What: Alpha-gal Syndrome?
Introduction
Alpha-gal syndrome( AGS) is a delayed-onset, IgE-mediated allergic reaction to galactose-α-1,3-galactose( alpha-gal). It is triggered by the ingestion of meat from non-primate mammals, including beef, pork, venison and goat. 1
This condition was first recognized following reports of anaphylactic reactions in patients with neoplastic diseases treated with cetuximab. 2, 3, 4 These infusion reactions were caused by pre-existing IgE antibodies directed against the oligosaccharide, alpha-gal, present on the Fab fragment of cetuximab’ s heavy chain. 2 Subsequently, similar alpha-gal – specific IgE antibodies were identified in individuals bitten by certain ticks, with the Lone Star tick( Amblyomma americanum) being the predominant vector in the U. S. AGS has also been reported in Europe, Asia and Australia. 3 The Lone Star Tick can also cause Ehrlichiosis, Southern Tick-Associated Rash Illness or STARI, and can transmit Tularemia and two separate viruses, including Bourbon virus( named after a Kansas county, not ours) and the Heartland virus.
Clinically, Alpha-gal syndrome can manifest with a spectrum of symptoms and signs of pathology including urticaria, angioedema, coughing, wheezing, hypotension, nausea, vomiting, diarrhea and / or anaphylaxis. Some patients present only with abdominal issues, constituting a gastrointestinal and predominant variant of AGS.
AGS primarily affects adults. Between 2010 and 2022, over 100,000 presumed cases were reported in the U. S. ⁵ Despite this, awareness among healthcare professionals remains limited. A survey of 1,500 clinicians found that 42 % were unaware of the syndrome, and many
22 LOUISVILLE MEDICINE
by Hamza Saleem, MD, and Steven Lippmann, MD
others were uncertain about its diagnosis or management. The analysis was limited to family medicine, general practitioners, internists, pediatricians, nurse practitioners and physician assistants.
Etiology
The pathogenesis of alpha-gal syndrome typically begins with a tick bite, which introduces alpha-gal from the tick’ s saliva into the bloodstream, initiating the production of alpha-gal – specific IgE antibodies. Approximately 80 % of individuals who develop AGS report a history of tick bites and exhibit elevated alpha-gal – specific IgE levels. 7
A glycolipid hypothesis clarifies the delayed onset of symptoms following the ingestion of mammalian meat. After consumption, alpha-gal – containing glycolipids are absorbed into the bloodstream a few hours post-ingestion. 2 Once in circulation, alpha-gal binds to IgE antibodies on the surface of mast cells and basophils, leading to the release of allergic mediators and the subsequent development of allergic reactions or anaphylaxis in severe instances. 8 This explains the characteristic delayed onset of AGS symptoms.
Clinical
AGS symptoms typically appear three to eight hours after exposure to alpha-gal, although immediate reactions occasionally occur. 9 The severity of manifestations vary widely. Mild symptoms often involve the skin, including pruritus, erythema, urticaria and angioedema, while gastrointestinal complaints such as nausea, vomiting and diarrhea are also common. In cases where patients experience systemic anaphylaxis, hypotension, wheezing and respiratory distress are present. 2, 10 This