Dupilumab Can Induce Remission of Eosinophilic Gastritis and Duodenitis: A Retrospective Case Series.

INTRODUCTION: Noneosinophilic esophagitis eosinophilic gastrointestinal disorders (non-EoE-EGIDs) have limited treatment options to induce histologic and clinical remission. Dupilumab is a human monoclonal antibody against the interleukin-4 receptor ɑ subunit, which has been reported to induce improvement in pediatric patients with non-EoE-EGIDs. METHODS: We conducted a retrospective chart review to identify if patients with eosinophilic gastritis (EoG) and/or eosinophilic duodenitis (EoD) experience clinical and histologic remission with dupilumab. RESULTS: Twelve patients were included (2 patients with EoG and EoD, 3 patients with EoG only, and 7 patients with EoD only). All patients experienced improvement of at least 1 symptom on dupilumab, 3 patients (25%) had no change in severity of 1 or more of their symptoms, and no patients had worsening symptoms. On dupilumab, 2 patients with EoG (40%) and 3 patients with EoD (33.3%) were completely asymptomatic. Histologic changes were investigated in a subanalysis including 8 patients (2 patients with EoG and EoD, 2 patients with EoG only, and 4 patients with EoD only). Median peak gastric eosinophil counts in patients with EoG reduced from 80.5 eos/hpf (min-max 32-150, Q1-Q3 45.5-111) to 7.5 eos/hpf (min-max 0-28, Q1-Q3 1.5-16.8). Median peak duodenal eosinophil counts in patients with EoD reduced from 39 eos/hpf (min-max 30-50, Q1-Q3 37.3-46.3) to 16.5 eos/hpf (min-max 0-50, Q1-Q3 8-38.5). All 4 patients (100%) with EoG and 4 patients (66.6%) with EoD had histologic remission on dupilumab. DISCUSSION: In this retrospective case series, we showed preliminary evidence that dupilumab may be effective in inducing histologic and symptomatic remission in patients with non-EoE-EGIDs.

Gastroduodenitis Associated with Active Ulcerative Colitis Treated with Infliximab: Different Clinical Course in the Colon and Gastroduodenal Lesions.

A 29-year-old man with severe ulcerative colitis and gastroduodenitis was initially treated with oral mesalamine and high-dose intravenous steroid therapy; however, his epigastralgia and vomiting did not improve. After initiating infliximab, the patient experienced prompt improvement in symptoms and inflammation. Although steroids were effective for the colon, they proved ineffective for gastroduodenal lesions, highlighting the necessity for molecular-targeted agents, such as infliximab, in these cases. The timing for administering such agents should be carefully considered.

Child with protein losing enteropathy as presentation of collagenous duodenitis and eosinophilic gastroenteritis.

Background: Collagenous duodenitis and gastritis are rare histopathological findings in children. Patients and methods: : We describe a four-year old girl, who presented with non-bloody diarrhea for two months and progressive edema with an albumin of 16g/dl. Results: The diagnosis of a protein losing enteropathy was made. Extensive investigations withheld only an infectious cause of the protein losing enteropathy (cytomegalovirus and adenovirus). However, the patients still required repetitive albumin infusions 3.5 months after onset of symptoms without spontaneous recovery. Therefore, a new endoscopic work-up was performed. Duodenal biopsies revealed collagen deposition, in association with a high number of eosinophils and mast cells throughout different parts of the gastrointestinal tract. Conclusions: The collagen deposition seems to be triggered by an eosinophilic gastrointestinal disorder. Treatment was started with amino acid-based formula, oral iron therapy, an antihistamine, and a proton pomp inhibitor that resulted in persistent normalization of serum albumin already after 1.5 weeks.

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.

Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population-Based Cohort Study.

BACKGROUND AND AIMS: Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation-wide population-based cohort in Sweden. APPROACH AND RESULTS: Using nation-wide registries, we identified all adults who received maintenance PPIs (≥180 days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow-up of 5.3 years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37-1.81), 1.77 (95% CI, 1.56-2.00), and 1.88 (95% CI, 1.57-2.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17-1.57) and 1.47 (95% CI, 1.19-1.80) for extra- and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with ≥5 years of PPIs use, ruling out confounding by indication. CONCLUSIONS: In this study, long-term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.

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.).

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.

Taurine regulates mucosal barrier function to alleviate lipopolysaccharide-induced duodenal inflammation in chicken.

The objective of the study was to investigate how taurine alleviates mucosal injury. Young chickens were fed with taurine for 1 week and then challenged with lipopolysaccharide. We found that, under lipopolysaccharide challenge, taurine could attenuate diarrhea and mucosal inflammation. Additionally, under LPS challenge, taurine could enhance epithelial proliferation and goblet cell function, could also decrease epithelial apoptosis by improving the mitochondrial membrane permeability. The high-performance liquid chromatography assay showed that taurine feeding could elevate taurine concentration in duodenum obviously. The antioxidant assay showed that taurine could reverse lipopolysaccharide-induced low GSH level, GSH/GSSG ratio, GSH-Px activity and SOD activity, high GSSG and MDA content. In summary, we suggested that taurine could enhance duodenal antioxidant status locally and further ameliorated lipopolysaccharide-induced chicken duodenal inflammation by improving mitochondrial membrane permeability and goblet cell function.

Cytomegalovirus duodenitis in immunocompetent patients: what else should we look for?

Cytomegalovirus (CMV) infection is a well-recognised complication of immunodeficiency, although the burden of CMV disease in immunocompetent adults is still unknown. We present the case of a 54-year-old male patient admitted due to severe diarrhoea, epigastric pain and fever. Initial diagnostic workup revealed pericardial and pleural effusion, enlarged abdominal lymph nodes and mild elevation of liver enzymes. CMV serology was IgM positive, and upper endoscopy revealed proximal enteritis. Histology and immunohistochemistry of duodenal samples confirmed CMV disease. An extensive investigation of possible immunodeficiency was conducted with positron emission tomography (PET) scan revealing an abnormal hypermetabolic pulmonary nodule. The patient underwent a right superior lobectomy which, on analysis, confirmed an atypical bronchopulmonary carcinoid tumour. We report this case to reinforce the importance of considering CMV infection as a differential diagnosis in apparent immunocompetent patients and to emphasise the importance of looking for any condition that may cause any degree of immune dysfunction.

An Atypical Case of Leishmaniasis Associated with Chronic Duodenitis in a Dog.

We describe an atypical case of duodenal leishmaniasis in a boxer dog presenting with chronic diarrhea and poor general condition. Antidiarrheic therapy was previously administered without success and inflammatory bowel disease localized to the small intestine was suspected, given the chronic clinical signs and by ruling out other known causes of gastrointestinal inflammation. Endoscopic biopsy of duodenum showed a moderate increase in lamina propria lymphocytes, plasma cells, and macrophages. Basophilic bodies were seen in the cytoplasm of numerous macrophages, suggestive of Leishmania spp, confirmed by immunostaining, and a diagnosis of granulomatous duodenitis associated to Leishmania infection was made. After 7 mo of therapy, a significant clinical improvement and weight gain were observed, and endoscopic histology showed no evidence of Leishmania. A progressive decline of anti-leishmanial antibody titer was also observed during follow-up. This report emphasizes the importance of atypical symptoms and the unusual location of visceral leishmaniasis, suggesting the need to consider leishmaniasis in the differential diagnosis of canine chronic enteritis, especially in endemic areas.

Kyoto global consensus report on Helicobacter pylori gastritis.

OBJECTIVE: To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. DESIGN: Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. RESULTS: All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. CONCLUSIONS: A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject.

[CLINICAL FEATURES AND OPTIMIZATION OF THE TREATMENT OF CHILDREN WITH COMBINATION GASTRODUODENAL PATHOLOGY AND PRIMARY HYPERTENSION].

The paper present dynamic of clinical picture, daily blood pressure monitoring results and subjective assessment of functional status in children with combination of chronic gastroduodenal pathology and primary hypertension when L-carnitine used with the standard treatment regimen.

[THE EFFECTIVENESS OF A 10-DAY DRUG THERAPY IN CHILDREN WITH CHRONIC GASTRODUODENAL PATHOLOGY ASSOCIATED WITH CAGA-POSITIVE STRAINS OF HELICOBACTER PYLORI].

The results of triple Helicobacter-therapy (omeprazole, amoxicillin, nifuratel) in the treatment of chronic gastroduodenal pathology in children depending on the duration of it's use. The effectiveness of drug therapy was evaluated in terms of eradication of Helicobacter pylori and dynamics of pain, dyspeptic syndrome and astenovegetative syndrome.

High-dose methylprednisolone pulse therapy for treatment of refractory intestinal involvement caused by Henoch-Schönlein purpura: a case report.

INTRODUCTION: Henoch-Schönlein purpura is an immunoglobulin A-mediated, small vascular inflammatory disease that can be associated with palpable purpura, arthralgia, abdominal pain, or nephritis. The presence of purpura facilitates the diagnosis of Henoch-Schönlein purpura at the onset of associated symptoms, whereas the absence of purpura makes the diagnosis challenging. It is important to diagnose Henoch-Schönlein purpura with delayed-onset skin purpura to avoid unnecessary surgery for acute abdomen. Most cases of Henoch-Schönlein purpura with severe abdominal pain are treated with low-dose steroids and intravenous immunoglobulin. CASE PRESENTATION: A 15-year-old Korean girl complained of severe abdominal pain and delayed-onset purpura on admission. Henoch-Schönlein purpura was diagnosed based on endoscopic findings of hemorrhagic duodenitis and duodenal vasculitis and abdominal computed tomography findings of edematous bowels. Two common initial treatments, a low-dose steroid and intravenous immunoglobulin, were administered, but there was no improvement for 1 month. Subsequently, we used high-dose intravenous methylprednisolone pulse therapy (30 mg/kg/day, with a maximum of 1g/day), which dramatically alleviated her abdominal symptoms. CONCLUSIONS: High-dose intravenous methylprednisolone pulse therapy can be used as the ultimate treatment for delayed-onset Henoch-Schönlein purpura with severe abdominal pain when symptoms do not improve after low-dose steroid and intravenous immunoglobulin treatments.