---
title: "Fatal Waterhouse–Friderichsen Syndrome at Autopsy: Systematic Review and Forensic Diagnostic Frame"
id: "pubmed-42665693"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42665693"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42665693/"
doi: "10.1007/s00414-026-03978-9"
published_at: "2026-08-29T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Fatal Waterhouse–Friderichsen Syndrome at Autopsy: Systematic Review and Forensic Diagnostic Frame
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42665693
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42665693/)
- **DOI:** [10.1007/s00414-026-03978-9](https://doi.org/10.1007%2Fs00414-026-03978-9)
- **Published At:** 2026-08-29T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Waterhouse–Friderichsen syndrome (WFS) is a fulminant septic condition defined by **bilateral adrenal hemorrhage** and rapid clinical decline; although classically linked to meningococcal infection, fatal WFS occurs with multiple infectious causes and heterogeneous clinical contexts. - The authors performed a systematic review following **PRISMA** guidelines, searching PubMed/MEDLINE, Scopus, and Google Scholar through 21 February 2026 to identify autopsy-confirmed fatal cases consistent with WFS. - Inclusion required human fatal cases with bilateral adrenal hemorrhage documented at autopsy and sufficient pathological and/or microbiological data; 65 studies reporting 86 individual fatal cases met criteria. - Across cases, bilateral adrenal hemorrhage was consistently part of a wider systemic septic pattern including multiorgan congestion, hemorrhagic manifestations, and variable changes related to **disseminated intravascular coagulation (DIC)**. - Histopathological appearances and microbiological results were heterogeneous; frequent discrepancies occurred between culture-based and molecular microbiology, and post-mortem microbiology had recurrent diagnostic limitations. - The authors argue WFS should be interpreted as a recurrent **forensic-pathological pattern** rather than a single morphological diagnosis, given variable etiologies and pathological presentations. - Based on recurring findings, the review developed practical forensic frameworks to support autopsy interpretation, microbiological sampling, and differential diagnosis in sudden septic deaths. - The proposed approach emphasizes integration of macroscopic morphology, histopathology, microbiology, and circumstantial data to improve consistency and reproducibility in medico-legal evaluations. - The review highlights the impact of heterogeneous case-level reporting on synthesis and the need to acknowledge limitations inherent to post-mortem investigations when attributing cause of death in suspected WFS cases.
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Online ahead of print. # Fatal waterhouse-friderichsen syndrome at autopsy: a systematic review and forensic diagnostic framework [Jessika Camatti](https://pubmed.ncbi.nlm.nih.gov/?term=Camatti+J&cauthor_id=42665693)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#full-view-affiliation-1 "University of Parma, Parma, Italy. jessika.camatti@unipr.it."), [Anna Laura Santunione](https://pubmed.ncbi.nlm.nih.gov/?term=Santunione+AL&cauthor_id=42665693)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#full-view-affiliation-2 "University of Modena and Reggio Emilia, Modena, Italy."), [Rossana Cecchi](https://pubmed.ncbi.nlm.nih.gov/?term=Cecchi+R&cauthor_id=42665693)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#full-view-affiliation-2 "University of Modena and Reggio Emilia, Modena, Italy."), [Erjon Radheshi](https://pubmed.ncbi.nlm.nih.gov/?term=Radheshi+E&cauthor_id=42665693)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#full-view-affiliation-3 "Azienda Unità Sanitaria Locale, IRCCS, Reggio Emilia, Italy."), [Edoardo Carretto](https://pubmed.ncbi.nlm.nih.gov/?term=Carretto+E&cauthor_id=42665693)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#full-view-affiliation-4 "Azienda Socio Sanitaria Territoriale "Papa Giovanni XXIII", Bergamo, Italy."), [Maria Paola Bonasoni](https://pubmed.ncbi.nlm.nih.gov/?term=Bonasoni+MP&cauthor_id=42665693)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#full-view-affiliation-3 "Azienda Unità Sanitaria Locale, IRCCS, Reggio Emilia, Italy.") Affiliations Expand ### Affiliations * 1 University of Parma, Parma, Italy. jessika.camatti@unipr.it. * 2 University of Modena and Reggio Emilia, Modena, Italy. * 3 Azienda Unità Sanitaria Locale, IRCCS, Reggio Emilia, Italy. * 4 Azienda Socio Sanitaria Territoriale "Papa Giovanni XXIII", Bergamo, Italy. * PMID: **42665693** * DOI: [ 10.1007/s00414-026-03978-9 ](https://doi.org/10.1007/s00414-026-03978-9) Item in Clipboard Review # Fatal waterhouse-friderichsen syndrome at autopsy: a systematic review and forensic diagnostic framework Jessika Camatti et al. Int J Legal Med. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Legal Med Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Legal+Med%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Legal+Med%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42665693/) . 2026 Aug 29. doi: 10.1007/s00414-026-03978-9. Online ahead of print. ### Authors [Jessika Camatti](https://pubmed.ncbi.nlm.nih.gov/?term=Camatti+J&cauthor_id=42665693)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#short-view-affiliation-1 "University of Parma, Parma, Italy. jessika.camatti@unipr.it."), [Anna Laura Santunione](https://pubmed.ncbi.nlm.nih.gov/?term=Santunione+AL&cauthor_id=42665693)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#short-view-affiliation-2 "University of Modena and Reggio Emilia, Modena, Italy."), [Rossana Cecchi](https://pubmed.ncbi.nlm.nih.gov/?term=Cecchi+R&cauthor_id=42665693)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#short-view-affiliation-2 "University of Modena and Reggio Emilia, Modena, Italy."), [Erjon Radheshi](https://pubmed.ncbi.nlm.nih.gov/?term=Radheshi+E&cauthor_id=42665693)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#short-view-affiliation-3 "Azienda Unità Sanitaria Locale, IRCCS, Reggio Emilia, Italy."), [Edoardo Carretto](https://pubmed.ncbi.nlm.nih.gov/?term=Carretto+E&cauthor_id=42665693)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#short-view-affiliation-4 "Azienda Socio Sanitaria Territoriale "Papa Giovanni XXIII", Bergamo, Italy."), [Maria Paola Bonasoni](https://pubmed.ncbi.nlm.nih.gov/?term=Bonasoni+MP&cauthor_id=42665693)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42665693/#short-view-affiliation-3 "Azienda Unità Sanitaria Locale, IRCCS, Reggio Emilia, Italy.") ### Affiliations * 1 University of Parma, Parma, Italy. jessika.camatti@unipr.it. * 2 University of Modena and Reggio Emilia, Modena, Italy. * 3 Azienda Unità Sanitaria Locale, IRCCS, Reggio Emilia, Italy. * 4 Azienda Socio Sanitaria Territoriale "Papa Giovanni XXIII", Bergamo, Italy. * PMID: **42665693** * DOI: [ 10.1007/s00414-026-03978-9 ](https://doi.org/10.1007/s00414-026-03978-9) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## 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. **Keywords:** Autopsy; Bilateral adrenal hemorrhage; Disseminated intravascular coagulation; Forensic pathology; Fulminant sepsis; Post-mortem microbiology; Waterhouse–Friderichsen syndrome. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Clinical trial number: Not applicable. Ethical approval: This study is a systematic review of published literature and did not involve new human participants or biological samples. Therefore, approval from an institutional review board or ethics committee was not required. Human ethics and consent to participate declaration: Not applicable. Competing interests: The authors declare no competing interests. One of the included studies is a previously published case report authored by members of the research team. ## References 1. 1. Karki BR, Sedhai YR, Bokhari SRA (2023) Waterhouse-Friderichsen syndrome. In: StatPearls [Internet]. StatPearls Publishing, Treasure Island (FL) 2. 1. Aloini ME, Manella S, Biondo I, Maggio R, Roberto G, Ricci F, Lardo P, Addario Chieco P, Stigliano A (2023) Bilateral adrenal hemorrhage: learning notes from clinical practice and literature review. Front Endocrinol (Lausanne) 14:1233710. - [DOI](https://doi.org/10.3389/fendo.2023.1233710) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/38027193/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/10656610/) 3. 1. Tormos LM, Schandl CA (2013) The significance of adrenal hemorrhage: undiagnosed Waterhouse-Friderichsen syndrome, a case series. J Forensic Sci 58:1071–1074. - [DOI](https://doi.org/10.1111/1556-4029.12099) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/23458363/) 4. 1. Hata Y, Chiba T, Ohtani M, Ishizawa S, Nishida N (2015) An autopsy case of pneumococcal Waterhouse-Friderichsen syndrome with possible functional asplenia/hyposplenia. Int J Clin Exp Pathol 8:7518–7525 - [PubMed](https://pubmed.ncbi.nlm.nih.gov/26261663/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/4525997/) 5. 1. Camatti J, Bonasoni MP, Santunione AL, Cecchi R, Radheshi E, Carretto E (2026) Postmortem microbiology in forensic diagnostics: interpretation of infectious causes of death and emerging applications. Diagnostics (Basel) 16:325. - [DOI](https://doi.org/10.3390/diagnostics16020325) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/41594301/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/12839914/) Show all 79 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42665693/) [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM **Send To** * [Clipboard](https://pubmed.ncbi.nlm.nih.gov/42665693/) * [Email](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42665693%2F%23open-email-panel) * [Save](https://pubmed.ncbi.nlm.nih.gov/42665693/) * [My Bibliography](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42665693%2F%23open-bibliography-panel) * [Collections](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42665693%2F%23open-collections-panel) * [Citation Manager](https://pubmed.ncbi.nlm.nih.gov/42665693/) [x] NCBI Literature Resources [MeSH](https://www.ncbi.nlm.nih.gov/mesh/) [PMC](https://www.ncbi.nlm.nih.gov/pmc/) [Bookshelf](https://www.ncbi.nlm.nih.gov/books) [Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 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