Fatal waterhouse-friderichsen syndrome at autopsy: a systematic review and forensic diagnostic framework
In brief
Review of 86 autopsies establishes forensic framework for diagnosing Waterhouse-Friderichsen syndrome
A systematic review of 86 fatal cases across 65 studies found bilateral adrenal hemorrhage consistently accompanied by multiorgan congestion and variable coagulation changes, highlighting the syndrome as a repeatable forensic pattern rather than a single pathology. The authors propose a practical framework that integrates morphology, histology, microbiology and case context to standardize post-mortem diagnosis of sudden septic deaths.
- Journal
- International journal of legal medicine (Q1)
- Published
- 29 August 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Jessika Camatti, Anna Laura Santunione, Rossana Cecchi, Erjon Radheshi, Edoardo Carretto, Maria Paola Bonasoni
- PMID
- 42665693
- DOI
- 10.1007/s00414-026-03978-9
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (paper of the day, 31 August 2026): Forensic framework for diagnosing adrenal hemorrhage at autopsy
Abstract
Waterhouse-Friderichsen syndrome (WFS) represents a fulminant septic condition characterized by bilateral adrenal hemorrhage and rapid clinical deterioration. Although classically associated with meningococcal infection, fatal cases occur across multiple infectious etiologies and heterogeneous clinical contexts. In forensic practice, diagnosis frequently relies on post-mortem interpretation rather than clinical recognition, making consistent pathological assessment essential. A systematic review was conducted according to PRISMA guidelines to identify autopsy-confirmed fatal cases consistent with WFS. PubMed/MEDLINE and Scopus were searched from database inception to 21 February 2026, with a supplementary search conducted in Google Scholar. Eligible studies included fatal human cases with bilateral adrenal hemorrhage documented at autopsy and sufficient pathological and/or microbiological data. Data were extracted on clinical course, gross and histopathological findings, microbiological investigations, pathogens, and predisposing factors. Owing to marked heterogeneity of case-level reporting, qualitative synthesis and semi-quantitative descriptive analysis were performed. Sixty-five studies, encompassing 86 individual fatal cases, met the inclusion criteria. Bilateral adrenal hemorrhage consistently occurred within a broader systemic septic pattern characterized by multiorgan congestion, hemorrhagic manifestations, and variable disseminated intravascular coagulation-related changes. Histopathological and microbiological findings were heterogeneous, with frequent discrepancies between culture-based and molecular results and recurrent diagnostic limitations related to post-mortem microbiology. The synthesis of evidence supports interpreting WFS as a recurrent forensic-pathological pattern rather than a single morphological diagnosis. Based on key findings identified across cases, practical forensic frameworks were developed to support autopsy interpretation, microbiological sampling, and differential diagnosis. Integration of morphology, histopathology, microbiology, and circumstantial data may improve consistency and reproducibility in the medico-legal evaluation of sudden septic deaths.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.