Intraepithelial Lymphocyte Infiltration Research Articles

An Unusual Occurrence of Immunoproliferative Small Intestinal Disease in Elderly Patient Presenting with Chronic Diarrhea - A Rare Case Report

Immunoproliferative small intestinal disease (IPSID) is a rare type of indolent B-cell lymphoma. It is a variant of extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue. It is commonly seen in older children and young adults in the age group of 10-35 years. It is more common in males with Male: Female ratio of 2.4:1. Duodenum and jejunum are the commonly involved areas in small intestine. Colicky abdominal pain and intermittent diarrhoea are the common symptoms. Here by, we report a rare case in a 74-year-old male patient presented with chief complaints of abdominal pain, diarrhea and weight loss for 3 months. CT scan findings revealed thickening of small intestinal wall and mesenteric lymphadenopathy. Upper gastrointestinal endoscopy findings revealed nodular and ulcerative mucosa in the duodenum. Histopathological examination revealed flattening of mucosa with villous atrophy, destruction of crypts and intraepithelial lymphocytic infiltrate is noted. Interstitium shows dense and diffuse collection of lymphoplasmacytic infiltrate. Immunohistochemistry was done and it showed CD20 positive lymphoid cells. Based on the above findings the case was reported as Immunoproliferative small intestinal disease. Clinicians should suspect IPSID in cases presenting with chronic diarrhea and abdominal pain refractory to treatment. Immunoproliferative small intestinal disease has indolent clinical course and it can be cured with antibiotics in early stages. Late stages have high mortality rate and has poor prognosis. Keywords: IPSID, Alphachain disease, B cell lymphoma, duodenum, villous atrophy, lymphoplasmacytic infiltrate

Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial.

Treatment of functional digestive disorders is not always effective. Therefore, a search for new application points for potential drugs is perspective. Our aim is to evaluate the effect of rebamipide on symptom severity, intestinal barrier status, and intestinal microbiota composition and function in patients with diarrheal variant of irritable bowel syndrome overlapping with functional dyspepsia (D-IBSoFD). Sixty patients were randomized to receive trimebutine (TRI group), trimebutine + rebamipide (T + R group), or rebamipide (REB group) for 2 months. At the beginning and end of the study, patients were assessed for general health (SF-36), severity of digestive symptoms (Gastrointestinal Symptom Rating and 7 × 7 scales), state of the intestinal barrier, and composition (16S rRNA gene sequencing) and function (short-chain fatty acid fecal content) of the gut microbiota. The severity of most digestive symptoms was reduced in the REB and T + R groups to levels similar to that observed in the TRI group. The duodenal and sigmoidal lymphocytic and sigmoidal eosinophilic infiltration was decreased only in the REB and T + R groups, not in the TRI group. Serum zonulin levels were significantly decreased only in the REB group. A decrease in intraepithelial lymphocytic infiltration in the duodenum correlated with a decrease in the severity of rumbling and flatulence, while a decrease in infiltration within the sigmoid colon correlated with improved stool consistency and decreased severity of the sensation of incomplete bowel emptying. In conclusion, rebamipide improves the intestinal barrier condition and symptoms in D-IBSoFD. The rebamipide effects are not inferior to those of trimebutine.

Prognostic value of increased intraepithelial lymphocytes and lymphocytic clonality in dogs with chronic enteropathy or small-cell lymphoma

The clinical significance of severe infiltration of small intraepithelial lymphocytes (IEL) and the results of polymerase chain reaction for antigen receptor rearrangement (PARR) in dogs with chronic enteropathy (CE) and small-cell lymphoma (SCL) are controversial. This cohort study aimed to evaluate the prognostic significance of the IEL and PARR results in dogs with CE or SCL. Although definitive diagnostic histopathological criteria for SCL in dogs have yet to be established, dogs with the histopathological findings of severe IEL infiltration were diagnosed with SCL in this study. One hundred and nineteen dogs were recruited, with 23 dogs classified as having SCL and 96 dogs as having CE. The positive rate of PARR was 59.6 % (71/119) in the duodenum and 57.7 % (64/111) in the ileum. Subsequently, three dogs with SCL and four dogs with CE developed large-cell lymphoma (LCL). The median overall survival (OS) of dogs with SCL was 700 days (range, 6–1410 days), and that of dogs with CE was not reached. In the log-rank test, shorter OS was observed in cases with histopathological SCL (P = 0.035), clonal TCRγ rearrangement in the duodenum (P = 0.012), and clonal IgH rearrangement in the ileum (P < 0.0001). The Cox proportional hazards model adjusted for sex and age showed that histopathological SCL (hazard ratio [HR] 1.74; 95 % confidence interval [CI], 0.83–3.65), duodenal clonal TCRγ rearrangement (HR, 1.80; 95 % CI, 0.86–3.75), and ileal clonal IgH rearrangement (HR, 2.28; 95 % CI, 0.92–5.70) could shorten overall survival, although their 95 % CIs included 1.0. These results indicate that severe IEL infiltration could be a useful histopathological feature for diagnosing SCL, and clonality-positive results could be a negative prognostic factor in dogs with CE. Furthermore, the development of LCL should be carefully monitored in dogs with CE and SCL..

Fecal Calprotectin in Self-Reported Milk Intolerance: Not Only Lactose Intolerance

The hypothesis is that inflammatory/allergic conditions should be considered in self-reported milk intolerance (SRMI) patients who test negative and/or are asymptomatic at Lactose Hydrogen Breath Test (LHBT). We analyzed fecal calprotectin (FCP) values in SRMI patients to investigate the frequency of a "positive" intestinal inflammation marker and its correlation with lactose tolerance/intolerance. Data from 329 SRMI patients were retrospectively analyzed; according to the positive/negative results (maldigester/digester) and the presence/absence of symptoms reported during LHBT (intolerant/tolerant), patients were divided into: 'lactose tolerants' (n. 104), 'maldigesters/intolerants' (n. 187), 'digesters/intolerants' (n. 38). FCP values were analyzed in all three subgroups. A percentage of SRMI patients complained of constipation (>15%), extraintestinal symptoms (>30% including anemia), multiple food hypersensitivity (7.6%) and had intraepithelial lymphocytic infiltration at duodenal biopsy (>50%). Over 50.0% showed FCP values above the normal limit. Lactose tolerants and maldigesters/intolerants had higher positivity frequencies (p < 0.0001, for both) and absolute values (p = 0.04, for maldigesters/intolerants) of FCP compared to digesters/intolerants. FCP was not useful to differentiate tolerant from intolerant subjects (AUC 0.58). Our data suggest the existence of an allergic/inflammatory pathogenetic mechanism in a subset of SRMI subjects. FCP results are in keeping with this hypothesis, even if they cannot differentiate lactose tolerant from intolerant patients.

MORPHOLOGICAL JUSTIFICATION OF IMMUNOREHABILITATION THERAPY OF CHRONIC NASOPHARYNGITIS ASSOCIATED WITH EBV

Adenotomy, the most widespread surgery in children, which does not solve the problem of symptoms in 19-26% patients. The main reasons are related diseases of nasopharynx, therefore, the indications for surgical intervention must be considered after evaluating the efficacy of conservative treatment. The relevant conservative treatment of CNP associated with EBV infection must include adequate immunorehabilitation effect on nasopharynx epitheliocytes, since the interaction of local immune response and cells infected with Epstein-Barr virus can lead to the control of virus infection.&#x0D; Objective of research: to establish the specific features of morphological changes in respiratory epithelium of pharyngeal tonsil in patients with chronic nasopharyngitis associated with EBV.&#x0D; Materials and methods. There was carried out the research of surgical material obtained as a result of endoscopic surgical intervention including the removal of hypertrophic part of pharyngeal tonsil in 15 patients diagnosed with chronic nasopharyngitis associated with EBV. The diagnosis was made on the ground of a typical clinical picture and determination of immunoglobulin M, G classes to Epstein-Barr virus in the blood.&#x0D; Results. It has been shown that intraepithelial lymphocytic and histiocytic infiltration can be determined morphologically and the edema of loose connective tissue, full blood vessels of the microcirculatory channel can be determined subepithelially which is the morphological sign of the chronic inflammation process.&#x0D; The identified structural reconstruction of epithelium reflects the development of virus-induced degenerative processes, namely, koilocytosis and spongiosis. The virus-induced changes in epithelium in the form of koilocytosis can be observed both in covering epithelia and in metaplastic epithelium, which demonstrates the persistence of viral infection in chronic inflammation.&#x0D; It has been found that on the background of chronic inflammation the cystic formations in the thickness of the lymphoid tissue are forming and the amphophilic masses of mucus can be visualized on the surface of epitheliocytes with hypersecretory changes, as well as similar mucous masses can be identified in the lumen of cysts of lymphoid tissue. The changes in epithelium in the form of koilocytosis can be seen in the epithelial crypts and cysts as well as indicating that the persistence of infection is viral.&#x0D; Conclusions:&#x0D; &#x0D; In CNP associated with EBV, the morphological changes of respiratory epithelium of nasopharynx are indications of both non-specific inflammatory processes (hyperplasia, metaplasia of epithelium, hypersecretory changes in cells, intraepithelial inflammatory cell infiltration), and specific for viral infections processes (koilocytosis, spongiosis, lymphocytes with wide cytoplasm).&#x0D; Structural changes are indications of the development of degenerative virus-induced processes (koilocytosis, spongiosis) combined with reactive changes in epithelial cells (hyperplasia, hypersecretion) that happen both in the surface epithelium and in the crypts with cyst formations.&#x0D; There can be seen phenomena of significant hypersecretory activities of epithelium including the accumulation of mucus on the surface of cells as well as in the lumen of crypts and cysts.&#x0D;

S3445 Microscopic Enteritis: A Rare Manifestation of T-cell Promyelocytic Leukemia

Introduction: An abnormal infiltration of intraepithelial lymphocytes in the intestinal mucosa is described as microscopic enteritis (ME). ME is a heterogeneous condition that can be found in, but not limited to, celiac disease, autoimmune disorders, food protein intolerance, parasitic infections, and NSAID use. Thus, an obvious cause of ME is difficult to elucidate and requires thorough work up. We report a case of a patient who was found to have ME thought to be secondary to infiltrative T-cell promyelocytic leukemia (T-PLL). Case Description/Methods: A 68-year-old male with a history of type II diabetes and hyperlipidemia presented with intermittent fever, abdominal pain, nausea, and emesis. He was found to have small bowel obstruction with severe enteritis of 3/4 of the small bowel (distal jejunum to the ileocecal valve). He had a small bowel resection with pathology revealing necrotizing lymphocytic enteritis. Bidirectional endoscopy revealed mild colonic, ileal and duodenal edema with biopsies revealing increased intraepithelial lymphocytes. He was empirically treated with intravenous methylprednisolone with resolution of fevers. He was discharged home with a follow up with gastroenterology for ME and with hematology for persistent leukocytosis. He continued to have recurrent fevers with persistent lymphocytic leukocytosis (14,200 WBC/microliter). Infectious (acid fast bacteria, fungi, cytomegalovirus, adenovirus, syphilis) and rheumatologic diagnostics were unrevealing. He underwent bone marrow biopsy and peripheral blood examination with immunostains, flow cytometry, and cytogenetic studies and was found to have clonal T-cell receptor gamma gene rearrangement concerning for T-PLL. He was treated with alemtuzumab; however developed worsening disease and disseminating opportunistic infections (cytomegalovirus and aspergillosis). He passed away shortly after his diagnosis. Discussion: ME is a challenging diagnosis as its etiology can be difficult to elucidate. Prompt, timely evaluation should be prioritized to improve outcomes. T-PLL is a rare leukemia due to abnormal growth of T-lymphocytes and typically presents with leukocytosis, weight loss, and infection; however, gastrointestinal symptoms may be a presenting symptom.

S3456 Olmesartan-Induced Enteritis: When Symptoms Do Not Improve With Drug Discontinuation

Introduction: Severe diarrhea is a well-known, but rare, complication of Olmesartan. The enteropathy caused by Olmesartan is histologically similar to Celiac disease, however celiac serologies are negative and it lacks a response to a gluten free diet. In most cases, symptoms resolve with the discontinuation of the medication. We present a case of Olmesartan induced enteropathy that only improved after the initiation of budesonide. Case Description/Methods: A 73-year-old female with a history of hypertension presented with complaints of nausea, vomiting and watery diarrhea. Initial workup with bloodwork, stool studies and imaging were all unremarkable. Recent outpatient colonoscopy was unremarkable. Review of her medications did not reveal any typical culprits of microscopic colitis. Given persistent nausea and vomiting, an upper endoscopy was pursued. Celiac serologic testing, including issue transglutaminase (tTg) IgA and IgG, anti-gliadin IgA and anti-endomysial IgA antibodies were all normal. Qualitative IgA levels were within normal limits. Upper endoscopy was performed with duodenal biopsies revealing moderate active chronic duodenitis with blunting of villous architecture and increased intraepithelial lymphocytic infiltrate, suspicious for celiac sprue. At this point, a closer review of her medications revealed a prescription for Olmesartan. Olmesartan was discontinued, however she continued to have significant diarrhea, up to 2.5L daily, for over a week after discontinuation. Given persistent diarrhea, nausea and vomiting, resulting in significant electrolyte abnormalities, the decision was made to initiate Budesonide. She experienced rapid improvement in symptoms after the initiation of Budesonide and only reported two loose stools per day on discharge. (Figure) Discussion: The initial workup for chronic diarrhea involves a thorough medication review. Physicians who prescribe Olmesartan should be aware of the enteropathy it can cause, as it is likely more common than expected. Other drugs such as azathioprine, colchicine, mycophenolate, methotrexate and neomycin have also been implicated in a similar enteropathy. Timely diagnosis can help decrease healthcare utilization and patient discomfort. In cases such as ours, the enteropathy can be severe enough to result in hospital admission. Immunosuppressant’s such as steroids or azathioprine have shown great efficacy in treatment of these refractory cases.Figure 1.: Histology of duodenal biopsy showing (A) Moderate active chronic duodenitis with blunting of villous architecture and (B) Increased intraepithelial lymphocytic infiltrate.

Increase of Deep Intraepithelial Lymphocytes in the Oxyntic Mucosa of Patients With Potential and Overt Autoimmune Gastritis.

Pathological correlates of potential autoimmune gastritis (AIG), defined by anti-parietal cell antibody (PCA) positivity in the absence of gastric atrophy, have never been described. We herein aimed to assess intraepithelial lymphocyte (IEL) infiltration in gastric corpus of AIG patients. From 2000 to 2021, among 53 potential AIG patients, we focused on nine (median age 61 years, IQR 53-82; four females) who subsequently developed overt AIG. IEL infiltration of the oxyntic mucosa was assessed before and after developing overt AIG by measuring deep and superficial CD3+ IEL. AIG patients with different degrees of corpus atrophy, healthy controls (HC), active H. pylori gastritis, celiac disease (CD), and Hashimoto’s thyroiditis patients were included as controls. Of note, deep, but not superficial, CD3+ IEL count was higher (p<0.001) in potential AIG compared to HC and H. pylori gastritis. Deep CD3+ IEL infiltration did not change before or after the evolution into atrophy (median 9.6, IQR 8.8-12.4, vs 11.3, IQR 9.4-12.9). No difference was found in deep CD3+ IEL infiltration among potential, mild, and severe AIG, and compared to Hashimoto’s thyroiditis or CD. A deep CD3+ IEL cut-off of >7/100 epithelial cells allowed discrimination of any AIG stage and severity (AUC=0.842). We conclude that an increased deep CD3+ IEL infiltration of the oxyntic mucosa could represent a marker of potential AIG. Prospective studies including a larger number of potential AIG patients are needed.

Impact of Activation of EGFL7 within Microenvironment of High Grade Ovarian Serous Carcinoma on Infiltration of CD4+ and CD8+ Lymphocytes.

Background: It has been demonstrated that Egfl7 promotes tumor cell escape from immunity by downregulating the activation of tumor blood vessels. Aim: to analyze mRNA expression of EGFL7 within the tumor microenvironment of high-grade ovarian serous carcinoma and its association with a number of intraepithelial CD4+/CD8+ lymphocytes and ICAM-1 expression. Methods: qPCR analysis of EGFL7 mRNA in cancer cells and adjacent stromal endothelium microdissected from formalin-fixed paraffin-embedded tumors of 59 high-grade ovarian serous carcinoma patients, was performed. Infiltration of intraepithelial lymphocytes (CD4+/CD8+) and expression of ICAM-1 were evaluated by immunohistochemistry and compared between tumors with different statuses of EGFL7 expression. Results: EGFL7 was expressed in cancer cells (9/59, 15.25%), endothelium (8/59, 13.56%), or both cancer cells and adjacent endothelium (4/59, 6.78%). ICAM-1 was expressed on cancer cells (47/59, 79.66%), stromal endothelium (46/59, 77.97%), or both epithelium and endothelium (40 of 59, 67.8%). EGFL7-positivity of cancer cells and endothelium was associated with lower intraepithelial inflow of CD4+ (p = 0.022 and p = 0.029, respectively) and CD8+ lymphocytes (p = 0.004 and p = 0.031, respectively) but impact neither epithelial nor endothelial ICAM-1 expression (p = 0.098 and p = 0.119, respectively). The patients’ median follow-up was 23.83 months (range 1.07–78.07). Lack of prognostic significance of EGFL7-status and ICAM-1 expression was notified. Conclusion: EGFL7 is activated in the cancer cells as frequently as in the endothelium of human high-grade ovarian serous carcinoma. Activation of EGFL7 in cancer cells and/or endothelial cells could negatively impact diapedesis regardless of localization.

Microinflammation in the intestinal mucosa and symptoms of irritable bowel syndrome.

Potential etiological mechanisms of irritable bowel syndrome (IBS) have been reported, and emerging data suggest that immune activation is present in a major subset of IBS, especially in those with diarrhea. Intestinal mucosal mast cell and intraepithelial lymphocyte (IEL) infiltration and related factors were examined in patients with IBS. In addition, the correlations of symptoms and micro-inflammation were assessed. Intestinal biopsy specimens were obtained from patients with IBS and controls. Mast cells and IELs were stained with specific antibodies. The mRNA levels of cytokines and chemokines were assessed by quantitative reverse transcription polymerase chain reaction. Infiltration of mast cells in the duodenum was significantly higher in IBS patients than in control subjects. The infiltration of IELs was higher in the duodenum and terminal ileum of IBS patients compared to the control subjects. The numbers of duodenal and ileal IELs were significantly correlated. The number of IELs but not mast cells in the duodenum and terminal ileum was significantly correlated with diarrhea frequency in control subjects and IBS patients. The expression level of the chemotactic chemokine CXCL11 was significantly higher in the duodenum of IBS patients. Duodenal mast cells and IELs were increased in IBS patients. In addition, a positive correlation was found between the number of duodenal and ileal IELs and the frequency of diarrhea. Given that the present study was strictly observational, further studies are needed to clarify the pathophysiological functions associated with micro-inflammation in IBS.

A RARE CASE STUDY OF MEDULLARY CARCINOMA OF DESCENDING COLON REPORTED ON HISTOPATHOLOGY

Medullary carcinoma (MC) of the colon is a rare and unique histologic subtype of colorectal cancer whichcharacterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. This has now been incorporated as a separate entity in the World Health Organization (WHO) classification of colorectal cancers.It is commonly associated with deficient mismatch repair proteins and has a strong association with Lynch syndrome. Diagnosis is challenging as it does not have the usual immunohistochemical stains on pathology seen in colorectal adenocarcinoma. Here, we discuss an interesting case of MC of the colon that was metastatic on presentation and constituted a diagnostic challenge1.&#x0D; Keywords: medullary carcinoma, colorectal carcinomas (CRC), medullary carcinoma of colon,poorly differentiated adenocarcinoma, undifferentiated adenocarcinoma.

Supplementation of a lacto-fermented rapeseed-seaweed blend promotes gut microbial- and gut immune-modulation in weaner piglets

BackgroundThe direct use of medical zinc oxide in feed will be abandoned after 2022 in Europe, leaving an urgent need for substitutes to prevent post-weaning disorders.ResultsThis study investigated the effect of using rapeseed-seaweed blend (rapeseed meal added two brown macroalgae species Ascophylum nodosum and Saccharina latissima) fermented by lactobacilli (FRS) as feed ingredients in piglet weaning. From d 28 of life to d 85, the piglets were fed one of three different feeding regimens (n = 230 each) with inclusion of 0%, 2.5% and 5% FRS. In this period, no significant difference of piglet performance was found among the three groups. From a subset of piglets (n = 10 from each treatment), blood samples for hematology, biochemistry and immunoglobulin analysis, colon digesta for microbiome analysis, and jejunum and colon tissues for histopathological analyses were collected. The piglets fed with 2.5% FRS manifested alleviated intraepithelial and stromal lymphocytes infiltration in the gut, enhanced colon mucosa barrier relative to the 0% FRS group. The colon microbiota composition was determined using V3 and V1-V8 region 16S rRNA gene amplicon sequencing by Illumina NextSeq and Oxford Nanopore MinION, respectively. The two amplicon sequencing strategies showed high consistency between the detected bacteria. Both sequencing strategies indicated that inclusion of FRS reshaped the colon microbiome of weaned piglets with increased Shannon diversity. Prevotella stercorea was verified by both methods to be more abundant in the piglets supplied with FRS feed, and its abundance was positively correlated with colonic mucosa thickness but negatively correlated with blood concentrations of leucocytes and IgG.ConclusionsFRS supplementation relieved the gut lymphocyte infiltration of the weaned piglets, improved the colon mucosa barrier with altered microbiota composition. Increasing the dietary inclusion of FRS from 2.5% to 5% did not lead to further improvements.

Histopathologic interpersonal overview of generalized pustular cutaneous reaction to Hydroxychloroquine (HCQ): New challenging clinical manifestation

Background: Pathologic examination of Acute Generalized Exanthematous Pustulosis (AGEP) and Pustular Psoriasis (PP) are similar. We encountered many patients with PP or AGEP who cannot be distinguished clinically, pathologically and based on disease course from each so we designed a comprehensive interpersonal histopathologic overview of these patients' samples. Method: Histopathological data of 16 patients over 3.5 years were analyzed. Four pathologists separately reviewed specimens based on eighteen criteria (9 Epidermal and 9 Dermal). Severity score for each criterion was considered as to be (0 to 3+). We compared the final pathologic diagnosis with primary one. Results: Neutrophilic and lymphocytic infiltration in dermis were seen in all cases of AGEP while intraepithelial pustules. Subcorneal and intraepithelial pustules, spongiosis, neutrophilic exocytosis, neutrophilic and lymphocytic infiltration in dermis were observed in all cases of PP. The most severe neutrophilic inflammation; acanthosis and neutrophilic or lymphocytic infiltration were seen in PP. The authors of this study have been reported generalized pustular clinical presentations of patients have been taken HCQ, and in the recent pandemic it is also one of the concerns that many studies have been focused (....). Conclusion: When primary histopathologic report is AGEP/PP overlap, clinical judgment is the best way to manage and it is more probable that the final diagnosis being PP. When only AGEP or PP is histopathologic diagnostic report, it is usually enough to make final diagnosis and appropriate management. Key words: hydroxychloroquine, HCQ, generalized pustular cutaneous eruption, Pustular Psoriasis (PP), Acute Generalized Exanthematous Pustulosism, AGEP, Histopathological overview, pathology, review

Loss of Cxcr4 in Endometriosis Reduces Proliferation and Lesion Number while Increasing Intraepithelial Lymphocyte Infiltration

Hyperactivation of the CXCL12-CXCR4 axis occurs in endometriosis; the therapeutic potential of treatments aimed at global inhibition of the axis was recently reported. Because CXCR4 is predominantly expressed on epithelial cells in the uterus, this study explored the effects of targeted disruption of CXCR4 in endometriosis lesions. Uteri derived from adult female mice homozygous for a floxed allele of CXCR4 and co-expressing Cre recombinase under control of progesterone receptor promoter were sutured onto the peritoneum of cycling host mice expressing the green fluorescent protein. Four weeks after endometriosis induction, significantly lower number of lesions developed in Cxcr4-conditional knockout lesions relative to those in controls (37.5% vs. 68.8%, respectively). In lesions that developed in Cxcr4-knockout, reduced epithelial proliferation was associated with a lower ratio of epithelial to total lesion area compared with controls. Furthermore, while CD3+ lymphocytes were largely excluded from the epithelial compartment in control lesions, in Cxcr4-knockout lesions, CD3+ lymphocytes infiltrated the Cxcr4-deficient epithelium in the diestrus and proestrus stages. Current data demonstrate that local CXCR4 expression is necessary for proliferation of the epithelial compartment of endometriosis lesions, that its downregulation compromises lesion numbers, and suggest a role for epithelial CXCR4 in lesion immune evasion.

A141 SPONTANEOUS ESOPHAGEAL PERFORATION: AN UNREPORTED COMPLICATION OF LYMPHOCYTIC ESOPHAGITIS

Abstract Background Lymphocytic esophagitis is a new and rare clinicopathological entity. It is a histological pattern characterized by lymphocytic infiltrate without granulocytes. Its etiology and clinical significance remains unclear. The clinical manifestations are typically mild, with reflux and dysphagia the most commonly reported symptoms. Aims We describe a case report of spontaneous esophageal perforation associated with lymphocytic esophagitis. Methods Case report Results A previously well 31-year-old male presented to the emergency department with acute food impaction. His antecedent symptoms were acute chest discomfort and continuous odynophagia following his most recent meal, with persistent globus sensation. The patient had no reported history of allergies, atopy, rhinitis, or asthma. A previous history of non-progressive dysphagia was noted after resuscitation. Emergent endoscopy revealed no food bolus, but a deep 6 cm mucosal tear in the upper-mid esophagus extending 24 to 30 cm from the incisors. Chest computed tomography observed small volume pneumoperitoneum consistent with esophageal perforation. The patient’s recovery was uneventful; he was managed conservatively with broad-spectrum antibiotics, proton pump inhibitor therapy, and a soft-textured diet. Endoscopy was repeated 48 hours later and revealed considerable healing with only a residual 3-4cm linear laceration. Histology of biopsies taken from the mid and distal esophagus demonstrated marked infiltration of intraepithelial lymphocytes. There were no eosinophils or neutrophils identified, consistent with a diagnosis of lymphocytic esophagitis. Autoimmune indices including anti-nuclear antibodies and immunoglobulins were normal, ruling out a contributory autoimmune or connective tissue process. The patient was maintained on a proton pump inhibitor (pantoprazole 40 mg once daily) following discharge. Nearly six months following his presentation, the patient had a recurrence of symptoms prompting representation to the emergency department. He described acute onset chest discomfort while eating turkey. Computed tomography of the chest redemonstrated circumferential intramural gas in the distal esophagus and proximal stomach. Conclusions Esophageal perforation is a potentially life-threatening manifestation of what had been considered and described as a relatively benign condition. From isolated dysphagia to transmural perforation, this case significantly expands our current understanding of the clinical spectrum of lymphocytic esophagitis. Funding Agencies None

First morphological-level insights into the efficiency of green tea catechins and grape seed procyanidins on a transgenic mouse model of celiac disease enteropathy.

Alternative or complementary treatments to a gluten-free diet are urgently needed for Celiac Disease. By exploiting the health-promoting properties of polyphenols on a transgenic mouse model of Celiac Disease enteropathy, this study provides the first in vivo evidence regarding the ability of 1 mg day-1 doses of green tea catechins and grape seed procyanidins to ameliorate some of the most characteristic histological changes of gliadin-treated DQ8 mice, including villus flattening, crypt hyperplasia, and infiltration of intraepithelial lymphocytes. Mechanistically, polyphenols were found to increase the intestinal nucleophilic tone of DQ8 mice by orchestrating an adaptive antioxidant response characterized by enhanced GSR enzyme activity and GSH content. Taken together, this work constitutes a highly relevant breakthrough as it provides the fundamental basis concerning the significance of natural polyphenols to be used in, for instance, the development of innovative functional foods aimed at CD individuals.

Human Leukocyte Antigen (HLA) Haplotype Does Not Influence the Inflammatory Pattern of Duodenal Lymphocytosis Linked to Irritable Bowel Syndrome.

Background and objectives: Duodenal lymphocytosis (DL) is a condition characterized by enhanced infiltration of intraepithelial lymphocytes (IELs) in the duodenal mucosa, and it can be linked to both gluten- and non-gluten-related diseases, such as irritable bowel syndrome (IBS). Materials and methods: We retrospectively selected patients with DL linked to IBS. Formalin-embedded biopsy samples of the duodenum were collected. CD3 lymphocyte immunohistochemistry was used for IELs. The real-time polymerase chain reaction was used to quantify the amount of mRNA coding for tissue transglutaminase 2 (tTG2), interferon-gamma (IFNγ), toll-like receptor 2 (TLR2), and myeloid differentiation primary response 88 (MyD88). All subjects underwent DQ2-8 haplotype analysis. Controls were represented by subjects with IBS without DL. Results: Thirty-two patients with IBS-DL were retrospectively recruited. Fourteen subjects (43.8%) had a DQ2-8 haplotype. DQ2-8 positive subjects had similar levels compared to negative ones for tTG2, IFNγ, TLR2, and MyD88. Cigarette smoke did not influence molecular expression in our study. Smokers had a statistically higher IELs count than non-smokers (54.2 ± 7.7 vs. 36.0 ± 8.8, p < 0.001). A significant, direct correlation between IELs and duodenal expression of IFNγ was found (r = 0.36, p = 0.04). Conclusions: IBS with DL showed higher expression of inflammatory markers than controls, but DQ2-8 haplotype did not seem to affect their expression. Smoking might increase IELs infiltration.

ORAL MANIFESTATIONS OF CELIAC DISEASES: CASE REPORT

Celiac disease is an autoimmune disorder that affects individuals who are genetically susceptible and intolerable to gluten. It is characterized by symptoms such as chronic diarrhea, vomiting, abdominal distension, and bloating. Oral manifestations are also present in celiac patients, with defects in dental enamel and recurrent aphthous stomatitis. In the present study, we report a case of a 59-year-old male celiac patient that presented ulcerative oral lesions after dental treatment and inadequate diet. On physical examination, there were shallow ulcers, with a necrotic fundus in buccal mucosa and tongue border. The diagnosis of celiac disease was performed by intestinal biopsy that revealed serration and atrophy of the duodenal villi and intraepithelial lymphocytic infiltrate. Laboratory tests were requested to rule out vitamin deficiency. Topical treatment with chamomile (Ad-muc), photobiomodulation therapy and diet adequacy were decisive for ulcerated lesions healing. Patient remains in clinical follow-up.

Vedolizumab for the Induction of Remission in Treatment-refractory Microscopic Colitis in a Pediatric Patient.

Vedolizumab for the Induction of Remission in Treatment-refractory Microscopic Colitis in a Pediatric Patient.

Pentadecapeptide BPC 157 Therapy in Rats with Cysteamine Induced‐Terminal Ileitis

AimWe introduce pentadecapeptide BPC 157 therapy in rats with cysteamine induced‐terminal ileitis, 1 h, 1 month, 2 months. We counteracted gross hyperemia, edema, erosion, bleeding, and, microscopically, significant loss of villous architecture, loss and shortening of villae and severe lymphocytic infiltrate. BPC 157 counteracts various lesions in the whole GI‐tract and free radicals formation (Curr Pharm Des 2018;24:1990–2001), and tested in ulcerative colitis trials and now in multiple sclerosis (Curr Pharm Des 2018;24:1990–2001). Previously, cysteamine, was known to induce gastric acid hypersecretion, as a prototype of duodenal lesion (Lancet 1979 Oct 27;2(8148):880–2). Subsequently, cysteamine induced duodenal lesions after gastrectomy, and applied as an enema, ulcerative colitis in rats. BPC 157 counteracts all of these lesions (Life Sci 1994;54(5):PL63‐8, Dig Dis Sci 1997 May;42(5):1029–37, J Physiol Paris 2001 Jan–Dec;95(1–6):283–8, J Physiol Paris 2001 Jan–Dec;95(1–6):261–70, Eur J Pharmacol 2003 Sep 5;477(1):73–80, J Physiol Pharmacol 2013 Oct;64(5):597–612)MethodsCysteamine (400 mg/kg, 1 ml/rat) was applied in female Albino Wistar rats, 200 g bw into the terminal ileum, 5 cm segment up to ileocecal valve, which was kept gently compressed for 1 min, and then released. Medication (/kg) (BPC 157 (10 μg, 10 ng), or saline (5 ml) (controls)) was applied as an abdominal bath immediately after the end of the cysteamine application procedure, and then if rats were not sacrificed at 1 h, continuously, perorally in drinking water (0.16 μg/ml, 0.16 ng/ml, 12 ml/rat/day) till the end of 1 or 2 months.ResultsFor gross assessment, the hyperemia, edema, erosion and bleeding scores (0–3) were summarized (giving the 0–12 scoring, and assessed as Min/Med/Max). Control rats exhibit the following scoring: 11/11/12 at 1 h, 8/8/9 at 1 month, and 8/8/9 at 2 months. Contrarily, all BPC 157 rats present markedly lower scoring (3/3/4 at 1 h, 0/1/1 at 1 month, and 0/1/1 at 2 months, 10 μg regimen Min/Med/Max, P&lt;0.05, vs. control, at least, while 10 ng regimen shows similar beneficial effect). Microscopically, much like in patients, cysteamine induced terminal ileitis goes with submucosal congestion, significant loss of villous architecture, loss and shortening of villae, lamina propria infiltrated with mild to severe lymphocytic infiltrate much like intraepithelial lymphocytes infiltration and some epithelial elevation from lamina propria. Contrarily, better preservation of mucosal architecture appears in pentadecapeptide BPC 157 treated rats. There is only mild villous edema with capillary congestion and mild lymphocytic infiltrate. No epithelial elevation from lamina propria is found (Fig. 1, Fig. 2, left control, right BPC 157).ConclusionFor further therapy, beneficial effect of the BPC 157 counteracts cysteamine‐terminal ileitis.Support or Funding InformationThis work was supported by the University of Zagreb, Zagreb, Croatia (Grant BM 099).Cysteamine Terminal Ileitis, 1 hourFigure 1