Food allergies and delayed anaphylaxis

New NIH-funded research from the University of Virginia Health System suggests tick bites may set off a cascade of events that not only defy current thinking about food allergies, but also create serious health risks for people with certain blood types.

UVA researchers describe a novel and severe allergic response, which they call delayed anaphylactic shock. The reaction occurs three to six hours after patients eat beef, pork or lamb. Symptoms begin with itching that intensifies as hives develop on the skin’s outer and deeper layers. Itching quickly escalates to swelling, intestinal irritation and the alarming, life-threatening symptoms of anaphylaxis: airway constriction, chaotic heartbeat, a rapid drop in blood pressure and loss of consciousness.

“Our conventional understanding is that anaphylaxis happens within seconds or minutes of exposure. The notion that it can be delayed for several hours is a paradigm-altering discovery,” says the senior study investigator, Thomas Platts-Mills, MD, PhD, Professor of Medicine and Microbiology at UVA and Head of the Division of Allergy and Clinical Immunology.

The researchers found that the delayed response is being triggered by an IgE antibody that binds to a sugar molecule known as galactose-α-1,3-galactose (alpha-gal). The antibody was found in the serum of all 24 adults assessed in the study and in more than 100 other individuals, including six children, now being tracked by the UVA study team.

“Alpha-gal is an unexpected culprit,” explains lead author, Scott Commins, MD, PhD, an allergy and immunology fellow at UVA who will join its medical faculty in July. “Today’s textbooks tell us that allergic reactions are caused by proteins in food, pollen, dander and venom. They are not supposed to be caused by sugars like alpha-gal.”

UVA researchers are still determining what triggers the production of the alpha-gal antibodies. So far, evidence strongly suggests that tick bites are the cause. “Eighty per cent of our study cohort reported being bitten by ticks either weeks or months before symptoms began. When we consider all the patients in our database, more than 90% had tick bites,” Commins notes. “We are continuing to investigate this link by gathering patient information from a network of allergists around the US and in four other countries.

“In our findings, we refer to ‘seed’ tick, which is the generic term for the larval form of ticks. Ticks such as dog tick, deer tick, Lone Star, etc are the adult forms. We believe all types of ticks can trigger this reaction,” Commins explains.

Blood typing performed at UVA indicates that individuals with Type B or AB blood seem protected from developing IgE to alpha-gal. Commins is concerned that people with other blood types may be unaware of the risks posed by tick bites. “A lot of people suffer symptoms for years without knowing the cause. We worry that the number of undiagnosed or potential cases of alpha-gal sensitivity may be on a dramatic rise,” Commins says. “However, we’ll need more data to make formal projections.”

The UVA study yielded other paradigm-challenging findings. First, the allergist’s key diagnostic tool, the skin prick test, proved ineffective in detecting red meat allergy in study patients. (As part of the UVA research effort, Commins developed a skin-testing technique to identify this allergy.) Second, most patients began experiencing symptoms as adults, defying the common belief that food allergies rarely develop after childhood.

According to Commins, the study is prompting new thinking about food allergies as well as continued investigation. “Our observations have turned a lot of conventional wisdom upside down while raising a number of important questions,” he notes. “We still need to figure out what triggers production of IgE to alpha-gal, why some blood groups are protected and why the allergic reaction is delayed and so severe.”

On a practical note, Commins advises quick removal of hitchhiking ticks and monitoring of bite sites. “People who develop the red meat allergy often report they experienced significant itching and redness around the bites,” he explains. “Anyone who is concerned about developing the alpha-gal antibody after tick bites should have a screening test. It’s far safer than waiting for an allergic reaction to occur.”