EGID Without Eosinophilia: Elevated Mucosal Mast Cell Counts

Patients with suspected eosinophilic gastrointestinal disease (EGID) in the stomach or duodenum had an increased number of mucosal mast cells with or without mucosal eosinophilia.

SAN ANTONIO — Patients with suspected eosinophilic gastrointestinal disease (EGID) in the stomach or duodenum had an increased number of mucosal mast cells with or without mucosal eosinophilia, suggesting that mast cells may play a role in these patients, and raising the possibility of a unique clinical presentation driven by mast cells, according to research presented at the ACG Annual Scientific Meeting, held October 25 to 30, 2019, in San Antonio, Texas.

EGIDs are inflammatory diseases subclassified according to site of abnormal accumulations of eosinophils (eos) in the gastrointestinal tract, such as gastroenteritis (EGE), eosinophilic esophagitis (EoE), and colitis. Although EGID pathogenesis is primarily believed to be driven by eos, increasing evidence has been found for the involvement of mast cells. The current study was designed to characterize symptomatic patients with suspected EGID in the stomach (EG) and/or the duodenum (EGE) who did not meet the histopathologic entry criteria for mucosal eosinophilia in a phase 2 randomized, double-blind, placebo-controlled study of AK002, an anti-Siglec-8 antibody.

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To receive a screening endoscopy for the study, patients were required to have an average symptom score ≥3 (on a 0-10 scale) for nausea, diarrhea, and/or abdominal pain for 2 or more weeks recorded on a daily, patient-reported questionnaire, with no other known cause for their gastrointestinal symptoms. Biopsies from the stomach and duodenum were systematically obtained during the screening endoscopy and were read by a single pathologist. Eos counts, which comprised the number of eos per high-power field (eos/hpf; hpf area=0.237 mm²) were assessed on H&E slides. Immunohistochemistry for tryptase was performed to quantify mast cells. The histopathologic entry criteria for the study included ≥30 eos/hpf in 5 hpfs in the stomach for EG and/or ≥30 eos/hpf in 3 hpfs in the duodenum for EGE. Normal mast cell counts in the gastrointestinal tract were determined by conducting a literature review.

Of the 88 patients undergoing screening endoscopy, 72 met the histopathologic eos criteria. The 16 patients who did not meet the criteria were found to have elevated mast cell counts and had a mean gastric eos count of 6 eos/hpf in 5 hpfs and a mean duodenal eos count of 15 eos/hpf in 3 hpfs. In contrast, these patients had a mean gastric mast cell count of 47 mast cells/hpf in 5 hpfs and a mean duodenal mast cell count of 49 mast cells/hpf in 3 hpfs. Almost all of the symptomatic patients who were screened had elevated mast cell counts (87/88; 99%).

The study investigators concluded, “Data from this large randomized EG/EGE study showed that symptomatic [patients] with suspected EG/EGE had increased mucosal [mast cells] with or without mucosal eosinophilia. These data suggest that [mast cells] may play a role in pts with suspected EG/EGE and raise the possibility of a unique clinical presentation driven by [mast cells].”

Disclosure: This study was supported by Allakos, Inc. Please see the original reference for a full list of authors’ disclosures.

Reference

Murray JA, Dellon ES, Peterson KA, et al. Symptomatic patients suspected of eosinophilic gastritis and/or enteritis have elevated mucosal mast cell counts without eosinophilia: A new diagnostic entity? Presented at: ACG Annual Scientific Meeting; October 25-30, 2019; San Antonio, TX. Abstract #P2665