Imagine eating a meal and repeatedly ending up with severe stomach pain and bloating, yet every test your doctor orders comes back normal. At the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2026, Dr Brian Lacy, a gastroenterologist at the Mayo Clinic, highlighted a major diagnostic blind spot: uncommon non-IgE-mediated food hypersensitivity disorders. Unlike classic IgE-mediated food allergies, which often trigger rapid symptoms such as hives, swelling, or anaphylaxis, these conditions primarily affect the digestive tract and can be far more difficult to recognize. One example is adult-onset food protein-induced enterocolitis syndrome (FPIES), a rare condition that can cause severe gastrointestinal symptoms several hours after eating a trigger food.
According to Dr Lacy, physicians evaluating patients with recurring abdominal pain should avoid assuming every case is caused by ulcers, gastritis, reflux disease, or other common gastrointestinal disorders. If symptoms repeatedly occur after eating but routine testing fails to identify a cause, clinicians should broaden their thinking to include less common immune-mediated conditions. While gastroenterologists play a key role in ruling out digestive diseases, Dr Lacy noted that many of these patients will ultimately benefit from evaluation by an allergist with expertise in these uncommon disorders.
The evaluation begins with a careful medical history. Physicians should ask detailed questions about the nature and timing of the pain, associated symptoms, previous treatments, prior diagnostic testing, and whether symptoms consistently follow specific foods. Lacy also recommends performing a simple bedside examination known as Carnett’s test, in which pressure is applied to the abdomen while the patient tenses their abdominal muscles. This quick maneuver can help distinguish pain arising from the abdominal wall—such as muscle strain or nerve entrapment—from pain originating within the abdominal cavity.
If the patient’s history suggests an underlying gastrointestinal disorder, the next step is a standard diagnostic workup. This typically includes routine blood tests, such as a complete blood count, inflammatory markers, liver function tests, and pancreatic enzymes, along with abdominal imaging such as a plain X-ray. If these initial studies are unrevealing and symptoms persist, referral to a gastroenterologist is appropriate for more comprehensive evaluation.
Specialists may then perform advanced imaging, including CT scans, along with endoscopic procedures such as upper endoscopy or colonoscopy to exclude structural disease, inflammatory bowel disease, ulcers, or other common gastrointestinal conditions. Lacy emphasized that when these evaluations fail to identify an explanation for persistent meal-related symptoms, physicians should consider less common allergic or immune-mediated disorders rather than assuming nothing is wrong.
The next stage of evaluation may include additional testing for allergic conditions. Depending on the suspected diagnosis, physicians may obtain serum tryptase levels, perform specialized blood testing, or collect multiple tissue biopsies during endoscopy to look for increased numbers of mast cells or eosinophils—immune cells that can drive allergic inflammation throughout the digestive tract.
Lacy highlighted several uncommon conditions that can mimic more familiar gastrointestinal disorders. Hereditary angioedema, a rare inherited disorder, can cause recurrent episodes of bowel swelling that produce severe abdominal pain while leaving patients symptom-free between attacks. Mast cell activation syndrome (MCAS) can also affect the digestive tract, but Lacy noted that it typically causes episodic attacks involving multiple organ systems rather than constant daily abdominal pain or bloating. He also discussed eosinophilic gastrointestinal disorders, which often require multiple biopsies from different areas of the digestive tract because abnormal immune cells may be distributed unevenly throughout the gastrointestinal tract.
Ultimately, Dr Lacy’s message was not that these disorders are common, but that physicians should avoid overlooking them when standard evaluations fail to provide answers. He encouraged colleagues to “keep your blinders off” and “think outside the box” when confronted with persistent, unexplained abdominal symptoms.
Most people with chronic abdominal pain do not have these rare immune-mediated disorders. However, for patients whose symptoms consistently occur after eating and remain unexplained despite a thorough gastrointestinal evaluation, considering these conditions may help lead to the correct diagnosis and more effective treatment.
