Beyond the numbers: Critical analysis of the role of postmortem tryptase in the forensic diagnosis of anaphylaxis

The postmortem diagnosis of anaphylaxis remains a forensic challenge due to the lack of specific external signs. Tryptase, a mast cell-derived protease, has emerged as a potential biomarker for fatal anaphylaxis. This systematic review critically examined 40 studies published between 2014 and 2024, including both biochemical and immunohistochemical analyses. Literature was identified through comprehensive searches of PubMed, Scopus, and Web of Science, following PRISMA guidelines. Biochemical studies consistently reported elevated postmortem β-tryptase levels in anaphylaxis-related deaths, with proposed diagnostic thresholds ranging from 30.4 to 64 μg/L. A diagnostic threshold of 53.8 μg/L demonstrated particularly strong discriminative capacity (AUC = 0.98; p < 0.001). Immunohistochemical analyses revealed an increased number of tryptase-positive mast cells in lung, pharynx, and skin tissues, but standardized protocols or quantification criteria were lacking. Notably, mast cell localization around bronchioles or vascular structures was more frequent in anaphylaxis cases. Despite promising findings, substantial heterogeneity in postmortem interval, sampling site, and analytical methodology limits the generalizability of current evidence. Elevated tryptase levels were also documented in non-anaphylactic deaths, underscoring its limited specificity. Overall, tryptase can support the postmortem diagnosis of anaphylaxis when interpreted in the context of autopsy findings, scene investigation, and clinical history. However, it should not be used as a standalone marker. Standardized protocols and combined biomarker panels are urgently needed to enhance diagnostic reliability in forensic settings.