A Vanderbilt University Medical Center joint study between the divisions of Pediatric Gastroenterology, Hepatology and Nutrition and Allergy, Pulmonary and Critical Care Medicine has found that some children with mystery digestive symptoms may actually have undiagnosed alpha-gal syndrome (AGS), commonly known as the red meat allergy linked to tick bites.
Alpha-gal is short for galactose-alpha-1,3-galactose, a carbohydrate molecule found in mammalian meats, of which beef, lamb and pork are the most common in the American diet. AGS is commonly contracted from being bitten by a tick, most typically the lone star tick.
This tick, which feeds on both humans and other animals, appears to carry alpha-gal in its digestive tract. It can then bite a human, thereby exposing the person to alpha-gal.
The human’s immune system then develops antibody molecules called IgE that are specific to the alpha-gal allergen. Once this occurs, they are prone to have allergic reactions two to six hours after consumption of alpha-gal containing foods or ingestion of alpha-gal-containing medications.
At Vanderbilt 30% of patients who have AGS will have a severe reaction — anaphylaxis symptoms such as swelling, hives, shortness of breath, increased blood pressure, increased heart rate and feeling like they are going to pass out, in addition to nausea, vomiting, diarrhea and abdominal pain. About 50% have hives and swelling plus gastrointestinal (GI) upset, and about 20% appear to have GI symptoms only.
Recent guidance from the American Gastroenterological Association raised awareness about the GI-only onset in adults. The VUMC study published online in the American Journal of Gastroenterology is the first to look at GI-only onset of AGS in children.
“Living in an endemic area for alpha-gal syndrome, we had an index of suspicion in those that reported tick bites or other symptoms consistent with a food allergy,” said Maribeth Nicholson, MD, MPH, associate professor of Pediatrics in the Division of Pediatric Gastroenterology, Hepatology and Nutrition, and the senior author of the VUMC study. “However, as adult data demonstrated that GI symptoms could be predominant, we realized that some children, particularly those with severe and/or intermittent symptoms, may be suffering from AGS.”
The study looked at 199 patients in the pediatric GI clinic at Monroe Carell Jr. Children’s Hospital at Vanderbilt. Of those patients, 40 were sensitized to alpha-gal (which doesn’t mean they are allergic, but they’ve had a tick bite that has exposed them to alpha-gal). Of the 40, 30 were willing to try a diet avoiding red meat, dairy and gelatin. Of those children, 16 reported improvements in their symptoms — eight said the symptoms disappeared and eight reported dramatic improvement.
“It’s not perfect evidence because we haven’t brought these children back to the hospital and given them observed challenges — the gold standard — to prove that they have AGS, but this is the same standard that has been used in adults to diagnose someone having this GI version of alpha-gal,” said Cosby Stone, MD, MPH, assistant professor of Medicine in the Division of Allergy, Pulmonary and Critical Care Medicine, an author of the study.
The first reports of AGS were in 2009. Within a year it was discovered to be more common than thought and by 2012 thousands of cases across large areas of the southern and eastern United States were reported.
Stone said there have been more than 1,200 patients with reported alpha-gal allergy seen at VUMC. More than 100 of those were children.
Once diagnosed, allergists typically recommend strict avoidance of beef, pork and lamb, and a smaller number of patients may also need to avoid mammal-derived foods such as milk or gelatin.
Not all patients with AGS have reactions to every ingredient containing alpha-gal. And patients with AGS should definitely avoid additional tick bites. New tick bites can reactivate allergic reactions to alpha-gal and worsen the severity of an active allergy.
Nicholson said symptoms can differ from patient to patient, and it’s still not known which GI symptoms are the most predictive for AGS. Future studies are needed to better detail this. “Generally, the children I care for at Monroe Carell who tested positive had intermittent, but severe, symptoms which did not respond to classic medications targeting irritable bowel syndrome (IBS) or reflux. These may be the patients who most warrant screening for AGS. It’s also important to ask about tick exposures and symptom association with mammalian meat,” she said.
Jordan Busing, MD, a second-year fellow in the Division of Gastroenterology, Hepatology and Nutrition and first author of the study, said that many of the patients had previous testing that yielded normal results — routine lab work, imaging studies and endoscopic evaluation. “This led clinicians within our clinic to expand the differential diagnosis to include other entities that could present in a similar manner to IBS,” he said.
Stone said the team is interested in conducting larger studies of AGS.
“We would like to understand all the different types of AGS — why one person shows up with one set of symptoms and another person shows up with something different, and to really understand which patients are at risk for which. We’d also really love to understand why some people get AGS in the first place and others don’t. Those are only some of the key questions we’d love to answer if the funding opportunities arise.”
