Three U.S tick species may cause a mysterious red meat allergy

Cathy Raley’s first bout of hives woke her in the middle of the night with itchy bumps that crept up her arms and spread to her legs and back. Her second bout took her to the hospital.

It was a June afternoon in 2017, and she was getting ready to take her dog, Jake, on a hike. The hives started suddenly, when she was about to load Jake into the car, but this time was different, Raley says. Her tongue was swelling, and her throat was getting tight. “That’s when I called 911.”

First responders gave Raley a shot of epinephrine in her thigh, but it didn’t help much. Her vision tunneled. Paramedics helped her into an ambulance and injected another shot into her arm. On the way to the hospital, Raley stopped being able to swallow.

Immediate treatment with a steroid and an epinephrine nebulizer, which delivered the medicine directly to her throat, eventually calmed her symptoms. By the time she arrived at the emergency room, she was able to swallow again. After four hours in the hospital, she was cleared to go home.

Raley had had an anaphylactic reaction — “a fairly major one,” doctors told her. But to what? She was 61 years old and wasn’t allergic to anything that she knew of. “I had absolutely no idea,” she said.

About a week later, Raley visited Seattle-based allergist William Butler, who combed through her history looking for clues to explain the symptoms. Her hives had erupted in the middle of the night, a sign that she was experiencing a delayed reaction. She hadn’t eaten anything out of the ordinary. Though on both occasions the hives had occurred after she’d cooked for visiting company — beef tacos one time, pork sausage the other.

 “I have no idea if it’s related,” Raley finally told Butler, but “two months ago, I got bitten by a tick.” Butler looked at her. “That opens up some real possibilities,” she recalls him saying.

Raley lives in the wooded outskirts of Olympia, Wash., and liked to hike with Jake, an energetic border collie, on the old logging roads near her property. After one hike earlier that year, she had pulled a tick off her shoulder. The bite became irritated and sore to the touch. That had never happened to Raley, a now-retired wildlife biologist who had been bitten by ticks in the past. 

Butler suspected she had alpha-gal syndrome, a red meat allergy that can develop in response to the bite of a lone star tick (Amblyomma americanum). The diagnosis was later confirmed by lab testing. There was just one problem: lone star ticks aren’t found in Washington. Their range is entirely east of the Rocky Mountains — thousands of kilometers from Raley’s hiking trails.

Her case and a different one reported in Maine suggest that the lone star tick isn’t the only species in the United States capable of triggering this allergy, researchers report in two papers published in Emerging Infectious Diseases in March. Two other tick species, the western blacklegged tick (lxodes pacificus) and the blacklegged tick (Ixodes scapularis), also called the deer tick, may be culprits.

“It was a very surprising finding to us,” says Hanna Oltean, an epidemiologist at Washington State Department of Health. The cases “offer pretty definitive evidence that there’s a risk for alpha-gal syndrome associated with ticks other than lone star ticks,” though current data suggest this is rare.

To learn more about this allergy and who may be at risk, Science News spoke to study authors Oltean, and Johanna Salzer, an epidemiologist at the U.S. Centers for Disease Control and Prevention in Atlanta, and Sarah McGill, a gastroenterologist at the University of North Carolina School of Medicine in Chapel Hill who has treated patients with alpha-gal syndrome. Here’s what to know.

Alpha-gal syndrome can occur after the bite of certain tick species

The saliva of certain tick species carry a sugar molecule called alpha-gal. These species include the lone star tick and others found in Europe and Australia. Scientists think that when these ticks bite, the sugar molecule and perhaps other factors in tick saliva get into people’s bodies and can somehow make their immune systems go haywire. The next time people encounter alpha-gal, which is abundant in red meat like beef, pork and lamb, and also in other mammalian products, like milk and gelatin, they may mount an allergic reaction — and symptoms can vary wildly.

“Alpha-gal syndrome can present very differently from patient to patient,” Salzer says. It can look like anaphylaxis, like Raley experienced. Or, as in the case from Maine, symptoms can be entirely gastrointestinal. In that case, a woman was bitten by a blacklegged tick and then later experienced abdominal pain, diarrhea and vomiting after eating different kinds of red meat.

The delayed onset of symptoms and the often mysterious nature of patients’ stomach issues can make alpha-gal syndrome hard to diagnose, McGill says. Traditionally, gastroenterologists haven’t been taught to consider food allergies when seeing adult patients with chronic GI problems, she says. That’s because most food allergies appear when people are young. “But alpha-gal syndrome is very unique,” she says. “Adults can get it suddenly.”

McGill has seen patients who’ve had their symptoms discounted by doctors or even had requests to be tested for the condition refused. Those experiences remind her of celiac disease, which was misunderstood for a long time. That disease is caused by the immune system overreacting to gluten, but patients were sometimes told their symptoms were in their head, McGill says. “I see that same pattern happening with alpha-gal syndrome.”

There’s no cure for the condition, but some people may eventually be able to eat red meat again without sparking an allergic reaction. 

Alpha-gal syndrome is not a well-known condition

Many doctors, nurses and physician assistants have never even heard of the condition. In 2023, Salzer and her colleagues reported the results of a nationwide survey of healthcare providers: 42 percent were not aware of alpha-gal syndrome.

Among those who were, about a third didn’t know how it was acquired and nearly half didn’t know what tests to order to diagnose it. “There are some large gaps in health care provider knowledge,” Salzer says. Increasing health care provider awareness could improve patient outcomes by shortening the time to diagnosis, she says.

Alpha-gal syndrome appears to be relatively rare, though exact numbers are hard to pin down. Salzer and her colleagues tallied about 110,000 suspected cases in the United States from 2010 to 2022. It’s possible this is an undercount, the researchers reported, and as many as 450,000 people may have been affected during this time period.

This condition can be life-threatening, Oltean says, which is why she wants health care providers and the general public alike to know it exists. “It’s important for people to be aware of the risk so that they can take appropriate precautions,” Oltean says.

Preventing tick bites is the best way to avoid alpha-gal syndrome

For Oltean, taking appropriate precautions means avoiding tick bites entirely. She knows that can be difficult, especially during tick season, which generally runs early spring to late fall, depending on location. In Washington state, where she lives, “March through May is when we see ticks coming out and questing, or seeking blood meals.”

After being outdoors, many people rely on tick checks, scanning their bodies to ensure they’re not inadvertently carrying any bloodsucking critters. For tick-borne illnesses like Lyme disease, Rocky Mountain spotted fever and anaplasmosis, quick identification and tick removal can prevent disease. That’s because the tick must be attached to a person’s body for hours or days to transmit disease-causing bacteria. “That does not seem to be the case with alpha-gal syndrome,” Oltean says. There’s no bacteria being transmitted in alpha-gal syndrome — it’s an allergic response that’s triggered following a tick bite. So it’s possible that a single bite from a tick, even one yanked away immediately, could spark the condition. 

Oltean is brimming with tips to prevent ticks from biting. Walk in the center of trails, she says, avoid tall brush and grassy areas, wear tightly woven clothing, which can prevent ticks from attaching, and light colors, which make ticks easy to spot and pick off. She recommends buying clothes pretreated with the insect repellent permethrin, applying a U.S. Environmental Protection Agency-registered tick repellent to exposed skin and showering soon after being outdoors to wash off any unattached ticks. 

Salzer thinks that bites from lone star ticks, not blacklegged or western blacklegged, are the primary drivers of alpha-gal syndrome. In her 2023 analysis, the map of suspected cases largely overlapped with the distribution of lone star ticks in the United States.

Taking steps to avoid bites could protect people from later developing the condition — as well as a slew of infectious diseases. “Preventing that bite is really the main message,” Salzer says.

There is still a lot to learn about alpha-gal syndrome biology

Alpha-gal syndrome is a relatively newly described condition, first reported in 2009. That means there’s still a lot to learn, scientists say. “Why are some people bitten by ticks all the time and they never develop alpha-gal syndrome?” Salzer asks. She also wants to know exactly how long a tick must be attached for someone to get the condition.

Oltean is interested in tick biology; specifically, why lone star ticks seem to be more adept than other tick species at stimulating an immune response to the alpha-gal sugar. “What’s different about these ticks?” And do multiple tick bites over time make a person more likely to develop the condition? 

For people with alpha-gal syndrome, McGill wonders why the allergic response to red meat is so delayed. “You’re getting sick hours later,” she says. “That’s not typical.”

As for Raley, she’s careful with her diet and has avoided red meat, and any resulting reactions, for the last eight years. She’s OK eating dairy but stays away from red meat-based broths and sauces, food made with lard, or desserts with gelatin. “It’s an odd thing to think about,” she says. She also takes precautions like spraying hiking clothes with repellent and keeping her dog on tick medication year-round.

These days, Raley’s curious if tick populations in western Washington state are growing. When she first moved to her wooded property around 2000, she and her dog never got ticks. Now, they’re both encountering them regularly during the spring and summer. “Something seems to have changed,” she says.