‘Not like any other allergy’: As alpha-gal cases rise, researchers work to understand the tick-borne enigma

In the United States, the culprit behind AGS is most commonly the lone star tick, though black-legged ticks—those that also spread Borrelia burgdorferi, the bacterium that causes Lyme disease—have also caused it. Lone star ticks thrive in the South and have expanded into the Midwest and Northeast. AGS also appears throughout the rest of the world, indicating that many types of ticks spread it. 

“The tick is thought to inject alpha-gal [galactose-α-1,3-galactose], that’s the sugar, into the bloodstream, and in people who are susceptible, they form an allergic reaction to alpha-gal,” Bobbi Pritt, MD, chair of the division of clinical microbiology at Mayo Clinic in Rochester, Minnesota, said. 

“Alpha-gal… is present on certain types of meat from mammals, and so when individuals develop these antibodies to alpha-gal, that means when they are exposed in the future, they can have anywhere from mild GI upset to severe life-threatening reactions,” she said.

The mechanisms behind why a tick bite triggers an allergic response remain somewhat unclear. It’s possible that if it were airborne or ingested, it wouldn’t cause such a reaction.  

“Because it’s happening to the skin, it becomes an allergic immune response,” Commins said. “It’s really the idea of going through the skin, and then the tick saliva probably having some alarming properties that really heighten that immune response.” 

Antibodies not diagnostic

A study last month involving people in five states with high rates of alpha-gal syndrome found that one in four people had AGS antibodies. But that doesn’t mean that everyone with AGS antibodies will develop the allergy. Experts don’t know why some people become allergic to mammal products while others don’t. 

“This is not entirely different with other kinds of allergic diseases,” said Jeffrey Wilson, MD, PhD, an assistant professor medicine in the Division of Asthma, Allergy, and Immunology at the University of Virgina School of Medicine. “If you have an allergy to peanut, for example, you have the allergic antibody to peanut, and you have a history of reacting to peanut.” 

Yet, when researchers examine large populations, many people have the allergic antibody to peanuts without having the reactions. “This same thing is true for all kinds of food allergies, and allergies in general,” Wilson said.

Simply having AGS antibodies isn’t enough for doctors to make a diagnosis. People also need to have indicators, which include signs and symptoms associated with allergic reactions, such as: 

• Itchiness/urticaria (hives)
• Swelling
• Difficulty breathing 
• Nausea
• Diarrhea
• Abdominal cramping 

“That’s the classic alpha-gal presentation, but there’s certainly patients who don’t necessarily have the full gamut of symptoms,” Wilson said. “There’s patients who can have some isolated hives. There’s definitely patients who can have isolated GI symptoms.” 

The timing of the reactions often assists in the diagnosis of AGS. 

“Symptoms tend to happen at nighttime, and I think that’s simply because in the US we often eat a big red meat meal in the evening,” Commins said. “Hives or GI distress in the middle of the night in an adult who may have been outside and lives in lone star tick territory, that’s most likely alpha-gal syndrome.” 

Often, people who have AGS develop “a large, exaggerated, itchy, red, inflamed response at the site of the tick bite,” he added. It’s the type of tick bite people notice. 

The severity of the allergy also varies. Some people can continue to enjoy dairy products, while others have to avoid everything with traces of mammals in it, including skin care products, gelatin, and medications such as over-the-counter gel caps or cetuximab, a monoclonal antibody used to treat certain cancers. 

“That’s how we first learned when people had this,” Pritt said. “They would develop these severe, sometimes immediate, anaphylactic reactions the first time [cetuximab] was infused.” 

‘A young diagnosis’ needs more research

The first paper in the United States to describe AGS was published in 2007. “In the world of medical science. that counts as a ‘young’ diagnosis,” Commins said. “We need both basic research, but I think we also need longitudinal studies where we follow people over time.” 

More research is needed for a better understanding of AGS, especially as ticks migrate to new areas of the country, tick seasons intensify, and tick-borne diseases increase, at least partly due to climate change. Experts are unsure of the true prevalence of it and why some people develop such severe responses, while others have a milder case. Treatment remains limited, with doctors advising patients to avoid mammal products. 

“It would be nice if there was more research about other drugs or vaccines that could be used to prevent or treat alpha-gal or to help reinstate tolerance to red meat, if you could do things to make alpha-gal go away quicker,” Wilson said. “Those are all interesting concepts.” 

Some people can overcome AGS and resume eating and using mammal products, experts say. But they must protect themselves from more tick bites, because they can fuel AGS. 

“If you get bitten by a tick again and you get more alpha-gal injected into your system, it just keeps making the antibody levels that your body is producing greater and greater,” Pritt said. 

The experts agree that avoiding tick bites in the first place is best. Following good tick-bite prevention practices—such as wearing longs sleeves and pants tucked into socks, wearing clothes treated with the tick repellant permethrin, and conducting tick checks on people and pets after being outside—can help people evade ticks. 

“Alpha-gal is a non-infectious disease transmitted by ticks, but there are so many infectious diseases transmitted by ticks that can be very serious and even deadly,” Pritt said. “What I don’t want people to do is avoid the great outdoors and be terrified to go outside. We have to be aware of it. We have to know what the risks are.” 

‘It got better with time’

Harmony has started her senior year of high school and is taking classes for a half day and spending the other half at a magnet school, where she’s taking veterinary science classes to become a vet tech. Still, she frequently travels to show rabbits, which she breeds, and always cares for 20 to 30 rabbits. 

“The best way to explain it is it’s like a Westminster dog show, but for rabbits,” her mother said. 

Harmony has been avoiding mammal products, but it’s been a learning curve. For example, the two learned that some bottled waters use bone char as a filter, and they needed to find out which brand was safe for the teen. Still, Litteral feels hopeful that her daughter might one day be able to eat red meat again. It’s been tough for the family, especially because so few doctors knew about AGS when Harmony first became ill.  

“I had this sick kid, and nobody believed me that she was sick,” Litteral said. “It got better with time, because we knew more.”