Craig A. Friesen

Diagnosing functional abdominal pain with the Rome II criteria: parent, child, and clinician agreement.

Objectives: To compare the Rome II diagnoses made in children with recurrent abdominal pain by physicians and by parent and child responses on the Questionnaire on Pediatric Gastrointestinal Symptoms. Rates of diagnostic agreement and reasons for disagreement were examined to determine whether changes to the Rome II criteria are needed to improve diagnostic classification. Methods: One hundred and forty-eight children and their parents or guardians completed the Questionnaire on Pediatric Gastrointestinal Symptoms during their first visit to a pediatric gastroenterology clinic. Parent- and child-report Rome II diagnoses were based on Questionnaire on Pediatric Gastrointestinal Symptoms scoring criteria, whereas the physicians Rome II diagnosis was based on clinical impression from history and physical examination completed at this visit. Statistical comparisons involved Pearson χ2 tests and Fisher exact tests. Kappa and weighted kappa measured agreement rates. Results: Most children met the criteria for a functional gastrointestinal disorder based on the Rome II criteria. Functional dyspepsia was the most common diagnosis made by all three sources. The percentage of children classified as “no diagnosis” was small and was often a function of symptom duration (especially when diagnosis rested on the child self-report). Diagnostic agreement was fair to moderate. Diagnoses based on parent and child questionnaires agreed more often on functional dyspepsia than irritable bowel syndrome. Diagnostic disagreement was most likely to result from parent and child disagreement on defecation symptoms. Conclusions: The Rome II classification system shows promise for improving diagnosis, study and treatment of children with recurrent abdominal pain. However, further refinement and clarification of the Rome II criteria for symptom duration and frequency may be needed to improve diagnostic agreement.

Clinical Characteristics in Children Case Analysis and Literature Review

Thirty-five cases of cholelithiasis diagnosed at a childrens hospital over a 7.5-year period are reviewed and compared to 693 cases of pediatric gallstones reported in the literature. Symptomatology and associated medical history are more important in diagnosing cholelithiasis than are laboratory tests. Hemolytic disease is the most common associated condition in our series (46%) as well as in the literature (30%), but the frequency of the various associated conditions varies with age. Isolated gallstone disease does occur, particularly in the young infant. Jaundice is the most common symptom in children less than 1 year of age, being present in greater than 90 percent of symptomatic patients previously reported. Overall, the most common symptom in our series is vomiting (60%). Right upper quadrant pain in the absence of vomiting does not appear to be significant, as this occurred in only one patient (3%) in our series.

Clinical Efficacy and Pharmacokinetics of Montelukast in Dyspeptic Children with Duodenal Eosinophilia

Background Montelukast, a competitive cysteinyl leucotriene-1 receptor antagonist, reduces airway eosinophilia in asthmatics. We evaluated the effect of this drug in children with eosinophilic duodenitis, defined histologically as duodenal mucosa with peak eosinophil count of more than 10 eosinophils/hpf. Methods Forty children and adolescents (6–18 yr) with dyspepsia and duodenal eosinophilia were enrolled in a double blind, randomized, placebo-controlled, cross-over study of monteleukast therapy. Subjects were randomized to receive either 10 mg montelukast or an identical placebo once daily and were evaluated on day 14 for symptomatic and biochemical responses. Subjects were also randomized to one of two blood sampling schemes to evaluate montelukast pharmacokinetics. Results Using a post treatment global pain assessment, a positive clinical response was observed in 62.1% of patients receiving montelukast compared with 32.4% on placebo (p < 0.02). Pain assessment score deteriorated in 45% of montelukast responders (5/11) after cross-over to placebo and improved in 62% (8/13) of placebo non-responders on cross-over to montelukast. In patients with peak duodenal eosinophil counts between 20–29/hpf (n=19), a positive pain assessment response was observed in 84% of patients receiving montelukast compared to 42% receiving placebo (p < 0.01). Response rate did not differ by age, gender or histologic findings at baseline. Pharmacokinetic analysis yielded parameter estimates for absorption rate constant (Ka), apparent volume of distribution (Vd/F) and elimination rate constant (Kel) of 0.42 h−1, 0.19 L/kg and 0.26 h−1, respectively. The relative extent of systemic drug exposure was comparable to that observed in previous pediatric investigations with similar weight-adjusted montelukast doses. Neither dose nor calculated drug exposure were associated with the level of post treatment pain assessment or the change in biochemical markers. Conclusions These data suggest a beneficial role for montelukast in the treatment of pediatric patients with dyspepsia associated with duodenal eosinophilia.

Severe Food Protein-Induced Enterocolitis Syndrome to Cow's Milk in Infants.

Cow’s milk is the most common cause of food-protein-induced enterocolitis syndrome (FPIES). The aim of this study was to examine the clinical features and treatment outcomes of infants with severe FPIES to cow’s milk. We reviewed all infants ≤12 months of age who were hospitalized and diagnosed with severe FPIES to cow’s milk between 1 January 2011 and 31 August 2014 in a tertiary Children’s Medical Center in China. Patients’ clinical features, feeding patterns, laboratory tests, and treatment outcomes were reviewed. A total of 12 infants met the inclusion criteria. All infants presented with diarrhea, edema, and hypoalbuminemia. Other main clinical manifestations included regurgitation/vomiting, skin rashes, low-grade fever, bloody and/or mucous stools, abdominal distention, and failure to thrive. They had clinical remission with resolution of diarrhea and significant increase of serum albumin after elimination of cow’s milk protein (CMP) from the diet. The majority of infants developed tolerance to the CMP challenge test after 12 months of avoidance. In conclusion, we reported the clinical experience of 12 infants with severe FPIES to cow’s milk, which resulted in malnutrition, hypoproteinemia, and failure to thrive. Prompt treatment with CMP-free formula is effective and leads to clinical remission of FPIES in infants.

Safety of infliximab treatment in pediatric patients with inflammatory bowel disease.

ABSTRACTBackground:Infliximab appears to be efficacious in the treatment of pediatric Crohn disease (CD). There are few large-scale pediatric studies on the complications of infliximab therapy.Methods:A retrospective review of all infliximab infusions administered to IBD patients at a tertiary child

Mucosal Eosinophilia and Response to H1/H2 Antagonist and Cromolyn Therapy in Pediatric Dyspepsia

Both eosinophils and mast cells have been implicated in the generation of abdominal pain. The purposes of this retrospective study were to determine the prevalence of duodenal eosinophilia in pediatric dyspepsia and to determine the clinical response rate of these patients to combined H1 and H2 receptor antagonist and mast cell stabilizer therapy. Fifty-nine patients (ages 3.5–17.7 years) with dyspepsia undergoing endoscopy were evaluated. All patients had a minimum of 2 forceps biopsies obtained from each of the esophagus, antrum, and duodenal bulb. Routine histologic evaluation was performed and duodenal biopsies were additionally evaluated to determine eosinophil counts. Patients with > 10 eosinophils/hpf were treated with ranitidine and hydroxyzine (H1/H2). Nonresponders were then treated with oral cromolyn. Patients were followed up and response recorded in an abdominal pain database and/or medical chart, which were reviewed for this study. Forty-two patients (71%) had duodenal eosinophilia. Twenty-one (50%) of these were responders to H1/H2. The response rate did not differ between patients with and without noneosinophilic esophagitis, gastritis, or duodenitis, respectively. Two patients were lost to follow-up and considered nonresponders. Seventeen of the remaining 19 (89%) were responders to cromolyn. Overall, the response rate to this treatment pathway was 90%. Duodenal eosinophilia is common in pediatric patients with dyspepsia. These patients appear to be clinically amenable to combination H1/H2 therapy and/or oral cromolyn.

Electrogastrography in Pediatric Functional Dyspepsia: Relationship to Gastric Emptying and Symptom Severity

Objectives: The aims of this study were to determine the electrogastrographic patterns in children with functional dyspepsia and to investigate the correlations among electrogastrogram (EGG), gastric emptying (GE), and pain severity. Methods: We studied 30 children (19 F; mean age 11.4 years) with functional dyspepsia. Electrogastrography was performed for 30 minutes fasting and for 1 hour during a GE test after ingestion of an isotope-labeled solid meal. The percent emptying was measured every 10 minutes for 1 hour after the meal. The dominant frequency of the EGG, the change in the postprandial peak power (&dgr;P), and percent dysrhythmia during each recording session were calculated. Specific symptoms were graded from 0 (none) to 4 (severe) by the patient. Results: Of 30 patients, 14 (47%) had slow GE, and 15 (50%) had abnormal EGG (dysrhythmia ≥ 30% or &dgr;P < 0). GE was slow in 73% of patients with an abnormal EGG but was slow in only 20% of patients with normal EGG (P = 0.009). GE was negatively correlated with fasting bradygastria (r = −0.383, P = 0.04). Abdominal pain was the most severe dyspeptic symptom, both during fasting and after the meal. Patients with an abnormal EGG had an increased mean pain severity score (3.5 ± 0.2 vs. 2.5 ± 0.2, P = 0.002). Conclusions: Sixty percent of functional dyspepsia subjects had either slow GE or abnormal EGG. Patients with abnormal EGG were more likely to have slow GE. EGG abnormalities were associated with more severe postprandial pain and should be considered a possible mechanism for dyspeptic symptoms.

Conceptualization and treatment of chronic abdominal pain in pediatric gastroenterology practice.

Objectives: The aim of this study was to examine how children with abdominal pain presently are viewed, assessed, and treated by pediatric gastroenterologists across North America, as well as how perspectives have changed since initial release of the Rome criteria for functional gastrointestinal disorders approximately 15 years ago. Patients and Methods: One hundred seventy-four full members of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition completed a pediatric gastroenterology practice survey designed by the authors in 2006. The responses were examined for practice patterns and specific knowledge/use of the Rome criteria. The responses were also compared with historical data from 151 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition members who completed a similar survey in 1992. Results: There were few changes in the evaluation, treatment, or outcomes for children with abdominal pain for the past 15 years. Knowledge of the Rome criteria was common, but use in practice was not; several specific problems with the criteria were identified. A mismatch also appeared between belief in the importance of psychological factors in the creation/maintenance of pediatric abdominal pain and integration of these factors as part of standard evaluation and treatment. Finally, controversy emerged regarding both the term “functional” and the importance of histologic inflammation in the pathophysiology of pediatric abdominal pain. Conclusions: The evolution and dissemination of the Rome criteria for the past 15 years have not substantially changed evaluation or treatment practices for children with abdominal pain. Many areas of inconsistency and controversy remain. More focused research is needed to better understand this common pain condition and to establish an effective treatment program that can be disseminated across practitioners.

Symptoms and Subtypes in Pediatric Functional Dyspepsia: Relation to Mucosal Inflammation and Psychological Functioning

Objectives: The aim of the present study was to explore relations between antral or duodenal inflammatory cells and aspects of psychological functioning with clinical symptom presentation in children with functional dyspepsia (FD), as well as to determine whether histologic inflammation and/or psychopathology are differentially associated with FD subtypes as defined by the Rome II and Rome III criteria. Patients and Methods: One hundred pediatric patients with dyspepsia completed a standardized history and physical examination at initial evaluation. Patients and parents also completed a measure of psychological functioning. Subsequently, 63 of these patients underwent upper endoscopy with biopsy (4 patients excluded from analysis because of mucosal disease). Inflammatory cells in the mucosa of stomach and duodenum were enumerated. Associations between specific symptoms and FD subtypes with inflammatory cell densities and anxiety, depression, and somatization scores were examined. Results: Rome III subtypes were more robustly related to differences in mast cell densities and scores on psychologic subscales than was true for Rome II subtypes. At the individual symptom level, having pain wake the patient from sleep was associated with higher duodenal mast cell density. Bloating was associated with lower levels of general antral inflammation, as well as higher self-reported levels of anxiety and somatization. Early satiety and bothersome postprandial fullness also were associated with higher levels of self-reported anxiety and depression. Conclusions: The present study provides preliminary evidence for a relation between clinical presentation, specific types of inflammatory cell infiltrates, and aspects of psychological functioning in children with FD. Rome III subtyping, adopted for adult dyspepsia, may be relevant to the pediatric population.

Activated duodenal mucosal Eosinophils in children with dyspepsia: A pilot transmission electron microscopic study

Background Activated eosinophils can be identified by electron microscopy (EM) Previous studies have shown EM evidence of eosinophil activation in a variety of gastrointestinal conditions associated with inflammation. The purpose of this study was to evaluate the activation state by EM of duodenal mucosal eosinophils in children who presented with dyspepsia and to determine if eosinophils are activated in patients with normal eosinophil counts on routine histology. Methods Twenty patients (ages 7–15 years) with dyspepsia were evaluated. All had normal gross endoscopies and Helicobacter pylori was excluded. Each patient had two endoscopic forceps biopsies taken from both the duodenal bulb (DB) and the second portion of the duodenum (DS) for routine histology to determine eosinophil counts. Two additional biopsies were taken from the adjacent mucosa of each site for EM evaluation. The eosinophil activation state was determined for each specimen and a degranulation index was calculated for DB specimens. Results On routine histology, peak eosinophil counts were greater than or equal to 20 per hpf in three patients, 11 to 19 per hpf in 12 patients, and less than or equal to 10 per hpf in 5 patients. All patients showed evidence of EM activation on DB specimens and 95% showed activation on DS specimens. The mean degranulation index was 50.5 + 12.0% with 65% of specimens revealing moderate (20 – 60%) degranulation and 30% of specimens revealing extensive (greater than 60%) degranulation. Conclusions Eosinophils present in the duodenal mucosa of children with dyspepsia are activated in a significant proportion of patients, even in those with normal eosinophil counts. The degree of degranulation is similar to that seen in other conditions where eosinophils have a pathogenic role.