Ticks cause meat allergies. Really?

Scientific detective work links red meat allergy to blood sucking ticks. Irony abounds.

People who eschew red meat do so for various reasons – health concerns, environmental impacts, disgusted indignation over the bacon sundae – but for some it’s not a matter of choice, they’re literally allergic to the stuff. Yes, there is such a thing as a meat allergy, and scientists are starting to get a better understanding of how it works. An article published online on July 20 in the Journal of General Internal Medicine presents three such cases and describes how researchers are unraveling the mystery of this unusual allergy. The strangest part of the tale is the possible cause of the syndrome. The current suspect in creating this involuntary vegetarianism is an insect – the lone star tick (Amblyomma americanum).

Meat rash

Red meat is a recent and rare (rare as in uncommon, not undercooked) addition to the cannon of food allergies. The novel hypersensitivity was announced in a 2009 article in The Journal of Allergy and Clinical Immunology, and by the time of a March 2012 review published in Clinical and Molecular Allergy, literature on the syndrome amounted to a total of only 32 cases.

Diagnosing the allergy can be challenging due to its delayed onset. Typical food allergies elicit reactions within 30 minutes of consumption, but individuals allergic to meat experience symptoms up to six hours after the offending meal. If they happen to partake of meat at dinner, the result can be a terrifying middle-of-the-night awakening with unexplained hives or even full-blown anaphylaxis*. It’s definitely an allergy, as opposed to an intolerance. For those allergic to meat, eating a hamburger doesn’t just cause digestive problems or make them feel ambiguously unwell, it creates an antibody-mediated allergic response.

IgE antibodies. They mean well. Image: NIH.

Food allergies are usually sensitivities to a particular protein found in these items. One might expect the same from a much-touted protein source like meat, but in this case it’s actually a sugar that sets off the reaction – galactose-alpha 1,3-galactose (known to its friends by the catchier nickname “alpha-gal”.) Alpha-gal is found in non-primate mammalian meat, so for those with the allergy cows, pigs, sheep, cats and dogs, etc., are all off limits, but poultry and fish are safe.

Like the bulk of allergies, reactions to meat are mediated by Immunoglobin E (IgE) antibodies, which the body produces in response to a particular allergen (in this case alpha-gal.) Why some people become “sensitized” (i.e., produce allergen specific antibodies) to relatively harmless things like pollen, peanuts, or meat is not entirely clear, but as with many physiological quirks, it’s likely a mix of genetic and environment factors.

Some sensitization occurs through excessive exposure to the allergen. For instance, health care workers, who interact more with latex than the general population, are also more likely to develop allergies to it. Other times it seems underexposure may be the culprit. Some studies suggest that children who aren’t exposed to peanuts prior to age 3 are more prone to developing an allergy once finally faced with peanut butter. Childhood is indeed the time when food allergies usually arise. The meat allergy, however, is cropping up in adults, many of who had previously eaten mammals for years without incident. And scientists suspect that an altogether different environmental factor – bites from a tick – is responsible for their condition.

Clues

How did we get from acknowledging meat allergies to blaming ticks? It wasn’t the steak-spawned hives that led scientists in that direction, but rather another allergic reaction – to the medication cetuximab. Administered in IV form, cetuximab, is used to treat certain kinds of cancer and has an alpha-gal component in its molecular structure. Soon after its approval for tumor treatment in 2005, reports of allergies began. While severe allergic reactions to medications are not unheard of, they normally occur only after the patient has been sensitized by earlier exposure to the drug. What made the cetuximab allergy unusual was that some patients experienced anaphylaxis upon being given their first dose. Clearly, they had been sensitized by something else.

Oncologists working with cetuximab also observed that these allergic reactions were far more common in patients residing in the southeastern United States, an area coincidently high in populations of the lone star tick. Patient histories revealed that many of those with hypersensitivities to cetuximab reported at least one tick bite. It was after the publication of these findings that doctors dealing with meat allergic patients noticed a similarity in the geographic distributions and began to wonder if the two allergies had a common cause.

Ticked off

So meat allergies occur more in the southeastern U.S., which also happens to be teeming with lone star ticks. So what? The correlation could be caused by any number of other demographic differences. After all, people in that part of the world also eat a lot of red meat. (Disclaimer: anecdotal information based entirely on high volume of BBQ restaurants seen in the south.) How do we know this isn’t just another instance of latex-style overexposure sensitization?

The lone star tick. it’s said to be “aggressive.” Image: CDC.

Well, there is some pretty interesting evidence to support the tick hypothesis. The patient histories, for one thing. When questioned, most of the meat allergic individuals recalled having run-ins with ticks. The ability to test blood serum for IgE antibodies has also turned up some useful data. A 2011 study in the Journal of Allergy and Clinical Immunology found a correlation between presence of alpha-gal IgE antibodies and IgE antibodies specific to proteins in the lone star tick. More intriguingly, the authors were able to test serum samples from three subjects both before and after they incurred tick bites. In all three cases levels of alpha-gal IgE rose following encounters with the blood sucking beasties. Three subjects is, of course, a very small number. But good luck getting approval for an experiment that deliberately exposes a large group of people to tick bites.

And Amblyomma americanum isn’t the only tick linked to meat allergies. Smaller numbers of cases have been documented as far as Australia, and in these too, most patients reported a history of tick bites (Ixodes holocyclus is the species currently accused of causing Australian meat allergies.)

Despite the strong correlation evidence, there is still no mechanism to explain how tick bites might sensitize people to alpha-gal. And with so few documented cases, it appears that not everyone bitten by a tick goes on to develop a meat allergy, suggesting that other underlying factors may contribute to sensitization. Though we may start to see more diagnosed cases as the syndrome gains recognition. That recent Journal of General Internal Medicine article, which added three case studies to the literature but no new insight as to the cause, did emphasize the need for doctors to be aware of this emerging allergy.

Naturally this allergy poses potential problems for hunters heading into the woods to shoot deer and whatnot (I know zilch about hunting, but I’ll still recommend pulling your socks up over your pants.) But on the bright side, if the condition does turn out to be more common than previously documented, this could be an excellent money making opportunity for the first person to figure out how to produce alpha-gal-free red meat. Any takers?

* Anaphylaxis is a potentially fatal, full body allergic reaction that tends to create enough swelling to close off airways. (FYI, it  can be derailed with epinephrine.)

† IgE antibodies are one of several types produced by the immune system to fight pathogens (or perceived pathogens). IgG is the most common of the of the pathogen thwarters.

Alex Reshanov

MORE ARTICLES