Alpha-gal syndrome can be mistaken for gastrointestinal illnesses, such as irritable bowel syndrome.

Galactose-α-1,3-galactose (alpha-gal) syndrome is an IgE-mediated allergic reaction to alpha-gal – a carbohydrate found in nonprimate mammalian meat – that is caused by bites from the lone star tick (NEJM JW Gen Med Sep 1 2023 and MMWR Morb Mortal Wkly Rep 2023; 72: 809-814 and 815-820). It easily can be missed, because reactions can be delayed by four to six hours after eating, and symptoms can vary from person to person. Investigators at the Mayo Clinic in Minnesota performed a chart review of about 120 patients who tested positive for alpha-gal syndrome (out of 1260 who were tested) based on specific IgE levels.

The most common symptoms were urticaria (56%), angioedema (38%), anaphylaxis (36%), diarrhoea (32%), nausea (31%), vomiting (23%), abdominal pain (22%) and cramps (18%); 11% of patients reported only gastrointestinal (GI) symptoms. Symptoms started within one hour of ingestion in 11% and were delayed by more than four hours in 29%. Most had symptoms only with red meat consumption, but 11% had symptoms after milk consumption. Among patients with two-year follow-up data, about one in six successfully reintroduced red meat into their diets. 

Comment: Due to its unusual presentation, alpha-gal syndrome is often misclassified as idiopathic anaphylaxis or irritable bowel syndrome. In patients who have delayed allergic or GI reactions to red meat, especially with a history of tick bites, alpha-gal IgE serology is diagnostic with a sensitivity of 100%. Management is avoidance of red meat and provision of an epinephrine autoinjector and allergy action plan. Many patients can eventually tolerate red meat again as long as they do not get additional tick bites.

Avid J. Amrol, MD, Associate Professor of Clinical Internal Medicine, Director of the Division of Allergy and Immunology, University of South Carolina School of Medicine, Columbia, USA.

Lesmana E, et al. Clinical presentation and outcomes of alpha-gal syndrome. Clin Gastroenterol Hepatol 2025; 23: 69-78.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine.