When patients present to the emergency department with unexplained anaphylaxis, the questions might be about both what bit them and what they bit.

That’s according to researchers at the National Institute of Allergy and Infectious Diseases (NIAID), who found that mysterious acute allergic reactions in some patients were caused by a relatively rare allergy to a molecule found naturally in red meat. The allergy is linked to a history of a specific type of tick bite and often is difficult for emergency physicians and other healthcare professionals to identify.

An article published in the journal Allergy notes that IgE antibodies (Ab) specific to galactose-α-1,3-galactose (alpha-gal) are responsible for a delayed form of anaphylaxis that occurs three to six hours after red meat ingestion. A study of 70 participants referred with a diagnosis of idiopathic anaphylaxis (IA), of whom six (9%) were found to have IgE to alpha-gal, added more information about those reactions.

The study found that adopting a diet free of red meat apparently prevented future anaphylaxis in those patients over the next 18 months to three years of monitoring.

The report also notes that two of the patients had indolent systemic mastocytosis (ISM), which caused severe clinical reactions but lower specific IgE to alpha-gal and higher serum tryptase levels, reflective of the mast cell burden.

“The identification of alpha-gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha-gal are delayed and thus may be overlooked,” study authors recommend.

So-called alpha-gal syndrome appears to be more common in the Southeast United States and certain areas of New York, New Jersey, and New England, study authors note, adding that the connection appears to be a history of bites from juvenile Ambylomma americanum, or Lone Star ticks.

Emergency physicians can mistakenly diagnose these patients as having unexplained anaphylaxis because alpha-gal allergy presents differently from more common food allergies. In addition, routine allergy tests do not typically scan for antibodies to alpha-gal.

Another issue is that most reactions to common food allergens occur about five to 30 minutes after exposure; allergic reactions to alpha-gal can occur as much as three to six hours after red meat consumption. In some cases, the article notes, episodes might begin overnight when a patient is sleeping – an especially uncommon presentation for anaphylaxis.

“This unusually long time gap between a meal and an allergic reaction is probably a big reason that alpha-gal allergies are often initially misdiagnosed,” explained Dean Metcalfe, MD, chief of the Mast Cell Biology Section in the Laboratory of Allergic Diseases in NIAID's Division of Intramural Research. “If you start to have trouble breathing in the middle of the night, you probably are not going to blame the hamburger you had for dinner.”