Alpha-Gal Syndrome in the Infectious Diseases Clinic: A Series of 5 Cases in Central North Carolina

Background Alpha-gal syndrome (AGS) is a recently described allergy to galactose-α-1,3-galactose, an oligosaccharide present in mammalian meat. AGS can present with angioedema, urticaria, and anaphylaxis arising 3–6 hours after ingestion, although symptoms such as gastrointestinal distress, fatigue, and arthralgias are also reported. Because AGS appears to be associated with tick bites, patients may present to infectious diseases (ID) clinics for evaluation. Methods We documented a series of 5 patients referred to the University of North Carolina ID Clinic between 2020 and 2022 for various tick-borne infections that were found to have symptoms and laboratory testing consistent with AGS. Patients were subsequently referred to the Allergy and Immunology Clinic. Results Patients were referred to the ID Clinic for persistent symptoms following positive tick-borne disease testing or presumed tick-borne infection. All patients had an elevated alpha-gal immunoglobulin E and clinical presentation consistent with AGS. Common symptoms included episodic gastrointestinal distress (eg, cramping, nausea, diarrhea), fatigue, arthralgias, and subjective cognitive impairment, but a notable absence of severe anaphylaxis. Four patients were seen by at least 1 nonallergy specialist prior to referral to ID. Patients reported substantial improvement in their symptoms following dietary restriction. Conclusions ID physicians should be aware of AGS as a cause of persistent, nonspecific symptoms following a tick exposure or tick-borne illness. Further research is needed to determine the prevalence of alpha-gal sensitization and AGS following tick-borne bites.