Understanding Alpha-Gal Syndrome: A Systematic Review and Meta-Analysis of Clinical Manifestations and Outcomes

Alpha-gal syndrome (AGS) is an IgE-mediated hypersensitivity to galactose-α-1,3-galactose, triggered by tick bites. It typically presents with delayed onset allergic or gastrointestinal symptoms after red meat consumption. This study aims to evaluate the prevalence of clinical symptoms and outcomes in AGS patients.

A systematic search of PubMed, Embase, and Cochrane Central was conducted to identify studies with at least five AGS patients that utilized alpha-gal IgE for diagnosis and reported symptomatology. A random-effects model calculated pooled prevalence and 95% confidence intervals (CIs) for clinical characteristics of AGS.

Of the 739 studies screened, 15 met the inclusion criteria, comprising 1162 AGS patients (57% female). Urticaria was identified as the most prevalent symptom (63.8%, CI: 34.5-88.3, I² = 98.8%). At least one gastrointestinal symptom was reported in 69.2% of patients (CI: 49.3-85.9, I² = 97.5%), including abdominal pain (58.3%, CI: 36.0-78.9, I² = 96.0%), diarrhea (41.7%, CI: 22.3-62.5, I² = 93.4%), nausea (39.1%, CI: 29.2-49.6, I² = 79.1%), and vomiting (31.1%, CI: 21.9-41.2, I² = 70.4%). Tick bite history was recalled by 78.7% (CI: 46.4-98.1; I² = 99.1%), and 91.8% (CI: 84.6-96.8; I² = 70.3%) had symptom onset ≥ 1 h post red meat intake. Symptomatic improvement was observed in 86.5% (CI: 73.9-95.4, I² = 80.9%) of patients, with complete resolution in 42.7% (CI: 26.4-59.8, I² = 73.8%).

AGS typically presents with delayed onset allergic and GI symptoms after red meat intake, often with tick bite history. Majority of patients report symptomatic improvement on follow-up.