Celiac disease and diabetes mellitus diagnosed in a pediatric patient with Hirschsprung disease.

Hirschsprung disease is a disorder of neural crest migration characterized by intestinal aganglionosis along a variable segment of the gastrointestinal tract. It is a complex disorder associated with several syndromes. Celiac disease is an autoimmune enteropathy characterized by dietary intolerance to gluten proteins and can be associated with autoimmune conditions such as diabetes mellitus. Celiac disease can mimic Hirschsprung disease when presenting with constipation and abdominal distention. We present the case of celiac disease diagnosed in a patient with Hirschsprung disease who subsequently developed type one diabetes mellitus.

Evaluation of gastroesophageal reflux in pediatric patients with asthma using impedance-pH monitoring.

OBJECTIVES: To determine the proportion of acid and nonacid reflux events in children with asthma suspected to have gastroesophageal reflux (GER) using combined impedance-pH monitoring, and to determine the symptom index (SI) for nonacid and acid reflux events. STUDY DESIGN: This was a prospective study of children with asthma (age 5 months to 6 years) referred for evaluation of GER. Exclusion criteria were congenital anomalies, cerebral palsy, mental retardation, and cardiac disease. The children underwent a 20-hour multichannel intraluminal impedance (MII)-pH study. RESULTS: A total of 24 children (17 male; mean age, 33 months) were enrolled from March 2004 to February 2005. MII-pH detected 1184 reflux events, versus 419 reflux events by pH alone; 51% (605 events) were nonacid. The proportion of nonacid reflux events decreased with time elapsed from last meal (P < .0001 by Pearson's chi2 test). A total of 555 symptoms were recorded, including 331 cases of cough, 243 of which (73.4%) were not associated with a reflux event. The SI for MII-pH was significantly different than that for the pH probe (37% vs 0%; P = .008). CONCLUSIONS: Acid and nonacid reflux occurs with equal frequency in children with asthma. Most symptoms occur in the absence of a reflux event.

Evaluation of infantile acid and nonacid gastroesophageal reflux using combined pH monitoring and impedance measurement.

OBJECTIVE: Characterize the proportion of acid and nonacid esophageal reflux events in young infants with suspected gastroesophageal reflux (GER) using combined pH-multichannel intraluminal impedance (MII) monitoring. Determine the symptom index correlation with nonacid reflux and acid reflux events. STUDY DESIGN: Prospective study of children, aged 2 weeks to 1 year, referred to The Children's Hospital of Denver Gastroenterology Clinic for evaluation of GER. Exclusion criteria were congenital anomalies or syndromes, cerebral palsy, mental retardation, and pulmonary or cardiac disease. The children were admitted to The Children's Hospital General Clinical Research Center for a 20 hour pH-MII study. Acid suppression was either never used or discontinued 2 weeks before testing. RESULTS: Thirty-four infants were enrolled from February 2004 to February 2005. Ages ranged from 2 months to 11 months, median = 7 (20 females/14 males). One thousand eight hundred ninety reflux events were detected by MII, and 588 reflux events were detected by pH probe alone. The percent of reflux that was acid was 47% (888 events) versus 53% of (1,002 events) nonacid reflux events. The proportion of nonacid reflux decreased with age (P < 0.0001 by Pearson chi test) and with increasing time elapsed from last meal. There were 958 total symptoms evaluated. The most frequently reported symptom was fussiness/pain, which correlated with nonacid reflux events 24.6% and acid reflux 25.2%. The proximal height of a reflux was predictive for symptoms of fussiness/pain, arching, and burping. CONCLUSION: MII detects more reflux events than pH monitoring alone. The proportion of nonacid reflux to acid reflux events in infants is more similar to adults than previously reported. Combined pH-MII esophageal monitoring identifies more reflux events and improves clinical correlation with symptoms.

Portopulmonary hypertension in pediatric patients.

OBJECTIVES: To investigate the clinical presentation, manifestations, and response to therapy of portopulmonary hypertension (PPHTN) in pediatric patients. STUDY DESIGN: This study was a retrospective chart review describing the evaluation and course of 7 patients with PPHTN. RESULTS: Causes of portal hypertension (HTN) included biliary atresia (3 cases), cavernous transformation of the portal vein (2 cases), and primary sclerosing cholangitis and cryptogenic cirrhosis (1 case each). The median interval from the diagnosis of portal HTN to PPHTN was 12.1 years. Four patients presented with a new heart murmur, 4 presented with syncope, and 3 presented with dyspnea. Although electrocardiograms (ECGs) and chest x-rays were normal in 3 and 2 patients, respectively, echocardiograms diagnosed pulmonary HTN in all 7 patients. Five patients had cardiac catheterizations; the average mean pulmonary artery pressure was 65 +/- 20 mm Hg. Response to therapy was variable, and 4 patients died. Postmortem lung tissue examination revealed plexiform lesions and pulmonary arteriopathy. CONCLUSIONS: Because symptoms are subtle and may be overlooked, pediatric patients with portal HTN who develop a new heart murmur, dyspnea, syncope, or who are being evaluated for liver transplantation require evaluation for PPHTN. ECG and chest x-ray are insensitive screens for PPHTN. An echocardiogram and cardiology evaluation is essential for the diagnosis.

Frequency of ASCA seropositivity in children with cystic fibrosis.

OBJECTIVE: To determine the frequency of anti-Saccharomyces cerevisiae antibodies (ASCA) seropositivity in pediatric patients with cystic fibrosis (CF) and correlate ASCA with clinical features. METHODS: Prospective study of children with CF aged 2 to 21 years enrolled from The Children's Hospital Cystic Fibrosis Center. Exclusion criteria included Crohn disease, immunodeficiency or immunoglobulin A deficiency. The frequency of ASCA (ASCA immunoglobulin A and immunoglobulin G) was measured by an enzyme-linked immunosorbent assay kit provided by Inova, Inc. (San Diego, CA). The CF Foundation database was queried for clinical data on ASCA seropositive patients. RESULTS: Seventeen (20.7%) of 82 patients were seropositive for ASCA. Of these, eight had immunoglobulin A antibodies, six had immunoglobulin G antibodies and three had both. ASCA seropositivity in CF patients was significantly greater than the general population (20.7% versus 4%, P < 0.0001), using an exact binomial test on a single proportion. The 95% confidence limits around our observed proportion were 12.6% to 31.1%. Of 17 ASCA positive patients, 1 (5.8%) had a history of meconium ileus, 14 (82.4%) had DeltaF508 gene mutation, 9 (52.9%) had positive sputum cultures for fungal organisms, and 17 (100%) had an ideal body weight % >or=85%. CONCLUSION: Patients with CF have a higher frequency of ASCA seropositivity than the general population. When evaluating CF patients for Crohn disease, ASCA should be used with caution. The reasons for higher ASCA seropositivity in CF patients are unknown, but may include exposure to fungal organisms via intestinal or pulmonary sources.

A home infliximab infusion program.

INTRODUCTION: Infliximab is a promising advance in the treatment of pediatric inflammatory bowel disease. Infliximab is an effective therapy for selected children with Crohn disease but is both costly and time consuming. OBJECTIVES: To analyze our center's experience with a program of home-based infliximab infusion. METHODS: Between September, 2001, and October, 2003 we reviewed the charts of all children receiving home infliximab infusions focusing on cost, safety, and patient satisfaction. Children were enrolled in the home infusion program if they were compliant with hospital-based infliximab infusions and other medications, had no adverse events during hospital-based infliximab infusions, were in remission and had access to experienced pediatric homecare nursing. RESULTS: Ten children received 59 home infusions with a dose range of 7.5 to 10 mg/kg/dose. The calculated average savings per patient was 1335 US dollar/100 mg infliximab. Home infusions ranged from 2 to 5 hours. Since infusions could be performed any day of the week, school absenteeism was decreased. The average patient satisfaction rating for home infusions was 9 on a scale from 1 to 10 (10 = most satisfied). Three patients experienced difficulty with IV access requiring multiple attempts, but all were able to receive their infusions. One infusion was stopped because of arm pain above the IV site. This patient had his next infusion in the hospital before returning to the home infusion program. No severe adverse events (palpitations, blood pressure instability, hyperemia, respiratory symptoms) occurred during home infusions. CONCLUSIONS: In our carefully selected patients, infliximab infusions administered at home were safe and are cost-effective. Patients and families preferred home infusions, since time missed from school and work was reduced.

Abnormal intestinal histology in neonates with congenital anomalies of the gastrointestinal tract.

In animal models, when swallowing is experimentally prevented in utero, bowel length and weight are reduced, and villus height, crypt depth, and villus function are retarded. Little is known about the intestinal histology in infants with gastrointestinal (GI) tract anomalies. We examined the histological architecture of the intestine in neonates with GI anomalies in comparison to that of normal fetuses. Villus height, area, and length and crypt depth of normal fetuses were quantified in the proximal small bowel (n = 11) and measurements compared to those of surgical specimens of neonates with congenital anomalies of the GI tract (n = 16). Villus height and area and lamina propria height and area increased linearly from 8 to 24 weeks of gestation. In infants with anomalies of the GI tract, the villi were blunted and lacked normal histological architecture, the crypts were disorganized, and the crypt depth was significantly decreased (p = 0.004). Enterocyte height and area were significantly greater in neonates with congenital anomalies of the GI tract. The intestinal histology in neonates with congenital anomalies of the GI tract differs significantly from that of normal fetuses.