Understanding fibrosis in eosinophilic esophagitis: Are we there yet?

Armbruster‐Lee, Jennifer; Cavender, Cary P.; Lieberman, Jay; Samarasinghe, Amali E.

doi:10.1002/jlb.5mr1017-395r

Cited by 21 publications

(20 citation statements)

References 115 publications

(284 reference statements)

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“…[3][4][5] In EoE, fibrosis leads to tissue remodeling with resultant esophageal rigidity and luminal narrowing, causing clinical dysphagia and food impactions. 2,3,6 Current EoE therapies have variable and limited effects on treating fibrostenotic EoE. 7 Tissue fibroblasts are likely central to fibrosis in EoE, shaping the extracellular matrix, but varying functions and phenotypes of fibroblasts in alternate disease states are just beginning to be appreciated.…”

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confidence: 99%

Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype

et al. 2020

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BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is an antigen-mediated eosinophilic disease of the esophagus that involves fibroblast activation and progression to fibrostenosis. Cytokines produced by T-helper type 2 cells and transforming growth factor beta 1 (TGFb1) contribute to the development of EoE, but other cytokines involved in pathogenesis are unknown. We investigate the effects of tumor necrosis factor superfamily member 14 (TNFSF14, also called LIGHT) on fibroblasts in EoE. METHODS: We analyzed publicly available esophageal CD3 þ Tcell single-cell sequencing data for expression of LIGHT. Esophageal tissues were obtained from pediatric patients with EoE or control individuals and analyzed by immunostaining. Human primary esophageal fibroblasts were isolated from esophageal biopsy samples of healthy donors or patients with active EoE. Fibroblasts were cultured; incubated with TGFb1 and/or LIGHT; and analyzed by RNA sequencing, flow cytometry, immunoblots, immunofluorescence, or reverse transcription polymerase chain reaction. Eosinophils were purified from peripheral blood of healthy donors, incubated with interleukin 5, cocultured with fibroblasts, and analyzed by immunohistochemistry. RESULTS: LIGHT was up-regulated in the esophageal tissues from patients with EoE, compared with control individuals, and expressed by several T-cell populations, including T-helper type 2 cells. TNF receptor superfamily member 14 (TNFRSF14, also called HVEM) and lymphotoxin beta receptor

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confidence: 99%

Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype

et al. 2020

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“…Moreover, they also noted that 25(OH)D can also influence T cell function, reducing the proliferation and differentiation of T helper (Th) cells and promoting a change from a pro-inflammatory to a more tolerogenic immune status (26) . Armbruster-Lee et al (2018) revealed that peripheral blood eosinophils in pediatric EoE patients have negative expression of VDR and negative expression of Transforming Growth Factor Beta (TGFB), indicating a profibrotic state, and that the negative regulation of VDR in eosinophils in patients with EoE may contribute to fibrosis in EoE (27) . These studies indicate the importance of monitoring 25(OH)D serum levels in EoE patients, since deficient/insufficient serum levels may cause an increased presence of eosinophils by the immune system and without a correct treatment to normalize 25(OH)D levels, esophageal fibrosis may occur.…”

Section: Discussionmentioning

confidence: 99%

“…This alerts us to pay more attention and provide correct guidance for exposure to the sun, at the right time, for sufficient time and with appropriate clothing to trigger a correct production of 25(OH)D, as its inadequate/ deficient levels of 25(OH)D can influence the manifestation of the disease. In addition, health professionals should focus, from the moment of diagnosis, on monitoring and adhering to treatment, since correct adherence is essential to control the disease and prevent it from becoming a case of esophageal fibrosis (27) .…”

Section: Discussionmentioning

confidence: 99%

Case-Control Study on Vitamin D Status in Children and Adolescents With Eosinophilic Esophagitis

Teixeira

Linden

Lomazi

et al. 2020

Arq. Gastroenterol.

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BACKGROUND: Vitamin D is an essential fat-soluble steroid hormone and vitamin D deficiency is a global public health problem especially among children and adolescents. Factors such as the low intake of vitamin D-rich food sources, poor absorption and less exposure to the sun influence this outcome. Vitamin D has an anti-inflammatory effect in the body by promoting regulatory T cell differentiation as well as recovering T helper 17 cell response and secretion of anti-inflammatory cytokines. Eosinophilic esophagitis (EoE) is a chronic disease, histologically characterized by predominantly eosinophilic inflammation. The most common therapeutic approaches are allergen-eliminating diets, such as excluding cow’s milk, egg, soy, wheat, peanuts and seafood, or more specific dietary restrictions. OBJECTIVE: To verify the serum levels of vitamin D in children and adolescents with eosinophilic esophagitis on a restricted food diet and to analyze their association with nutritional status, consumption of different food sources, exposure to the sun and skin color. METHODS: Case-control study conducted in the city of Campinas-SP, Brazil, in which included patients were aged 2 to 18 years old, and those diagnosed with eosinophilic esophagitis was referred to as the case group (n=15), meanwhile a control group (n=17) was also formed. Epidemiological data, nutritional status, data on vitamin D intake (24-hour recall - performed only by EoE patients - and self-reported intake of vitamin D food sources: milk and dairy products, canned tuna and sardines, Bull’s liver, chicken eggs - applied in both groups), and daily time of sun exposure (≥30 min or ≤30 min) were recorded. The samples were collected for serum levels of 25-hydroxy-vitamin D, where sufficiency levels >30 ng/mL were considered, insufficiency 21 to 30 ng/mL, deficiency <20 ng/mL. RESULTS: There was a higher frequency of vitamin D insufficiency/ deficiency in the Eosinophilic Esophagitis group (P=0.035), even with longer sun exposure (P= 0.035). Skin color was not associated with lower levels of vitamin D in both groups studied. No difference was found in nutritional status between the groups. CONCLUSION: The present study demonstrated a higher frequency of inadequate/ deficient levels of vitamin D in children and adolescents with EoE on a restricted diet. When necessary, serum levels should be investigated and correct exposure to the sun should be encouraged, with special attention to the recommended guidelines, time spent in the sun and the appropriate clothing for correct absorption. Since exposure for more than 30 minutes in the sun does not appear to have provided a protective effect in the EoE group, even in a region with high levels of solar radiation. There was a significant difference only in the consumption of cow’s milk between the case and control groups, demonstrating the low adherence to the restriction diet by the case group. No association was found between serum 25 hydroxyvitamin D levels and nutritional status. Moreover, no association regarding the adequate or inadequate status of 25 hydroxyvitamin D and the consumption vitamin D-rich foods was identified. Multicentered studies with a larger number of cases should be performed to assess serum 25 hydroxyvitamin D levels and associated factors in pediatric patients with EoE.

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“…In our own patients, we found fibrosing inflammation only in a fraction of mucosal biopsies but that does not rule out fibrosis of deeper layers. Unfortunately, systematic assessment of these layers would have required deep transmucosal biopsies, which are hazardous and ethically questionable and, therefore, not routinely obtained [41]. We can on only speculate that circular fibrosis may contribute to ring formation and that these rings form at the site of maximum chronic inflammation.…”

Section: Histologymentioning

confidence: 99%

Clinical and endoscopic characteristics of diffuse esophageal intramural pseudo-diverticulosis

Hentschel

Lüth²

2020

Esophagus

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Introduction With 250 published cases worldwide, diffuse esophageal intramural pseudo-diverticulosis (DEIPD) is a poorly understood disease. The aim of this study was to determine the prevalence of DEIPD in our own population, identify risk factors and clinical symptoms, and characterize its typical endoscopic signs. Methods Retrospective search in our center's endoscopic and clinical database. Reviewing of all cases by re-examining stored endoscopic photographs. Reviewing of all cases regarding age, sex, risk factors, comorbidities, histology, and clinical symptoms.Results In a population of 150.000 we found 21 cases of DEIPD. Mean age was 56 ± 10 years. 86% were males, 76% had alcohol abuse, 57% had nicotine abuse, 38% had arteriosclerosis, 33% had COPD, 29% had malignancies, 24% had liver cirrhosis, 19% had impaired kidney function, and 15% had diabetes. Dysphagia was present in 62% and food bolus impaction (single or repeated) in 48%. Endoscopically, 95% of patients had multiple (> 4), small (0.25-2.5 mm) pseudodiverticle openings in the esophageal wall. In 62%, openings were aligned longitudinally. 86% showed edematous swelling of mucosa ("frosted glass look"), 76% showed a fine-grained pattern of small (10-100 µm) red dots ("faux uni pattern"), and 76% had a rigid, narrow lumen with multiple rings ("trachealization"). Conclusion With a prevalence of approximately 5 to 50/100.000, DEIPD may be more frequent than previously estimated. It preferably affects middle-aged male alcoholics. Key symptoms are chronic dysphagia and food impaction. Typical endoscopic findings are multiple, small, longitudinally aligned pseudodiverticle openings, frosted glass look, faux uni pattern, and trachealization of the esophagus.

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Understanding fibrosis in eosinophilic esophagitis: Are we there yet?

Cited by 21 publications

References 115 publications

Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype

Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype

Case-Control Study on Vitamin D Status in Children and Adolescents With Eosinophilic Esophagitis

Clinical and endoscopic characteristics of diffuse esophageal intramural pseudo-diverticulosis

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