Risk Assessment for Gastrointestinal Diseases via Clinical Dimension and Genome-Wide Polygenic Risk Scores of Type 2 Diabetes: A Population-Based Cohort Study.

OBJECTIVE: We aimed to evaluate whether individuals with type 2 diabetes (T2D) were at higher risk of developing a wide range of gastrointestinal diseases based on a population-based cohort study. RESEARCH DESIGN AND METHODS: This study included 374,125 participants free of gastrointestinal disorders at baseline; of them, 19,719 (5.27%) with T2D were followed-up by linking to multiple medical records to record gastrointestinal disease diagnoses. Multivariable Cox models were used to estimate the hazard ratios (HRs) and CIs. Logistic models were used to examine the associations between polygenic risk scores (PRS) and clinical gastrointestinal phenotypes. RESULTS: During a median follow-up of 12.0 years, we observed the new onset of 15 gastrointestinal diseases. Compared with nondiabetes, participants with T2D had an increased risk of gastritis and duodenitis (HR 1.58, 95% CI 1.51-1.65), peptic ulcer (HR 1.56, 95% CI 1.43-1.71), diverticular disease (HR 1.19, 95% CI 1.14-1.24), pancreatitis (HR 1.45, 95% CI 1.24-1.71), nonalcoholic fatty liver disease (HR 2.46, 95% CI 2.25-2.69), liver cirrhosis (HR 2.92, 95% CI 2.58-3.30), biliary disease (HR 1.18, 95% CI 1.10-1.26), gastrointestinal tract cancers (HR 1.28, 95% CI 1.17-1.40), and hepatobiliary and pancreatic cancer (HR 2.32, 95% CI 2.01-2.67). Positive associations of PRS of T2D with gastritis, duodenitis, and nonalcoholic fatty liver disease were also observed. CONCLUSIONS: In this large cohort study, we found that T2D was associated with increased risks of a wide range of gastrointestinal outcomes. We suggest the importance of early detection and prevention of gastrointestinal disorders among patients with T2D.

Upper gastrointestinal endoscopic findings in functional constipation and irritable bowel syndrome diagnosed using the Rome IV criteria: a cross-sectional survey during a medical check-up in Japan.

BACKGROUND: The Rome IV criteria have been established as an international standard for diagnosing disorders of gut-brain interaction. In this study, we aimed to examine the upper gastrointestinal (GI) endoscopic findings and symptoms of subjects with functional constipation (FC) and irritable bowel syndrome (IBS) of individuals undergoing a medical check-up. METHODS: A total of 13,729 subjects underwent a medical check-up at Osaka City University-affiliated clinic, MedCity21, between April 2018 and March 2019. Among the 5,840 subjects who underwent screening upper GI endoscopy and completed a questionnaire based on the Rome IV criteria, 5,402 subjects were consecutively enrolled after excluding subjects with a large amount of gastric residue (n = 6), those who had previously undergone partial or total gastrectomy (n = 40), or those with daily use of low-dose aspirin (n = 82), nonsteroidal anti-inflammatory drugs (n = 63), or acid secretion inhibitors (n = 308). RESULTS: Robust Poisson regression analyses adjusted for age, sex, Helicobacter pylori infection status, alcohol intake, and smoking habits showed a significant association between FC and corpus erosion (adjusted prevalence ratio [aPR], 2.93; 95% confidence interval [CI], 1.51-5.67; p < 0.01) and red streaks (aPR, 3.83; 95% CI, 2.53-5.79; p < 0.01), whereas IBS was significantly associated with erosive gastritis (aPR, 8.46; 95% CI, 4.89-14.67; p < 0.01) and duodenitis (aPR, 7.28; 95% CI, 3.64-14.59; p < 0.01). Red streaks tended to be associated with IBS (aPR, 1.96; 95% CI, 1.00-3.83; p = 0.05). Subjects with IBS were the most to complain of both upper and lower GI symptoms and psychological symptoms, followed by those with FC and controls. IBS subjects with erosive gastritis or duodenitis had significantly more complaints of stomachache and feeling stressed than those without erosive gastritis or duodenitis (54.5% vs. 18.8%; p = 0.03 and 66.7% vs. 25.0%; p = 0.01). CONCLUSIONS: Subjects with FC and IBS had a variety of upper GI and psychological symptoms. In the upper GI endoscopic findings, corpus erosion and red streaks were associated with FC, and erosive gastritis, duodenitis, and possibly red streaks were associated with IBS.

EVALUATION OF THE EFFECTIVENESS OF THE GASTRODUODENITIS PREVENTION PROGRAM IN PATIENTS OF RETIREMENT AGE WITH ESSENTIAL ARTERIAL HYPERTENSION WHO TOOK PART IN THE PROGRAM ,AFFORDABLE MEDICINES- UNDER THE IBCR.

OBJECTIVE: The aim: To assess the e!ectiveness of the gastroduodenitis prevention program we have developed in patients of retirement age with essential arterial hypertension who participate in the «A!ordable Medicines¼ program. PATIENTS AND METHODS: Materials and methods: A combined (retrospective and prospective) study was conducted, in which 150 patients took part. The main group consisted of 100 patients of retirement age with essential arterial hypertension and gastroduodenitis, which arose against the background of treatment of essential arterial hypertension. The control group consisted of 50 patients of retirement age with essential arterial hypertension without gastroduodenitis. For this category of the population developed a program for the prevention of gastroduodenitis. To assess the e!ectiveness of this prevention program, an «incremental cost-benefit ratio¼ (#C$R) is used. RESULTS: Results: An assessment of the e!ectiveness of the gastroduodenitis prevention program we developed in patients of retirement age with essential arterial hypertension who participate in the «A!ordable Medicines¼ program. CONCLUSION: Conclusions: Identified categories of patients for whom the developed prevention program is effective.

Clinical Characteristics of Children with Eosinophilic Esophagitis and Bulbar Duodenitis.

We describe a cohort of 33 patients with eosinophilic esophagitis (EoE) and incidental duodenal bulb inflammation, termed bulbar duodenitis (BD). We conducted a single-center retrospective cohort study and recorded demographics, clinical presentation, endoscopic, and histological findings. BD was observed at the initial endoscopy in 12 cases (36%) and at a subsequent endoscopy in the remainder. Bulbar histology was usually a mix of chronic and eosinophilic inflammation. Patients were more likely to have active EoE (n = 31, 96.9%) at time of BD diagnosis. Our data indicate that the duodenal bulb of children with EoE should be carefully examined at each endoscopy and mucosal biopsies considered. Larger studies are needed to explore this association.

Gastric ulcer and duodenitis associated with coinfection of human herpesvirus-8 and cytomegalovirus in a renal transplant recipient: a case report.

BACKGROUND: The coinfection between cytomegalovirus (CMV) and either human herpesvirus-6 (HHV-6) or HHV-7 in renal transplant recipients is well known; however, there have been few reports of coinfection of CMV associated with HHV-8. This paper presents a first case of acute gastric ulcer and duodenitis associated with CMV and HHV-8 coinfection after renal transplantation. CASE PRESENTATION: A 33-year-old male with a history of kidney transplantation was admitted to hospital because of postural epigastric pain. The recipient was CMV seropositive prior to transplantation and received trimethoprim-sulfamethoxazole without universal prophylaxis. Approximately 5 months after renal transplant, the recipient complained postural epigastric pain. An endoscopy revealed diffuse ulcerative lesions in the lower body and in the antrum of the stomach, as well as several erythematous mucosal lesions in the duodenum. Histopathologic examination identified CMV inclusions consistent with invasive CMV disease and immunohistochemical staining showed positive results for HHV-8 and CMV. No tumorous diseases such as Kaposi's sarcoma were detected. After 3 weeks of intravenous ganciclovir treatment, we observed that serum CMV PCR remained within the normal range and clinical symptoms improved. A follow-up endoscopy performed 3 weeks later showed that the severity of the above mentioned lesions had improved. CONCLUSIONS: We report the first case of a renal transplant recipient diagnosed with acute gastric ulcer and duodenitis associated with coinfection of CMV and HHV-8. Ganciclovir appears to be effective in diseases associated with coinfection of CMV and HHV-8.

Clinical features of upper gastrointestinal endoscopy in 3146 patients: a 9-year retrospective cohort study in Zanzibar Archipelago, Tanzania.

Background/objectives: To investigate the demographic features, primary endoscopic findings, and the status of Helicobacter Pylori (H. pylori) infection of the enrolled subjects who underwent upper gastrointestinal endoscopy (UGIE) in the Zanzibar Archipelago, Tanzania. Methods: Between December 2013 and October 2021, a total of 3146 eligible participants were finally recruited in present retrospective cohort. Demographic information and endoscopic findings of each participant was retrieved. H. pylori infection was confirmed by rapid-urease test of gastric antral and body biopsies at endoscopy. Results: Among the recruited subjects, 1691 (53.76%) are females, remaining 1455 (46.24%) are males. The median age of this retrospective cohort was 40 years ranging from 8 to 97 years. The common identified endoscopic findings included gastro-duodenitis, normal endoscopic finding, peptic ulcer disease (PUD), esophagitis, esophagogastric varices, esophageal and gastric cancer, respectively. After adjustment for sex and age, a significant risk of gastric and/or duodenal ulcer (OR, 2.51; 95% CI, 1.82-3.48, P<0.001) and gastric cancer (OR, 3.49; 95% CI, 1.27-9.58, P=0.015) in H. pylori positive group was observed. Stratified analysis indicated a significant relationship between duodenal ulcer with younger age (adjusted OR, 0.98; 95% CI, 0.97-0.99, p = 0.002), and the presence of H. pylori (OR, 2.01; 95% CI, 1.12-3.91, p= 0.021). Conclusions: The present study revealed that gastro-duodenitis, PUD, and normal finding are the most common endoscopic diagnoses in Zanzibar. The presence of H. pylori is significantly associated with duodenal ulcer and gastric cancer.

[Assessment of ten-year dynamics of cases of hospitalizations of patients with peptic ulcer disease, chronic gastritis and chronic duodenitis].

AIM: To assess of the ten-year dynamics of cases of hospitalizations of patients with peptic ulcer disease (PUD), chronic gastritis and chronic duodenitis relative to the total number of people treated in the gastroenterological departments of the hospital in 20102019. MATERIALS AND METHODS: Data of the annual reports of the work of the hospital departments were studied retrospectively. RESULTS: The relative number of persons hospitalized for chronic duodenitis decreased 2.8 times (p0.001), but the proportion of patients with chronic gastritis did not tend to decrease. This is most likely due to diagnostic errors. The cases of hospitalization of persons with uncomplicated PUD decreased by 3.1 times (p0.001), the proportion of men with duodenal ulcer decreased by 6.3 times (p0.001), with gastric ulcer decreased 1.9 times (p0.01). The proportion of women hospitalized with duodenal ulcer decreased 2.3 times (p0.01). The number of hospitalized men with duodenal ulcer is 3.8 times more than females (p0.001). It can be explained by a decrease in social stressful influences and active anti-Helicobacter pylori therapy. CONCLUSION: Over the period of follow-up, the cases of hospitalization of patients with uncomplicated PUD decreased, primarily due to a decrease in the proportion of persons with ulcer of the duodenum and duodenitis, while the number of patients with chronic gastritis not undergoing modern examination did not have significant dynamics.

Hallazgos endoscópicos no relacionados con hipertensión portal en pacientes con cirrosis hepática sometidos a un programa de cribado de varices / Endoscopic findings unrelated to portal hypertension in patients with liver cirrhosis undergoing a varicose vein screening programme

Objetivo: El consenso de Baveno VI para el cribado endoscópico de varices esofagogástricas recomienda evitar la endoscopia en algunos pacientes. Bajo esta estrategia, podrían pasar desapercibidas lesiones no relacionadas con hipertensión portal, algunas de ellas potencialmente graves. El objetivo de este estudio es determinar la prevalencia de dichas lesiones e identificar los factores clínicos asociados a las mismas. Pacientes y métodos: Estudio transversal unicéntrico sobre una cohorte consecutiva de pacientes cirróticos sometidos a endoscopia digestiva alta en el contexto de un programa de cribado de varices esofagogástricas entre noviembre del 2013 y noviembre del 2018. Se analizaron los factores de riesgo para la presencia de lesiones no relacionadas con hipertensión portal mediante regresión logística uni y multivariante. Resultados: Se incluyó a 379 pacientes. La etiología mayoritaria de la cirrosis fue etílica (n=229; 60,4%). La prevalencia de lesiones endoscópicas no relacionadas con hipertensión portal fue del 39,6% (n=150). Entre los 96 pacientes con enfermedad péptica (25,3%) se tomó test de ureasa en 54 (56,2%), siendo positiva en 24 (44,4%). La presencia de lesiones endoscópicas no relacionadas con hipertensión portal no estuvo influida por la edad (p=1), el género (p=0,28), la función hepática (MELD p=0,20, Child-Pugh p=0,77) o la presencia de datos ecográficos de hipertensión portal (p=0,14). Los pacientes fumadores presentaron tendencia a mayor prevalencia de lesiones endoscópicas no relacionadas con la hipertensión portal (43,2% vs. 34,6%; p=0,09), particularmente úlcera péptica (6,4% vs. 0,6%; p=0,05) y duodenitis péptica (17,3% vs. 6,3%; p=0,002). El tabaquismo activo fue el único factor predictivo independiente de ulcus o duodenitis péptica (odds ratio=2,56; intervalo de confianza del 95%: 1,18-5,56; p=0,017).(AU)

Aim: To determine the prevalence of endoscopic lesions unrelated with portal hypertension in patients with cirrhosis. Patients and methods: Cross-sectional study including a consecutive cohort of patients with liver cirrhosis enrolled in a screening program of oesophageal varices who underwent an upper gastrointestinal endoscopy from November, 2013, to November, 2018. Clinical predictors of endoscopic lesions unrelated to portal hypertension were analyzed by univariate and multivariate logistic regression. Results: A total of 379 patients were included. The most frequent aetiology of liver disease was alcohol consumption (60.4%). The prevalence of endoscopic lesions unrelated with portal hypertension was 39.6% (n=150). Among 96 patients with peptic lesions, urease was obtained in 56.2% of patients (positive in 44.4% of them). The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. Smokers had a trend to increased prevalence of endoscopic lesions unrelated to portal hypertension (43.2% vs. 34.6%; p=0.09), particularly peptic ulcer (6.4% vs. 0.6%; p=0.05) and peptic duodenitis (17.3% vs. 6.3%; p=0.002). Active smoking was the only independent predictor of peptic ulcer or duodenitis (OR=2.56; p=0.017). Conclusion: Active smoking is a risk factor for endoscopic lesions unrelated to portal hypertension. This finding should be further investigated to reassess endoscopic screening programs in cirrhotic smokers.(AU)

CLINICAL, ENDOSCOPIC, AND HISTOLOGICAL CHARACTERISTICS OF HELICOBACTER PYLORI POSITIVE AND NEGATIVE ARMENIAN CHILDREN WITH RECURRENT ABDOMINAL PAIN AND/OR DYSPEPSIA.

Recurrent abdominal pain (RAP) and dyspepsia are common complaints in children. These symptoms are often associated with Helicobacter pylori (Hp) infection. The aim of the present study was to prospectively analyze clinical, endoscopic, and histological characteristics of Hp+ and Hp- children with RAP and/or dyspepsia. Patients aged 2-18 years with RAP and/or dyspepsia, referred for an upper endoscopy to Arabkir Medical Center - Institute of Child and Adolescent Health (Arabkir MC-ICAH) from November 2015 to December 2017, were involved in the study. Histology was assessed according to the updated Sydney system. Gastric and duodenal specimens were stained by modified Giemsa staining for Hp infection. One antral biopsy was cultured in Hp selective media. 150 patients were included into the study: 70.7% Hp+, 29.3% Hp-. Nausea and vomiting were significantly more common in Hp+ patients (p<0.05). Gastric nodularity (p=0.02), erosions in the stomach (p=0.056), and duodenal erosions (p=0.019) were more common in Hp+. Chronic active (p=0.027) and non-active gastritis (p=0.002), cumulative findings of metaplasia/dysplasia/atrophy in the stomach (p=0.014) and chronic non-active duodenitis (p=0.016), were significantly more common in Hp+ patients. Hp infection prevalence is high in Armenian children with dyspepsia and/or RAP. Clinical symptoms, endoscopic findings, and histopathological findings were significantly different in Hp+ patients as compared to Hp- patients.

Association of Preinjury Medical Diagnoses With Pediatric Persistent Postconcussion Symptoms in Electronic Health Records.

OBJECTIVE: To identify risk factors and generate hypotheses for pediatric persistent postconcussion symptoms (PPCS). SETTING: A regional healthcare system in the Southeastern United States. PARTICIPANTS: An electronic health record-based algorithm was developed and validated to identify PPCS cases and controls from an institutional database of more than 2.8 million patients. PPCS cases (n = 274) were patients aged 5 to 18 years with PPCS-related diagnostic codes or with PPCS key words identified by natural language processing of clinical notes. Age, sex, and year of index event-matched controls (n = 1096) were patients with mild traumatic brain injury codes only. Patients with moderate or severe traumatic brain injury were excluded. All patients used our healthcare system at least 3 times 180 days before their injury. DESIGN: Case-control study. MAIN MEASURES: The outcome was algorithmic classification of PPCS. Exposures were all preinjury medical diagnoses assigned at least 180 days before the injury. RESULTS: Cases and controls both had a mean of more than 9 years of healthcare system use preinjury. Of 221 preinjury medical diagnoses, headache disorder was associated with PPCS after accounting for multiple testing (odds ratio [OR] = 2.9; 95% confidence interval [CI]: 1.6-5.0; P = 2.1e-4). Six diagnoses were associated with PPCS at a suggestive threshold for statistical significance (false discovery rate P < .10): gastritis/duodenitis (OR = 2.8; 95% CI: 1.6-5.1; P = 5.0e-4), sleep disorders (OR = 2.3; 95% CI: 1.4-3.7; P = 7.4e-4), abdominal pain (OR = 1.6; 95% CI: 1.2-2.2; P = 9.2e-4), chronic sinusitis (OR = 2.8; 95% CI: 1.5-5.2; P = 1.3e-3), congenital anomalies of the skin (OR = 2.9; 95% CI: 1.5-5.5; P = 1.9e-3), and chronic pharyngitis/nasopharyngitis (OR = 2.4; 95% CI: 1.4-4.3; P = 2.5e-3). CONCLUSIONS: These results support the strong association of preinjury headache disorders with PPCS. An association of PPCS with prior gastritis/duodenitis, sinusitis, and pharyngitis/nasopharyngitis suggests a role for chronic inflammation in PPCS pathophysiology and risk, although results could equally be attributable to a higher likelihood of somatization among PPCS cases. Identified risk factors should be investigated further and potentially considered during the management of pediatric mild traumatic brain injury cases.

Endoscopic findings unrelated to portal hypertension in patients with liver cirrhosis undergoing a varicose vein screening programme. / Hallazgos endoscópicos no relacionados con hipertensión portal en pacientes con cirrosis hepática sometidos a un programa de cribado de varices.

AIM: To determine the prevalence of endoscopic lesions unrelated with portal hypertension in patients with cirrhosis. PATIENTS AND METHODS: Cross-sectional study including a consecutive cohort of patients with liver cirrhosis enrolled in a screening program of oesophageal varices who underwent an upper gastrointestinal endoscopy from November, 2013, to November, 2018. Clinical predictors of endoscopic lesions unrelated to portal hypertension were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 379 patients were included. The most frequent aetiology of liver disease was alcohol consumption (60.4%). The prevalence of endoscopic lesions unrelated with portal hypertension was 39.6% (n=150). Among 96 patients with peptic lesions, urease was obtained in 56.2% of patients (positive in 44.4% of them). The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. Smokers had a trend to increased prevalence of endoscopic lesions unrelated to portal hypertension (43.2% vs. 34.6%; p=0.09), particularly peptic ulcer (6.4% vs. 0.6%; p=0.05) and peptic duodenitis (17.3% vs. 6.3%; p=0.002). Active smoking was the only independent predictor of peptic ulcer or duodenitis (OR=2.56; p=0.017). CONCLUSION: Active smoking is a risk factor for endoscopic lesions unrelated to portal hypertension. This finding should be further investigated to reassess endoscopic screening programs in cirrhotic smokers.

Clinical Impacts of Juxtapapillary Duodenal Diverticulum Detected on Computed Tomography.

BACKGROUND: Diverticula are commonly observed in the duodenum. Duodenal Diverticulum (DD) usually does not give symptoms throughout life and is diagnosed by coincidence. However, it may present with different symptoms in patients. OBJECTIVE: This study aims to evaluate the prevalence of DD and Juxtapapillary Duodenal Diverticulum (JDD) and its association with other possible pathologies and to determine its clinical impact by using Computed Tomography (CT). METHODS: This retrospective observational study, which was taken consecutively between the years of 2013-2020, was evaluated in the Radiology Department. The total number of cases was 4850 (male-2440; female-2410). CT images were evaluated by two experienced radiologists at the workstation. DD and JDD prevalence and clinical findings in the hospital registry system were examined. RESULTS: The age of the patients included in the study ranged from 17 to 92 years (mean age 46.94±16.42). In patients with DD (female-130; male-101), mean age was 62.24 ± 12.69 (21-92). The prevalence of DD was 4.76% (n=231). The prevalence of JDD was 4.02% (n=195) and increased with age (p<0.01). The average diameter of the JDD was measured as 23.29±8.22 (9.5-55.3) mm. A significant positive correlation was found between age and DD diameter (p=0.039). DDs were found most commonly 84.42% (n=195) in the second segment of the duodenum as JDD. In patients with JDD, the mean diameter of choledochus and wirsung canal were 6.7 ± 2.4 (3-15.3) mm and 0.31 ± 0.1 (0.1-6.5) mm respectively. The choledochal diameter was correlated with the JDD size (p = 0.004). Cholelithiasis (n=56), choledocholithiasis (n=20), cholecystitis (n=52), diverticulitis (n=15), duodenitis (n=37), pancreatitis (n=5) and hiatal hernia (n=60) with JDD were observed. Periampullary carcinoma was detected in one patient. CONCLUSION: Our study shows that cholelithiasis, choledocholithiasis, cholecystitis, diverticulitis, duodenitis, pancreatitis may be associated with JDD. Therefore, in contrast-enhanced abdominal CT scans taken for various reasons, investigation of the presence and characteristics of JDD and detection of pathologies that may be associated with JDD are important for patients to benefit from early diagnosis and treatment opportunities and to take precautions against possible complications.

[Eosinophilic duodenitis associated to food allergy debuting as acute visceral pain in an adult with vitiligo: a case report]. / Duodenitis eosinofílica asociada a alergia alimentaria debutando como dolor visceral agudo en un adulto con vitíligo: reporte de un caso.

BACKGROUND: Eosinophilic duodenitis has a prevalence of 5.1 to 8.2 per 100000 persons. The underlying molecular mechanisms are unknown, but hypersensitivity (seasonal and food allergies, asthma, eczema) response plays a major role in its pathogenesis, allergic predisposition can be found up-to 25-35% of cases. The diagnosis includes clinical manifestation, imaging findings and histological evidence of eosinophilic infiltration >20 eosinophils per high-power field. This is a clinical case report. a 25-years old man with vitiligo consult to emergency department referring dyspepsia symptoms, vomiting and abdominal pain of maximal intensity, in the medical exam upper abdominal pain was found, blood laboratories were unremarkable except a high net eosinophil-count >2000 cells/ul, abdominal ultrasound were normal, upper endoscopy revealed duodenitis with rigid and thickened folds, colonoscopy show hemorrhoids grade I. Coproscopy exam was negative for parasites, total IgE, IgA and IgG were in normal range, a positive IgG to Toxoplasma gondii was reported, autoimmunity panel was negative. In the following 4 days the abdominal pain and eosinophils count increase, a new abdomin-pelvic tomography was done showing thickened duodenum with a new endoscopy showing marked edema in duodenum with severe biliary reflux with biopsies describing an atrophic chronic duodenitis. Allergy tests -skin prick and patch tests- were done resulting positive to cereals (rye, soy, barley), Manihot esculenta, green banana, tomato, cow milk, orange and pineapple. A restrictive diet and protons pump inhibitor was indicated, ambulatory control at 45 days after show symptoms resolution with a normal blood eosinophils count. Here is reported a case of eosinophilic duodenitis related to food allergy in a young man with vitiligo debuting with an unusual clinical presentation of acute visceral pain and biliary reflux which resolved with elimination diet and pantoprazole without use of corticoids, with both, IgE and non-IgE mechanisms playing important roles explaining food sensitization.

Novel Case Report: A Previously Reported, but Pathophysiologically Unexplained, Association Between Collagenous Colitis and Protein-Losing Enteropathy May Be Explained by an Undetected Link with Collagenous Duodenitis.

Collagenous colitis (CC) is associated with non-bloody, watery diarrhea, which is pathophysiologically reasonable because normal colonic absorption (or excretion) of water and electrolytes can be blocked by the abnormally thick collagen layer in CC. However, CC has also been associated with six previous cases of protein-losing enteropathy (PLE), with no pathophysiologic explanation. The colon does not normally absorb (or excrete) amino acids/proteins, which is primarily the function of the small bowel. Collagenous duodenitis (CD) has not been associated with PLE. This work reports a novel case of CD (and CC) associated with PLE; a pathophysiologically reasonable mechanism for CD causing PLE (by the thick collagen layer of CD blocking normal intestinal amino acid absorption); and a novel association of PLE with severe COVID-19 infection (attributed to relative immunosuppression from hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and malnutrition from PLE).

Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis.

BACKGROUND: Eosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate treatments. Mast-cell activity may contribute to the pathogenesis of the conditions. AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis. METHODS: In this phase 2 trial, we randomly assigned adults who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo. The primary end point was the change in gastrointestinal eosinophil count from baseline to 2 weeks after the final dose; to maximize statistical power, we evaluated this end point in the placebo group as compared with the combined AK002 group. Secondary end points were treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) and the change in total symptom score. RESULTS: Of the 65 patients who underwent randomization, 43 were assigned to receive AK002 and 22 were assigned to receive placebo. The mean percentage change in gastrointestinal eosinophil count was -86% in the combined AK002 group, as compared with 9% in the placebo group (least-squares mean difference, -98 percentage points; 95% confidence interval [CI], -121 to -76; P<0.001). Treatment response occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo (difference, 58 percentage points; 95% CI, 36 to 74; P<0.001). The mean change in total symptom score was -48% with AK002 and -22% with placebo (least-squares mean difference, -26 percentage points; 95% CI, -44 to -9; P = 0.004). Adverse events associated with AK002 were similar to those with placebo, with the exception of higher percentages of patients having mild-to-moderate infusion-related reactions with AK002 (60% in the combined AK002 group and 23% in the placebo group). CONCLUSIONS: In patients with eosinophilic gastritis or duodenitis, AK002 reduced gastrointestinal eosinophils and symptoms. Infusion-related reactions were more common with AK002 than with placebo. (Funded by Allakos; ENIGMA ClinicalTrials.gov number, NCT03496571.).

Esophageal, Gastric, and Duodenal Histologic Findings in Patients with Feeding Difficulties.

Currently, there are inconsistencies in the recommendations of when to obtain an esophagogastroduodenoscopy (EGD) in children with feeding difficulties. The aim of our study was to identify EGD findings in patients presenting to a large, outpatient feeding program. Additionally, we investigated the presence of any relationship between abnormal pathology seen on biopsies (inflammation) and symptoms of feeding intolerance such as vomiting, gagging, retching, or abdominal pain. Retrospective analysis of electronic medical records (EMRs) was conducted for all new patients aged 0-17 years presenting to the Multidisciplinary Feeding Clinic. Three hundred and thirty patients (50.2%) had an EGD with complete biopsies. Of these 330 patients, biopsies revealed esophagitis in 40%, gastritis in 33.6%, and duodenitis in 15.2%. Overall, 61.21% had an abnormal pathology in at least one site. We found that children with feeding disorders commonly have esophagitis, gastritis, and/or duodenitis and that symptoms are poor predictors of pathology. This study underscores the importance of gastrointestinal evaluation as part of a multidisciplinary evaluation in patients with feeding difficulties.

Immune checkpoint inhibitor-associated celiac disease.

BACKGROUND: Rare cases of immune checkpoint inhibitor (ICI)-associated celiac disease (ICI-CeD) have been reported, suggesting that disruption of tolerance mechanisms by ICIs can unmask celiac disease (CeD). This study aims to characterize the clinicopathological and immunophenotypic features of ICI-CeD in comparison to ICI-associated duodenitis (ICI-Duo) and usual CeD. METHODS: A medical and pathological records search between 2015 and 2019 identified eight cases of ICI-CeD, confirmed by tTG-IgA. Nine cases of ICI-Duo, 28 cases of moderate CeD, as well as 5 normal controls were used as comparison groups. Clinical information was collected from the electronic medical records. Immunohistochemistry for CD3, CD8, T-cell receptor gamma/delta (γδ), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) were performed, with quantification of intraepithelial lymphocyte (IEL) subsets in three well-oriented villi. CD68, PD-L1, and PD-1 were assessed as a percentage of lamina propria surface area infiltrated by positive cells. Statistical significance was calculated by the Student's t-test and Fisher's exact test. RESULTS: The eight patients with ICI-CeD (F:M=1:3) and nine patients with ICI-Duo (F:M=5:4) presented similarly with diarrhea (13/17) and abdominal pain (11/17) after a median of 1.6 months on ICI therapy. In patients with ICI-CeD, tTG-IgA ranged from 104 to >300 IU/mL. Histological findings in ICI-CeD and ICI-Duo were similar and included expansion of the lamina propria, active neutrophilic duodenitis, variably increased IELs, and villous blunting. Immunohistochemistry showed that the average number of IELs per 100 enterocytes is comparable between ICI-CeD and ICI-Duo, with increased CD3+ CD8+ T cells compared with normal duodenum but decreased γδ T cells compared with CeD. Average PD-L1 percentage was 9% in ICI-CeD and 18% in ICI-Duo, in comparison to <1% in CeD and normal duodenum; average PD-1 percentage was very low to absent in all cases (<3%). On follow-up, five patients with ICI-CeD improved on a gluten-free diet (GFD) as the sole therapeutic intervention (with down-trending tTG-IgA) while the other three required immunosuppression. All patients who developed ICI-Duo received immunosuppression with variable improvement in symptoms. CONCLUSIONS: ICI-CeD resembles ICI-Duo clinically and histologically but shares the serological features and response to gluten withdrawal with classic CeD. Immunophenotyping of IELs in ICI-CeD and ICI-Duo also shows similar CD3, CD8, γδ T cell subsets, and PD-L1 populations, all of which differed quantitatively from usual CeD. We conclude that ICI-CeD is biologically similar to ICI-Duo and is likely a variant of ICI-Duo, but treatment strategies differ, with ICI-CeD often improving with GFD alone, whereas ICI-Duo requires systemic immunosuppression.

Duodenal inflammation: an emerging target for functional dyspepsia?

Introduction: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders and is classified into postprandial distress and epigastric pain syndrome. Despite the recognition of duodenal inflammation as a potential trigger of symptoms, only limited anti-inflammatory therapies exist.Areas covered: This narrative review summarizes the recent advances in the pathophysiology and treatment of FD; it identifies potential therapeutic targets and gaps in the field. An electronic literature search was conducted in Pubmed up to 31st of December 2019.Expert opinion: There is compelling evidence for the role of duodenal inflammation and the eosinophil-mast cell axis in the pathogenesis of dyspeptic symptoms. Traditional prokinetic drugs and neuromodulators target gastric dysmotility and visceral hypersensitivity but are hampered by limited efficacy and side effects. Independent of acid suppression, the anti-inflammatory action of proton pump inhibitors, which remain the first-line therapy in FD, may also explain their therapeutic effect. Other existing and newly established anti-inflammatory drugs should be investigated while trials including probiotics and selective antibiotics should examine the host microbiome and immune activation. Targeted treatments for potential causes of duodenal pathology, such as impaired permeability and dysbiosis, are likely to emerge in the future.

HLA-DQ Genotyping, Duodenal Histology, and Response to Exclusion Diet in Autistic Children With Gastrointestinal Symptoms.

OBJECTIVES: A correlation between autism spectrum disorders (ASDs) and gastrointestinal (GI) problems, and a possible link between gluten consumption and ASD have been increasingly reported. Gluten/casein-free diet (GCFD) is often undertaken, with conflicting results. This study aimed at evaluating the distribution of human leukocyte antigen (HLA)-DQ2/DQ8 typing among patients with ASD with GI symptoms, together with its correlation with duodenal histology and response to GCFD. METHODS: Between 2002 and 2015 all patients with ASD with GI symptoms referred to our outpatient clinic, displaying clinical, laboratory, or ultrasound findings suggestive of organic disease, underwent endoscopy, celiac disease (CD) serum antibodies testing and HLA-DQ2/DQ8 genotyping. Patients were prescribed a 6-month GCFD, and then clinically reassessed. RESULTS: Among 151 enrolled patients, 134 (89%) were negative for CD-specific antibodies; 72 (48%) were positive for HLA-DQ2/DQ8; and 56 (37%) showed duodenal microscopic inflammation. Clinical improvement was observed in non-CD patients irrespective of the rigorous or partial adherence to the diet, being the difference nonstatistically significant. Response to diet was related to the presence of histological duodenal alterations at baseline (odds ratio 11.323, 95% confidence interval 1.386-92.549 for Marsh 2 pattern), but not to HLA-DQ2/DQ8 positivity (odds ratio 1.120, 95% confidence interval 0.462-2.716). CONCLUSIONS: Our data suggest that children with ASD with GI symptoms have a high prevalence of duodenal intraepithelial lymphocytic infiltration, which seems to be linked to a mechanism other than autoimmune response to gluten consumption. Alteration of duodenal histology, but not the HLA-DQ2/DQ8 status, was associated with clinical response to the diet.

Gastroduodenal motility disorders.

PURPOSE OF REVIEW: This review summarizes recent progress in the epidemiology, pathophysiology and treatment of gastroduodenal motility disorders with an emphasis on functional dyspepsia and gastroparesis. RECENT FINDINGS: Pathophysiological research has focused on the association of delayed emptying and impaired accommodation with symptom pattern. Studies also confirmed the presence of altered mucosal integrity and low-grade immune activation in the duodenum in functional dyspepsia, while changes in numbers of interstitial cells of Cajal and myenteric neurons were confirmed in gastroparesis. Treatment advances in gastroparesis include new prokinetics such as the ghrelin receptor agonist relamorelin and the antiemetic agent aprepitant. The efficacy and use of neuromodulators were reviewed and new management guidelines for functional dyspepsia were published. SUMMARY: Pathophysiological research has focused on cellular changes in gastroparesis and gastroduodenal motility disorders. New treatments include relamorelin and aprepitant for gastroparesis.