As confirmed diagnoses of alpha-gal syndrome are rising, experts urge GI clinicians to familiarize themselves with this condition, its often-challenging presentation, and the necessary steps for its diagnosis and management.
Physicians in certain regions of the United States should consider alpha-gal allergy in patients with unexplained abdominal pain, diarrhea, nausea and vomiting, according to a recently released clinical practice update from the American Gastroenterological Association (Clin Gastroenterol Hepatol 2023;21[4]:891-896).
This increased vigilance is particularly warranted for patients who live or have lived in an alpha-gal–prevalent area, which includes the Southeast, Mid-Atlantic, Midwest and East Central regions of the country. According to author Sarah McGill, MD, MSc, an associate professor of medicine at the University of North Carolina at Chapel Hill and expert on alpha-gal syndrome, the GI manifestations of this syndrome are still under the radar, having been described only a few years ago in a case report series (Gastroenterology 2021;160[6]:2178-2180).
A Mammalian Allergy
A result of the bite of a lone star tick, alpha-gal syndrome causes an immunoglobulin E (IgE)-mediated allergic reaction to ingestion of mammalian meat and other food products derived from mammals, such as dairy. Symptoms of GI distress usually begin two to six hours after consumption of mammalian food products. The syndrome also can cause hives, flushing of the skin, facial swelling and fainting. In patients presenting with these symptoms, a blood test to check for IgE antibodies to alpha-gal should be conducted to check for alpha-gal allergy. Management of this allergy is a diet that excludes mammalian meat as well as other mammalian food products.
“Patients are showing up to GI clinics because the allergic reaction can manifest with GI symptoms alone, without rash or facial swelling or other ‘typical’ allergic reactions,” Dr. McGill told Gastroenterology & Endoscopy News. “The current paradigm is that GI doctors should rarely think about food allergies because those are problems of kids, not adults, and symptoms in allergies should occur reproducibly after exposure.
“But that’s just not true in alpha-gal allergy,” she added. “Mostly this has been reported in adults, and the delay of hours from eating the meat to reaction means that almost no patient can actually link the two. The GI phenotype of the allergy has been documented not only by GI doctors like myself, but also by allergists when they’ve challenged alpha-gal allergic patients with meat in a monitored setting.”
She added that smaller amounts of alpha-gal are in mammalian products like dairy and gelatin, and some patients with alpha-gal allergy can tolerate these foods.
One such patient is Bruce Allen, MD, a retired dermatologist living in Macon, Ga., who has lived with an alpha-gal allergy for about a decade, even before the condition was widely recognized.
“About 10 years ago, I started waking up at about [2 a.m.] with severe abdominal pain and diarrhea. The diarrhea was so bad that on two occasions, when I stood back up, I completely passed out due to the massive fluid shift,” he said. “That was my first symptom of alpha-gal that I can recall.”
After about a year of experiencing significant GI distress after eating red meat, he also began to develop urticaria. He eventually realized that these symptoms always occurred about four to five hours after eating at his favorite steak restaurant.
“It was a very specific kind of hive—very small, about the size of two or three pinheads per lesion—but I’d have hundreds of them all over my body,” he recalled. “And it almost always started with itching in my palms and under my belt line. That’s a classic symptom for an IgE allergy.”
Since alpha-gal was not widely discussed at the time in the medical literature, he guessed he might have a different food allergy, so he cut back on eating out at restaurants and his symptoms improved. But after stumbling on a brief article on alpha-gal in a medical magazine by pure chance, he eventually surmised that the alpha-gal allergy might be to blame for his symptoms.
According to Dr. Allen, he’s been able to control his alpha-gal symptoms over the past decade by avoiding mammalian meat (while still occasionally lamenting others eating filet mignon while he’s forced to order the chicken). However, he is able to enjoy dairy products without an allergic reaction, as well as foods like beef broth, noting that he has to eat the actual muscle of the animal to have an allergic reaction.
“Having practiced dermatology for so long, and having seen so many different allergies during my time in practice, I think that alpha-gal is probably going to turn out to be one of the most missed diagnoses for people who we’d otherwise code as urticaria of undetermined etiology,” he explained. “I would suggest to anyone who’s having urticaria of undetermined etiology, especially if they’ve had any GI symptoms, [to] think about getting alpha-gal antibody levels tested and see if that’s the case.”
Bringing New Visibility to the Condition
Commenting on the clinical practice update, Andrew Y. Wang, MD, the director of interventional endoscopy at the University of Virginia, in Charlottesville, said: “As a gastroenterologist who is referred patients from the Southeast and Mid-Atlantic states, … I have been aware of alpha-gal syndrome for some time. I’m glad that this AGA clinical practice update brings visibility and offers guidance on this important clinical issue.”
Dr. Wang noted two important take-home messages from the update. First, alpha-gal can manifest with GI symptoms such as abdominal pain, nausea, vomiting and diarrhea, without anaphylaxis or skin changes. “These symptoms also occur with other GI diseases, so clinicians who see patients for other GI conditions—particularly in regions populated by the lone star tick—need to think about alpha-gal syndrome,” he advised.
“In my GI practice, I see it relatively frequently among people who are presenting with new-onset or chronic GI distress,” Dr. McGill added. “But if you were to survey someone in Seattle, they may not have ever heard of this, much less diagnosed it.”
Dr. Wang also noted the importance of referring alpha-gal patients to an allergist when the patient reports skin or systemic changes such as swelling of the face or throat, voice changes, difficulty breathing, hives, or fainting, since these patients are at risk for anaphylaxis. Referral is particularly prudent as more gastroenterologists and primary care clinicians diagnose alpha-gal syndrome, he added.
Jana G. Al Hashash, MD, MS, an associate professor of medicine and a gastroenterologist at Mayo Clinic in Jacksonville, Fla., and a co-author of the update, agreed that confirmed diagnoses of alpha-gal are increasing as recognition of the condition grows in the medical community. She noted that the guidance can assist providers through the appropriate diagnostic steps and treatment of alpha-gal syndrome, while an accompanying patient handout answers the most common questions patients may have about this condition.
“Our hope is that this [clinical practice update] increases awareness about alpha-gal among gastroenterologists,” she said. “We’re hopeful that physicians will keep this diagnosis in their differential when evaluating patients with GI symptoms like abdominal pain, diarrhea, nausea and vomiting and will be more familiar with this condition.”
—Meg Barbor, MPH
The sources reported no relevant financial disclosures.
This article is from the September 2023 print issue.