Diagnostic Performance of Biomarkers for Perioperative Hypersensitivity Reactions in Adults: A Systematic Review and Meta-Analysis on Tryptase and Histamine Dosing

Background: The clinical intra-anesthetic changes of perioperative hypersensitivity (POH) are not specific and require a thorough differential diagnosis with other mimicking conditions. Biomarkers such as tryptase and histamine provide supportive evidence for POH. From the suggested cutoffs, a common decision threshold has not been validated for use in daily practice. The aim of this systematic review and meta-analysis is to identify biomarkers investigated for POH and to evaluate their diagnostic performance. Methods: This meta-analysis included original diagnostic accuracy studies comparing patients with clinically suspected POH and controls with no signs of intraoperative hypersensitivity reactions, in whom allergy biomarkers were evaluated, aiming to investigate diagnostic performance of the assays. Data was pooled to evaluate sensitivity and specificity. Results: In seven studies on tryptase and three studies on histamine dosing for the diagnosis of POH/POA, different fixed or dynamic thresholds for positivity were proposed. For tryptase, fixed thresholds had 59.8% sensitivity and 95.2% specificity for an optimal cutoff of 12.68 ng/mL, while dynamic thresholds yielded 77.2% sensitivity and 88.5% specificity. For histamine, fixed cutoffs presented 78% sensitivity and 85% specificity, while dynamic thresholds investigated in a single study yielded 78.2% sensitivity and 91.1% specificity. Estimates for histamine are unreliable due to limited data. Conclusions: From published data, tryptase is clearly the most robust biomarker, dynamic thresholds boost sensitivity without major specificity loss and confirm the added diagnostic value of relative changes over fixed absolute cutoffs. Preliminary results suggest that histamine might have optimal diagnostic performance, but estimates are severely limited by small sample sizes.