Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

[Effect of 6-month S-methylmethionine intake on the quality of life and dyspepsia symptoms in patients with chronic gastritis].

S-methylmethionine (methylmethionine sulfonium chloride), better known as vitamin U, is a metabolic substrate that affects many metabolic processes in the human organism. Since its discovery, a large number of studies has been produced demonstrating its safety and effectiveness in various diseases, especially in diseases of the gastrointestinal tract. The purpose of the study was to evaluate the effect of methylmethionine sulfonium chloride (vitamin U) intake on the symptoms of dyspepsia and the quality of life of patients with chronic gastritis. Material and methods. The study included 37 patients (21 men and 16 women) aged 35-60 years with chronic gastritis of various etiologies. After inclusion in the study, all patients were prescribed S-methylmethionine at a dose of 300 mg per day. Clinical manifestations of dyspepsia were assessed using the GSRS questionnaire (Gastrointestinal Symptom Rating Scale), quality of life was assessed using the SF 36 questionnaire. The survey was conducted before the start of the therapy, after 3 and 6 months of complex diet therapy. Results. The most pronounced manifestations were dyspeptic (from 3 to 9 points) and diarrheal syndromes (from 2 to 5 points). Other indicators of the GSRS scale did not exceed 4 points. The total score was 15 points. By the 3rd month of therapy, there was a statistically significant decrease in the total score to 9 points (p<0.05). By the 6th month of therapy, the total GSRS score averaged 5.5 points (p<0.05). According to the SF 36 questionnaire, by the end of the 3rd month of therapy, indicators such as PF - physical functioning, BP - Bodily pain and SF - social functioning improved. By the end of the 6th month of therapy, several other indicators also improved (RP - role-physical functioning, GH - general perception of health, VT - viability, RE - Role-Emotional; MH - mental health) (p<0.05). Conclusion. The study showed that the appointment of dietary supplements containing methylmethionine sulfonium chloride at a dose of 300 mg per day helps to reduce the severity of dyspeptic symptoms in patients with chronic gastritis and their quality of life.

A Case Series on the Use of Dupilumab for Treatment of Refractory Eosinophilic Gastrointestinal Disorders.

The incidence and prevalence of eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC) are increasing ( 1 ). These conditions will inevitably become more widely recognized and better understood. There is currently no Food and Drug Administration (FDA)-approved treatment for EoE, but there are standard-of-care treatments that are well established and widely used. In contrast, there is a paucity of data regarding standard-of-care treatment for non-EoE eosinophilic gastrointestinal disorders (EGID). We identified 3 patients that all achieved clinical and histopathologic remission on dupilumab, a monoclonal antibody that blocks the downstream signaling of interleukin (IL)-4 and IL-13. These patients had extra-esophageal forms of EGID with two patients failing to achieve remission on standard-of-care therapies and one patient experiencing significant side effects on swallowed budesonide therapy. The reduction in mucosal eosinophilia in several GI tract segments in these 3 patients highlights a new potential clinical indication for dupilumab in the treatment of pediatric EGID patients.

Clinical features of pediatric eosinophilic gastroenteritis.

BACKGROUND: No study has analyzed more than100 cases of eosinophilic gastroenteritis (EGE) in children in a single center. We aimed to describe the clinical features of pediatric EGE. METHODS: This retrospective study was conducted at a single center. Between April 2007 and December 2017, 860 children between the ages of 1 year and 15 years underwent endoscopy for gastrointestinal symptoms of unknown cause. Among them, 109 (12.7%) were diagnosed with EGE according to the diagnostic criteria for EGE developed by the research group of the Ministry of Health, Labour and Welfare of Japan for eosinophilic gastrointestinal disorder in 2015. We investigated their symptoms, comorbidities, endoscopic findings, pathological findings, treatments, and outcomes. RESULTS: Seventy-one boys (65.1%) and 38 girls (34.9%) were diagnosed with EGE. The median age at diagnosis was 11 years (range, 1-15 years). The chief complaints were abdominal pain in 83 (76.1%) and diarrhea in 26 (23.9%). Upper and lower gastrointestinal endoscopies showed normal findings in 32 patients (29.4%). The most common treatment was a combination of elimination of foods suspected of causing EGE and anti-allergic agents in 50 cases (45.9%). The outcomes were symptom disappearance in 43 patients (39.4%) and symptom improvement in 53 patients (48.6%). CONCLUSIONS: For gastrointestinal symptoms of unknown cause in children, EGE should be considered as a differential diagnosis. Although the symptoms and endoscopic findings are nonspecific, cracked mucosa may be a specific endoscopic finding for pediatric EGE. An elimination diet and/or anti-allergic drugs were effective in most patients with pediatric EGE.

Emphysematous gastritis associated with mucormycosis in a patient with fulminant myocarditis requiring veno-arterial extracorporeal membrane oxygenation.

We present the case of a 37-year-old male who was admitted to our hospital with fever, weakness, limb pain for six days and dyspnea for 14 hours. The patient had no immune related diseases and was rapidly diagnosed with fulminant myocarditis, which progressed to severe cardiogenic shock during the early stage. Subsequently, he was treated with V-A extracorporeal membrane oxygenation (ECMO). It is worth mentioning that the patient's peripheral blood was taken for metagenomic next-generation sequencing (mNGS) upon admission and the results did not find any pathogenic bacteria. However, there was no further examination (such as coronary angiography and myocardial biopsy) to determine the etiology of myocarditis.

Super selective arterial embolization to treat radiation-induced hemorrhagic gastritis: a case report and review of the literature.

Radiation-induced hemorrhagic gastritis (RIHG) is a rare but potentially fatal event following radiotherapy for locally advanced gastric cancer; the treatment of this condition is not standardized. Only few cases of RIHG have been reported, treated with different therapeutic approaches. Here we report the case of a 79-year-old patient who underwent subtotal gastrectomy for gastric cancer, followed by adjuvant chemo-radiotherapy. Approximately 3 months after the end of the treatment, she developed recurrent diffuse bleeding originating from the entire mucosa of the gastric pouch and from a marginal ulcer. As the bleeding was refractory to several endoscopic treatments and surgery was not indicated, the patient underwent two sessions of transcatheter selective arterial embolization, with resolution of bleeding. Arterial embolization has already been reported for the treatment of hemorrhagic cystitis, developing after irradiation of the pelvis for prostate, bladder, rectum, and cervix cancer. However, to our knowledge, it has never been reported as a treatment for hemorrhagic gastritis. Based on this case, we suggest arterial embolization as an option in the management of RIHG, when standard endoscopic treatment fails.

Primary Eosinophilic Gastrointestinal Diseases Beyond Eosinophilic Esophagitis in Children.

OBJECTIVES: There are many unknowns about primary eosinophilic gastrointestinal disease (EGID) in childhood. The aim of this study is to provide data about the frequency, management, control level, and prognosis of well documented primary EGID in childhood. METHODS: This study was conducted in children who underwent endoscopy and/or colonoscopy at a single center over 10-year period up to August 2018. Primary EGID was diagnosed after exclusion of secondary EGID and classified as eosinophilic gastritis (EG), eosinophilic enteritis (EE), eosinophilic gastroenteritis (EGE: eosinophilic gastritis with eosinophilic enteritis) and eosinophilic colitis (EC) according to histopathological evaluation. The pathological number of eosinophil counts were accepted as >30 hpf for gastric mucosa in 5 hpf area, ≥20/hpf for duodenal, jejunal, and ileal mucosa, >50/hpf for right colonic mucosa, >35/hpf for transverse colonic mucosa, and >25/hpf for left colonic mucosa. Presenting symptoms, signs, management, follow-up, disease control level, and remission were analyzed. Remission is defined if the patient is controlled with all clinical, endoscopic/colonoscopic, and histopathologic parameters without any treatments or diet for at least a year. RESULTS: During the study period, 7457 biopsies were taken in 8262 endoscopy and/or colonoscopy procedures. Primary and secondary EGID frequencies were found 0.23% (n = 17 patients) and 0.1% (n =8 patients) per procedure with biopsy in children, respectively. Endoscopy/colonoscopy procedures were not able to performed in 9 patients because of short follow-up period (n = 6) or patients leaving follow-up (n = 3). Nine of the primary EGID patients had esophageal eosinophilia (EsE) at the time of diagnosis, 5 of them were previously managed as EoE. The median follow-up period of primary EGID patients excluding the ones without a control endoscopy/colonoscopy procedure was 3.35 years (min-max: 1.1-9.0 years). Proton pump inhibitors (PPI) were the most frequently used treatment alone or in combination with diet, systemic and/or topical corticosteroids. Disease control was evaluated in 8 of 17 patients and it was uncontrolled in 4, partially controlled in 1, and controlled in 3 patients. Remission was achieved in 2 patients. CONCLUSIONS: The frequency of primary EGID beyond eosinophilic esophagitis (EoE) in children is low. It may be difficult to achieve control in children with primary EGID in the long-term follow-up.

Treatment with proton pump inhibitors as a cofactor in adverse reactions of patients undergoing oral food immunotherapy.

BACKGROUND AND OBJECTIVES: Based on previous studies revealing acid-suppression medication as a risk factor for food allergy tolerance induction, we aimed to establish the importance of those findings in patients undergoing oral immunotherapy (OIT). MATERIALS AND METHODS, RESULTS: We describe a case series of four patients who underwent milk OIT with a concomitant use of proton pump inhibitor (PPI) medication and who developed anaphylaxis after a known, previously tolerated dose of milk. CONCLUSIONS: PPIs may act as a cofactor in patients undergoing OIT, triggering adverse reactions, irrespective of the PPI used or the dosage. It would be necessary to separate the administration of drug from food intake.Since OIT is a new form of treatment, long-term adverse events arising from PPI treatment and other possible triggers are still uncertain. Consequently, monitoring of patient must be prolonged over time. Additional investigations on the influence of different drugs in OIT maintenance phase are required.

Advancing patient care through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR).

Recent advances in rare disease research are accelerated by the work of consortia that have been supported by the National Institutes of Health. Development of such consortia rely on multidisciplinary relationships and engagement with patient advocacy groups, as well as the National Institutes of Health and industry and academic partners. In this rostrum we present the development of such a process that focuses on eosinophilic gastrointestinal diseases. Principal investigators, patient advocacy groups, research assistants, and trainees work together to perform natural history studies that promote clinical trial readiness tools, conduct clinical trials, train a new generation of investigators, and perform innovative pilot studies.

Future therapies for eosinophilic gastrointestinal disorders.

OBJECTIVE: To review novel therapeutics in development for treatment of eosinophilic gastrointestinal disorders (EGIDs). DATA SOURCES: Clinical trial data (clinicaltrials.gov) and literature search on PubMed. STUDY SELECTIONS: Studies on treatment and clinical trials in EGIDs were included in this review. RESULTS: During the past decade, significant progress has been made in understanding disease mechanisms in EGIDs. As a result, a variety of novel therapeutics have been developed for treatment of these disorders. Several monoclonal antibodies against targets, including interleukin (IL) 4, IL-5, IL-13, integrins, and siglec-8, have shown promise in early trials. Novel formulations of corticosteroids are also in development. CONCLUSION: The field of EGID research has advanced rapidly, and disease-modifying therapeutics are closer to clinical application.

Autoimmune Gastritis in Pediatrics: A Review of 3 Cases.

OBJECTIVES: To bring heightened awareness to a condition, autoimmune gastritis (AIG), which is a well-established entity in adults; however, rarely described in pediatrics. Currently, the literature describes AIG in pediatric patients who also suffer from other autoimmune disorders, which precedes the diagnosis of AIG, and often presents with unexplained anemia. Additionally, there have been case reports describing patients with immunodeficiencies and AIG, which progress to gastric adenocarcinoma. AIG is a histopathologic diagnosis, demonstrating chronic inflammatory process with loss of parietal cells with or without intestinal metaplasia and enterochromaffin-like cell hyperplasia. Management of these patients includes nutritional replacement as well as routine surveillance endoscopy with biopsy in search of metaplastic and dysplastic changes. METHODS: We queried the pathology database at Children's Hospital Los Angeles (CHLA) for cases with a final diagnosis of AIG and for those with a differential diagnosis that includes AIG in the diagnostic comment. All cases that were identified were selected as long as they did not only meet the histopathologic criteria, but also the biochemical criteria for this condition. RESULTS: Of the 3 patients, 2 were referred to gastroenterology for the evaluation of iron-deficiency anemia in the context of diabetes mellitus and Addison's disease; and diabetes mellitus and Hashimoto's thyroiditis. AIG was confirmed on the biopsies, which showed a reduction in parietal cell mass, pseudopyloric metaplasia and enterochromafin-like cell hyperplasia. Both patients were treated with iron replacement therapy. The third patient presented with symptomatic anemia and diagnosed with pernicious anemia without other autoimmune disorders. She was successfully treated with oral vitamin supplementation. In this case, serial gastric biopsies demonstrated stable intestinal metaplasia without evidence of dysplasia. CONCLUSION: Although AIG is rare in children, pediatric gastroenterologists and pathologists should have a heightened suspicion for this entity in those patients with a history of autoimmune disorders and/or pernicious anemia.

More than Just a Hole in the Wall: Evolving Management and Treatment Paradigms of Suppurative Gastritis.

Suppurative gastritis is an uncommon lesion and often an occult cause of upper abdominal pain without florid signs of a septic focus. There are two main phenotypic forms: (1) localized, also referred to as gastric abscess; and (2) diffuse, in which the differential diagnosis includes a more diverse range of benign and malignant lesions. Cross-section imaging such as CT allows for rapid diagnosis and demonstrates the location and extent, but not the specific etiology, of the lesion. High-frequency endoscopic ultrasound (EUS) and fine needle aspiration (FNA) have greatly improved the safety and diagnostic accuracy of suppurative gastritis. EUS/FNA provides an opportunity to arbitrate among infectious and malignant or benign tumors, to identify specific pathogens, and in cases of localized gastric abscesses, for resolution by decompression. More advanced endoscopic procedures are rapidly emerging to supplement EUS/FNA, which already demonstrate the promise of improved, minimally-invasive diagnosis and effective management for the diverse range of lesions causing suppurative gastritis.

Acute gastric necrosis caused by a ß-hemolytic streptococcus infection: a case report and review of the literature.

Acute necrotizing gastritis, which appears to be a variant of phlegmonous gastritis is the rarest cause of gastric necrosis. We report a case of a 57-year-old female patient with an acute necrotizing gastritis caused by a Group A ß-hemolytic streptococcus. The case presented herein is of unusual interest because only a limited number of case reports on this etiology have been published. Diagnosing infectious necrotizing gastritis remains complex because of its rarity and nonspecific clinical presentation. Nevertheless, prompt diagnosis is of high importance because necrotizing gastritis can progress rapidly into a more advanced stage causing septic shock or even death. In our opinion, early resection of necrotic gastric wall combined with adequate antimicrobial therapy is the cornerstone in treatment of necrotizing gastritis. We will present a case in which adequate medical treatment was not successful.

Illnesses Encountered During Medical Volunteering in Takeo Province, Cambodia.

Background and Objectives: Medical volunteering seeks to meet the clinical needs of underserved areas, but has been criticized for difficulties in addressing local health issues and resultant lack of sustainability. Our team has visited rural Cambodia annually since 2012. This study reports the illnesses encountered during the recent mission and share our experiences to improve the efficiency of medical volunteering. Materials and Methods: Infrastructure, such as public electricity or water, was unavailable, hence most medical care and records were hand-performed. We categorized (1) primary diagnoses (chief complaints) by duration of symptoms, and (2) primary and secondary diagnoses (illnesses that were not related to the chief complaint) by severity of illness since patients commonly reported multiple symptoms. Blood pressure and anthropometric values were also checked and analyzed. Results: We encountered 317 adult and 141 pediatric patients. Among adults, 61.3% had persistent chronic (>6 month) symptoms of their chief complaints. The commonest diagnoses of chronic symptoms were musculoarthritis (31.5%) and gastroesophageal reflux disease and/or gastritis (21.7%). Hypertension and/or cardiac problems were relatively common among males (13.6%). The most common diagnosis among the severest cases (specialized or intensive care recommended) was cardiac problems (14.8%), often with abnormalities in sonography or electrocardiogram. For children, the overwhelming majority of diagnoses were related to acute symptoms and low severity, and approximately half were cases of the common cold. Commonly prescribed drugs were antacids or mucosal protectors (31.3%), Non-steroidal anti-inflammatory drugs (NSAIDs) or other painkillers (27.6%), and antiparasites (17.7%) in adults, and NSAIDs (44.7%) and antiparasites (23.2%) in children. Among adults, 32.7% were diagnosed with hypertension, and body mass index (p = 0.003) and age (p < 0.001) were both correlated with hypertension and its grade. Conclusion: Our study offers practical help to volunteer health workers planning to visit Southeast Asia.

Retrospective study recommends endoscopy when diagnosing lymphocytic colitis or eosinophilic gastrointestinal disorder in children with abdominal pain.

AIM: This study assessed the prevalence, clinical presentation and outcome of lymphocytic colitis (LC) and eosinophilic gastrointestinal disease (EGID) in children with severe, recurrent abdominal pain (RAP), by describing the predominant symptoms, diagnostic approaches and treatment options. METHODS: We performed a retrospective follow-up study at a Danish regional hospital by reviewing the histology reports of the children who had undergone gastrointestinal endoscopy for RAP. Data were retrieved from the medical records of those who met the diagnostic criteria for LC and, or, EGID from 2011 to 2016. The study population comprised 381 patients who underwent a diagnostic process to clarify RAP. RESULTS: A total of 74 patients (39 females) aged 2-17 years, with severe RAP as the most predominant symptom underwent gastrointestinal endoscopy. This identified 16/74 (21.6%) with LC (n = 6) and, or, EGID (n = 11), which equated to 4.2% with RAP. No biochemical patterns of abnormalities were found. Medical treatment and, or, diet generally induced and maintained clinical remission. CONCLUSION: We found 16 children with LC and, or, EGID. The predominant symptom was severe RAP. All patients had a macroscopically normal mucosa at endoscopy, a specific histopathological feature and no characteristic biochemical findings. Endoscopy should be considered in these cases.

[Proinflammatory cytokines in the gastric juice in acid-related diseases before and after standart therapy.]

The aim of research was to evaluate the effectiveness of the effect of eradication therapy on the cytokine status of gastric juice in patients with chronic non-atrophic gastritis (CNG) and duodenal ulcer (DU) associated with Helicobacter pylori. Clinical observations and laboratory-instrumental studies performed in 95 patients aged 20 to 55 years with CNG and duodenal ulcer with determination of cytokine content of IL-1ß, IL-6 and TNF-α in the fasting portion of gastric juice. The most pronounced decrease in the content of proinflammatory cytokines in gastric juice on the background of treatment was found in patients of the 1st group who received combined therapy according to the scheme omeprazole + clarithromycin + amoxicillin. Analysis of the content of proinflammatory cytokines (IL-1ß, IL-6 and TNF-α) in gastric juice in patients with acute exacerbation showed that their concentration in all 8 patients after the course of therapy exceeded the norm (P < 0.05) and was IL -1ß - 30,30 + 1,15 pg/l, IL-6 - 10,4 + 0,83 pg / l and TNF-α - 32,5 + 1,13 pg / l. At the same time, the level of proinflammatory cytokines in gastric juice correlated with the degree of dissemination of H. pylori in the mucosa of the gastroduodenal zone. Helicobacter pylori infection in inflammation and ulceration in the mucous membrane of the stomach and duodenum, possibly in addition to other mechanisms, affects the activation of pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) in gastric juice. Incomplete eradication of H. Pylori after treatment during clinical endoscopic remission in patients with duodenal ulcer in the vast majority of cases is accompanied by the preservation of an increased level of pro-inflammatory cytokines in gastric juice, which may be one of the reasons for the relapse of the disease.

Eosinophilic gastrointestinal diseases beyond eosinophilic esophagitis.

OBJECTIVE: Eosinophilic gastrointestinal diseases (EGIDs) are a rare group of disorders that can have varied clinical presentations dependent on the involved segment within the gastrointestinal tract. Eosinophilic gastritis presents with abdominal pain or vomiting, eosinophilic gastroenteritis presents with diarrhea and anemia or hypoalbuminemia, and eosinophilic colitis can present with diarrhea or bloody stools. These nonspecific symptoms remain poorly understood in their relation to the underlying pathogenesis, but a significant percentage of patients have atopy. In this review, we discuss the current literature on EGIDs to promote a practical approach to diagnosis and care. DATA SOURCES: Review of published literature. STUDY SELECTIONS: Clinically relevant literature from 1900 through 2018 was obtained from a PubMed search. Those that addressed prevalence, diagnosis, clinical manifestations, natural history, and treatment of EGIDs were reviewed and are summarized in this article. RESULTS: Of the 485 articles found in the search, most of which were case reports, 71 were selected for review. The natural history of EGIDs is based primarily on case series and small numbers of patients, making therapeutic decisions difficult. Treatment remains limited to dietary restriction that is not effective in many patients and topical or systemic corticosteroids whose long-term use is to be avoided if possible. CONCLUSION: With the seeming increase in all types of EGIDs, phenotypic descriptions are emerging that will likely promote better understanding of the pathogenesis and identification of novel therapeutic targets.

Nonesophageal Eosinophilic Gastrointestinal Disorders: Clinical Care and Future Directions.

Eosinophilic gastrointestinal disorders are a set of conditions with a wide range of clinical manifestations and treatment modalities. The disorders are suspected to result from an abnormal inflammatory response to allergen (s), and individuals may develop a relapsing or chronic disease, if the allergen is not eliminated. Mechanisms of disease pathogenesis, including the humoral immune response, need to be fully elucidated. A variety of therapies are used, although there is a lack of well-defined randomized, prospective studies. Other therapeutic options are needed as the current treatments have potential concerns; elimination diets may impair a child's quality of life, and corticosteroids have adverse risks with long-term use. We review what is known about nonesophageal eosinophilic gastrointestinal disorders, and discuss research investigations which need to be conducted to facilitate diagnosis and enhance treatment methods.