Alpha-gal syndrome is usually thought of as a red meat allergy, but it can also spur allergies to mammalian-derived ingredients like gelatin.
Jennifer Wallace was reacting badly to medication she takes for chronic pancreatitis. She broke out in hives, her heart beating fast. And she suffered an unstoppable, intense itching all over her body. Several times, she went into anaphylactic shock, which can be deadly, and was rushed by ambulance to a hospital.
It took doctors a long time, however, to figure out the unlikely cause: alpha-gal syndrome, also known as red meat allergy, which Wallace probably got from lone star tick bites in her backyard in North Carolina.
According to one study, in the parts of the United States where lone star ticks are common, North Carolina included, as many as 9 percent of unexplained anaphylactic reactions may be due to alpha-gal syndrome -- an allergy to a carbohydrate called galactose-alpha-1,3-galactose, alpha-gal for short, found in all mammals except humans and some old-world primates.
"Because it's present in cows and pigs and sheep, when we eat meat or products [derived] from those animals, we can get a reaction," says Scott Commins, an immunologist at the University of North Carolina at Chapel Hill. Wallace's pancreatitis medicine is made using some of those products.
When alpha-gal syndrome was first described 15 years ago, it was usually portrayed simply as a red meat allergy, and it still often is. Yet scientists are now "acutely aware that it's well more than a food allergy," Commins says.
Besides reacting to red meat, people with alpha-gal syndrome may be allergic to such mammalian-derived ingredients as gelatin, which can be found in gummy bears and yogurt. If you are highly sensitive, you may react to cosmetics, including certain shampoos (which may contain keratin derived from horns or hooves) and deodorants (because of lanolin, from sheep's wool).
Lastly, there are drugs and other medical products with ingredients of mammalian origin, from pancreatic enzymes derived from pork, like the ones Wallace took, to anti-venoms, thyroid medications and heparin, a commonly used blood thinner. What's more, many drugs come in mammalian-derived gelatin capsules and contain other pork- or cow-based inactive ingredients.
Experts now recognize that in addition to being a food allergy, alpha-gal syndrome "is a major drug allergy," says Sharon Forsyth, a founder of the nonprofit Alpha-gal Alliance and an AGS patient. Among the drugs that doctors and their patients should be particularly aware of are cetuximab, a cancer drug, intravenous heparin, and anti-venoms for snake bites
According to the CDC, there may be as many as 450,000 people living with alpha-gal syndrome in the United States, with the highest prevalence in states such as Arkansas, Virginia, Kentucky and Missouri. This pattern can be explained by the geographic distribution of the lone star tick, the main culprit behind AGS, whose range is expanding because of climate change. (Other ticks may trigger the condition, too, just much less frequently.)
Scientists still don't fully understand how a tick bite can kick off an allergy to red meat and other mammalian-derived products, but Commins says "we're very confident about the tick story," not only because most patients recall a bite, but also because several experiments on mice have confirmed the link.
It's not just how the allergy starts that's unusual; the symptoms are, as well. For one, they often are delayed by three to six hours after someone eats meat. "A hamburger for dinner results in hives or gastrointestinal distress in the middle of the night," Commins says.
Certain symptoms of alpha-gal syndrome are also not typical of other allergies. Some people report joint pains, for instance, while others have nonspecific gastrointestinal issues that may be misdiagnosed as irritable bowel syndrome.
Alpha-gal syndrome was discovered because of unexpected severe drug reactions, including anaphylaxis, in some patients who took cetuximab, a cancer drug. A 2008 study found antibodies to alpha-gal in the blood of those patients.
Because such antibodies were also present in patients with tick bites, Commins and his colleagues linked the cancer drug data to beef and pork allergies they were seeing.
However, even though it was evident early on that drugs can cause allergic reactions in people with alpha-gal sensitivity, "awareness is really lacking" among primary care doctors, Commins says. A recent CDC study showed that 42 percent of U.S. health-care providers have never heard of alpha-gal syndrome, while 35 percent said they don't know how to treat such patients.
Doctors often tell people to just avoid red meat. Yet for those who react to drugs as a result of alpha-gal, that advice is not enough -- and they end up frustrated, "trying to figure out why they're still having reactions," says Andrew Mize, a pharmacist at Debbie's Family Pharmacy in Arizona, who says he sees many patients with AGS.
The drugs most likely to cause severe allergic reactions are those that are administered intravenously, like cetuximab, says Jeffrey Wilson, an immunologist at the University of Virginia. One such example is "plasma expanders," gelatin-based solutions that increase blood volume. Not only do they have "a lot of alpha-gal" because of the gelatin, Wilson says, but because patients receive these drugs intravenously, "it's all at once."
"When we eat things, there is this whole process of absorption and digestion," he says, but when things go into the vein, a "severe, scary reaction" may begin immediately.
If there is one drug that has many patients worried, it's the blood thinner heparin. It's derived from pig intestines and is used to prevent and treat blood clots. In some cases, heparin is administered intravenously. "It's one of those medicines that you could receive in an emergency situation," Commins says. In one small study co-authored by Wilson, 24 percent of people with alpha-gal syndrome undergoing heart bypass surgery had a serious allergic reaction to intravenous heparin.
Anti-venoms used for snake bites may be a problem, too. Over a period of three months, one midsize hospital in Arkansas had three such cases. One of them was a 66-year-old man with red meat allergy who was bitten by a rattlesnake. Once he received an anti-venom infusion, his face swelled up, and he had trouble breathing. In lab experiments, Christiane Hilger, an allergist at the Luxembourg Institute of Health, and her colleagues confirmed a link between alpha-gal syndrome and anti-venoms, which are usually produced from horse or sheep blood.
Yet to Wilson, the benefits of anti-venoms still outweigh the risks, even for those who know they have alpha-gal. If you get a snake bite, "get the anti-venom; you're in the emergency room, they can treat an allergic reaction" to the drug, he says.
While medicines that aren't delivered intravenously tend to be "relatively lower risk," Wilson says, pills and capsules may still cause trouble. Corrie Newman, a pharmacist at Debbie's Family Pharmacy, spends hours on the phone talking to drug manufacturers, trying to figure out whether certain medications that her patients were prescribed contain alpha-gal. Many "have inactive ingredients that you don't know if it's mammal-derived or plant-derived," she says.
Gelatin capsules, which can be made from animal skin or bones or plant-based alternatives, are one such case. Another is magnesium stearate, used to bind ingredients in tablets, such as acetaminophen.
Other potentially problematic medical products and devices are collagen sutures, bandages with mammalian-derived adhesives, and bioprosthetic heart valves, which are made from cow or pig tissue. A 2022 study by Commins and his colleagues suggested that patients with AGS who have such heart valves implanted may experience chronic inflammation, which "could lead to an earlier destruction of those implanted valves," Commins says.
For those who react intensely to medications, some researchers suggest that taking omalizumab, a newly approved drug for food allergies, could reduce risks of surgery or treatments. In the future, however, more medications could be made with plant-based ingredients. Some biotechnology companies are also working with genetically engineered pigs that don't produce alpha-gal to develop new materials and drugs.
For now, one of the best approaches for AGS patients is to wait because antibody levels to alpha-gal tend to go down as the post-tick bite time increases. That's why, Wilson says, if you "want this thing to go away," the No. 1 thing to do is avoid more ticks.