S2142 Explosive Rise in Alpha-Gal Syndrome: A Real-World Analysis

Introduction: Alpha-gal syndrome (AGS) is an IgE-mediated allergy to galactose-α-1,3-galactose, a carbohydrate found in mammalian meat, with sensitization linked to tick bites—particularly the Lone Star tick in the U.S. AGS is unique due to delayed-onset symptoms and frequent gastrointestinal (GI) manifestations such as abdominal pain, diarrhea, and nausea. Despite rising recognition, population-level demographic and clinical features remain poorly characterized. Methods: This retrospective observational study used the TriNetX US Collaborative Network to identify adults with alpha-gal specific IgE ≥0.1 kU/L from 2010 to 2025. The study was Institutional Review Board-exempt. Demographics, diagnosis codes, and medication usage prior to or on the date of testing were extracted. Geographic distribution was based on the location of the healthcare organization headquarters. Incidence proportion was defined as the number of patients newly meeting the event definition (positive IgE) in each 2-year window (numerator), divided by patients whose records overlapped the window, had no prior alpha-gal sensitization, and met cohort criteria (denominator). Incidence rates (cases/100 patient-years) were then calculated by dividing incidence proportion by the window duration and multiplying by 100. Results: Among 3,828 patients tested for alpha-gal IgE, 749 (23%) were positive. Median age was 63 years (interquartile range [IQR] 52–72); 48% were women, 78% White. Most patients were in the Northeast (69%) or South (23%). Median body mass index was 26 (IQR 23–29). Common comorbidities included joint disorders (76%), hyperlipidemia (60%), food allergy (59%), vitamin D deficiency (39%), asthma (27%), and Lyme disease (17%). Frequent medications: albuterol (30%), cetirizine (29%), diphenhydramine (21%), and pantoprazole (22%). Incidence proportion rose from 1.8% (2013–2014) to 14.2% (2019–2020), 38% (2021–2022), and 100% (2023–2024). Corresponding incidence rates increased from 0.95 (2013-2014) to 94.55 cases/100 PY (2023-2024). Conclusion: This is the largest real-world AGS cohort to date, showing regional clustering and characteristic comorbidity patterns. The 100-fold rise in incidence rates among those who tested positive from 2013 to 2024 reflects increased clinical recognition and testing. AGS should be considered in patients with unexplained abdominal pain or diarrhea, especially in endemic areas. Awareness among gastroenterologists is essential for timely diagnosis and management.