Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study

Abstract

Background: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools. Objective: We aimed to develop tissue-and blood-based diagnostic platforms for EG. Methods: Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP 18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels. Results: Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n 5 74; control subjects without EG, n 5 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve > _ 0.95), (2) effectively monitored disease activity in longitudinal samples (P 5 .0078), (3) highly correlated in same-patient samples (antrum vs body, r 5 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r 5 20.83, P < .0001), periglandular circumferential collars (r 5 20.73, P < .0001), and endoscopic nodularity (r 5 20.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve > _ 0.91), (2) correlated with gastric eosinophil levels

Beyond Helicobacter: dealing with other variants of gastritis—an algorithmic approach

“…Such endoscopic abnormalities are only found with Helicobacter-associated and idiopathic LG, although idiopathic LG can mimic any of the other forms of LG. 45 The intraepithelial lymphocytosis of Helicobacter-associated LG and some idiopathic LG cases is often also visible at low power, with increased cellularity of gastric pits, very similar to the low-power changes seen in the duodenum in coeliac disease. It is usually corpus-dominant, and when there is antral involvement it is usually at least of equal severity in the antrum and corpus.…”

“…The inflammatory infiltrate can be band-like (mild diffuse superficial chronic gastritis), a finding that was thought to indicate H. pylori-associated gastritis, but it appears that this can also be seen in NSAID-associated LG, and in the antrum in coeliac disease. 45 Other medications, such as sartans, especially olmesartan, can produce a very similar picture ( Figure 4C-H). Checkpoint inhibitors can produce a range of changes from intraepithelial lymphocytosis to severe chronic active gastritis, or focal enhanced gastritis, and sometimes granulomas.…”

“…LG associated with coeliac disease is usually subtle, often focal and so has to be searched for, and antral-predominant. 45 Immunostaining with CD3 is rarely needed, as the lesion is of no clinical consequence. The lamina propria may show no increase in the number of plasma cells, indicating a pure intraepithelial lymphocytosis, 44 and at most there is a modest increase ( Figure 4A,B).…”

“…It may also have the targetoid summit lesions as in the original varioliform description, although these seem to be quite uncommon. Such endoscopic abnormalities are only found with Helicobacter ‐associated and idiopathic LG, although idiopathic LG can mimic any of the other forms of LG 45 …”

Advancing patient care through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)

“…The relative newness of EGIDs to the medical landscape speaks to the immense opportunities available that will shape the field for decades to come and that can improve the lives of patients in a relatively rapid manner. Research emanating from CEGIR2 will include further characterization of non-EoE EGID, 74 with a particular emphasis on developing consensus guidelines for these disorders, pursuing a randomized clinical trial with novel biologic therapy for EGID, and supporting innovative pilot studies. Access to CEGIR research studies can be found at the CEGIR Web site (https://www.rarediseasesnetwork.…”