Isolated gastrointestinal symptoms without classic allergic features delayed recognition of anaphylaxis, according to a recent clinical communication published in The Journal of Allergy and Clinical Immunology: In Practice.
Investigators reported the first documented fatal anaphylactic reaction occurring approximately four hours following consumption of mammalian meat in a patient with immunoglobulin E (IgE) antibodies to galactose-alpha-1,3-galactose (alpha-gal). The case highlights that delayed-onset alpha-gal syndrome (AGS) may result in rapid collapse and death without cutaneous or respiratory manifestations. Postmortem testing revealed serum tryptase levels exceeding 2,000 ng/mL—a level seen in only one of 47,045 samples from living patients tested at Mayo Clinic laboratories—strongly supporting anaphylaxis as the cause of death despite an initially unremarkable autopsy.
The clinical communication, led by Thomas A.E. Platts-Mills, MD, PhD, of the Division of Allergy and Immunology at the University of Virginia School of Medicine, and colleagues, described a 47-year-old airline pilot with no significant past medical history who experienced fatal collapse following delayed anaphylaxis following eating beef. Two weeks before his death in summer 2024, the patient developed severe abdominal pain, vomiting, and diarrhea approximately four hours following eating beef steak while camping—an unusual meal for the family, which typically ate chicken. The episode resolved spontaneously following two hours, and despite its severity—the patient told his son "I thought I was going to die"—neither he nor his wife recognized the event as anaphylaxis or connected it to the beef consumed hours earlier. No medical evaluation occurred.
He later consumed a hamburger at a barbecue at approximately 3:00 PM and returned home to mow the lawn. He remained asymptomatic when his wife left at 7:00 PM (four hours post-meal), but developed symptoms at 7:20 PM and collapsed by 7:30 PM—approximately four to 4.5 hours following eating. Emergency medical services initiated resuscitation, which continued for two hours following transport to hospital, but the patient was pronounced dead that evening. Postmortem examination showed no structural abnormalities of the cardiac, respiratory, neurologic, or gastrointestinal systems, and the death was initially classified as sudden unexplained death. Toxicology revealed blood ethanol of 0.049% and diphenhydramine level of 440 ng/mL.
To investigate a potential allergic mechanism, postmortem blood was analyzed using ImmunoCAP assays for total IgE and a comprehensive panel of allergen-specific IgE antibodies including foods, inhalants, and venoms. Total IgE measured 16.7 IU/mL. IgE specific to galactose-alpha-1,3-galactose measured 0.57 IU/mL, accounting for 3.4% of total IgE, a proportion regarded as clinically relevant when exceeding 1%. Specific IgE to beef measured 0.17 IU/mL, whereas IgE levels to pork, chicken, and other tested food allergens were below the detection limit. The patient also had positive IgE to seasonal allergens including rye grass (0.99 IU/mL, 5.9% of total IgE) and ragweed (0.42 IU/mL, 2.5% of total IgE), consistent with the detected blood diphenhydramine level indicating recent antihistamine use.
Postmortem serum tryptase, measured using a validated assay for postmortem samples (TRYPA), exceeded 2,000 ng/mL, far above the normal upper limit of 200 ng/mL and consistent with levels reported in fatal anaphylaxis. Mayo Clinic laboratory data from the period May 1, 2024, to May 1, 2025, showed that among 47,045 samples from living patients, only one had tryptase exceeding 2,000 ng/mL; among 40 postmortem samples, only two (including this case) exceeded this threshold.
Further history revealed multiple pruritic papular lesions around the patient's ankles earlier that summer, initially described as "chigger" bites but consistent with exposure to larvae of Amblyomma americanum (Lone Star tick). The investigators noted that such larvae are often called "chiggers" in the eastern United States but are not generally recognized as ticks, contributing to underrecognition of tick exposure. Amblyomma americanum is a well-established cause of sensitization to galactose-alpha-1,3-galactose.
Potential cofactors that may have augmented the reaction severity included alcohol consumption with the hamburger, ragweed pollen exposure (consistent with positive IgE and antihistamine use), and exercise that afternoon ending one hour before symptom onset. However, the investigators emphasized that none of these factors explain the characteristic four-hour delay between meat consumption and symptom onset.
The investigators emphasized that delayed symptom onset, absence of cutaneous or respiratory findings, and isolated severe gastrointestinal pain contributed to failure to recognize anaphylaxis following the initial episode. The case underscores that severe abdominal pain without other allergic features can be an important and dangerous manifestation of anaphylaxis in AGS. The authors noted that neither the patient nor his wife considered the first episode to be "anaphylaxis," and therefore they did not connect it with beef consumption or consider avoiding mammalian meat subsequently.
The case has broader public health significance, as Lone Star tick populations are moving northward, with white-tailed deer serving as the primary breeding host. Recent reports describe New Jersey's deer population as "an unsustainable statewide emergency," contributing to dramatically increased tick exposure in previously unaffected regions. Centers for Disease Control and Prevention data indicate that a large proportion of health care providers remain unaware of AGS. Expanding tick populations and limited physician awareness increase the risk of missed diagnosis in affected regions, highlighting the need for both professional and public education about AGS, particularly regarding the characteristic delay between meat consumption and symptom onset (typically three to five hours), the potential for isolated gastrointestinal manifestations, and the role of tick larvae as well as mature ticks in sensitization.
The researchers reported support from the National Institutes of Health and reagent supplies from Phadia Thermo Fisher, with no conflicts of interest declared.