In:
American Journal of Gastroenterology, Ovid Technologies (Wolters Kluwer Health), Vol. 114, No. 1 ( 2019-10), p. S693-S694
Abstract:
Eosinophilic gastrointestinal diseases (EGIDs) are a set of inflammatory diseases subclassified according to the site(s) of abnormal accumulation of eosinophils (eos) in the gastrointestinal (GI) tract such as eosinophilic esophagitis (EoE), gastroenteritis (EGE), and colitis. These conditions often decrease quality of life due to debilitating symptoms. While the pathogenesis of EGIDs is primarily thought to be driven by eos, there is increasing evidence for the involvement of mast cells (MCs). AIM: To characterize symptomatic patients (pts) with suspected EG/EGE who did not meet histopathologic entry criteria for mucosal eosinophilia for a Phase 2 randomized, double-blind, placebo-controlled study of AK002, an anti-Siglec-8 antibody. METHODS: To undergo screening endoscopy for this study, pts were required to report an average symptom score ≥3 (0 to 10 scale) for abdominal pain, nausea, and/or diarrhea on a daily patient-reported outcome questionnaire for ≥2 weeks and have no other known cause for GI symptoms. During the screening endoscopy, biopsies were systematically obtained from the stomach and duodenum, and read by a single pathologist. Eos counts (eos/hpf; hpf area = 0.237 mm 2 ) were assessed on H & E slides. To quantify MCs, immunohistochemistry for tryptase was performed. We quantified eos and MCs in the stomach and duodenum. Histopathologic entry criteria for the randomized study was ≥30 eos/hpf in 5 hpfs in the stomach (EG) and/or ≥30 eos/hpf in 3 hpfs in the duodenum (EGE). A literature review was conducted to determine normal MC counts in the GI tract. RESULTS: Eighty-eight pts underwent screening endoscopy based upon suspected EG/EGE and active symptoms, and 72 pts met histopathologic eos criteria. All pts whose eos did not meet entry criteria (n = 16) were found to have elevated MC counts (Figure 1; reported normal range = 12-19 MCs/hpf). In these pts, the mean gastric eos count was 6 eos/hpf in 5 hpfs and mean duodenal eos count was 15 eos/hpf in 3 hpfs. In contrast, these pts exhibited a mean gastric MC count of 47 MC/hpf in 5 hpfs and a mean duodenal MC count of 49 MC/hpf in 3 hpfs. Almost all symptomatic pts screened (87/88; 99%) had elevated MC counts. CONCLUSION: Data from this large randomized EG/EGE study showed that symptomatic pts with suspected EG/EGE had increased mucosal MCs with or without mucosal eosinophilia. These data suggest that MCs may play a role in pts with suspected EG/EGE and raise the possibility of a unique clinical presentation driven by MCs.
Type of Medium:
Online Resource
ISSN:
0002-9270
,
1572-0241
DOI:
10.14309/01.ajg.0000594504.91508.61
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
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