Abdominal Pain and Bloating: When to Consider HAE, MCAS, and EGIDs

Abdominal pain and bloating rank among the most common complaints in clinical medicine and the hardest to pin down.¹ For allergists and immunologists, the challenge is knowing when to step in and what to look for when traditional GI workups come back unremarkable. Conditions including hereditary angioedema (HAE), mast cell activation syndrome (MCAS), and eosinophilic GI disorders can all present with episodic abdominal symptoms, yet they remain low on the radar of most primary care providers and even gastroenterologists seeing these patients first.

The topic was among those addressed at the Eastern Allergy Conference (EAC) 2026 in Palm Beach, Florida.² HCPLive spoke with presenter Brian E. Lacy, PhD, MD, a board-certified gastroenterologist at the Mayo Clinic in Jacksonville, about how he approaches this differential from the gastroenterology side and where collaboration with allergy and immunology becomes essential.

When a patient presents with intermittent bloating and no clear etiology, Lacy organizes the differential around 5 major causes: dietary indiscretion such as lactose or fructose excess, constipation, intestinal methanogen overgrowth or SIBO, visceral hypersensitivity as seen in IBS and functional dyspepsia, and abdominophrenic dyssynergia, a motility disorder in which patients become severely bloated after eating and often describe looking pregnant.

He noted that abdominal pain requires a separate framework. He said that he breaks it down into new-onset versus chronic abdominal pain to help clinicians narrow down the impacted pathway.

HAE is typically the last condition a clinician thinks to check for. Because the condition affects roughly 1 in 50,000 people, it sits well below more common diagnoses on most clinicians' working lists. Rather, clinicians will often look for more prevalent conditions, such as an ulcer, a hernia, or new-onset inflammatory bowel disease.

After standard workup fails to produce a diagnosis, Lacy said that a clinician should start thinking about allergic etiologies. Clinically, HAE abdominal attacks tend to present as discrete episodes separated by symptom-free intervals, with significant bloating and distension and, crucially, dilated intestinal loops on imaging.

"Usually, the diagnostic test, some imaging study, sets a light bulb off in a lot of clinicians' heads that something else is going on,” he said.

MCAS presents a related but distinct diagnostic challenge. Lacy cautioned that despite growing patient awareness of the condition, true MCAS is uncommon. He uses episodic symptom patterns and multi-organ involvement as the primary clinical filters.

"When somebody reports daily abdominal pain or daily bloating, that is not likely to be MCAS," he said. "They should have episodes separated in time by where they don’t have symptoms, [and] they should have at least two different organ systems involved.”

He noted that skin and GI tract symptoms are a classic pairing. If a patient has these episodes, Lacy recommends checking the serum tryptase to ensure it is above baseline.

For eosinophilic GI disorders, the diagnostic gap lies largely in procedural practice. Because the mucosa can appear grossly normal on endoscopy, the condition is frequently dismissed after a "normal" scope. Lacy stressed that gastroenterologists need to take multiple biopsies across GI segments and alert the pathologist in advance to stain specifically for eosinophils—and for mast cells when MCAS is also on the table.

"There has to be a heightened sense of awareness and…good communication with the person doing the procedure [and] the pathologist,” he said.

Editor’s note: Relevant disclosures for Lacy include Ardelyx, Salix Pharmaceuticals, and IRONWOOD PHARMACEUTICALS.

References

1. Upper Abdominal Pain. Cleveland Clinic. Accessed June 15, 2026. https://my.clevelandclinic.org/health/symptoms/24736-upper-abdominal-pain

2. Lacy B. Evaluation and Management of Intermittent Abdominal Pain and Bloating. Poster presented at the Eastern Allergy Conference (EAC) in Palm Beach, Florida, on May 29.