Clinical Presentation and Outcomes of Alpha-Gal Syndrome

Background And Aims: Alpha-gal syndrome (AGS) is an IgE-mediated allergic reaction to galactose-α-1,3-galactose, primarily linked with Lone Star tick bites in the United States. It presents with symptoms ranging from urticaria and gastrointestinal (GI) manifestations to delayed anaphylaxis following red meat consumption. We aimed to study AGS patients' clinical manifestations, diagnosis, and outcomes. Methods: A retrospective chart review of patients who underwent serological testing for suspected AGS between 2014 and 2023 at Mayo Clinic was performed. Patients with positive serology were age and sex matched with those who tested negative. Clinical characteristics of seropositive cohort with and without GI symptoms were compared, and outcomes assessed. Results: Of 1260 patients who underwent testing, 124 tested positive for AGS. They were matched with 380 seronegative control subjects. AGS patients reported a higher frequency of tick bites (odds ratio [OR], 26.0; 95% confidence interval [CI], 9.8–68.3), reported a higher prevalence of urticaria (56% vs 37%; P = .0008), and were less likely to have asthma (OR, 0.4; 95% CI, 0.3–0.7). They had a lower prevalence of heartburn (6% vs 12%; P = .03) and bloating (6% vs 13%; P = .03). A total of 47% had GI symptoms, and a higher proportion were female than those without GI symptoms (69% vs 35%; P = .002). During a mean follow-up of 27 months, 22 of 40 patients reported symptom resolution after avoiding red meat, and 7 were able to transition to regular diet. Conclusions: A diagnosis of AGS should be strongly considered in patients with a history of tick bites and clinical presentation of allergic or GI manifestations. Dietary intervention is effective in most but not all patients.