In rare cases, a tick bite creates the antibodies for delayed anaphylaxis in patients after eating red meat.
On a Saturday evening in April, a 36-year-old male presented with symptoms of anaphylaxis to a rural emergency department in North Carolina. The patient, who happened to be an emergency medicine nurse, reported progressive onset of lightheadedness and hives. In the ED, his blood pressure was 70/30 mmHg. The patient received immediate IM epinephrine. After steroids, diphenhydramine, and 3 liters of saline, the patient felt better. The cause of anaphylaxis was unclear. The patient denied prior allergic reactions, recent bee stings or medications, and hadn’t eaten anything before symptom onset. A week later at an allergy clinic, two critical pieces of history were obtained: He had a tick bite in the past month, and he had eaten beef stew four hours before symptom onset. A serum test for antibodies to galatose-alpha-1, 3-galactose (alpha-gal) was positive, confirming the diagnosis.
Discovering this new cause of anaphylaxis resulted from a confluence of several events. In the early 2000’s, oncologists in North Carolina and Tennessee recognized a troublingly high rate of anaphylaxis to Cetuximab, an epidermal growth factor receptor inhibitor used to treat colorectal cancer. In collaboration between several oncologists, Imclone, and Bristol-Myers Squibb, as well as Vanderbilt and the University of Virginia, IgE antibodies to alpha-gal, an oligosaccharide on the FAB portion of the Cetuximab molecule, were identified as the cause of these reactions. Alpha-gal is found in all non-primate mammals, meaning that oral exposure to the antigen is common worldwide. But while the reaction and the antibodies were observed in approximately 20% of patients in the Southeast, the reaction and antibodies were rare in cohorts from Boston and California. The cause for the regional distribution of the condition was unclear.
Concurrent with the Cetuximab research, investigators at the University of Virginia evaluated several patients with unexplained anaphylaxis who thought their symptoms might have been due to the consumption of red meat several hours prior. Tests for alpha-gal antibodies in these patients were positive. Similar investigations elsewhere on the East Coast revealed that delayed anaphylaxis to red meat with positive antibodies to alpha-gal had, not surprisingly, the same distribution as the hypersensitivity to Cetuximab. Further consideration of this regional distribution revealed a tight agreement with the regional distribution of Rocky Mountain Spotted Fever, implicating bites from the Lone Star Tick as the cause of the antibodies. Detailed histories of tick exposure from patients with allergic reactions to red meat provided evidence to support the link to the tick bites, as did some accidental exposures to ticks by individual allergists who enjoyed hiking and routinely tested themselves for IgE to alpha-gal.
Allergists practicing from Georgia to Long Island and as far west as Arkansas have now identified hundreds of cases of alpha-gal anaphylaxis, suggesting that tens of thousands of patients have this condition. However, the cases were not easily recognized at first because alpha-gal doesn’t enter the bloodstream until several hours after eating meat, making it hard for patients and physicians to recognize the link. Why the Lone Star Tick bite induces this form of allergic response remains a subject of further inquiry. But the implication for emergency physicians in Southeast is clear: For patients with anaphylaxis without an obvious cause, ask your patients about tick bites and consumption of red meat or pork in the past 6 hours. For patients with positive IgE antibodies to alpha gal, allergists recommend avoiding red meat and pork for two years prior to retesting for the antibody.
REFERENCE
- Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, Murphy BA, Satinover SM, Hosen J, Mauro D, Slebos RJ, Zhou Q, Gold D, Hatley T, Hicklin DJ, Platts-Mills TA. Cetuximab-induced anaphylaxis and IgE specific for galactose-β-1, 3-galactose. New England Journal of Medicine. 2008 Mar 13;358(11):1109-17.