Fatal Alpha-Gal Syndrome: Recognizing and Managing Tick-Borne Allergies

University of Virginia investigators report the first confirmed death attributed to alpha-gal syndrome, based on a clinical course of delayed reactions after beef ingestion and postmortem immunologic testing consistent with fatal anaphylaxis. The patient developed severe gastrointestinal symptoms hours after eating beef, suffered a collapse after a subsequent exposure, and postmortem blood showed high levels of alpha-gal–specific IgE—together forming the evidence linking the event to the allergy.

The presenting syndrome began with severe abdominal pain, vomiting, and diarrhea about three to four hours after a steak dinner and recurred before the fatal collapse on a later meat exposure. Earlier episodes included cutaneous and gastrointestinal symptoms; the fatal event was marked by sudden cardiovascular collapse with no alternate cause identified at autopsy. Recent camping‑associated larval tick exposures were consistent with Lone Star tick contact, demonstrating that unrecognized delayed‑onset meat allergy can progress to fatal systemic reaction.

Diagnostic confirmation combined a characteristic history of delayed reactions after mammalian meat with targeted immunologic testing, including postmortem alpha‑gal IgE. Investigators excluded other likely causes: the autopsy found no anatomic explanation for sudden death while serology showed patterns and levels consistent with extreme IgE‑mediated reaction seen in fatal anaphylaxis. The clinical history plus supportive immunologic findings therefore supported attribution to alpha‑gal–mediated anaphylaxis in this case.

Galactose‑alpha‑1,3‑galactose is the offending epitope that elicits IgE responses after sensitization via tick saliva, with Lone Star tick larval exposures implicated in affected regions. The immunopathology produces a characteristic delayed IgE‑mediated response to mammalian meat that typically appears several hours after ingestion. A focused history of tick exposure is central to the diagnostic evaluation of suspected alpha‑gal reactions.

Expanding distributions of deer and Lone Star ticks increase regional exposure and the population‑level risk of alpha‑gal sensitization, raising the likelihood of severe, underrecognized allergic outcomes. Underrecognition can permit preventable severe events and may have implications for local donor screening and education programs where prevalence is high. Clinician‑facing education and local public‑health awareness campaigns are needed to reduce risk and improve recognition.