There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia (FD). Importantly, inflammation may serve as a mediator between psychologic and physiologic functions. This manuscript reviews the literature implicating two inflammatory cell types, mast cells and eosinophils, in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD. There are a number of inciting events which may initiate an inflammatory response, and the subsequent recruitment and activation of mast cells and eosinophils. These include internal triggers such as stress and anxiety, as well as external triggers such as microbes and allergens. Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils. Evidence exists to suggest that combining "anti-inflammatory" medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD.

Both mucosal inflammation and psychologic dysfunction have been implicated in irritable bowel syndrome (IBS). While some relationships between inflammation (mast cells and eosinophils) and depression have been reported in adults with IBS, relationships between inflammation and psychologic function have not been studied in children and adolescents. The aims of the current study were to: (1) assess densities of colonic mast cells, eosinophils, and TH17 cells in youth with IBS; and, (2) explore relationships between these cells and specific IBS symptoms and psychologic functioning. Utilizing previously obtained biopsies from the descending and rectosigmoid colons, densities were determined for mast cells, eosinophils, and TH17 cells, respectively, in 37 youth with IBS and 10 controls. In IBS patients, densities were assessed in relation to specific IBS symptoms and in relation to self-report anxiety and depression scores. In both the descending and rectosigmoid colons, densities of mast cells, eosinophils, and TH17 cells were higher in IBS patients as compared to controls. In IBS patients, rectosigmoid mast cell density was higher in those reporting pain relief with defecation. Also, in IBS patients, rectosigmoid eosinophilia was associated with higher anxiety scores and eosinophil density correlated with depression scores. In the descending colon, eosinophil and mast cell densities both correlated with depression scores. In conclusion, mucosal inflammation (mast cells and eosinophils) is associated with pain relief with defecation and with anxiety and depression in youth with IBS. Chronic or recurrent abdominal pain affects a substantial proportion of children and adolescents 1,2. The majority of youth with chronic abdominal pain will not have an identified organic disease but will report symptoms consistent with one of the functional gastrointestinal disorders (FGIDs) as defined by Rome criteria 3,4. There are four pain related FGIDs with irritable bowel syndrome (IBS) being one of the two most common 5. Rome IV, the most current version of Rome criteria, defines IBS by the presence of one of the following symptoms: pain related to defecation, pain associated with a change in stool frequency, or pain associated with a change in stool form 4. IBS is further subcategorized as IBS with predominant constipation (IBS-C), IBS with predominant diarrhea (IBS-D), mixed IBS with alternating constipation and diarrhea (IBS-M), and as unsubtyped 4,6. Among a variety of other factors, visceral hyperalgesia, inflammation and psychosocial factors have been highly implicated in the pathogenesis of IBS 7,8. Inflammatory cells which have been evaluated in IBS include mast cells, eosinophils, and lymphocytes, particularly T cells. Mast cells have been highly implicated in IBS pathogenesis in both IBS-C and IBS-D 9,10. IBS has been associated with an increase in the density of degranulating mast cells, while the density of mast cells in close proximity to enteric nerves correlates with abdominal pain severity 11 .

Functional gastrointestinal disorders (FGID) are common clinical syndromes diagnosed in the absence of biochemical, structural, or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age, geography, and culture. Etiology of abdominal pain associated FGIDs, including functional dyspepsia (FD), remains incompletely understood, but growing evidence implicates the importance of visceral hypersensitivity and electromechanical dysfunction. This manuscript explores data supporting the role of visceral hypersensitivity and electromechanical dysfunction in FD, with focus on pediatric data when available, and provides a summary of potential therapeutic targets. Visceral sensitivity and intestinal electromechanical function both are demonstrated to be altered in some FD patients and are potential targets for treatment. Limited studies in pediatric FD are available, but available evidence supports adult data that targeting visceral hypersensitivity and electromechanical dysfunction is warranted, particularly in the context of the biopsychosocial model. Future studies in pediatrics are needed to determine optimal therapy and appropriate patient application.Rosen JM, Cocjin JT, Schurman JV, Colombo JM, Friesen CA. Visceral hypersensitivity and electromechanical dysfunction as therapeutic targets in pediatric functional dyspepsia. World

Ranitidine has been the topic of recent media reports. Current findings, confirmed by the US Food and Drug Administration, indicate that some ranitidine products contain a substance that may be carcinogenic. Providers and patients require additional information on the risks of continuing therapy vs. the benefits of the medication. This article comments on what is currently known about the evolving situation of elevated N‐nitrosodimethylamine levels in ranitidine and the limits of the existing information to assess best practices.

Educational Gap A recent study in Pediatrics concluded that 25% of children with functional constipation continued to experience symptoms at adult age, suggesting that referral to specialized clinics at an early stage for children who are unresponsive to first-line treatment may help improve outcomes. (1) Objectives After completing the article, the reader should be able to: 1. Know that constipation is a common problem in childhood with a diverse clinical presentation. 2. Understand that functional constipation is a symptom-based diagnosis that does not require extensive testing. 3. Recognize that most children who present with fecal incontinence or encopresis have associated constipation. 4. Describe the treatment of constipation and encopresis, which should include a medical-behavioral approach that focuses on maintaining soft and regular bowel movements and improving toileting behavior. AUTHOR DISCLOSURE Drs Colombo, Wassom, and Rosen have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Chronic abdominal pain is very common in children and adolescent and results in high personal and social costs. Most youth with chronic abdominal pain fulfill criteria for a functional abdominal pain disorder (FAPD) as defined by Rome criteria. These are complex conditions with a wide array of biological, psychological, and social factors contributing to the experience of pain. The purpose of the current review is to provide an overview of the pathophysiology of FAPDs and an up-to-date summary of the literature related to FAPDs in children and adolescents, with additional focus on several areas (eg, diet and probiotics) where patients and families frequently have questions or implement self-directed care. We also provide an approach to the assessment and treatment of pediatric FAPDs focusing on the robust literature regarding psychological interventions and much sparser literature regarding medication treatment.

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