S4283 Eosinophilic Gastrointestinal Disorders and Marked Leukocytosis in Alpha-Gal Syndrome: Infection, Allergy, or Hematologic Malignancy?

Introduction: Alpha-gal syndrome (AGS) is a tick-borne, delayed hypersensitivity reaction to galactose-α-1,3-galactose, manifesting as urticaria, anaphylaxis, or gastrointestinal symptoms following the consumption of mammalian meat products. While eosinophilia can occur in allergic conditions, the literature contains no reports of patients with AGS concurrently developing eosinophilic gastrointestinal disorders. We present a rare case of AGS manifesting with eosinophilic gastrointestinal symptoms and bone marrow findings consistent with eosinophilic proliferation and myeloid atypia. Case Description/Methods: A 63-year-old man with a history of AGS presented with dysphagia, dyspnea, and a generalized pustular rash a few days after consuming a hamburger. After a recent visit to the urgent care unit, cefepime was started for fever and mild leukocytosis. Upon hospital admission, imaging revealed bilateral pulmonary infiltrates, and laboratory tests showed marked leukocytosis exceeding 100,000/µL and an eosinophil count above 42,000/µL. Upper endoscopy revealed severe mucosal inflammation of the esophagus and stomach with dense eosinophilic infiltrates, consistent with eosinophilic esophagitis and eosinophilic gastritis. A skin biopsy also showed eosinophilic infiltration. The initial differential diagnosis included eosinophilic pneumonia, drug-induced eosinophilia (cefepime), leukemoid reaction, and primary eosinophilic disorders such as hypereosinophilic syndrome or chronic eosinophilic leukemia. The patient was started on empiric antibiotics and high-dose corticosteroids. Due to worsening leukocytosis, a bone marrow biopsy was performed, revealing hypercellularity with myeloid predominance and increased eosinophils and eosinophilic precursors. Molecular and cytogenetic studies were negative for PDGFRA, PDGFRB, FGFR1, JAK2, BCR-ABL1, and CBFB rearrangements, leading to a diagnosis of idiopathic hypereosinophilic syndrome. Discussion: A potential link between AGS and eosinophilic gastrointestinal disorders is highlighted through this case. While AGS is typically considered a food allergy, it may act as a trigger for eosinophilic infiltration of the gastrointestinal tract, as seen in this patient with findings consistent with eosinophilic esophagitis and eosinophilic gastritis. More studies are needed to clarify the relationship between AGS and primary eosinophilic disorders and to explore whether AGS may unmask or exacerbate underlying eosinophilic gastrointestinal pathology.