A Pilot Study of Ketotifen in Patients Aged 8-17 Years with Functional Dyspepsia Associated with Mucosal Eosinophilia.

BACKGROUND AND OBJECTIVE: Mast cells have been implicated in abdominal pain-associated disorders of gut-brain interaction, such as functional dyspepsia. As such, ketotifen, a second-generation antihistamine and mast cell stabilizer, could represent a viable treatment option in these conditions. The primary aim of the current pilot study was to assess clinical response to ketotifen and assess pharmacokinetics in youth with functional dyspepsia. METHODS: We conducted a pilot randomized, double-blind, placebo-controlled, cross-over trial of ketotifen in 11 youth with functional dyspepsia and duodenal mucosal eosinophilia with 4 weeks of active treatment at a dose of 1 mg twice daily. Global clinical response was graded on a 5-point Likert Scale. A single plasma sample was obtained at steady state for pharmacokinetic analysis. RESULTS: Ketotifen was not superior to placebo with regard to global clinical response. Only 18% of patients demonstrated a complete or near-complete clinical response. The estimated half-life was 3.3 h. CONCLUSIONS: While ketotifen was not superior to placebo, this study highlights several important challenges for developing drug trials for youth with chronic abdominal pain. Recommendations are made for designing a larger treatment trial for ketotifen in this patient group. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov: NCT02484248.

Meal related symptoms in youth with chronic abdominal pain: Relationship to anxiety, depression, and sleep dysfunction.

OBJECTIVE: The objective of the current study was to describe meal-related symptoms in youth with chronic abdominal pain fulfilling criteria for a disorder of gut-brain interaction (DGBI) and their associations with anxiety, depression, and sleep disturbances. METHODS: This was a retrospective evaluation of 226 consecutive patients diagnosed with an abdominal pain-associated DGBI. As part of routine care, all had completed a standardized symptom history, the Sleep Disturbances Scale for Children (utilized to assess for disorders of initiation and maintenance of sleep and excessive daytime somnolence) and the Behavior Assessment System for Children-Third Edition (utilized to assess for anxiety and depression). Four meal related symptoms were assessed: early satiety, postprandial bloating, postprandial abdominal pain, and postprandial nausea. RESULTS: Overall, 87.6% of patients reported at least one meal related symptom and the majority reported at least three symptoms. All meal related symptoms were significantly related to each other. Postprandial pain and nausea were more often reported by females. Early satiety, postprandial bloating, and postprandial nausea, but not postprandial pain demonstrated significant though variable associations with anxiety, depression, disorders of initiation and maintenance of sleep, and disorders of excessive somnolence, but only in adolescents. CONCLUSIONS: Meal related symptoms are very common in youth with abdominal pain-associated DGBIs. Early satiety, bloating, and postprandial nausea demonstrate variable associations with anxiety, depression, and disordered sleep while increased postprandial pain was not associated with psychologic or sleep dysfunction, suggesting a different pathway for symptom generation.

Overactive bladder syndrome symptoms in youth with abdominal pain-associated disorders of gut-brain interaction.

The purpose of the current study was to assess the frequency of overactive bladder syndrome (OBS) symptoms and their relationship to gastrointestinal symptoms in youth with abdominal pain-associated disorders of gut-brain interaction (AP-DGBI). This is a retrospective study of 226 youth diagnosed with an AP-DGBI. As part of standard care, all patients completed a symptom questionnaire regarding gastrointestinal and non-gastrointestinal symptoms including increased urinary frequency, nighttime urination, and urinary urgency. Overall, 54% of patients reported at least one OBS symptom. Increased frequency of urination was reported by 19%, urinary urgency by 34%, and nighttime urination by 36%. Increased frequency of urination and urinary urgency were associated with a change in stool form, a change in stool frequency, and in those fulfilling criteria for IBS. Increased frequency of urination was reported more frequently in those reporting predominantly loose stools (33% vs. 12%). Urinary symptoms are common in youth with AP-DGBI. Increased urinary frequency and urinary urgency are specifically associated with IBS, with increased urinary frequency being primarily associated with diarrhea predominant IBS. Further studies are needed to determine the impact of OBS on AP-DGBI severity and quality of life, and whether they impact DGBI treatment.

A Cross-Sectional Study of Sleep Disturbances in Children and Adolescents With Abdominal Pain-Associated Disorders of Gut-Brain Interaction.

The aims of the current study were to determine the frequencies of specific sleep disturbances in youth with abdominal pain-associated disorders of gut-brain interaction (AP-DGBIs) and to assess relationships with psychological dysfunction. This was a retrospective evaluation of 226 consecutive patients diagnosed with an AP-DGBI. All had undergone a systematic evaluation of gastrointestinal symptoms, the Sleep Disturbance Scale for Children, and the Behavior Assessment System for Children. Disorders of initiation and maintenance of sleep (DIMS; 40%) and disorders of excessive daytime somnolence (DOES; 14%) were each present in more than 10% of the patients. Both DIMS and DOES scores were more likely to be elevated in patients with anxiety and/or depression scores in the at-risk or elevated-risk ranges. Sleep disorders are common in youth with AP-DGBIs and are associated with anxiety and depression, even in those patients with anxiety and depression in the at-risk range.

Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils.

BACKGROUND: Eosinophilic esophagitis (EoE) is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies. A non-invasive and cost-effective alternative for management of EoE is being researched. Previous studies assessing utility of fractional exhaled nitric oxide (FeNO) in EoE were low powered. None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO. AIM: To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity. METHODS: Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study. Patients on steroids and with persistent asthma requiring daily controller medication were excluded. FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer (NIOX MINO, Aerocrine, Inc.; Stockholm, Sweden) prior to endoscopy. Based on the esophageal peak eosinophil count (PEC)/high power field on biopsy, patients were classified as EoE (PEC ≥ 15) or control (PEC ≤ 14). Mean FeNO levels were correlated with presence or absence of EoE, eosinophil counts on esophageal biopsy, and abnormal downstream eosinophilia in the stomach (PEC ≥ 10) and duodenum (PEC ≥ 20). Wilcoxon rank-sum test, Spearman correlation, and logistic regression were used for analysis. P value < 0.05 was considered significant. RESULTS: We recruited a total of 134 patients, of which 45 were diagnosed with EoE by histopathology. The median interquartile range FeNO level was 17 parts per billion (11-37, range: 7-81) in the EoE group and 12 parts per billion (8-19, range: 5-71) in the control group. After adjusting for atopic diseases, EoE patients had significantly higher FeNO levels as compared to patients without EoE (Z = 3.33, P < 0.001). A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels (r = 0.30, P < 0.005). On subgroup analysis within the EoE cohort, higher FeNO levels were noted in patients with abnormal gastric (n = 23, 18 vs 15) and duodenal eosinophilia (n = 28, 21 vs 14); however, the difference was not statistically significant. CONCLUSION: After ruling out atopy as possible confounder, we found significantly higher FeNO levels in the EoE cohort than in the control group.

Nonanaphylactic Variant of Alpha-Gal Syndrome as an Etiology for Chronic Gastrointestinal Symptoms in Children.

We report 3 pediatric patients who presented with only nonanaphylactic symptoms of alpha-gal syndrome. This report highlights the necessity of not discounting alpha-gal syndrome from a differential diagnosis for patients with recurrent gastrointestinal distress and emesis after consuming mammalian meat, even in the absence of an anaphylactic reaction.

Microtemporal Relationships in the Fear Avoidance Model: An Ecological Momentary Assessment Study.

OBJECTIVES: Current literature in pediatric pain evaluates the Fear Avoidance model (FAM) pathways at the trait (or macrotemporal) level, but it is unknown if these pathways also occur at the state (or microtemporal) level. Identifying microtemporal processes can improve our understanding of how the relationships within the Fear Avoidance constructs vary when specific Fear Avoidance variables wax and wane. We hypothesized that changes in FAM constructs would be associated with changes in the next variable in the sequence on a microtemporal level, including: (1) higher pain when there is more pain-related fear, (2) higher pain-related fear when there is more avoidance, and (3) higher avoidance when there is more reported disability. METHODS: 71 pediatric patients with chronic abdominal pain ( M =13.34 y, SD=2.67 y) reported pain severity, pain-related fear, and avoidance via ecological momentary assessments over 14 days. RESULTS: Our results indicated significant microtemporal relationships between Fear Avoidance constructs for pain predicting pain-related fear, pain-related fear predicting avoidance, and avoidance predicting disability. DISCUSSION: The current study suggests that the ways in which the FAM is related to various aspects of pain functioning differs on a state-level, which adds new clinical and research opportunities.

The effect of neuropsychiatric medication on pediatric nonalcoholic fatty liver disease.

Obese and overweight children are at risk of developing nonalcoholic fatty liver disease (NAFLD), which can lead to steatohepatitis, cirrhosis, and liver transplantation. Neuropsychiatric conditions affect an increasing proportion of children and often require neuropsychiatric medications (NPMs) that are associated with weight gain and/or drug-induced liver injury. We sought to evaluate the role that the extended use of NPMs play in pediatric NAFLD. Medical chart review was conducted for 260 patients with NAFLD (NPM = 77, non-NPM = 183) seen in the Liver Care Center at Children's Mercy Hospital between 2000 and 2016. Outcome measures included body mass index (BMI) percentile, BMI z-score, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and gamma glutamyltransferase, and were collected at diagnosis, 6-18 month follow-up, and 18-36 months. Controlling for race and metformin, there was a significant increase over time in BMI z-score (p < 0.01) and total bilirubin (p = 0.03), with only initial decreases in ALT (p < 0.01) and AST (p < 0.01). Except for higher total bilirubin in the non-NPM group, no main effect of group or interaction effect was found. Similar patterns remained when subjects were analyzed by NPM drug class. Further study is needed to confirm these findings and to evaluate the effects of NPM dose and duration of exposure, by drug class, on pediatric NAFLD outcomes.

Pediatric Rome IV diagnosis agreement is greater than agreement on diagnostic testing.

BACKGROUND: Pediatric Rome IV criteria are used to diagnose childhood functional gastrointestinal disorders (FGIDs). This study of pediatric gastroenterology physicians measured their agreement in (1) Making a pediatric Rome IV FGID diagnosis; and (2) Diagnostic testing for patients with FGIDs. METHODS: Pediatric gastroenterologists and pediatric gastroenterology fellows at two medical centers completed a survey containing clinical FGID vignettes. For each vignette, raters identified the most likely Rome IV diagnosis(es) and selected which diagnostic test(s) (if any) they typically would obtain. The survey was re-administered within 3 months. Inter-rater and intra-rater weighted percent agreement was determined. Linear mixed modeling identified sources of variability in diagnostic testing. KEY RESULTS: Thirty-four raters completed the initial survey of whom thirty-one (91%) completed the repeat survey. Overall inter-rater agreement on Rome IV diagnoses was 68% for initial and repeat surveys whereas intra-rater agreement was 76%. In contrast, overall inter-rater agreement on diagnostic testing was <30% for both initial and repeat surveys and intra-rater agreement was only 57%. Between-physician differences accounted for 43% of the variability in the number of tests selected. Rater identified use of Rome criteria in clinical practice was associated with 1.1 fewer diagnostic tests on average (95% CI 0.2-2.0, p = 0.015). Higher intra-rater agreement was noted for diagnostic testing in faculty when compared to fellows (p = 0.009). CONCLUSIONS & INFERENCES: In a multicenter evaluation among pediatric gastroenterology physicians, pediatric Rome IV diagnostic agreement was higher than that reported for previous Rome versions, and higher than agreement on diagnostic testing.

High Rate of Emergency Department Care in Youth With Abdominal Pain-Associated Functional Gastrointestinal Disorders.

OBJECTIVES: The primary objective was to describe patterns of care delivery locations in youth with abdominal pain-associated functional gastrointestinal disorders (AP-FGID) and assess for differences in patterns of care delivery by sex and race. A secondary objective was to describe cost variability within the emergency department (ED). METHODS: Data were obtained using a large, single-vendor database that extracts and deidentifies data from the electronic health record across the outpatient, ED, and inpatient continuum of care. We evaluated patients 8 to 17 years of age seen over an 8-year period for a priority 1 diagnosis of an AP-FGID. Data collected included age, sex, race, encounter location, and total cost of ED encounters. We specifically assessed how often patients seen in the ED were also seen in outpatient or inpatient settings. RESULTS: A total of 53,750 patients (64% female; mean age, 13.3 ± 2.8 years) were identified and assessed. The most common location of care was the ED (48.8%) followed by the outpatient setting (46.2%). Of patients seen for a priority 1 AP-FGID diagnosis in the ED, only 3.7% were seen for a priority 1 diagnosis in the outpatient setting, and only 1% were seen in an inpatient setting. Overall, females received 42.5% of their care and males received 44.8% of their care in the ED. The overall rate of ED care was 66.9% for Hispanic, 61.5% for African American, 55.1% for Asian, 46.6% for Native American, and 36.9% for Caucasian patients. CONCLUSIONS: The ED is the most common location for care for youth with AP-FGIDs and, for the majority, seems to be the only location. This seems to be particularly true for Hispanic and African American patients. Given the often complex psychosocial needs of this patient group, processes need to be developed to transition these patients into the outpatient setting, ideally to programs specializing in chronic pain.

Presence of Increased Mast Cells in Infants and Children with Volume and Variety Limited Intake.

BACKGROUND: Reports indicate patients with feeding difficulties demonstrate signs of inflammation on biopsies, notably eosinophilia, but it is unknown whether mast cell density contributes to variety or volume limitation symptoms. The aim of our study was to evaluate eosinophil and mast cell density of EGD biopsies in pediatric patients with symptoms of decreased volume or variety of ingested foods. METHODS: We conducted a single-center, retrospective chart review of EMRs for all new feeding clinic patients between 0 and 17 years of age. Patients were categorized by symptoms at the initial visit as well as eosinophil and mast cell densities in those with EGD biopsies. Ten patients were identified as controls. RESULTS: We identified 30 patients each with volume and variety limitation. Antral mast cell density was increased in 32.1% of variety-limited patients, 37.5% of volume limited patients, and in no controls; Duodenal mast cell density was increased in 32.1% of variety-limited patients, 40.6% of volume-limited patients, and in no controls. CONCLUSIONS: In both variety- and volume-limited patients, antral and duodenal mast cell densities were increased. These associations warrant further investigation of the mechanism between mast cells and development of feeding difficulties, allowing more targeted pediatric therapies.

Healthcare System-to-System Cost Variability in the Care of Pediatric Abdominal Pain-Associated Functional Gastrointestinal Disorders.

The purpose of this study was to assess cost variability in the care of abdominal pain-associated functional gastrointestinal disorders (AP-FGIDS) in youth across health systems, races, and specific AP-FGID diagnoses. Patients, aged 8-17 years, with a priority 1 diagnosis corresponding to a Rome IV defined AP-FGID were identified within the Health Facts® database. Total costs were obtained across the continuum of care including outpatient clinics, emergency department, and inpatient or observation units. Cost variability was described comparing different health systems, races, and diagnoses. Thirteen thousand two hundred and fourteen patients were identified accounting for 17,287 encounters. Total costs were available for 38.7% of the encounters. There was considerable variability in costs within and, especially, across health systems. Costs also varied across race, urban vs. rural site of care, and AP-FGID diagnoses. In conclusion, there was considerable variability in the costs for care of AP-FGIDs which is sufficient to support multi-site studies to understand the value of specific tests and treatments. Significant differences in costs by race merit further investigation to understand key drivers.

Rumination Syndrome in Children and Adolescents: A Mini Review.

Introduction: Rumination syndrome involves recurrent regurgitation of food and is believed to be underdiagnosed with patients experiencing long delays in diagnosis. It can be associated with significant social consequences, high rates of school absenteeism, and medical complications such as weight loss. The primary aims of the current review are to assess the literature regarding prevalence, pathophysiology, and treatment outcomes with a focus on neurotypical children and adolescents. Results: Population studies in children/adolescents, 5 years of age or older, range from 0 to 5.1%. There are fewer studies in clinical settings, but the prevalence appears to be higher in patients with other gastrointestinal symptoms, particularly chronic vomiting. While physiologic changes that occur during a rumination episode are well-described, the underlying cause is less well-defined. In general, rumination appears to have similarities to other functional gastrointestinal disorders including dysmotility, possibly inflammation, and an interaction with psychologic function. While diaphragmatic breathing is considered the mainstay of treatment, pediatric data demonstrating efficacy is lacking, especially as an isolated treatment. Conclusion: Pediatric rumination syndrome remains greatly understudied, particularly regarding treatment. There is a need to better define prevalence in both the primary care and subspecialty clinical settings, especially in patients presenting with vomiting or apparent gastroesophageal reflux. There is a need to determine whether treatment of co-morbid conditions results in improvement of rumination. Diaphragmatic breathing needs to be studied and compared to other competing responses.

An Update on the Assessment and Management of Pediatric Abdominal Pain.

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.

Update on the Role of Allergy in Pediatric Functional Abdominal Pain Disorders: A Clinical Perspective.

Both functional abdominal pain disorders (FAPDs) and food allergies are relatively common in children and adolescents, and most studies report an association between FAPDs and allergic conditions. FAPDs share pathophysiologic processes with allergies, including both immune and psychological processes interacting with the microbiome. No conclusive data are implicating IgE-mediated reactions to foods in FAPDs; however, there may be patients who have IgE reactions localized to the gastrointestinal mucosa without systemic symptoms that are not identified by common tests. In FAPDs, the data appears stronger for aeroallergens than for foods. It also remains possible that food antigens initiate an IgG reaction that promotes mast cell activation. If a food allergen is identified, the management involves eliminating the specific food from the diet. In the absence of systemic allergic symptoms or oral allergy syndrome, it appears unlikely that allergic triggers for FAPDs can be reliably identified by standard testing. Medications used to blunt allergic reactions or symptomatically treat allergic reactions may be useful in FAPDs. The purpose of the current manuscript is to review the current literature regarding the role of allergy in FAPDs from a clinical perspective, including how allergy may fit in the current model of FAPDs.

Mucosal eosinophils, mast cells, and intraepithelial lymphocytes in youth with rumination syndrome.

BACKGROUND: Rumination syndrome has been associated with increased duodenal eosinophils and intraepithelial lymphocytes in adults. The aims of the current study were to assess densities of antroduodenal eosinophils and mast cells and duodenal intraepithelial lymphocytes in youth with rumination syndrome and to compare cell densities in those with and without abdominal pain or early satiety. METHODS: Twenty-eight youth fulfilling Rome IV criteria for rumination syndrome who had undergone endoscopy were identified and compared to 10 controls. Antral and duodenal biopsies were assessed to determine densities of eosinophils, mast cells, and intraepithelial lymphocytes. Cell densities were also compared between rumination patients with and without abdominal pain and those with and without early satiety. KEY RESULTS: Antral mast cell (peak 18.5±6.5 vs. 12.5±2.7) and eosinophil (peak 9.6±5.2 vs. 4.9±2.1) densities were significantly greater in patients with rumination syndrome as compared to controls. Duodenal intraepithelial lymphocyte densities were also increased in rumination syndrome (18.9 ± 5.1 vs. 11.7 ± 1.5; p<.001). Associations were independent of the presence of abdominal pain or early satiety. CONCLUSIONS AND INFERENCES: In conclusion, we found an increase in eosinophil and mast cell densities in the gastric antrum and an increase in intraepithelial lymphocytes in the duodenum in youth with rumination syndrome which was independent of the presence of abdominal pain or early satiety. These findings suggest a potential role for inflammation in the pathophysiology of rumination syndrome. Future studies should address whether treatment directed at these cells are beneficial in treating rumination syndrome.

Colonic mucosal eosinophilia in children without inflammatory bowel disease.

Children undergoing colonoscopy and mucosal biopsies may show increased colonic mucosal eosinophils, which may or may not be associated with inflammatory bowel disease. There is not much clinical data on American children who have isolated increased colonic mucosal eosinophils. We sought to study the clinical correlates of children without inflammatory bowel disease who show increased mucosal eosinophils to understand their clinical presentation, etiological associations, and outcome. A retrospective analysis of children seen at a tertiary-level Children's hospital was performed by reviewing their medical charts and extracting pertinent data. There were 110 children in the study who had increased colonic mucosal eosinophils. Most children presented with abdominal pain, but several of them also had constipation, blood in stools, and diarrhea. Food allergies, irritable bowel syndrome, asthma, and lactase deficiency were the top four conditions present in these patients. Pathology of the colonic distribution revealed involvement of more than two colonic regions in 86% of the subjects, and only two subjects showing epithelial or crypt involvement by eosinophils. All subjects had a good outcome. Children with colonic mucosal eosinophilia (CME) who do not have an inflammatory bowel disease most frequently present with abdominal pain and primarily an increase of lamina propria eosinophils in two or more colonic regions. Based on the etiological associations we noted in the study, a work-up of children with CME may encompass detailed history for functional gastrointestinal disorders and lactose intolerance, testing for food and environmental allergies, stool examination for parasites, and peripheral blood counts. Almost all children had resolution of symptoms in the studied period suggesting that CME in children has a good clinical outcome.

Leveraging Institutional Support to Build an Integrated Multidisciplinary Care Model in Pediatric Inflammatory Bowel Disease.

While the biopsychosocial nature of inflammatory bowel disease (IBD) is now well accepted by clinicians, the need for integrated multidisciplinary care is not always clear to institutional administrators who serve as decision makers regarding resources provided to clinical programs. In this commentary, we draw on our own experience in building successful integrated care models within a division of pediatric gastroenterology (GI) to highlight key considerations in garnering initial approval, as well as methods to maintain institutional support over time. Specifically, we discuss the importance of making a strong case for the inclusion of a psychologist in pediatric IBD care, justifying an integrated model for delivering care, and addressing finances at the program level. Further, we review the benefit of collecting and reporting program data to support the existing literature and/or theoretical projections, demonstrate outcomes, and build alternative value streams recognized by the institution (e.g., academic, reputation) alongside the value to patients. Ultimately, success in garnering and maintaining institutional support necessitates moving from the theoretical to the practical, while continually framing discussion for a nonclinical/administrative audience. While the process can be time-consuming, ultimately it is worth the effort, enhancing the care experience for both patients and clinicians.

Heartburn in children and adolescents in the presence of functional dyspepsia and/or irritable bowel syndrome correlates with the presence of sleep disturbances, anxiety, and depression.

ABSTRACT: The aim of this study was to assess the relationship of heartburn in pediatric patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS) with gastrointestinal symptoms, sleep disturbances, and psychologic distress.The overlap in symptoms of FD, IBS, and gastroesophageal reflux disease (GERD) predicts greater symptom severity and decreased quality of life and presents opportunities for improved diagnostic classification and personalized therapeutics.A cross-sectional observational study of 260 pediatric patients with abdominal pain was conducted. Patients completed standardized questionnaires assessing clinical symptoms, sleep quality, and psychologic symptoms during routine clinical care. Questionnaire data were compared for patients reporting heartburn and not reporting heartburn using χ2 and t tests where appropriate.Gastrointestinal symptoms were significantly more prevalent among patients with a positive report of heartburn (vs a negative report of heartburn): pain with eating (83% vs 67%, P = .007), bloating (63% vs 44%, P = .005), acid regurgitation (47% vs 24%, P ≤ .001), and chest pain (45% vs 20%, P ≤ .001). Likewise, initiating and maintaining sleep (P = .007), arousal/nightmares (P = .046), sleep-wake transition (P = .001), hyperhidrosis during sleep (P = .016), and anxiety (P = .001) and depression (P = .0018) were also significantly increased in patients who reported heartburn versus patients who did not report heartburn.Patients with a positive report of heartburn, whether classified as having FD and/or IBS, had increased gastrointestinal symptoms, sleep disturbances, anxiety, and depression than patients with a negative report of heartburn. A better understanding of these associations may allow for personalized treatment for youth with abdominal pain and heartburn as a primary symptom.

Relationships between disaccharidase deficiencies, duodenal inflammation and symptom profile in children with abdominal pain.

Abdominal pain has been associated with disaccharidase deficiencies. While relationships with individual symptoms have been assessed, relationships between disaccharidase deficiencies and symptom complexes or inflammation have not been evaluated in this group. The primary aims of the current study were to assess relationships between disaccharidase deficiency and symptoms or symptom complexes and duodenal inflammation, respectively. Patients with abdominal pain who underwent endoscopy with evaluation of disaccharidase activity levels were identified. After excluding all patients with inflammatory bowel disease, celiac disease, H. pylori, or gross endoscopic lesions, patients were evaluated for disaccharidase deficiency frequency. Disaccharidase were compared between patients with and without histologic duodenitis. Lastly, relationships between individual gastrointestinal symptoms or symptom complexes were evaluated. Lactase deficiency was found in 34.3% of patients and disaccharidase pan-deficiency in 7.6%. No individual symptoms or symptom complexes predicted disaccharidase deficiency. While duodenitis was not associated with disaccharidase deficiency, it was only present in 5.9% of patients. Disaccharidase deficiency, particularly lactase deficiency, is common in youth with abdominal pain and multiple deficiencies are not uncommon. Disaccharidase deficiency cannot be predicted by symptoms in this population. Further studies are needed to assess the clinical significance of disaccharidase deficiency.