Duodenal Pathology in Patients with Rumination Syndrome: Duodenal Eosinophilia and Increased Intraepithelial Lymphocytes

Halland, Magnus; Talley, Nicholas J.; Jones, Michael; Murray, Joseph A.; Cameron, Raquel; Walker, Marjorie M.

doi:10.1007/s10620-018-5387-7

Cited by 18 publications

(16 citation statements)

References 30 publications

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“…In spite of the attention that duodenal eosinophilia has received, some pediatric studies, including ours, that have not reproduced this association 21,51 . Some studies have also associated duodenal eosinophilia with other GI disorders such as rumination syndrome, 52 non‐celiac gluten sensitivity 53 and new‐onset gastroesophageal reflux 54 . Although our study and others cast some doubt on the role of tissue eosinophilia in FD and its relationship to clinical symptoms, especially in pediatric FD, methodologic variations should be taken into consideration as the results are interpreted.…”

Section: Discussionmentioning

confidence: 67%

Characterizing clinical features and location‐specific gene expression profiles associated with pain burden in children with functional dyspepsia

Mokha

Hyams

Glidden

et al. 2021

Neurogastroenterology Motil

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Background In children with functional dyspepsia (FD), genes involved in pain modulation may be differentially expressed contributing to chronic pain. Methods Children with suspected FD (cases) and known eosinophilic esophagitis (controls) undergoing esophagogastroduodenoscopy completed the Rome IV Diagnostic, Pain Burden and Frequency Severity‐Duration questionnaires. Two antral and two duodenal biopsies were collected and relative fold differences in gene expression for 84 pain‐associated genes compared to pain‐free controls were calculated. Results Sixty‐six subjects with FD (postprandial distress syndrome = 34, epigastric pain syndrome = 7, both = 25; 65% female; mean age 13.7 years) and 13 pain‐free controls (8% female; mean age 12.7) were studied. There were no significant differences in antral and duodenal eosinophilic counts or distribution between the pain and pain‐free groups. Pain severity and burden did not differ significantly between FD subgroups and neither measure significantly correlated with eosinophil counts in the antrum or duodenum. Analysis of 47 antral and 39 duodenal biospecimens revealed 5 candidate genes significantly associated with pain burden: antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A (p < 0.01). Subsequent stringent statistical analysis comparing those with significant pain versus no pain revealed antral PTGES3 and duodenal SCN3A were the highest priority candidate genes (p < 0.001). Conclusions Pain burden in pediatric FD may be linked to antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A differential expression. These genes are known to be involved in pain conduction, modulation, and neurotransmission, suggesting potential therapeutic targets for managing pain in FD.

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Section: Discussionmentioning

confidence: 67%

Characterizing clinical features and location‐specific gene expression profiles associated with pain burden in children with functional dyspepsia

Mokha

Hyams

Glidden

et al. 2021

Neurogastroenterology Motil

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“…Increased IELs are seen in celiac disease, a gluten protein-driven immune response in a genetically primed host ( 23 ). Hence, another possibility is increased IELs in the terminal ileum may reflect a food antigen driven process, although the expected changes may often occur more proximally in the small intestine, as has been reported in rumination syndrome where increased IELs in the duodenum have been observed with eosinophils (and rumination syndrome strongly overlaps with FD in terms of gastroduodenal symptom profile) ( 32 ). Recent work has also found that in non-IgE food allergy in IBS, IELs become acutely increased in the duodenum after a food challenge consistent with our findings ( 33 ).…”

Section: Discussionmentioning

confidence: 94%

Ileocolonic Histopathological and Microbial Alterations in the Irritable Bowel Syndrome: A Nested Community Case-Control Study

Talley

Alexander

Walker

et al. 2020

Clin Transl Gastroenterol

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INTRODUCTION: Histopathological alterations in the ileum and colon in irritable bowel syndrome (IBS) are controversial, and normal values are poorly established. We hypothesized that changes in mucosal immune cells characterize IBS and key changes in immune composition are associated with the mucosa-associated microbiota (MaM). METHODS: A nested case-control study (48 IBS and 106 controls included) from 745 colonoscopy participants in a random population sample. Intraepithelial lymphocytes (IELs)/100 enterocytes and eosinophils/5 nonoverlapping high-power fields counted; mast cells identified by immunocytochemistry (CD117)/5 high-power fields. Paneth cells quantified per 5 crypts. 16S rRNA gene amplicon sequencing performed on available sigmoid MaM, n = 55 and fecal microbiota, n = 20. Microbiota profiles compared between samples with high and low IEL counts. RESULTS: IBS had increased IELs in the terminal ileum (relative risk ratio = 1.70, 95% confidence interval 1.08–2.76, P = 0.022 adjusted for age, sex, and smoking). Cecal IELs were increased in IBS—diarrhea (relative risk ratio = 2.03, 95% confidence interval 1.13–3.63, P = 0.017). No difference was observed in alpha diversity of MaM or fecal microbiota based on IEL count. There was no difference in beta diversity of the MaM according to IEL count in the terminal ileal (TI) ( P = 0.079). High TI IEL counts associated with a significant expansion of the genus Blautia ( P = 0.024) and unclassified Clostridiales ( P = 0.036) in colon MaM. DISCUSSION: A modest but significant increase in IELs was observed in IBS vs. controls in a population-based setting. Subtle TI and cecal inflammation may play a pathogenic role in IBS but needs confirmation. Modest but discernible differences in the colonic MaM were seen according to TI IEL count but not IBS status.

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“…The aim of the current study was to extend the previous work of Halland and colleagues by assessing densities of antral and duodenal eosinophils and mast cells and duodenal intraepithelial lymphocytes in youth with rumination syndrome 16 . An additional aim was to assess whether these cells were associated with the presence of abdominal pain or early satiety.…”

Section: Introductionmentioning

confidence: 90%

Mucosal eosinophils, mast cells, and intraepithelial lymphocytes in youth with rumination syndrome

Friesen

Rosen

Kapalu

et al. 2021

Neurogastroenterology Motil

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Background Rumination syndrome has been associated with increased duodenal eosinophils and intraepithelial lymphocytes in adults. The aims of the current study were to assess densities of antroduodenal eosinophils and mast cells and duodenal intraepithelial lymphocytes in youth with rumination syndrome and to compare cell densities in those with and without abdominal pain or early satiety. Methods Twenty‐eight youth fulfilling Rome IV criteria for rumination syndrome who had undergone endoscopy were identified and compared to 10 controls. Antral and duodenal biopsies were assessed to determine densities of eosinophils, mast cells, and intraepithelial lymphocytes. Cell densities were also compared between rumination patients with and without abdominal pain and those with and without early satiety. Key results Antral mast cell (peak 18.5±6.5 vs. 12.5±2.7) and eosinophil (peak 9.6±5.2 vs. 4.9±2.1) densities were significantly greater in patients with rumination syndrome as compared to controls. Duodenal intraepithelial lymphocyte densities were also increased in rumination syndrome (18.9 ± 5.1 vs. 11.7 ± 1.5; p<.001). Associations were independent of the presence of abdominal pain or early satiety. Conclusions and Inferences In conclusion, we found an increase in eosinophil and mast cell densities in the gastric antrum and an increase in intraepithelial lymphocytes in the duodenum in youth with rumination syndrome which was independent of the presence of abdominal pain or early satiety. These findings suggest a potential role for inflammation in the pathophysiology of rumination syndrome. Future studies should address whether treatment directed at these cells are beneficial in treating rumination syndrome.

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Duodenal Pathology in Patients with Rumination Syndrome: Duodenal Eosinophilia and Increased Intraepithelial Lymphocytes

Cited by 18 publications

References 30 publications

Characterizing clinical features and location‐specific gene expression profiles associated with pain burden in children with functional dyspepsia

Characterizing clinical features and location‐specific gene expression profiles associated with pain burden in children with functional dyspepsia

Ileocolonic Histopathological and Microbial Alterations in the Irritable Bowel Syndrome: A Nested Community Case-Control Study

Mucosal eosinophils, mast cells, and intraepithelial lymphocytes in youth with rumination syndrome

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