Intraepithelial Lymphocytosis Research Articles

Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital.

Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. To improve overall understanding of this disease's diagnosis and prognosis. We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin's lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.

Clinicopathologic Analysis of Malabsorption Syndrome in a Tertiary Care Center in South India

ABSTRACT Background: Malabsorption syndrome is an umbrella term for manifestations consisting of diarrhea, steatorrhea, malnutrition, unexplained weight loss, persistent or recurrent abdominal pain, and anemia. Celiac disease and Tropical sprue remain the two important causes among many more. Materials and Methods: The objectives of this study were to assess the spectrum of histological features of malabsorption at a tertiary care center and to correlate the clinical, endoscopic, and histological features between the various etiologies. Biopsy specimens of 547 subjects formed the sample for this institutional-based, retrospective research. All subjects who had a clinical diagnosis of malabsorption and underwent subsequent endoscopic evaluation along with biopsy were considered. The hematoxylin and eosin-stained sections were analyzed for villous architecture and intraepithelial lymphocytes (IELs). The histopathological findings were further correlated with the endoscopic findings. Data thus obtained were statistically analyzed using Microsoft Excel for Windows (2010). Results: The mean age of the subjects was 46.65 ± 17.31 years and with 330 males (60.33%) and 217 female (39.63%) subjects. Chronic diarrhea was the major presenting symptom in 95% of the subjects (n = 520). Normal villous architecture was noted in 68.19%, while the remaining cases showed varying degrees of atrophy ranging from mild in 27.61% (n = 151) to moderate in 2.56% (n = 14) to severe in 1.65% (n = 9). IELs were noted in 70.78% of cases. Conclusion: Histopathological findings, when analyzed, showed intraepithelial lymphocytosis as the major diagnosis in 34.19% of cases (n = 187), followed by tropical sprue in 19.56% (n = 107) cases. The pathology was nonspecific in about 13.89% (n = 76).

Diagnosis and Pharmacological Management of Microscopic Colitis in Geriatric Care.

Microscopic colitis, a diagnosis under the umbrella term of inflammatory bowel disease, is a prevalent cause of watery diarrhea, often with symptoms of urgency and bloating, typically observed in older adults aged ≥60years. Its incidence has been reported to exceed those of ulcerative colitis and Crohn's disease in some geographical areas. Although nonpathognomonic endoscopic abnormalities, including changes of the vascular mucosal pattern; mucosal erythema; edema; nodularity; or mucosal defects, e.g., "cat scratches" have been reported, a colonoscopy is typically macroscopically normal. As reliable biomarkers are unavailable, colonoscopy using random biopsies from various parts of the colon is compulsory. Based on the histological examination under a microscope, the disease is divided into collagenous (with a thickened subepithelial collagenous band) and lymphocytic (with intraepithelial lymphocytosis) colitis, although incomplete forms exist. In routine clinical settings, the disease has a high risk of being misdiagnosed as irritable bowel syndrome or even overlooked. Therefore, healthcare providers should be familiar with clinical features and rational management strategies. A 6-8-week oral budesonide treatment course (9 mg/day) is considered the first-line therapy, but patients often experience relapse when discontinued, or might become intolerant, dependent, or even fail to respond. Consequently, other therapeutic options (e.g., bismuth subsalicylate, biologics, loperamide, bile acid sequestrants, and thiopurines) recommended by available guidelines may be prescribed. Herein, clinically meaningful data is provided based on the latest evidence that may aid in reaching a diagnosis and establishing rational therapy in geriatric care to control symptoms and enhance the quality of life for those affected.

Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Uptake of Jejunal Lymphocytosis Due to Giardiasis Mimicking Lymphoma Recurrence.

Giardia lamblia is an intestinal protozoan with oral-fecal transmission. Infection is predominantly located in the small intestine. Giardiasis causes intraepithelial lymphocytosis in the small intestine which causes false-positive fluorodeoxyglucose (FDG) uptake mimicking malignancy. We present here an interesting image of fluorine-18 FDG positron emission tomography/computed tomography showing jejunal uptake caused by giardiasis in a known case of lymphoma.

Pro-inflammatory cytokine expression and the STAT1/3 pathway in canine chronic enteropathy and intestinal T-cell lymphoma.

The accumulation of intraepithelial lymphocytes (IELs) is a histopathological feature of canine chronic enteropathy (CE), and IELs are considered the cells of origin of intestinal T-cell lymphoma (ITCL). However, the pathogenic mechanism of IEL activation in CE remains unclear. This study hypothesized that the expression of proinflammatory cytokines, associated with cytotoxic T/NK-cell activation, is upregulated in CE and ITCL, and examined the expression of IFN-γ, IL-2, IL-12p35, IL-12p40, IL-15, and IL-21 and the downstream signal transducers and activators of transcription (STAT) pathway in the duodenal mucosa of dogs without lesions (n = 11; NC), with IEL-CE (n = 19; CE without intraepithelial lymphocytosis), IEL+CE (n = 29; CE with intraepithelial lymphocytosis), and with ITCL (n = 60). Quantitative polymerase chain reaction (PCR) revealed that IFN-γ and IL-21 were higher in IEL+CE than in IEL-CE or NC. Western blot revealed upregulation of STAT1 and STAT3 in IEL+CE. Double-labeling immunohistochemistry revealed a positive correlation between the Ki67 index of CD3+ T-cells and IFN-γ expression levels. Immunohistochemistry revealed a higher ratio of p-STAT1-positive villi in IEL+CE and ITCL than IEL-CE and NC, which positively correlated with IFN-γ expression levels. Among the 60 ITCL cases, neoplastic lymphocytes were immunopositive for p-STAT1 in 28 cases and p-STAT3 in 29 cases. These results suggest that IFN-γ and IL-21 contribute to the pathogenesis of IEL+CE, and IFN-γ may be involved in T-cell activation and mucosal injury in CE. STAT1 and STAT3 activation in ITCL cells suggests a role for the upregulation of the STAT pathway in the pathogenesis of ITCL.

Case Report: Tropical sprue, diagnostic challenges of an old but unrecognized disease

Tropical sprue (TS) is a post-infective disease of the small bowel characterized by a malabsorption syndrome affecting tropics inhabitants and visitors. Diagnosis of TS remain challenging since it can be confused with common diarrheal diseases, especially in non-endemic areas. We report a Tunisian case of latent TS. A 58-year-old male with a history of chronic watery diarrhea, was admitted to the intensive care unit for confusion which was related to dehydration[J1] . Despite the neurological improvement after hydro-electrolytic resuscitation and acid-base disorders correction, the patient continued to have three to five loose stools daily. A nutritional assessment showed a malabsorption syndrome: iron, Vitamin B12 and folate deficiencies; normochromic normocytic anemia and hypoalbuminemia. Gastrointestinal endoscopy showed duodenal villous atrophy and biopsy confirmed subtotal villous atrophy with increased intraepithelial lymphocytosis and a thickened hyalinized [J2] sub-epithelial basal lamina. Celiac disease was evoked, however the patient did not improve on a gluten-free diet and the celiac serology was negative. On re-interviewing, we discovered that the patient had spent two months in India three years prior. Given the travel history, clinico-biological and histological data TS was highly considered and a good response to a five-month antibiotic course combined to nutritional supplementation supported this diagnosis. Clinico-biological, endoscopic and histological findings were overlapping between TS and other malabsorption diseases, explaining diagnosis difficulties. TS should be systematically discussed in tropics visitors presenting with chronic diarrhea. Improvement after micronutrient and vitamin deficiencies replacement combined to a prolonged antibiotic course supports the diagnosis of TS. [J

Successful Management of Malakoplakia in a Patient Combined Variable Immunodeficiency

Malakoplakia is a rare tumor-like inflammatory condition often affecting the urogenital and gastrointestinal tract of immunocompromised individuals. Malakoplakia is posited to be secondary to impaired macrophages with an inability to phagocyte bacteria completely. The resulting inflammation may trigger CVID-associated enteropathy. Treatment is challenging, often requiring prolonged antibiotics, and reducing immunosuppression.Our patient is a 45-year-old female with heterozygous TNFRSF13B c.310T>C common variable immunodeficiency (CVID). She has granulomatous lymphocytic interstitial lung disease (GILD), CVID-enteropathy in remission, immune thrombocytopenia requiring splenectomy, and chronic norovirus shedding. She was on mycophenolate mofetil, immunoglobulin replacement, and trimethoprim/sulfamethoxazole prophylaxis.She presented with two months history of progressive diarrhea, weight loss, and abdominal pain. Stool calprotectin was 131 uG/G. GI pathogen panel was only positive for Norovirus. Endoscopy showed intraepithelial lymphocytosis and villus blunting (seen on previous scopes). Colonoscopy demonstrated rectal polyps, submucosal atypical lymphoid proliferation, abundant histiocytes with Michaelis-Gutman bodies, positive calcium deposits with Von-Kossa stain, consistent with malakoplakia, with no evidence of malignancy.We started ciprofloxacin 500 milligrams twice daily, Vitamin C, oral immunoglobulin, and probiotics. We continued mycophenolate mofetil to avoid GLILD flares. Diarrhea resolved several weeks after starting ciprofloxacin. However, attempts to wean ciprofloxacin led to recurrence of diarrhea. She completed nine months of ciprofloxacin, after which calprotectin normalized, and repeat scopes showed no evidence of malakoplakia; diarrhea did not recur after stopping ciprofloxacin.We highlight a rare CVID GI complication that successfully responded to a prolonged course of antibiotics. Balancing immune suppression with worsening malakoplakia requires vigilant diagnostic and therapeutic decision-making. Malignancy surveillance will be warranted.

A227 CTLA-4 DEFICIENCY PRESENTING AS CROHN DISEASE IN A TEENAGE BOY WITH MULTI-SYSTEM INVOLVEMENT : A CASE REPORT

Abstract Background Cytotoxic-T-lymphocyte-antigen-4 is a negative immune regulator. CTLA-4 deficiency can cause a complex immune dysregulation syndrome that may present as inflammatory bowel disease. Purpose Case Description: A 14-year-old male presented with several years of abdominal pain, diarrhea, short stature and poor weight gain. Endocolonoscopy diagnosed Crohn disease, with patchy chronic colitis, an ileal granuloma and active duodenitis with intraepithelial lymphocytosis and villous blunting. MRE showed multiple abnormal small bowel loops. Past history included appendicitis, immune thrombocytopenic purpura and an episode each of Aeromonas, Y enterocolitica and C difficile colitis. Family history was negative for consanguinity, autoimmune conditions or immune defects. The patient received sulfasalazine, exclusive enteral nutrition and then budesonide MMX with limited response. His pre-biologic workup identified bilateral pulmonary nodules, which were negative for infection or malignancy on further investigation. He began Adalimumab, and after 2 months had nearly normalized his fecal calprotectin to 90 ug/g. His history, together with chronic neutropenia and hypogammaglobulinemia (IgG 3.3 g/L, IgA 0.29g/L) led to a comprehensive immune and cytopenia panel, which revealed heterozygous pathogenic variants in the CTLA4 gene c.424G>C, p.(Gly142Arg), associated with CTLA-4 deficiency related immunodeficiency. Parental testing was negative, indicating a de novo mutation. The patient was subsequently admitted to hospital with severe headache and transient aphasia. Brain MRI found hyperintense foci concerning for CTLA-4 deficiency-associated CNS inflammation. He had papilledema and lumbar puncture found increased ICP. During this admission he developed Salmonella sepsis. Repeat chest CT found extensive worsening multifocal parenchymal lesions. Extensive investigations to exclude malignancy or infection were negative, and the lung findings were felt to be Granulomatous and Lymphocytic Interstitial Lung Disease. He had elevated soluble IL-2 receptor level (2884 U/ml) and elevated CD4+PD1+ T cells in peripheral blood. Adalimumab was stopped, and he received IVIg, then Diamox with resolution of headache, followed by pulse methylprednisolone. He has since been maintained on Abatacept (a soluble CTLA-4 analog that inhibits T-cell activation). Follow up soluble IL2 receptor level was normal. PJP prophylaxis was started, as well as prophylactic dosing of IVIg and regular screening for EBV and CMV. Method - Result(s) - Conclusion(s) Discussion: Our patient had CTLA-4 deficiency and immune dysregulation affecting multiple organs (CNS, lung, and intestinal inflammation, autoimmune neutropenia and previous ITP). Abatacept is the preferred steroid-sparing treatment of enteropathy in CTLA-4 deficiency. Soluble IL2 receptor level is an indicator of T cell activation used for treatment monitoring. This case illustrates the importance of considering immune defects even in older children presenting with apparent IBD. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared INTESTINAL DISORDERS

A235 “WHAT’S SPRUE WITH YOU?”: OLMESARTAN-INDUCED ENTEROPATHY AS AN UNCOMMON MIMICKER OF CELIAC DISEASE

Abstract Background Olmesartan-induced enteropathy is an uncommon mimicker of celiac disease. Symptoms include diarrhea and weight loss and pathology shows villous atrophy, intraepithelial lymphocytes, and subepithelial collagen deposition. In contrast to celiac disease, tissue transglutaminase (TTG) is not elevated and gluten avoidance does not induce clinical or histologic improvement. Both clinical and histologic findings are reversible with cessation of pharmacologic therapy. Purpose To raise clinician awareness of an uncommon but reversible cause of enteropathy. Method A 67-year old man presented with 3 months of progressive diarrhea and 35lb weight loss on a background of hypertension, dyslipidemia, and type 2 diabetes. His medications included olmesartan, amlodipine, metformin, aspirin, and atorvastatin, none of which were new. Infectious stool studies, serum and fecal inflammatory markers, imaging, TTG and IgA were normal. Panendoscopy revealed duodenitis with biopsies consistent with active enteritis, intraepithelial lymphocytosis and villous shortening suggestive of olmesartan-induced enteropathy given negative TTG. Olmesartan was discontinued. Result(s) His symptoms completely resolved over several weeks after discontinuation. Conclusion(s) Olmesartan is an uncommon but reversible mimicker of celiac disease. It was first described in 2012 in a case series of 22 patients, all of whom had negative celiac serology and demonstrated histologic and clinical improvement with cessation of olmesartan. Time from medication initiation to onset of symptoms ranged from 6 months to 7 years, with a mean of 3.1 years. While case reports exist of angiotensin-receptor blockers as causative agents, the most common is olmesartan, implicated in 94% of ARB-induced enteropathy cases in a recent systematic review. The exact mechanism of injury is unknown. The delay in onset of symptoms suggests a cell-mediated immunity phenomenon. An immune-mediated reaction is also supported by the high prevalence of HLA-DQ2/DQ8 haplotypes (71%) among affected individuals vs. 30-40% in the general population. Olmesartan may be implicated more strongly than other ARBs due to its higher affinity for AT1 receptors; theoretically leaving unsaturated AT2 receptors to bind angiotensin. AT2 receptors are known to induce cellular apoptosis, and unopposed cellular death could theoretically lead to villous atrophy. The overall risk of developing enteropathy on olmesartan is rare, but not well quantified. This is likely due to both underrecognition, and variability in study designs leading to inability to perform meta-analysis on currently available data. Data from a French cohort estimates a crude incidence rate of 5.6 per 100,000 person years for patients on olmesartan developing intestinal malabsorption requiring hospitalization. Despite its rarity, prescribers should be cognizant of this side effect which can evolve even after years of medical therapy. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

« …ites » lymphocytaires, de l’œsophage au côlon

Intra-epithelial lymphocytosis is an elementary lesion frequently observed in the gastrointestinal tract, which can be found from the esophagus to the colon. Many conditions of a varied nature (dysimmunitary diseases, drugs, infections…) are associated with intra-epithelial lymphocytosis, and the etiological diagnosis most often requires an anatomo-clinical correlation. The pathologist will have to identify histological lesions associated with intra-epithelial lymphocytosis allowing the diagnosis to be oriented in order to propose appropriate treatment. In this review, the main entities associated with digestive intra-epithelial lymphocytosis will be presented, detailing the key elements allowing their diagnosis.

Severity of coeliac disease and clinical management study when using a non-metabolised medication: a phase I pharmacokinetic study

ObjectiveThe non-metabolised antihistamine fexofenadine has oral absorption resulting from transporter activity. Uptake by enterocyte organic anion transporting polypeptides and efflux by an ATP-binding cassette transporter (P-glycoprotein) are primary determinants. Coeliac...

Vasculitis of the gallbladder: a case series of an unusual pattern of cholecystitis

Vasculitis isolated to the gallbladder is uncommon, with few cases reported in the literature. We present a series of nineteen cases of cholecystitis with associated vasculitis. The male to female ratio was 7:12 and average age 75.6 (range 49–97). Most resections were performed for the clinical or imaging impression of cholecystitis, with two removed at the time of a larger resection for malignancy elsewhere. The majority (18/19) of cases showed venous involvement (phlebitis), sparing arteries. Most of the vasculocentric infiltrates were lymphohistiocytic, with five cases showing granulomatous vasculitis. The background mucosal inflammatory pattern in just over half (11/19) of cases showed a lymphofollicular cholecystitis, with the remainder showing typical chronic cholecystitis (6/19) or active chronic cholecystitis (1/19). Two of the cases (2/19) showed striking intraepithelial lymphocytosis. Eight of the samples were acalculous. It is unclear why this pattern occurs, with no patients in this series having a known history of vasculitis, and no association with IgG4 or autoimmune disease identified. The pattern may represent an unusual response to local mucosal injury or to constituents/metabolites in bile. The clinical significance is uncertain. The purpose of this case series is to contribute to the sparse literature describing this striking but uncommon histological reaction pattern.

Intestinal Epithelial Digestive, Transport, and Barrier Protein Expression Is Increased in Environmental Enteric Dysfunction

Environmental enteric dysfunction (EED) is characterized by malabsorption and diarrhea that result in irreversible deficits in physical and intellectual growth. We sought to define the expression of transport and tight junction proteins by quantitative analysis of duodenal biopsies from patients with EED. Biopsies from Pakistani children with confirmed EED diagnoses were compared to those from age-matched North American healthy controls, patients with celiac disease, and patients with nonceliac disease with villous atrophy or intraepithelial lymphocytosis. Expression of brush border digestive and transport proteins and paracellular (tight junction) proteins was assessed by quantitative multiplex immunofluorescence microscopy. EED was characterized by partial villous atrophy and marked intraepithelial lymphocytosis. Epithelial proliferation and enteroendocrine, tuft, and Paneth cell numbers were unchanged, but there was significant goblet cell expansion in EED biopsies. Expression of proteins involved in nutrient and water absorption and that of the basolateral Cl− transport protein NKCC1 were also increased in EED. Finally, the barrier–forming tight junction protein claudin-4 (CLDN4) was significantly upregulated in EED, particularly within villous enterocytes. In contrast, expression of CFTR, CLDN2, CLDN15, JAM-A, occludin, ZO-1, and E-cadherin was unchanged. Upregulation of a barrier–forming tight junction protein and brush border and basolateral membrane proteins that support nutrient and water transport in EED is paradoxical, as their increased expression would be expected to be correlated with increased intestinal barrier function and enhanced absorption, respectively. These data suggest that EED activates adaptive intestinal epithelial responses to enhance nutrient absorption but that these changes are insufficient to restore health.

The Afflicted Assimilation-Coeliac Disease

Coeliac disease or gluten sensitive enteropathy is an immune mediated inflammatory disease of small intestine. The condition arises within genetically predisposed individuals and may be engendered due to sensitivity to prolamins as wheat (gliadin), barley (hordein), rye (secalin) and oats (avenin). Activated innate and adaptive immune response to prolamins characteristically induces inflammatory infiltration of lamina propria and mucosal epithelium by chronic inflammatory cells as lymphocytes in concurrence with villous atrophy, features which engender intestinal malabsorption. Intraepithelial lymphocytosis within small bowel appearing secondary to gluten ingestion is associated with partial or total atrophy of intestinal villi and hyperplasia of intestinal crypts along with chronic inflammatory exudate confined to lamina propria.

Automated analysis of small intestinal lamina propria to distinguish normal, Celiac Disease, and Non-Celiac Duodenitis biopsy images

Background and objectiveCeliac Disease (CD) is characterized by gluten intolerance in genetically predisposed individuals. High disease prevalence, absence of a cure, and low diagnosis rates make this disease a public health problem. The diagnosis of CD predominantly relies on recognizing characteristic mucosal alterations of the small intestine, such as villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. However, these changes are not entirely specific to CD and overlap with Non-Celiac Duodenitis (NCD) due to various etiologies. We investigated whether Artificial Intelligence (AI) models could assist in distinguishing normal, CD, and NCD (and unaffected individuals) based on the characteristics of small intestinal lamina propria (LP). MethodsOur method was developed using a dataset comprising high magnification biopsy images of the duodenal LP compartment of CD patients with different clinical stages of CD, those with NCD, and individuals lacking an intestinal inflammatory disorder (controls). A pre-processing step was used to standardize and enhance the acquired images. ResultsFor the normal controls versus CD use case, a Support Vector Machine (SVM) achieved an Accuracy (ACC) of 98.53%. For a second use case, we investigated the ability of the classification algorithm to differentiate between normal controls and NCD. In this use case, the SVM algorithm with linear kernel outperformed all the tested classifiers by achieving 98.55% ACC. ConclusionsTo the best of our knowledge, this is the first study that documents automated differentiation between normal, NCD, and CD biopsy images. These findings are a stepping stone toward automated biopsy image analysis that can significantly benefit patients and healthcare providers.

Case Report: Tropical sprue, diagnostic challenges of an old but unrecognized disease

Tropical sprue (TS) is a post-infective disease of the small bowel characterized by a malabsorption syndrome affecting tropics inhabitants and visitors. Diagnosis of TS remain challenging since it can be confused with common diarrheal diseases, especially in non-endemic areas. We report a Tunisian case of latent TS. A 58-year-old male with a history of chronic watery diarrhea, was admitted to the intensive care unit for confusion which was related to severe metabolic acidosis. Despite the neurological improvement after hydro-electrolytic resuscitation and acid-base disorders correction, the patient continued to have three to five loose stools daily. A nutritional assessment showed a malabsorption syndrome: iron, Vitamin B12 and folate deficiencies; normochromic normocytic anemia and hypoalbuminemia. Gastrointestinal endoscopy showed duodenal villous atrophy and biopsy confirmed subtotal villous atrophy with increased intraepithelial lymphocytosis and a thickened hyalonalized sub-epithelial basal lamina. Celiac disease was evoked, however the patient did not improve on a gluten-free diet and the celiac serology was negative. On re-interviewing, we discovered that the patient had spent two months in India three years prior. Given the travel history, clinico-biological and histological data TS was highly considered and a good response to a five-month antibiotic course combined to nutritional supplementation supported this diagnosis. Clinico-biological, endoscopic and histological findings were overlapping between TS and other malabsorption diseases, explaining diagnosis difficulties. TS should be systematically discussed in tropics visitors presenting with chronic diarrhea. Improvement after micronutrient and vitamin deficiencies replacement combined to a prolonged antibiotic course supports the diagnosis of TS.

S2001 Chronic Norovirus Infection in a Double Solid Organ Transplant Patient

Introduction: Infectious diarrhea is a common complication in the postoperative course of a solid organ transplant (SOT) recipient. While self-limiting in immunocompetent patients, transplant patients on long-term immunosuppression can have severe, prolonged disease with significant morbidity. We present a case of chronic diarrhea due to recurrent norovirus infection in a double SOT patient to encourage early recognition. Case Description/Methods: A 61-year-old male presented with 35-pound weight loss despite a good appetite and large-volume watery diarrhea intermittently for 2 years. He had a liver-kidney transplant 14 years prior secondary to cryptogenic cirrhosis and renal cell carcinoma. Immunosuppression consisted of prednisone, tacrolimus, and mycophenolate mofetil (MMF). Stool PCR was positive for norovirus and negative for other viruses, bacteria, and parasites. His MMF dose was reduced with no benefit. He was discharged with supportive care with initial improvement in the diarrhea but returned to the hospital 4 other times with worsening diarrhea and weight loss. Infectious workup was persistently positive for norovirus. Bi-directional endoscopy with biopsies revealed colonic mucosa with rare epithelial apoptosis, chronic duodenitis, and increased intraepithelial lymphocytosis in the duodenum and ileum consistent with chronic norovirus (Figure). The full diagnostic workup is detailed in Table 1. He was managed conservatively during each hospitalization with fluids and antimotility agents and recently discharged home with plans to start nitazoxanide outpatient. Discussion: Norovirus infection among SOT patients can lead to severe and symptomatic chronic infection. Patients can develop dehydration, transplant rejection, and malnutrition making them higher risk for hospitalizations and death. It is unclear why some immunocompromised patients recover spontaneously while others demonstrate a protracted course but supportive care is the mainstay of therapy. Limited case series have shown nitazoxanide to be effective in treating SOT patients with chronic norovirus infection. However, nitazoxanide needs to be continued until stool RNA studies become negative. This case highlights the importance of considering chronic norovirus when a SOT patient presents with chronic diarrhea and weight loss. Early initiation of supportive care and nutrition consultation are imperative in reducing morbidity in these patients. Nitazoxanide can be effective in patients that are refractory to supportive therapy.Figure 1.: Duodenal biopsy (A): Focal intraepithelial lymphocytosis and lamina propria plasma cell infiltrates. Terminal ileum biopsies (B,C): Focal intraepithelial lymphocytosis and lamina propria plasma cell infiltrates (B); popcorn-like epithelial apoptosis (C). Table 1. - Diagnostic Workup Test/Procedure Result Creatinine, serum 2.1 mg/dl (baseline 1 mg/dl) Stool PCR -Positive for norovirus-Negative for Clostridium difficile toxins, Salmonella, Shigella, Yersinia, and Campylobacter Osmolality, feces 420 mOsm/kg Fecal fat Abnormal Duodenal biopsy -Mucosa with intraepithelial lymphocytosis, dense plasma cell infiltrates in the lamina propria, and rare apoptotic bodies-Negative for CMV, EBV, HSV Stomach biopsy -Gastric antral and oxyntic gland mucosa with chronic inactive gastritis-Negative for H. pylori Right colon biopsy Rare epithelial apoptosis Left colon biopsy Rare epithelial apoptosis Terminal ileum biopsy Mucosa with intraepithelial lymphocytosis, dense plasma cell infiltrates in lamina propria, and rare apoptotic bodies

ADULT AUTOIMMUNE ENTEROPATHY IN INDIA : A RARE ENTITY AND AN UNUSUAL PRESENTATION

Introduction: Autoimmune enteropathy is an X-linked autoimmune disease. A syndrome of intractable diarrhea, varying levels of villous atrophy of small intestine , presence of circulating autoantibodies to enterocytes. Diagnostic criteria is any 3 of the following features 1) features of malabsorption 2) Diarrhea > 6 weeks 3) HPE showing villous blunting with crypt and intraepithelial lymphocytosis 4) exclusion of other causes of villous atrophy like celiac disease and refractory sprue 5) serology positive for antibodies like anti-enterocyte and anti-goblet. Aims & objectives : The aim of this case report was to report a rare case of autoimmune enteropathy in an Indian female , with an atypical presentation with diagnostic and treatment challenges. The typical presentation of autoimmune enteropathy i Discussion: s chronic diarrhea with features of malnutrition and weight loss. But the presentation in this patient was more in favour of presentation of koch's abdomen , mostly of TB peritonitis with ascitic component. . Adult autoimmune enteropathy being a rare entity is thought late in differential diagnosis. The presence of antibodies , intraop ndings and response to steroids favour autoimmune enteropathy. Although AIE is a rare entity,a multifactorial and a high degree of suspicion is necessary for diagnosis. In a country like India, where tuberculosis is so prevalent, Conclusion: other differential diagnosis should also be thought of before coming to a conclusion.,as other diseases like autoimmunity previously thought to be rare are not so. ATT should only be started after conrming the diagnosis with histopathology report

S3524 A Rare Case of Autoimmune Enteropathy Misdiagnosed as Celiac Disease

Introduction: Autoimmune enteropathy (AIE) is an increasingly rare condition characterized by immune mediated intestinal mucosal injury that manifests as intractable diarrhea. Originally thought to be a pediatric condition, increasing cases have been reported in the adult population. While AIE can affect all parts of the GI tract, the duodenum is the most common site of GI tract involvement. The management of AIE is centered around optimizing nutritional status in addition to steroids, immunosuppression and biologic agents. Case Description/Methods: A 29-year-old man with a childhood diagnosis of celiac disease presented for weakness and electrolyte abnormalities in the setting of chronic watery diarrhea. Laboratory findings were significant for WBC 6k uL, Potassium 2.5 mmol/L, Chloride 117 mmol/L, Creatinine 2.43 mg/dL, and decreased levels of Vitamins A, B, E, Zinc. Further investigation showed negative Tissue Transglutaminase IgA and negative workup for C. diff, Giardia, Cryptosporidium, and Campylobacter. Endoscopic evaluation showed atrophic duodenitis with erythema but no endoscopic evidence of celiac disease (Figure A,B). Histological examination of duodenal biopsies showed loss of goblet cells and Paneth cells in addition to villous blunting, intraepithelial lymphocytosis and increased apoptotic bodies consistent with AIE (Figure C). Discussion: Among the causes of chronic diarrhea and malabsorption, AIE is a rare disorder that is often misdiagnosed and mistaken for celiac disease or IBD. The pathophysiology of AIE is related to abnormal expression of self-antigens on mucosal epithelial cells, activating CD4 T lymphocytes, which leads to the destruction of enterocytes through cytotoxic effects and apoptosis. Immunohistological studies have shown that autoantibodies can be directed against enterocytes and goblet cells but are not pathognomonic for AIE. Endoscopic findings include mucosal hyperemia, ulcerations and mucosal atrophy. While difficult, the management of AIE is centered around managing malnutrition and treating the underlying autoimmune disorder. Initial recommended treatment includes corticosteroids, however, in refractory cases immunosuppressive therapy such as azathioprine, 6-mercaptopurine, and monoclonal antibodies have been shown to be beneficial. Highlighted by the case we present, AIE can be undiagnosed for years and establishing an early diagnosis is critical in reducing morbidity and improving long-term outcomes.Figure 1.: 1A: Duodenal bulb inflammation 1B: Erythema of 2nd portion of duodenum 1C: High power view of duodenal biopsy shows absent villi, expansion of the lamina propria with a lymphoplasmacytic infiltrate, and absence of goblet cells. Scattered intraepithelial lymphocytes and crypt apoptotic figures can be seen.

Differential diagnosis and long-term outcomes of non-atrophic duodenal changes in children

Objectives and studyGastrointestinal endoscopy is often performed when investigating abdominal complaints in children. While atrophic changes of the duodenal mucosa are usually caused by celiac disease, the prevalence and clinical significance of non-atrophic duodenal changes are less clear. We studied these issues in a large pediatric endoscopic cohort.MethodsComprehensive data on clinical features, diagnostic findings and long-term outcomes of children who had undergone upper gastrointestinal endoscopy with systematic duodenal sampling were collected. Study variables were compared between children with non-atrophic changes and normal histology, and between those with non-atrophic changes who did and did not receive a diagnosis.ResultsThe study comprised 1,170 consecutive children, of whom 51 (4.4%) had non-atrophic and 315 (26.9%) atrophic duodenal changes and 804 (68.7%) normal histology. The most common non-atrophic findings were non-specific inflammation (n = 19) and intraepithelial lymphocytosis (n = 14). Patients with non-atrophic changes presented more often with blood in stools (23.5 vs. 11.3%; p = 0.009), anemia (43.2 vs. 36.5%; p = 0.028) and positive celiac serology (34.3 vs. 12.9%; p < 0.001) than those with a normal duodenum. Twenty-four (44%) of those with non-atrophic changes received an initial diagnosis, the most common of which were inflammatory bowel disease (IBD) (n = 8), Helicobacter pylori infection (n = 3) and food allergy (n = 3). The prevalence of the diagnoses did not differ from those with a normal duodenum. Those who received a diagnosis had more often blood in stools (37.5 vs. 11.1%; p = 0.027), anemia (70.6 vs. 20.0%; p = 0.002) and negative celiac serology (50.0 vs. 7.7%; p = 0.013) than those without diagnosis. During a follow-up of 6.1–13.3 years, five of the 12 initially undiagnosed seropositive patients developed celiac disease, and one patient also developed ulcerative colitis.ConclusionNon-atrophic duodenal changes are relatively common and associated with anemia, blood in stools, and positive celiac disease serology. Excluding potential celiac disease, those without an initial diagnosis have a favorable long-term prognosis.