Want hives with that burger?

Almost every time he eats a steak, Mack Halsey develops hives on his arms and legs. Burgers are no better. About two to four hours after a meal, his skin starts to itch and break out in hives.

For a long time, Halsey, who lives in Charlottesville, Va., blamed the additives in meat, the antibiotics, the hormones. It was only after he went to Scott Commins, a University of Virginia immunologist, that he got his diagnosis: alpha-gal allergy, a reaction to red meat that results from having been bitten by a tick.

Scientists agree that this allergy can be very dangerous, sometimes causing anaphylactic shock and potentially even death, and that the allergy is on the rise.

Until recently, the medical world was unaware that tick bites could cause an allergy to red meat. “When 10 years ago two people came to see me and told me their stories” that they were allergic to meat and that the symptoms took several hours to show up, “I didn’t believe them,” admits Thomas Platts-Mills, a professor of medicine at the University of Virginia and the author of several studies on alpha-gal allergy.

Sheryl van Nunen, an associate professor of medicine for immunology and infectious disease at the University of Sydney Medical School in Australia, was the first to connect tick bites and meat allergies after she began seeing unusual cases of anaphylaxis (severe whole-body allergic reactions) in the late 1990s and finally published the evidence in 2007.

The allergic reaction was unusual in several ways.

First, it was always delayed: Symptoms appeared three to six hours after a person ate meat, while the classic understanding about food allergies was that they are rarely delayed beyond an hour.

Second, the symptoms were often severe. A study by Platts-Mills of 45 children with alpha-gal allergy that was published last spring found that 46 percent of them had severe enough problems that they had to visit an emergency department at least once after eating red meat. Van Nunen notes that “in the Sydney area, it is the most common reason for an anaphylaxis in adults.”

Third, alpha-gal allergy can develop late in life, where most allergies develop in childhood. Spanish and Portuguese scientists have recently described the case of a meat factory worker who had first symptoms of meat allergy — in this case, a reaction to pork — at age 61.

And, finally, there are the ticks, which include the paralysis tick in Australia, the lone star tick common in the southeast United States and the castor bean tick in Europe. How, the scientists wondered, could a tick bite cause someone to develop a food allergy?

The key, it appears, is a sugar, commonly called alpha-gal, that is found in the meat of all non-primate mammals, including cows, pigs, sheep and goats.

But that link emerged only after van Nunen published her discoveries, as Platts-Mills and Commins were trying to answer a seemingly unrelated question: Why did certain people have severe allergic reactions to alpha-gal molecules in a cancer drug called cetuximab? It didn’t take long for them to notice that the reactions to cetuximab and to red meat seemed restricted to the Southeast.

“We asked ourselves: ‘Could it be that the patients who are allergic to that sugar in the drug are also allergic to red meat?’ We did blood tests and, sure enough, that was it. So we kept doing more tests, and here we are, four years later, with several thousand people identified with this allergy,” Platts-Mills says.

They didn’t blame ticks right away, though, thinking that some regional plant or fungus might be responsible. “Our work would have gone much quicker if we were aware what Dr. van Nunen was saying in Australia,” Commins admits. By 2009, though, they had connected the dots: The location of cases of alpha-gal allergy was similar to the geographic range of lone star ticks.

Within a few years, the U-Va. researchers and scientists in Europe and Australia had all clearly established that some people who have a severe reaction to the bite of certain ticks — bites that cause welts and lingering red circles — may also develop a tremendously heightened sensitivity to alpha-gal in red meat.

What left the scientists puzzled was the mechanism of that dangerous sensitivity. Was some parasite in a tick’s saliva responsible? Or was the sugar itself present in a tick’s mouth?

Marianne van Hage, a professor of clinical immunology at the Karolinska Institute in Stockholm, recently discovered alpha-gal in European castor bean ticks. With that finding, she and the U-Va. researchers believe that the allergy develops as follows:

First, the bite of a tick injects alpha-gal into the skin, which causes the immune system of some people to release a flood of immunoglobulin E antibodies. These IgE antibodies prompt the body to release histamines to fight off an allergen, in the process causing sneezing, itchy eyes, runny nose and other symptoms. (The tick doesn’t have to stay on for long: It needs to attach just long enough to leave a bite mark.)

A few weeks later, with any mark of the tick bite long gone, that person eats a piece of red meat. For two or three hours, nothing happens. Then, hives appear, often followed by swelling on the face, a steep drop in blood pressure and, in severe cases, anaphylaxis. Having been sensitized to alpha-gal by the tick bite, the body is now overreacting to the meat’s alpha-gal, and IgE antibodies are going into overdrive against the allergen.

To diagnose a red meat allergy, a blood test is needed. If an alpha-gal allergy is confirmed, you’ll probably have to give up most red meats, especially fatty ones. (Alpha-gal is most concentrated in animal fat, which is why the reaction is delayed: Fat takes a long time to digest.) You may also need to be careful with gelatin and drugs that contain alpha-gal, such as the intravenous fluid replacement products gelofusine and haemaccel.

Mack Halsey learned this the hard way during surgery last year to replace a heart valve. He suddenly went into anaphylaxis. The reason? Commins thinks that the pig-derived heart valve that surgeons gave Halsey or perhaps the blood thinner they used, which is derived from pig intestines, might have contained some alpha-gal.

There is good news, though. Alpha-gal allergy goes away with time, as long as you don’t get bitten by another tainted tick. “We have patients who recovered completely. Depending how bad your allergy was, it can take from about eight months to three years,” Commins says. And for those who have not yet recovered, there’s this compensation: A vegetarian diet can boost your health. A growing body of data shows that giving up red meat can help ward off cancer, heart disease, Type 2 diabetes, even cataracts.