Clinical Protocol for Evaluating Ectoparasite-Induced Allergies with Emphasis on Alpha-Gal Syndrome

Alpha-gal syndrome (AGS) is an ectoparasite-associated IgE-mediated hypersensitivity in which reactions occur after exposure to galactose-alpha-1,3-galactose (alpha-Gal) in mammalian foods, biologics, medications, and other mammalian-derived products. The delayed onset after oral exposure and the imperfect correlation between sensitization and clinical allergy complicate diagnosis. This chapter provides a practical clinical protocol for evaluating suspected ectoparasite-induced allergy with emphasis on AGS. The protocol integrates structured history taking, tick and other ectoparasite exposure assessment, focused clinical examination, serum IgE testing, skin prick and prick-to-prick testing, basophil activation testing (BAT), and medically supervised oral challenge when needed. A consensus BAT workflow is incorporated, including whole-blood handling, negative and positive controls, stimulation, antibody staining, erythrocyte lysis, flow cytometry acquisition, gating, quality-control criteria, and reporting. The protocol is intended for implementation in specialist allergy clinics and translational research settings where diagnostic safety, reproducibility, and standardized data capture are required.