Introduction: Alpha-Gal Syndrome (AGS) is an IgE-mediated allergic reaction to galactose-α-1,3-galactose (alpha-gal) induced by Lone Star tick bite with symptoms typically triggered by mammalian meat consumption. These include anaphylaxis, angioedema, urticaria, as well as gastrointestinal (GI) symptoms such as nausea, vomiting, abdominal pain, and diarrhea. This study aims to explore the clinical presentation, diagnosis, and outcomes of AGS patients at Mayo Clinic. Methods: Patients who underwent serological testing for suspected AGS from February 2014 to September 2023 at the Mayo Clinic, Rochester, MN, were identified. A retrospective chart review collected data on demographics, symptoms, laboratory values, management, and outcomes. Positive AGS serology patients were age- and sex-matched (1:3) with those who tested negative, then categorized into two groups: with and without GI symptoms. Results: Of 1260 patients undergoing testing, 124 tested positive for AGS and were compared against 380 randomly obtained negative patients. Baseline characteristics were similar between groups. Those with positive serologies had a significantly greater risk of urticaria (56.4% vs 36.8%; p=0.0008) and anaphylaxis (OR 1.5 [95%CI 1.003-2.3]), as well as decreased risk of heartburn (5.6% vs 12.4%; p=0.036) and bloating (6.4% vs 13.4%; p=0.036) compared to those with negative AGS serologies. Positive AGS were more likely to report a history of a tick bite (OR 26.0 [95%CI 9.8-68.3]) and less likely to report a history of asthma (OR 0.45 [95%CI 0.3 to 0.7]). Within AGS, those with GI symptoms (58/124) had a higher proportion of females vs those without GI symptoms (66/124) (69% vs 35%; p=0.002). However, other demographic characteristics, non-GI symptoms, and serological titers were similar. Among those with positive testing, urticaria (p-trend=0.001) and a history of a tick bite (p-trend=0.005) were associated positively with increasing serological titers. 30% of patients with AGS reported symptoms >4 hours after exposure to red meat and its derivatives, and only 11% of patients reported symptoms in less than 1 hour after ingestion. Of the 124 AGS-positive patients, 40 received follow-up treatment at Mayo Clinic ranging from 0.5 to 105 months (average 27), with >50% of the patients (22/40) reporting symptom resolution after dietary restrictions and 14/40 reporting symptom improvement. Of these, ~30% had normalization of serological titers. Conclusion: AGS diagnosis should be highly considered in GI patients, especially females, with a history of tick bites and associated symptoms of urticaria and anaphylaxis. Symptoms like GERD, bloating, and a history of asthma are less likely to be associated with AGS. Nearly 90% of patients may show symptom improvement or resolution, especially on a restricted diet, but this may not be associated with normalization of serologies.

Alpha-Gal Syndrome Patient Outcomes on Follow-up at Mayo Clinic

Sameer Rao

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