ALPHA-GAL SYNDROME AND INCREASED RISK OF EARLY ADVERSE REACTIONS

Practice implication: Alpha-gal Syndrome is not a contraindication to antivenom when envenomation is life or limb threatening but warrants pre-treatment with epinephrine and up-tiering of risk management (infusion strategy, ICU capable monitoring, product selection). There are NO absolute contraindications to antivenom for a patient with a significant symptomatic envenomation).

Early but compelling clinical evidence suggests that patients with Alpha-Gal syndrome (a mammalian meat allergy) may experience higher rates of reaction in response to antivenoms due to conservation of the alpha-gal epitope in mammalian antibody proteins. Some early studies from the United States indicated higher rates of reactions with with the F(ab’)2 Anavip versus CroFab which is a F(ab), but other studies have shown that patients who reacted to CroFab tolerated Anavip.274–276 Regardless, pretreatment should be considered for patients with elevated risk factors (patient from high prevalence area, medical Hx suspicious for alpha-gal, etc) and in patients with known or suspected alpha-gal syndrome. If both CroFab and Anavip are available for a CONUS bite with a known history or high risk of alpha-gal, it may be worth discussing CroFab as first line if available due to possible lower risk of reaction with a medical toxicologist. If a patient had a reaction to CroFab or Anavip CONUS, it may be worth discussing switching to the alternative product with a medical toxicologist.

While additional research is needed, the key points are as follows:

1. In US servicemembers and other patients with a known or suspected history of alpha-gal syndrome, pretreatment with 1:1000 epinephrine prior to antivenom may be advisable due to early evidence indicating higher incidence of EARs including anaphylaxis. Pretreatment with epinephrine has not been proven to reduce the incidence of these reactions, but has strong evidence base to support its use in typical EARs and the MAST cell stabilization resulting from epinephrine may also benefit these patients.
2. If a patient with known or suspected alpha-gal syndrome has a reaction to one antivenom and a second line alternative exists, it may be appropriate to try a different product if additional doses are needed.
3. In all cases, it is advisable to contact DoD advisor line and consult a toxicologist (or contact poison control if CONUS) in cases where an alpha-gal sensitivity is known or suspected.
4. In all cases, antivenom should not be delayed for patients suffering from instability or other possible threats to life or limb due to envenomation. Be prepared to treat the reaction if it occurs but do not delay antivenom for sick patients.