Leonard J. Newman

Fructose intolerance in children presenting with abdominal pain.

Objectives: We determined the occurrence of fructose malabsorption in pediatric patients with previous diagnoses of abdominal pain caused by a functional bowel disorder, whether the restriction of fructose intake changes the reporting of symptoms, the role of fructose dosage, and the severity of resultant symptoms. Patients and Methods: We administered a fructose breath test to children presenting with persistent unexplained abdominal pain. Patients randomly received 1, 15, or 45 g fructose, and breath hydrogen was measured for 3 hours after ingestion. Test results were positive when breath hydrogen was 20 ppm greater than baseline and was accompanied by gastrointestinal symptoms. Results: A total of 32 patients was enrolled, and none of the 9 who received 1 g had positive results. Three of 10 who received 15 g and 8 of 13 who received 45 g had positive results. All patients with positive test results restricted their fructose intake. Among the group with positive results, 9 of 11 had rapid improvement of their gastrointestinal symptoms. After 2 months, all 9 patients continued to report improvement. Conclusions: We concluded that fructose malabsorption may be a significant problem in children and that management of dietary intake can be effective in reducing gastrointestinal symptoms.

Campylobacter pylori-related gastrointestinal disease in children

Over a one-year period, 95 children and adolescents presenting with epigastric pain and/or vomiting, and without associated risk factors for development of peptic disease, underwent endoscopic antral biopsies for pathologic diagnosis and to detect presence of Campylobacterss. pylori (C. pylori). Additional biopsies of the esophagus, stomach, and duodenum were obtained for histologic evaluation. C. pylori was identified in 16 patients (16.8%), all of whom had evidence of acute and/or chronic gastritis. Significant discriminating factors between C. pylori-positive and -negative subjects included age at presentation (positive vs negative=14.6 vs 9.9 years, P<0.01, biopsy-confirmed gastritis (100% vs 30.4%, P<0.001), and diagnosis of duodenitis alone (0% vs 46.8%, P<0.001). Risk for bacterial colonization was significantly higher in the presence of endoscopic gastritis (P<0.001). Among C. pylori-positive patients, none responded to standard antiulcer therapy (H2-receptor antagonists, antacids). Symptomatic and histologic remission was achieved utilizing combined therapy with bismuth subsalicylate and antibiotics. Seven of 79 C. pylori-negative patients with biopsyproven gastritis who responded poorly to antisecretory therapy had the organism identified in follow-up antral biopsies; these patients improved clinically following treatment for C. pylori. These data suggest that C. pylori is a significant factor in the etiology of upper gastrointestinal tract inflammatory disease in pediatrics, and presence of the organism should be evaluated, particularly in children with evidence of acute and/or chronic gastritis.

Esophageal food impaction in children.

Objectives To determine the clinical presentation, radiographic, endoscopic and manometric findings, and clinical outcome of esophageal food impaction (EFI) in pediatric patients. Methods We retrospectively reviewed the clinical course of 12 pediatric patients with EFI over a 10-year period. Results All 12 patients described initially presented to our emergency department for care. Four patients (25%) required previous endoscopic intervention for disimpaction of EFI. Eleven required endoscopic removal of their EFI, and 1 patient’s food impaction resolved spontaneously. The mean duration of food impaction was 20 hours prior to endoscopic intervention. Endoscopy demonstrated an esophageal stricture in 1 patient with a history of trisomy 21 and tracheoesophageal fistula repair. While there was no visual evidence of esophagitis in any patient, 5 of 7 had histologic evidence of esophagitis. Upper gastrointestinal series demonstrated the esophagus to be anatomically normal in 10 of 12 patients (83%); 1 patient had an esophageal stricture and another an esophageal web. Four of 8 patients studied had nonspecific esophageal motility abnormalities. Conclusions EFI in children is not generally associated with underlying esophageal anatomic abnormalities. Esophagitis and nonspecific esophageal motility disorder abnormalities may be etiologic factors. Endoscopic removal of the EFI was safe and effective and is recommended as there is little likelihood of spontaneous resolution of EFI in children.

Patterns of gastroesophageal reflux (GER) in patients with apparent life-threatening events.

The incidence and temporal patterns of gastroesophageal reflux (GER) in infants presenting with an apparent life-threatening event (ALTE) was compared with GER characteristics of infants evaluated for persistent emesis, utilizing continuous 24 h intraesophageal pH monitoring. These data indicate that the incidence of significant GER was similar in both groups, despite the absence of a clinical vomiting history in 46% of ALTE patients. Furthermore, infants with ALTE demonstrate a significantly higher incidence of steep reflux when compared with control infants presenting with vomiting alone (27 vs. 0%, p < 0.001). Awake GER beyond the first two postprandial hours was not observed in either study group. Monitoring results, therefore, indicate that significant GER is common in infants with ALTE; and these infants manifest an apparently unique pattern of GER distinct from that observed in age-matched controls with GER alone. Possible relationships between GER in ALTE patients and the development/onset of apneic episodes are discussed.

Hypercalcemia in childhood renal tumors

Hypercalcemia is an uncommon complication of childhood renal tumors. It is exclusively seen in infants 6 months of age or younger with malignant rhabdoid tumor of the kidney (MRTK) or congenital mesoblastic nephroma (CMN). Secretion of parathormone or prostaglandin E2 by the tumor cells is responsible for the hypercalcemia in most of these patients. Bone metastasis has been notably absent in these patients, and the hypercalcemia completely resolves with the removal of the tumor. Hypercalcemia in itself probably does not have any prognostic significance; however, it may serve as a tumor marker in some patients. Early recognition and effective management of this complication may prevent the acute life‐threatening as well as the longstanding complications of this serious metabolic disorder.

Lung Lesions in Children With Crohn's Disease Presenting as Nonresolving Pneumonias and Response to Infliximab Therapy

Lung lesions in children with Crohns disease are often difficult to diagnose and treat. We report here 3 children (aged 13, 14, and 17 years) on immunosuppressive therapy for previously diagnosed Crohns disease who presented with nonresolving pneumonias. All 3 had unfavorable response to empiric antibiotics and had progression of lesions. Cultures of sputum and blood did not yield any organisms. Subsequent lung biopsies revealed noncaseating granulomas with giant cells in 2 subjects and bronchiolitis obliterans with organizing pneumonia in the third. All patients were treated with infliximab, a novel anti–tumor necrosis factor monoclonal antibody, and showed rapid clinical and radiologic response. We emphasize that a high index of suspicion for noninfectious etiologies needs to be maintained in patients with Crohns disease who present with lung lesions to ensure timely intervention. Infliximab therapy seems to be effective and well tolerated in such patients.

Isolation of fatty acids covalently bound to the gastric mucus glycoprotein of normal and cystic fibrosis patients

Covalently bound fatty acids were found in strictly purified and delipidated gastric mucus glycoprotein of normal and cystic fibrosis individuals. The susceptibility of this linkage to methanolic KOH and hydroxylamine treatment indicated the ester bond between fatty acids and glycoprotein. On the average, 2.9 nmol fatty acid/mg glycoprotein were found in normal samples, and 12.2 nmol/mg glycoprotein in samples derived from cystic fibrosis. In normal gastric mucus glycoprotein the covalently linked fatty acids consisted of hexadecanoate (47.0%), octadecanoate (22.0%), tetracosanoate (5.9%), octadecenoate (14.5%) and tetracosenoate (6.0%). In cystic fibrosis mucus glycoprotein the covalently bound fatty acids were comprised mainly of hexadecanoate (36.5%), octadecanoate (48.7%) and octadecenoate (8.6%). These data indicate that cystic fibrosis gastric mucus glycoprotein is highly acylated and perhaps this is the major defect of glycoproteins in this disease.

Spectrum of esophageal disorders in children with chest pain

The charts of 83 children with chest pain who underwent esophageal manometry followed by esophagogastroscopy were reviewed. Forty-seven (57%) had normal esophageal histology and normal motility (group I). Esophagitis and normal motility were demonstrated in 15 children (group II), normal esophageal histology and esophageal dysmotility in 13 (group III), and both esophagitis and abnormal motility in 8 (group IV). Diffuse esophageal spasm and achalasia were the most common motility disorders identified (in seven and four patients, respectively). The presence and duration of symptoms, the age, and the gender were not different among the four patient groups. After six months of H2-receptor blockade, 12 of 15 group II patients were asymptomatic, whereas a significantly smaller percentage (five of 18) of patients with abnormal esophageal motility responded to esophageal dilation or treatment with calcium channel blockade, H2-receptor antagonist, and/or prokinetic agents (P<0.01). These data suggest that the evaluation of children with chest pain should include esophageal motility testing and esophagoscopy, even in the absence of other gastrointestinal-associated symptoms, and that while treatment of esophagitis results in resolution of symptoms, motility disorders were relatively refractory to therapy.

Nonspecific esophageal motility disorders in children without gastroesophageal reflux.

BACKGROUND Nonspecific esophageal motility disorders (NEMDs) have been identified in up to 50% of adults with noncardiac chest pain or dysphagia. This study sought to determine the incidence of NEMDs in children with upper gastrointestinal tract symptoms and to evaluate the clinical course of pediatric patients with these manometric abnormalities. METHODS The study involved 154 children aged 4 to 18 years (mean age, 11.6+/-2.6 years [SE]) who had upper gastrointestinal, swallowing-related symptoms. The children were evaluated by 24-hour intraesophageal pH monitoring, esophageal manometry, and esophagogastroduodenoscopy. RESULTS Gastroesophageal reflux (GER) was diagnosed by pH study in 109 (71%) of 154 patients, and examination of biopsy specimens demonstrated esophagitis in 70 children with GER. Results of esophageal manometry were abnormal in 30 (67%) of 45 children without GER. A variety of motility disorders were diagnosed in 17 of the patients without GER, whereas NEMDs were diagnosed in the remaining 13 children (mean age, 10.6+/-2.7 years; 10 boys, 3 girls). Patients with GER showed normal esophageal wave propagation; however, mean lower esophageal sphincter pressure was significantly lower in patients with GER than in children with NEMDs. The children with NEMDs exhibited a diverse array of symptoms, including esophageal food impaction in 4 of the 13 patients. During a 36.2+/-4.3-month follow-up period, no correlation was found between therapeutic intervention and clinical course in the 13 patients with NEMDs. Symptomatic improvement occurred in 6 of 13 patients, including 3 children for whom no pharmacologic therapy was prescribed. CONCLUSIONS These data indicate that NEMDs represent a common group of esophageal manometric abnormalities in children with upper gastrointestinal tract symptoms and without GER. Food impaction appears to be a relatively frequent complication, and NEMDs should be considered in children who have this finding.

Noncardiac chest pain in adolescents and children with mitral valve prolapse

Chest pain in adolescents and children is usually not of cardiac origin. Of cardiac conditions commonly linked to chest pain in childhood, mitral valve prolapse (MVP) is the most prevalent, but this association has recently been questioned. In light of recent reports of gastroesophageal sources of chest pain in adults with MVP, we performed a comprehensive gastroesophageal evaluation of 17 preadolescents and adolescents with mitral valve prolapse who had chest pain as their presenting symptom. Evaluation consisted of esophageal manometry, Bernstein test, esophageal pH probe, and/or esophagogastroscopy. Fourteen of the 17 patients had at least one abnormal finding. Five patients had esophagitis, five had gastritis, one had high-amplitude esophageal contractions, one had abnormal esophageal manometry with positive Bernstein test, one had esophageal reflux and positive Bernstein test, and one had abnormal manometry with esophageal reflux. The 13 patients with esophagitis, gastritis, reflux, or positive Bernstein test were treated with antacid, with resolution of chest pain in 12 patients. Two of these patients underwent follow-up endoscopy with documentation of improvement. The patient with high-amplitude esophageal contractions was treated with dicyclomine, which resulted in resolution of chest pain. The observation that the chest pain was not related to mitral valve prolapse is important in clinical practice and raises further questions as to whether mitral valve prolapse causes chest pain.