Tick bites drive allergies to sugar in alpha-gal syndrome

Key takeaways:

• Alpha-gal syndrome is an allergy to galactose-alpha-1,3-galactose.
• Lone star ticks transmit alpha-gal through their bite.
• Detailed histories are required for accurate diagnosis.

Editor’s Note: In Healio Allergy/Asthma’s column, “Food Allergy: Fact vs. Fiction,” Douglas H. Jones, MD, breaks down what’s true and what’s myth for a variety of topics related to food allergies. If you have a question you would like answered in this column, email Jones at rmaaimd@gmail.com or Richard Gawel at rgawel@healio.com.

Usually when people are allergic to something, the protein causes the allergy. Contrary to myth, sugars typically do not cause allergic reactions. Rather, they can contribute to different issues such as food intolerances and sensitivities.

There is an often misdiagnosed yet emerging syndrome called alpha-gal syndrome (AGS) where people can become allergic to a specific sugar in red meats and other animal food products. Tick bites cause this allergy.

A recent study by the CDC showed that up to 450,000 people in the U.S. may be affected, and that number is rising.

What makes AGS unique?

AGS is different from most food allergies because the person becomes allergic to a sugar, galactose-alpha-1,3-galactose, not a protein, which is the most common issue. This alpha-gal sugar is present in the meat of most mammals but not humans, birds, fish, or apes.

So where do the ticks come into play? I’m so glad you asked. Lone star ticks transmit alpha-gal through their bite. Some patients develop allergic antibodies to the sugar that cause an allergic reaction the next time the person eats the meat of mammals, such as beef, pork and lamb. People can also be exposed through gelatin or a host of other mammal-based products.

Other unique features include the symptoms, timing of symptoms, and how patients present to the doctor. Allergic reactions can range from mild to severe and include symptoms of abdominal pain, diarrhea, nausea, hives, swelling and even anaphylaxis. Some patients may only have isolated gastrointestinal symptoms.

Unlike most food allergies, which cause reactions within minutes after eating, AGS usually doesn’t appear until 2 to 8 hours after exposure. So, it is a more delayed reaction. You can develop AGS even if you have never had food allergies before. All these factors make it an elusive diagnosis for many clinicians. Even if doctors have heard of AGS, they may not know how to diagnose it.

Meat and products such as lard, broth and stock made from mammals including beef, pork, lamb, venison and rabbits include alpha-gal. Their organs include even higher amounts of alpha-gal. Milk also includes alpha-gal, but many patients can tolerate milk. Seafood, poultry and eggs do not include alpha-gal.

Medications or medical products that include mammal products such as cetuximab include alpha-gal as well. Patients also should pay attention to medical products that include gelatin, with special caution taken in parenteral administration of products that include bovine or porcine gelatin, which can cause anaphylaxis in AGS patients even if gelatin tests are negative.

How is alpha-gal syndrome diagnosed?

Like any allergy, AGS diagnosis starts with a detailed history. In a test-oriented society, the conversations that allergists have with patients are the most important piece of the diagnostic puzzle. History of possible tick exposure or bites as well as the timing of the symptoms after the trigger exposure are critical.

Patients should be referred to an allergist for testing, as the correct tests need to be conducted, and those tests need proper interpretation based on the history. Blood tests can confirm the diagnosis by measuring alpha-gal IgE antibodies (galactose-alpha-1,3-galactose IgE).

There is a high false-positive rate for this test, like other food allergy tests, which means it may come back showing someone may have alpha-gal syndrome when they do not actually have it. Further, traditional tests to beef, pork and rabbit with commercial extracts are often negative and will not be diagnostic.

Again, it is important to know the history as an allergist must distinguish between true allergy to beef or pork as opposed to AGS. Additionally, more in-depth testing may be needed to evaluate for something called pork-cat syndrome, which is another topic for another day.

Other considerations include testing for specific IgE to porcine or bovine gelatin. There are a few centers in the United States equipped to utilize basophil activation testing as well.

These are all reasons why it may be beneficial to have the testing done by an allergist who has experience knowing what tests to order for AGS and how to interpret the results within the context of the person and their history. It is important to understand the nuance behind AGS and any other potential disorders the person may have.

How is AGS treated and prevented?

As with any food allergy, AGS treatment involves avoiding the foods that cause a reaction. Ensure that the patient always has injectable epinephrine with them. The effectiveness of immunotherapy for AGS is currently being investigated.

Preventing tick bites is the most important thing we can do to avoid AGS. Patients should be advised to:

• take proper precautions when they are outside and always check themselves for ticks;
• stay on trails and avoid walking through long grasses or bushes;
• wear long sleeves and pants and treat their clothing with permethrin spray;
• use an EPA-registered insect repellent;
• check their gear and pets for ticks after being outdoors;
• make sure there are eyes on the spots they can’t see; and
• remove any ticks they find immediately and wash the area thoroughly.

Finally, as the climate is warming and the tick populations increasing, we must be more aware of this condition. It can go from something that was less common to an emerging health problem. It is important to also realize the uniqueness of the history and presentation of AGS so patients can be referred and properly evaluated and treated.

References:

• Alpha-gal syndrome. https://www.cdc.gov/ticks/alpha-gal/index.html. Updated Oct. 27, 2023. Accessed May 6, 2024.
• Diagnosis and testing: A patient guide to the diagnosis of alpha-gal syndrome. https://alphagalinformation.org/diagnosis-and-testing/. Updated May 6, 2023. Accessed May 6, 2024.
• Emerging tick bite-associated meat allergy potentially affects thousands. https://www.cdc.gov/media/releases/2023/p0727-emerging-tick-bites.html. Updated July 27, 2023. Accessed May 6, 2024.
• Tick removal. https://www.cdc.gov/ticks/removing_a_tick.html. Updated May 13, 2022. Accessed May 6, 2024.

For more information:

Douglas H. Jones, MD, FAAAAI, FACAAI, is cofounder of Global Food Therapy, Food Allergy Support Team and OITConnect, the director at Rocky Mountain Allergy at Tanner Clinic, and a Healio Allergy/Asthma Peer Perspective Board Member. He can be reached at rmaaimd@gmail.com or on Instagram @drdouglasjones.