A systematic review of the diagnostic value of post-mortem blood tryptase in fatal anaphylaxis: assessment of sensitivity and specificity

Objective: The post-mortem diagnosis of fatal anaphylaxis presents significant challenges due to the absence of pathognomonic findings. Serum tryptase has been proposed as a potential biomarker to support forensic diagnosis, but optimal post-mortem thresholds remain undefined. This systematic review investigates the sensitivity and specificity of post-mortem blood tryptase in diagnosing fatal anaphylaxis. Methods: We conducted a systematic literature review adhering to the PRISMA guidelines, with searches across major databases. Studies published between 1990 and 2024 were screened to identify those addressing fatal anaphylactic shock, applying strict inclusion criteria to ensure relevance. A total of 20 studies met our criteria, representing 1033 individuals, including 221 anaphylactic deaths. Sensitivity and specificity of tryptase were analyzed using various thresholds, with data synthesis conducted using the Mann–Whitney–Wilcoxon test and ROC analysis to identify optimal diagnostic cut-offs. Results: Our findings demonstrated that the cut-off of 30.4 ng/mL proposed by the most recent meta-analysis offers a balanced sensitivity (88.20 %) and specificity (87.00 %). Sensitivity remains stable across tryptase values ranging from 30 to 60 ng/mL, while specificity tends to increase. Youden's J index was applied to identify the cut-off with the optimal combination of sensitivity and specificity, namely 74.2 ng/mL. Additionally, Negative Likelihood Ratio allowed to identify 12.00 ng/mL as the cut-off at which the possibility of an anaphylactic death can be ruled out. Conclusion: This review highlights the optimal balance of sensitivity and specificity of post-mortem blood tryptase enhancing forensic diagnostic accuracy for fatal anaphylaxis cases.