Alpha-Gal Allergy Is on the Rise: A Practical Guide for Clinicians

It sounds like something out of a science fiction movie: a person gets bitten by a tick and then, months later, develops a mysterious allergy to red meat. Short of Peter Parker’s fateful spider bite and the superpowers it conferred on him, how can an insect bite — which may go completely unnoticed at the time — cause such a change in a person’s health? And how can clinicians diagnose and manage this unusual condition in everyday practice?

What is Alpha-Gal?

Alpha-gal allergy or alpha-gal syndrome is an underrecognized, growing cause of mammalian meat allergy in humans. More specifically, it is an IgE-mediated allergy to the oligosaccharide galactose-ɑ-1,3,-galactose (known as alpha-gal). This oligosaccharide is found in high concentrations in mammalian meat, such as cow, pig, and sheep meat, as well as in dairy products from these same animals. 

When a Lone Star tick bites a human, the alpha-gal found naturally in the tick’s saliva can be transferred to the person’s bloodstream, generating an immunologic response that manifests later as an allergy to red meat and dairy products. 

Rare, but on the Rise

It’s hard to know exactly how many people may be affected by alpha-gal allergy, given that it’s likely underdiagnosed and underreported. The CDC estimates roughly 450,000 people may be affected by it in the U.S. Lone Star ticks tend to live in the South, East, and Central portions of the United States, and most cases are identified in those regions, though their geographic reach has expanded with warmer temperatures. 

It turns out that many front-line clinicians aren’t aware that this diagnosis even exists. According to a nationwide survey of 1,500 clinicians by the CDC in 2022, 42% of providers weren’t aware of alpha-gal syndrome, while 35% weren’t confident in diagnosing or treating it. 

Presentation Pearls

The symptoms of alpha-gal allergy can range from subtle post-prandial discomfort all the way to anaphylaxis. After ingesting a meal containing mammalian meat, it can take anywhere from 1 to 6 hours for the person to experience generalized itching, GI distress (such as nausea, vomiting, cramping, or diarrhea), or even urticaria, angioedema, wheezing, and hypotension in extreme cases. 

While most people don’t remember if they were bitten by a tick, it’s important for clinicians to know that the alpha-gal allergy can present up to 3 months after the tick bite. Asking about possible tick bites or even exposures in the preceding 3 months is an important part of our history-gathering for any patient presenting with allergy or anaphylaxis after consuming red meat or dairy. 

Making the Diagnosis

It’s important to keep alpha-gal syndrome on our differential. Start by asking the right history questions: Was there a tick bite? Did the patient eat meat in the past 6 hours? In terms of testing, depending on the workplace, we can order an alpha-gal IgE antibody panel that includes components like total IgE, alpha-gal IgE, and beef/pork/lamb IgE.  A positive test result is when the alpha-gal IgE levels reach a cutoff of 0.10 to 0.35 kU/L, or >2% of the total IgE. 

Treatment

For the acutely anaphylactic patient, treatment remains the same as in any other case of anaphylaxis: airway protection, intramuscular epinephrine, corticosteroids, antihistamines such as diphenhydramine, and likely referral to a higher level of care.

Patients with milder allergic symptoms will need supportive care and should see an allergist when they are able. Crucially, they will need to avoid mammalian meat, such as red meat, pork, lamb, venison, and rabbit, in the future, as well as any dairy products from these animals. 

Living With Alpha-Gal

Patients with alpha-gal syndrome will also need to avoid gelatin products and other animal-derived products found in some medications, including heparin, some chemotherapy agents, certain vaccines, and pancreatic enzymes. The American Academy of Allergy, Asthma, and Immunology recommends that patients with alpha-gal syndrome consult a resource called Pill Clarity to look up any medication to ensure it is free of potentially dangerous animal products. In reality, many of these patients will need to carry auto-injectable epinephrine with them. 

An ounce of prevention is worth a pound of cure, so people living in endemic areas should try to prevent being bitten by ticks in the first place. Remember to use an appropriate insect repellent and wear long, light-colored layers tucked into socks. 

For more information on alpha-gal syndrome, check out this month’s episode of Hippo Education Presents: The Monthly Rounds on Spotify or Apple Podcasts.