{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:49:49Z","timestamp":1793141389898,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The diagnosis of anaphylaxis comprehensively depends on both situational information and laboratory investigations. For this purpose, serum tryptase concentration is examined as an indicator of systemic mast cell mediator release, linked to an underlying anaphylactic process. Increased levels of tryptase may occur in some events different from anaphylaxis, but usually information from crime scene investigations is lacking and autoptic findings are not specific. For legal reasons, it is required to achieve a definite diagnosis of mast cell degranulation that can lead to a certain diagnosis of death from anaphylaxis. Immunohistochemistry seems to be a relatively simple, reliable, and easily repeatable method that can assist the forensic pathologist in the differential diagnosis of death from anaphylaxis. Materials and Methods: This work provides an overview of the current literature on immunohistochemical methods useful in the determination process of anaphylactic-related deaths. A systematic search, according to the PRISMA statement, was performed in databases to identify studies investigating immunohistochemical targets related to anaphylaxis death. Results: This work underscores the importance of anaphylaxis mediators such as tryptase, CD117, and chymase in the immunohistochemical analysis of anaphylactic deaths. Conclusions: According to the reviewed literature, the diagnosis of death due to anaphylaxis should depend not just on the suspicion of an anaphylactic reaction but also on confirming mast cell degranulation through the identification of IHC positivity for inflammatory mediators, particularly in the respiratory tract.<\/jats:p>","DOI":"10.3390\/medicina59122184","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T11:26:52Z","timestamp":1702639612000},"page":"2184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Death Due to Anaphylactic Reaction: The Role of the Forensic Pathologist in an Accurate Postmortem Diagnosis"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6934-9791","authenticated-orcid":false,"given":"Fabio","family":"Del Duca","sequence":"first","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2664-028X","authenticated-orcid":false,"given":"Alice","family":"Manetti","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniello","family":"Maiese","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Medical, Molecular and Critical Area, Institute of Legal Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5248-6896","authenticated-orcid":false,"given":"Gabriele","family":"Napoletano","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Ghamlouch","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"Pascale","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Hospital \u2018San Carlo\u2019, 85100 Potenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolino","family":"Giorgio","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0358-7965","authenticated-orcid":false,"given":"Frati","family":"Paola","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-7122","authenticated-orcid":false,"given":"Raffaele","family":"Russa","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Public Health, Life Sciences, and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.jaci.2010.06.022","article-title":"The Diagnosis and Management of Anaphylaxis Practice Parameter: 2010 Update","volume":"126","author":"Lieberman","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"400","DOI":"10.5694\/j.1326-5377.2006.tb00619.x","article-title":"2. Anaphylaxis: Diagnosis and Management","volume":"185","author":"Brown","year":"2006","journal-title":"Med. J. Aust."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1136\/jcp.53.4.273","article-title":"Postmortem Findings after Fatal Anaphylactic Reactions","volume":"53","author":"Pumphrey","year":"2000","journal-title":"J. Clin. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.forsciint.2010.04.039","article-title":"Post-Mortem Diagnosis of Anaphylaxis: A Difficult Task in Forensic Medicine","volume":"204","author":"Moreschi","year":"2011","journal-title":"Forensic Sci. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105906","DOI":"10.1016\/j.ijsu.2021.105906","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"88","author":"Page","year":"2021","journal-title":"Int. J. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0379-0738(00)00469-2","article-title":"Immunohistochemical Quantication of Pulmonary Mast-Cells and Post-Mortem Blood Dosages of Tryptase and Eosinophil Cationic Protein in 48 Heroin-Related Deaths","volume":"120","author":"Fineschi","year":"2001","journal-title":"Forensic Sci. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1046\/j.1365-2222.1999.00679.x","article-title":"Increased Mast Cell Tryptase in Sudden Infant Death \u00d0 Anaphylaxis, Hypoxia or Artefact?","volume":"29","author":"Edston","year":"1999","journal-title":"Clin. Exp. Allergy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.forsciint.2006.08.001","article-title":"Differential Accumulation of Pulmonary and Cardiac Mast Cell-Subsets and Eosinophils between Fatal Anaphylaxis and Asthma Death","volume":"169","author":"Perskvist","year":"2007","journal-title":"Forensic Sci. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.legalmed.2007.10.002","article-title":"Postmortem Diagnosis of Fatal Anaphylaxis during Intravenous Administration of Therapeutic and Diagnostic Agents: Evaluation of Clinical Laboratory Parameters and Immunohistochemistry in Three Cases","volume":"10","author":"Osawa","year":"2008","journal-title":"Leg. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1016\/j.forsciint.2008.03.021","article-title":"Anaphylactic Latex Reaction during Anaesthesia: The Silent Culprit in a Fatal Case","volume":"179","author":"Turillazzi","year":"2008","journal-title":"Forensic Sci. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.forsciint.2008.08.011","article-title":"Immediate Anaphylactic Death Following Antibiotics Injection: Splenic Eosinophilia Easily Revealed by Pagoda Red Stain","volume":"181","author":"Trani","year":"2008","journal-title":"Forensic Sci. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.forsciint.2010.01.007","article-title":"Postmortem Diagnostics of Assumed Food Anaphylaxis in an Unexpected Death","volume":"198","author":"Unkrig","year":"2010","journal-title":"Forensic Sci. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1258\/msl.2010.010059","article-title":"Histopathological Markers for the Diagnosis of Anaphylactic Death","volume":"51","author":"Luongo","year":"2011","journal-title":"Med. Sci. Law"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s12024-013-9468-9","article-title":"Accumulation of Eosinophils, Mast Cells, and Basophils in the Spleen in Anaphylactic Deaths","volume":"9","author":"Edston","year":"2013","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.forsciint.2014.04.006","article-title":"Measurement of \u03b2-Tryptase in Postmortem Serum, Pericardial Fluid, Urine and Vitreous Humor in the Forensic Setting","volume":"240","author":"Comment","year":"2014","journal-title":"Forensic Sci. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00414-014-1004-2","article-title":"Splenic Hypereosinophilia in Anaphylaxis-Related Death: Different Assessments Depending on Different Types of Allergens?","volume":"129","author":"Maccio","year":"2015","journal-title":"Int. J. Leg. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13288","DOI":"10.3748\/wjg.v21.i47.13288","article-title":"Mast Cell Tryptase and Carboxypeptidase A Expression in Body Fluid and Gastrointestinal Tract Associated with Drug-Related Fatal Anaphylaxis","volume":"21","author":"Guo","year":"2015","journal-title":"WJG"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jflm.2015.12.001","article-title":"Postmortem Diagnosis of Anaphylaxis in Presence of Decompositional Changes","volume":"38","author":"Radheshi","year":"2016","journal-title":"J. Forensic Leg. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.forsciint.2016.04.025","article-title":"Postmortem Detection of Antibiotic-Specific Immunoglobulin E in the Case of Anaphylactic Death","volume":"266","author":"Takahashi","year":"2016","journal-title":"Forensic Sci. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/PAF.0000000000000572","article-title":"Reliable Postmortem Molecular Diagnosis of Anaphylaxis: Co-Localization of Mast Cell Degranulation and Immunoglobulin E in Allergic Throat Tissues","volume":"41","author":"Wang","year":"2020","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"D\u2019Errico, S., Frati, P., Zanon, M., Valentinuz, E., Manetti, F., Scopetti, M., Santurro, A., and Fineschi, V. (2020). Cephalosporins\u2019 Cross-Reactivity and the High Degree of Required Knowledge. Case Report and Review of the Literature. Antibiotics, 9.","DOI":"10.3390\/antibiotics9050209"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Esposito, M., Montana, A., Liberto, A., Filetti, V., Nunno, N.D., Amico, F., Salerno, M., Loreto, C., and Sessa, F. (2021). Anaphylactic Death: A New Forensic Workflow for Diagnosis. Healthcare, 9.","DOI":"10.3390\/healthcare9020117"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s12024-021-00373-1","article-title":"Postmortem Diagnostics of Assumed Suicidal Food Anaphylaxis in Prison: A Unique Case of Anaphylactic Death Due to Peach Ingestion","volume":"17","author":"Tambuzzi","year":"2021","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s12024-021-00405-w","article-title":"Expression of Fc\u03b5RI\u03b1 and Tryptase in Human Lung Tissue during Drug-Induced Anaphylactic Death","volume":"17","author":"Feng","year":"2021","journal-title":"Forensic Sci. Med. Pathol"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.jaip.2016.03.008","article-title":"Adverse Drug Reactions Associated with Ceftaroline Use: A 2-Center Retrospective Cohort","volume":"4","author":"Blumenthal","year":"2016","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0140-6736(18)32218-9","article-title":"Antibiotic Allergy","volume":"393","author":"Blumenthal","year":"2019","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.1111\/all.14352","article-title":"Fatal Anaphylaxis in Italy: Analysis of Cause-of-death National Data, 2004-2016","volume":"75","author":"Corsi","year":"2020","journal-title":"Allergy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.jaci.2013.10.029","article-title":"Case Fatality and Population Mortality Associated with Anaphylaxis in the United States","volume":"133","author":"Ma","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/ACI.0b013e32834694d8","article-title":"Food-Induced Anaphylaxis","volume":"11","year":"2011","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11882-016-0616-7","article-title":"Food Allergy: Our Evolving Understanding of Its Pathogenesis, Prevention, and Treatment","volume":"16","author":"Iweala","year":"2016","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6814","DOI":"10.2174\/1381612822666161004125143","article-title":"Old, New and Hidden Causes of Perioperative Hypersensitivity","volume":"22","author":"Garvey","year":"2017","journal-title":"CPD"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6784","DOI":"10.2174\/1381612822666160928142814","article-title":"Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs","volume":"22","author":"Dona","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.chest.2017.07.033","article-title":"Anaphylaxis","volume":"153","author":"LoVerde","year":"2018","journal-title":"Chest"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s12024-016-9799-4","article-title":"Anaphylaxis at Autopsy","volume":"13","author":"Byard","year":"2017","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0065-2776(05)88004-6","article-title":"Role of Human Mast Cells and Basophils in Bronchial Asthma","volume":"Volume 88","author":"Marone","year":"2005","journal-title":"Advances in Immunology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nrd2266","article-title":"Antagonism of the Prostaglandin D2 Receptors DP1 and CRTH2 as an Approach to Treat Allergic Diseases","volume":"6","author":"Pettipher","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1136\/archdischild-2015-309887","article-title":"How to Interpret Mast Cell Tests","volume":"101","author":"Waterfield","year":"2016","journal-title":"Arch. Dis. Child. Educ. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1056\/NEJMoa070030","article-title":"Platelet-Activating Factor, PAF Acetylhydrolase, and Severe Anaphylaxis","volume":"358","author":"Vadas","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1542\/peds.2011-0539","article-title":"NIAID-Sponsored 2010 Guidelines for Managing Food Allergy: Applications in the Pediatric Population","volume":"128","author":"Burks","year":"2011","journal-title":"Pediatrics"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/12\/2184\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:39:38Z","timestamp":1760132378000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/12\/2184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,15]]},"references-count":39,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["medicina59122184"],"URL":"https:\/\/doi.org\/10.3390\/medicina59122184","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,15]]}}}