptase concentrations and MCA are consistent with an IgE-mediated mechanism, our results showed that identifying the underlying mechanism of POHRs with a high degree of certainty is still not possible using the tools currently applied in daily clinical practice.