Anaphylaxis to Antivenom in a Patient With Asymptomatic Alpha-Gal IgE Antibodies: A Case Report

Snakebite envenoming affects an estimated 10,000 people annually in the United States. Two FDA-approved antivenoms, ANAVIP® (equine F(ab')2) and CroFab® (ovine Fab), are standard treatments. However, higher-than-expected adverse reactions to ANAVIP have been reported in the southeastern United States, paralleling the regional prevalence of alpha-gal syndrome (AGS), an IgE-mediated allergy induced by lone star tick (Amblyomma americanum) bites. Although AGS typically manifests after ingestion of mammalian meat, parenteral exposure to alpha-gal-containing biologics may trigger immediate hypersensitivity. We describe a patient in central North Carolina who developed severe hypotensive anaphylaxis shortly after ANAVIP initiation for copperhead (Agkistrodon contortrix) envenomation. Despite elevated alpha-gal-specific IgE, he reported tolerating mammalian meat and subsequently received ovine Fab antivenom without complication. This case underscores the need for clinicians in alpha-gal-endemic regions to anticipate antivenom-associated hypersensitivity and be prepared for rapid recognition and management.