Steven L. Werlin

Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition.

Gastroesophageal reflux (GER), defined as passage of gastric contents into the esophagus, and GER disease (GERD), defined as symptoms or complications of GER, are common pediatric problems encountered by both primary and specialty medical providers. Clinical manifestations of GERD in children include vomiting, poor weight gain, dysphagia, abdominal or substernal pain, esophagitis and respiratory disorders. The GER Guideline Committee of the North American Society for Pediatric Gastroenterology and Nutrition has formulated a clinical practice guideline for the management of pediatric GER. The GER Guideline Committee, consisting of a primary care pediatrician, two clinical epidemiologists (who also practice primary care pediatrics) and five pediatric gastroenterologists, based its recommendations on an integration of a comprehensive and systematic review of the medical literature combined with expert opinion. Consensus was achieved through Nominal Group Technique, a structured quantitative method. The Committee examined the value of diagnostic tests and treatment modalities commonly used for the management of GERD, and how those interventions can be applied to clinical situations in the infant and older child. The guideline provides recommendations for management by the primary care provider, including evaluation, initial treatment, follow-up management and indications for consultation by a specialist. The guideline also provides recommendations for management by the pediatric gastroenterologist. This document represents the official recommendations of the North American Society for Pediatric Gastroenterology and Nutrition on the evaluation and treatment of gastroesophageal reflux in infants and children. The American Academy of Pediatrics has also endorsed these recommendations. The recommendations are summarized in a synopsis within the article. This review and recommendations are a general guideline and are not intended as a substitute for clinical judgment or as a protocol for the management of all patients with this problem.

EPIDEMIOLOGIC AND CLINICAL CHARACTERISTICS OF CHILDREN WITH NEWLY DIAGNOSED INFLAMMATORY BOWEL DISEASE IN WISCONSIN: A STATEWIDE POPULATION-BASED STUDY

OBJECTIVE To define epidemiologic and clinical characteristics of newly diagnosed pediatric inflammatory bowel disease (IBD) in a large population-based model. STUDY DESIGN All pediatric gastroenterologists providing care for Wisconsin children voluntarily identified all new cases of IBD during a 2-year period. Demographic and clinical data were sent to a central registry prospectively for analysis. RESULTS The incidence of IBD in Wisconsin children was 7.05 per 100,000, whereas the incidence for Crohns disease was 4.56, more than twice the rate of ulcerative colitis (2.14). An equal IBD incidence occurred among all ethnic groups, and children from sparsely and densely populated counties were equally affected. The majority (89%) of new IBD diagnoses were nonfamilial. CONCLUSIONS This study provides novel, prospective, and comprehensive information on pediatric IBD incidence within the United States. The surprisingly high incidence of pediatric IBD, the predominance of Crohns disease over ulcerative colitis, the low frequency of patients with a family history, the equal distribution of IBD among all racial and ethnic groups, and the lack of a modulatory effect of urbanization on IBD incidence collectively suggest that the clinical spectrum of IBD is still evolving and point to environmental factors contributing to the pathogenesis.

Prolonged duration of response to infliximab in early but not late pediatric Crohn's disease.

OBJECTIVES:Tumor necrosis factor-α plays a central role in chronic intestinal inflammation of Crohns disease. Targeting this cytokine with the chimeric monoclonal antibody infliximab has emerged as an effective form of therapy in adult Crohns disease patients. We sought to determine whether infliximab treatment would benefit pediatric patients with medically refractory Crohns disease. We also assessed the duration of response, comparing children with early disease to children with long-standing (late) Crohns disease.METHODS:Fifteen consecutive children (mean age 12.8 ± 3.2 yr) with medically refractory Crohns disease were enrolled in a prospective, open-label trial of a single, 5-mg/kg infliximab intravenous infusion. Medically refractory disease was defined as an inability to taper steroids, lack of response to immunomodulator therapy over 4 months, and active disease as measured by the Pediatric Crohns Disease Activity Index (PCDAI). Primary endpoints included measurements of disease activity (PCDAI), steroid use, and duration of clinical response.RESULTS:In all, 14/15 children (94%) improved after infliximab infusion, with a significant decrease of both PCDAI and daily steroid use by 4 wk. Ten patients (67%) achieved complete remission by 10 wk. Among the 14 patients who responded, three of six children (50%) with early disease maintained clinical response through the 12-month trial period, compared to none of eight children with late disease. There were no serious complications associated with the use of infliximab in any of the patients.CONCLUSIONS:Infliximab is safe and effective in the short-term treatment of medically refractory pediatric Crohns disease. More importantly, there is a remarkably prolonged duration of response after infliximab therapy in children with early compared to late Crohns disease.

Nutritional basis of growth failure in children and adolescents with Crohn's disease.

In order to investigate the mechanisms of severe growth failure in children with Crohns disease, 7 affected patients (ages 9–17 yr) were studied before, during, and after parenteral nutrition as a supplement to oral intake. At the time of entrance into the study, patients had had cessation of linear growth for at least 1 yr, or a decrease of one standard deviation in height percentiles and/or a bone-age delay greater than 2 yr. Nutritional status was evaluated in all patients, and endocrinologic and metabolic balance studies were performed in 5 of the 7 pa tients. Neither endocrine dysfunction nor malabsorption accounted for the severe growth failure. Patients received approximately 8 wk of combined oral and parenteral nutrition achieving at least 75 calories per kilogram per day or greater. Weight gain averaged 4.8 ± 1.6 kg, while total body potassium (indicative of lean body mass) demonstrated a parallel significant rise (P

Pancreatitis in children

Objectives To determine the incidence, etiology and outcome of pancreatitis at a regional childrens hospital. Methods Chart review of all patients with pancreatitis seen during a 6 year period at the Childrens Hospital of Wisconsin. The diagnosis of pancreatitis required either a serum amylase or lipase >3 times normal or radiographic evidence of pancreatitis. Results Two hundred fourteen episodes of pancreatitis in 180 patients were documented. The most common etiologies were systemic disease (14%), trauma (14%), drug induced (12%), biliary tract disease (12%), infectious (8%), and idiopathic (8%), which made up 68% of the total cases. Eleven patients died, all from underlying systemic illnesses. The serum amylase and lipase were elevated in 82% and 83% of patients respectively. Conclusions Pancreatitis is more common in children than previously thought. Upon careful assessment fewer cases were found to be idiopathic than in previous series. The outcome of pancreatitis depends on co-morbid conditions.

Mechanisms of gastroesophageal reflux in children

We studied the lower esophageal sphincter in 29 children with known or suspected gastroesophageal reflux using a sleeve sensor and micro pH electrode. Mean lower esophageal sphincter pressure for a ten-minute monitoring period was 19 +/- 13 mm Hg; however, considerable temporal variation occurred in each child. Gastroesophageal reflex was infrequently associated with a low basal sphincter pressure (< 5 mm Hg) but usually associated with an increase in intra-abdominal pressure or with transient inappropriate relaxation of the lower esophageal sphincter.

Definitions of pediatric pancreatitis and survey of present clinical practices.

Objectives: There is limited literature on acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP) in children. The International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) consortium was formed to standardize definitions, develop diagnostic algorithms, investigate disease pathophysiology, and design prospective multicenter studies in pediatric pancreatitis. Methods: Subcommittees were formed to delineate definitions of pancreatitis, and a survey was conducted to analyze present practice. Results: AP was defined as requiring 2 of the following: abdominal pain compatible with AP, serum amylase and/or lipase values ≥3 times upper limits of normal, and imaging findings of AP. ARP was defined as ≥2 distinct episodes of AP with intervening return to baseline. CP was diagnosed in the presence of typical abdominal pain plus characteristic imaging findings, or exocrine insufficiency plus imaging findings, or endocrine insufficiency plus imaging findings. We found that children with pancreatitis were primarily managed by pediatric gastroenterologists. Unless the etiology was known, initial investigations included serum liver enzymes, triglycerides, calcium, and abdominal ultrasound. Further investigations (usually for ARP and CP) included magnetic resonance or other imaging, sweat chloride, and genetic testing. Respondents’ future goals for INSPPIRE included determining natural history of pancreatitis, developing algorithms to evaluate and manage pancreatitis, and validating diagnostic criteria. Conclusions: INSPPIRE represents the first initiative to create a multicenter approach to systematically characterize pancreatitis in children. Future aims include creation of patient database and biologic sample repository.

Fecal calprotectin is useful in predicting disease relapse in pediatric inflammatory bowel disease.

Background: Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker to determine the degree of intestinal inflammation and predicting relapse in patients with inflammatory bowel disease (IBD). The aim was to compare FC levels in IBD and healthy controls, to correlate FC levels with clinical disease activity, and to assess whether FC levels can be used to predict clinical relapse in children with IBD. Methods: Enzyme‐linked immunosorbent assay (ELISA) determined levels of FC were measured in more than 1 stool samples (n) from 32 IBD patients (n = 97) and from 34 healthy controls (n = 37). Disease activity was assessed by the Harvey–Bradshaw index in Crohns disease (CD) and by Physicians Global Assessment (PGA) in both CD and ulcerative colitis (UC). Clinical events were recorded up to 9 months following stool collection in CD patients. Wilcoxon rank sum test and Fishers exact tests were used to compare FC levels in IBD patients and in control. Kaplan–Meyer analysis was used to determine a risk of clinical relapse in relation to FC levels. Results: The IBD group had higher FC levels (range 17–7500 g/g) compared with control (16–750 g/g, P < 0.0001). FC levels were higher during relapse (CD, 3214 ± 2186; UC, 2819 ± 1610) compared to remission (CD, 1373 ± 1630; UC, 764 ± 869; P < 0.0001). Among those with clinical relapse, 90% had FC levels more than 400 &mgr;g/g in CD. Eighty‐nine percent of CD encounters with FC levels less than 400 &mgr;g/g remained in clinical remission. Conclusions: FC levels differentiate active IBD from controls. Among children with CD and in remission, FC levels may be useful in predicting impending clinical relapse.

Emerging New Clinical Patterns in the Presentation of Celiac Disease

OBJECTIVE To evaluate changes in the clinical presentation of celiac disease in southeastern Wisconsin. DESIGN Retrospective medical record review. SETTING Clinical specialty practice in pediatric gastroenterology. Patients The medical records of all patients diagnosed with celiac disease at the Childrens Hospital of Wisconsin between 1986 and 2003 were reviewed. Data extracted from the medical records included year of diagnosis, demographics, indications for endoscopy and biopsy, signs, symptoms, and laboratory data. Biopsy specimens were read by the pediatric pathologist and graded according to the Marsh criteria. Main Exposure Date of initial diagnosis of celiac disease. MAIN OUTCOME MEASURES Presenting symptoms of patients with newly diagnosed celiac disease. RESULTS One hundred forty-three patients were diagnosed with celiac disease. The number of patients diagnosed with celiac disease increased from 1 in 1986 to 93 in 2003. The mean age at diagnosis increased from 5.32 years for patients diagnosed before 1995 to 8.70 years for patients diagnosed after 1995. Gastrointestinal symptoms dominated in children younger than 3 years, whereas in children older than 3 years, the majority presented with non-gastrointestinal indications. The percentage of patients presenting with gastrointestinal symptoms alone decreased during the study period; 11.2% of patients diagnosed with celiac disease were overweight (body mass index > 90). CONCLUSIONS Our study provides a unique longitudinal follow-up of clinical practice over a 17-year period. Currently, patients with celiac disease usually do not present with classic symptoms; they are more likely to be asymptomatic school-aged children who belong to a high-risk group.

Evidence of Intestinal Inflammation in Patients With Cystic Fibrosis

Objectives: Treatment with pancreatic enzymes fails to completely correct malabsorption and gastrointestinal symptoms in patients with cystic fibrosis (CF). The aim of the present study was to examine the small intestine of patients with CF without overt evidence of gastrointestinal disease using capsule endoscopy (CE). Methods: Patients with CF received the agile patency capsule and, depending on the result of that procedure, then underwent standard CE using the PillCam SB capsule (Given Imaging, Yokneam, Israel). A stool specimen was taken on the same day as the CE for determination of the calprotectin level. Results: Forty-two patients with CF ages 10 to 36 years were included; 29 had pancreatic insufficiency. One patient failed to excrete the patency capsule after 36 hours and was withdrawn from the study. Pulmonary function was mild to moderate with FEV1 68.5% ± 16% predicted. Review of the CE videos showed that most of the patients had varying degrees of diffuse areas of inflammatory findings in the small bowel including edema, erythema, mucosal breaks, and frank ulcerations. There were no adverse events. Fecal calprotectin levels were markedly high in patients with pancreatic insufficiency, 258 μg/g (normal <50). Conclusions: Small bowel mucosal pathology may be detected using CE in most of the patients with CF. The high fecal calprotectin levels found are suggestive of mucosal inflammation, which may correlate with the CE findings. Additional study is required to examine the possible relation of these mucosal lesions, which may be part of a newly identified enteropathy associated with CF, with persistent intestinal malabsorption in many of these patients.