The prevalence and clinical characteristics of celiac disease in juvenile diabetes in Wisconsin.

BACKGROUND: The relationship between celiac disease and juvenile diabetes has long been known. Only a single study in the United States, from Buffalo, New York, has reported the prevalence of celiac disease in a pediatric diabetic population. This study was conducted to determine the prevalence and clinical presentation of celiac disease in children and adolescents with juvenile diabetes in Wisconsin, USA, using serum antiendomysial antibody as a screening test. METHODS: Two hundred eighteen patients with diabetes (113 males; age range, 4-21 years) and 117 age-and gender-matched control participants were tested for immunoglobulin A endomysial antibody. Patients with positive results were offered a small bowel biopsy. A questionnaire regarding abdominal pain, diarrhea, and growth failure was completed by the parents. RESULTS: Seventeen of 218 diabetic patients (7.7%) had positive endomysial antibody. All control participants had negative results for the endomysial antibody. Small bowel biopsy was performed in 14 patients. Ten patients had villous atrophy. In one patient without villous atrophy, a repeat biopsy 2 years later showed villous atrophy, and two patients had increased intraepithelial lymphocytes without villous atrophy. Seventy percent of the patients with celiac disease were asymptomatic. The reported symptoms were abdominal pain and diarrhea (n = 1) and growth failure (n = 2). Two patients with celiac disease had Down syndrome. CONCLUSIONS: The prevalence of celiac disease in children with juvenile diabetes in Wisconsin is at least 4.6%, which is comparable with European and Canadian studies. Because patients without villous atrophy may have latent celiac disease, the prevalence may be even higher. All children with juvenile diabetes should be screened for celiac disease.

Percutaneous colonoscopic cecostomy for management of chronic constipation in children.

BACKGROUND: Chronic constipation and encopresis are common problems in children with spina bifida and anorectal anomalies. Commonly used therapies include complicated bowel regimens and antegrade continence enemas delivered via surgically placed appendicostomies and radiologically placed cecostomies. METHODS: A technique is described for percutaneous placement of cecostomies for the delivery of continence enemas or venting. RESULTS: Percutaneous cecostomies were placed in 12 patients. Improvement in bowel management occurred in all patients. CONCLUSIONS: Percutaneous endoscopic cecostomy is a safe and effective method for the treatment of intractable constipation.

Oral tacrolimus treatment of severe colitis in children.

OBJECTIVE: To evaluate the efficacy of oral tacrolimus as an induction agent in steroid-refractory severe colitis. STUDY DESIGN: Open-label, multicenter trial of oral tacrolimus in patients with severe colitis. Patients not responding to conventional therapy received tacrolimus, 0.1 mg/kg/dose given twice a day, and the dosage was adjusted to achieve blood levels between 10 and 15 ng/mL. Response was defined as improvement in a number of clinical parameters (including abdominal pain, diarrhea, rectal bleeding, and cessation of transfusions). Patients who responded by 14 days continued to receive tacrolimus, and 6-mercaptopurine or azathioprine was added as a steroid-sparing agent 4 to 6 weeks after the tacrolimus was instituted. RESULTS: Fourteen patients were enrolled in the study. One patient elected to withdraw after 48 hours. Of the 13 remaining, 9 (69%) responded and were discharged. Tacrolimus was continued for 2 to 3 months in the responders, except for 1 patient who was given tacrolimus for 11 months. After 1 year of follow-up, only 5 (38%) patients were receiving maintenance therapy; the other 4 responders had undergone colectomy. CONCLUSION: Although tacrolimus is effective induction therapy for severe ulcerative or Crohn's colitis, fewer than 50% of patients treated will successfully achieve a long-term remission.

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

OBJECTIVES: Tumor necrosis factor-alpha plays a central role in chronic intestinal inflammation of Crohn's disease. Targeting this cytokine with the chimeric monoclonal antibody infliximab has emerged as an effective form of therapy in adult Crohn's disease patients. We sought to determine whether infliximab treatment would benefit pediatric patients with medically refractory Crohn's disease. We also assessed the duration of response, comparing children with early disease to children with long-standing (late) Crohn's disease. METHODS: Fifteen consecutive children (mean age 12.8 +/- 3.2 yr) with medically refractory Crohn's 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 Crohn's 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 Crohn's disease. More importantly, there is a remarkably prolonged duration of response after infliximab therapy in children with early compared to late Crohn's disease.

Esophageal biopsy does not predict clinical outcome after percutaneous endoscopic gastrostomy in children.

Clinically symptomatic gastroesophageal reflux may occur after percutaneous endoscopic gastrostomy (PEG). Preoperative evaluation for gastroesophageal reflux does not reliably predict those individuals who will develop reflux unresponsive to medical management after PEG. Esophageal histology at the time of PEG might be used to identify patients at risk for developing intractable gastroesophageal reflux. The study aim was to correlate the clinical outcome after PEG with esophageal histology at the time of PEG insertion. A retrospective review of 68 consecutive children who had an esophageal biopsy obtained at the time of PEG insertion was undertaken. Preoperative evaluation, esophageal histology, and clinical outcomes were compared. Preoperative gastroesophageal reflux was present in 23% of upper gastrointestinal series performed, in 10% of pH probe studies, and in 29% of reflux scans. Histology was normal in 57% of esophageal biopsies obtained at the time of PEG insertion. Symptomatic gastroesophageal reflux requiring antireflux surgery or conversion to gastrojejunostomy developed in 10% of patients after PEG placement. Only one of these patients had esophagitis on biopsy. In conclusion, preoperative esophageal histology does not reliably predict the development of symptomatic gastroesophageal reflux after PEG placement.

Electrogastrography in gastrostomy-tube-fed children.

Following gastrostomy tube placement some children develop gagging, retching, vomiting, pain, or irritability during feedings. Conventional medical management is not always successful. It is possible that intolerance of gastrostomy tube feedings reflects an underlying motility disorder of the foregut. The study aim was to determine whether children with gastrostomy tube feeding difficulties demonstrate abnormal gastric electrical control activity as measured by electrogastrography. Cutaneous electrogastrography of interpretable quality was performed in 25 feeding-tolerant and 23 feeding-intolerant children less than 10 years of age. Dominant frequencies, rhythm indices, and postprandial power measurements were recorded during the fasting and postprandial periods. Differences between groups were compared using the Student's t test. The groups were similar in method of gastrostomy tube placement, antireflux surgery, neurological impairment, duration of gastrostomy feeding dependence, formula type, volume, and administration. The feeding-tolerant group was significantly older (P<0.01). There were no significant differences between groups in the mean dominant frequencies or rhythm indices. The feeding-intolerant children had a mean postprandial power change that was significantly lower than that of the feeding tolerant group (P<0.003), although overlap was present. Children who are intolerant of gastrostomy tube feeding have an abnormal postprandial power decrease. EGG dominant frequency and rhythm indices are not predictive of gastrostomy feeding tolerance in predominantly neurologically impaired children.

Presenting symptoms and diagnostic lag in children with inflammatory bowel disease.

Presenting symptoms and their duration may affect the time that elapses prior to definitive diagnosis of inflammatory bowel disease (IBD). This study was undertaken to determine the mean duration of presenting symptoms and diagnostic lag in children with IBD. The medical records of all patients less than 19 years of age diagnosed with IBD at the pediatric gastroenterology clinic of Children's Hospital of Wisconsin between 1990-1995 were reviewed. The age at diagnosis, gender, presenting symptoms and duration, disease location, and diagnostic lag were analyzed. There were 91 children (49 male) diagnosed with IBD. Crohn's disease (CD) was diagnosed in 58, ulcerative colitis (UC) in 24, and indeterminate colitis in 9. The mean ages at diagnosis were 11.4 years for CD, 9.7 years for UC, and 7.8 years for indeterminate colitis. The most frequent presenting symptoms were abdominal pain, diarrhea, hematochezia, and weight loss. The average lag in diagnosis of CD was 7.1 months, which varied by disease location: small intestine 10.5 months, ileocolonic 7.5 months, and colonic 6.4 months. The average lag in diagnosis was 6.7 months for UC and 14 months for indeterminate colitis. Children presenting with growth failure had the longest diagnostic lag. (a) The elapsed time between symptom onset and the diagnosis of CD has decreased. (b) The diagnostic lag in CD decreases with distal colonic involvement. (c) Following onset of symptoms UC was diagnosed only slightly more rapidly than CD.

Disorders of the pancreas in children.

In the past year, major advances in understanding pancreatic disease have been made through the tools of molecular biology. Genes responsible for both hereditary pancreatitis and pancreatic agenesis have been identified. The first description of magnetic resonance cholangiopancreatography, a new noninvasive imaging study of the pancreatobiliary tree, was reported in children. Reviews of autoimmune pancreatitis, a newly described condition, pancreatitis in inflammatory bowel disease, tropical pancreatitis, and pancreatitis following liver transplantation were also published, as well as surgical and endoscopic therapy of pancreatitis.

Hyperammonemic encephalopathy after chemotherapy. Survival after treatment with sodium benzoate and sodium phenylacetate.

A 16-year-old boy had hyperammonemia and encephalopathy develop after high-dose chemotherapy for acute lymphoblastic leukemia. He was treated successfully with the ammonia-trapping agents sodium benzoate and sodium phenylacetate.

Hepatocellular injury in Streptococcus pneumoniae-associated hemolytic uremic syndrome in children.

Streptococcus pneumoniae is an uncommon etiological organism in hemolytic uremic syndrome (HUS). Production of neuraminidase by S. pneumoniae results in exposure of red blood cell T-antigen, resulting in hemolysis, thrombocytopenia, and acute renal failure. Hepatic involvement in this form of HUS has not been described in the literature. We report in three children with S. pneumoniae-associated HUS the presence of severely elevated transaminases and conjugated hyperbilirubinemia. Increases in asparagine transaminase ranged from 11 to 46 times normal values and an increase in alanine transaminase ranged from 1.6 to 8 times normal. In all patients the rise in total bilirubin was 7-15 times normal. Biliary tree obstruction and viral causes for liver dysfunction were absent. Hepatocellular injury in S. pneumoniae-associated HUS likely results from mechanisms involved in sepsis and pneumonia-induced jaundice, combined with severely increased bilirubin production following massive hemolysis. The hepatic injury in all three patients resolved within 9, 5, and 10 days. Our experience suggests that an extensive evaluation including liver biopsy is not indicated.

Pancreatitis associated with brain tumor therapy.

PURPOSE: Four children with prolonged emesis during brain tumor therapy were diagnosed with pancreatitis. PATIENTS AND METHODS: All were exposed to medications or radiotherapy that potentially contributed to pancreatitis. CONCLUSIONS: Because recognition of pancreatitis may necessitate changes in supportive care, pancreatitis should be included in the differential diagnosis of vomiting in this population.

Endoscopic retrograde cholangiopancreatography in children.

Endoscopic retrograde cholangiopancreatography (ERCP) is playing an increasingly important role in the evaluation and treatment of children with disorders of the pancreas and biliary tree. In this article the technique, indications, and complications of diagnostic and therapeutic ERCP in children are reviewed. ERCP, when used properly, improves the ability of the clinician to diagnose and treat. Therapeutic ERCP reduces the need for surgery, and preoperative ERCP provides surgeons with a "road map" when surgery is required.

Crohn's disease presenting as unilateral labial hypertrophy.

We describe a child who had unilateral hypertrophy of the vulva, a rare extraintestinal manifestation of Crohn's disease. A biopsy specimen revealed a noncaseating granuloma. Flexible sigmoidoscopic examination revealed punctate 1 mm lesions with surrounding erythema in the rectum and sigmoid colon. Response to treatment with sulfasalazine was excellent. Gastrointestinal symptoms developed 1 year later when sulfasalazine was discontinued.

Pancreatitis associated with bone marrow transplantation in children.

Vomiting, abdominal pain and distension, common findings in children who receive bone marrow transplants (BMT), are usually attributed to chemo-irradiation and mucositis, universally found in these patients. We report seven children, 3.5% of BMT patients at our institutions, with these symptoms who were found to have mild to severe pancreatitis during conditioning for or after receiving BMT. All patients were receiving drugs known to cause pancreatitis, such as adrenocorticosteroids and sulfonamides as well as numerous putative pancreatotoxins such as cyclosporin A and cytosine arabinoside. Five of the seven patients had suffered from graft-versus-host disease. In patients who have received BMT, upper gastrointestinal symptoms should not be attributed to mucositis or chemo-irradiation without first testing for pancreatitis.

Cholecystectomy and cholelithiasis in sickle cell anemia.

Elective cholecystectomy was performed on 12 children (eight male and four female; age range, 4 to 19 years; and mean age, 11.2 years) with abdominal pain that was related to gallstones. Seven patients had jaundice, six had nausea, five had fat intolerance, and three had biliary colic. Two simple transfusions (10 mL/kg of packed red blood cells), designed to decrease the hemoglobin S content to less than 30% and to increase the total hemoglobin level to greater than 100 g/L, were given preoperatively two to three weeks apart. A third transfusion was given on the day before surgery if the total hemoglobin level was less than 100 g/L. The preoperative mean hemoglobin S content was decreased from 88% to 31%, and the mean total hemoglobin level was raised to 122 g/L. There were no preoperative or intraoperative complications. Post-operatively, no patients developed complications that were related to sickle cell anemia. Hospitalization averaged 6.3 days. Recurrent abdominal pain resolved shortly after surgery in all patients. With proper preoperative transfusions, elective cholecystectomy is safe in children with sickle cell anemia. Elective cholecystectomy should be recommended at the time of diagnosis of cholelithiasis.

Endoscopic retrograde cholangiopancreatography in children.

Endoscopic retrograde cholangiopancreatography (ERCP) is a universally used diagnostic and therapeutic modality in adults with pancreaticobiliary tract disease; its use in children with similar problems has been limited. We have performed ERCP procedures in 39 children and adolescents (aged 6 months to 18 years; mean 12.5 years), using the standard adult and pediatric side-viewing endoscopes. In selected cases, ERCP manometric study of the sphincter of Oddi, endoscopic sphincterotomy, or balloon extraction of common bile duct stones was performed. Nineteen patients had significant or abnormal structural findings, including pancreas divisum (four patients); sclerosing cholangitis (three); and choledochal cyst, chronic pancreatitis, choledochocele, pancreatic pseudocyst, common bile duct stone, and sphincter of Oddi motor dysfunction (two each). In all instances in which patients required operation, ERCP examination provided specific anatomic detail that was useful for planning appropriate intervention. The only significant complication after ERCP was mild pancreatitis, which occurred in four patients and responded to supportive, short-term measures.

Intrahepatic biliary tract abnormalities in children with corrected extrahepatic biliary atresia.

Three children with surgically corrected extrahepatic biliary atresia developed recurrent cholangitis associated with bile lakes that failed to drain via the hepatoportoenterostomy. Surgical or percutaneous drainage of these cysts was followed by both resolution of the infection and spontaneous internal drainage. We postulate that the ongoing inflammatory process resulted in intrahepatic biliary obstruction, which caused cholangitis and bile cysts. Successful treatment required not only antibiotics but drainage of the bile lakes. Development of bile cysts is a new cause of recurrent cholangitis seen in extrahepatic biliary atresia.

Aeromonas hydrophila colitis in a child.

A 5-year-old girl presented with chronic bloody diarrhea. Evaluation including sigmoidoscopy, rectal biopsy, and barium enema was consistent with the diagnosis of ulcerative colitis. Culture of the stool grew Aeromonas hydrophila. A. hydrophila colitis may be more common than presently realized.

Pancreatic structure and function in the immature reserpinized rat.

Immature rats were reserpinized to determine whether the model used for adults may be suitable for the study of pancreatic exocrine insufficiency seen in infants with cystic fibrosis. Rats were reserpinized by injections either into pregnant dams or into newborn rats. The dose of reserpine used by others was lethal to immature rats, so lower doses were used. Pancreas from 1-day-old fetal-treated pups was hypoplastic, but concentration of chymotrypsinogen was elevated. At age 7 days hyperplasia was seen. When rats were reserpinized as neonates, hypoplasia and decrease in all parameters measured was observed at age 7 days. Progressive recovery occurred during the following 2 weeks in both groups. Electron microscopic study of the fetal-treated 24-hr-old pancreas revealed evidence of acinar cell degeneration with the presence of abnormal zymogen granules. At age 7 days the pancreas from neonatal-treated rat pups appeared to have a reduced number of granules. At ages 14 and 21 days the pancreas was similar to that seen at age 7 days except that the granules were larger and some acinar lumina were filled with a finely granular, homogeneously dense material. It is concluded that prenatal and neonatal reserpinization of rats induces changes in pancreas similar to those found in cystic fibrosis.