Clostridium difficile infection in children: epidemiology and risk of recurrence in a low-prevalence country.

Clostridium difficile infection (CDI) is increasingly found in children worldwide, but limited data are available from children living in southern Europe. A 6-year retrospective study was performed to investigate the epidemiology, clinical features, treatment, and risk of recurrence in Italy. Data of children with community- and hospital-acquired CDI (CA-CDI and HA-CDI, respectively) seen at seven pediatric referral centers in Italy were recorded retrospectively. Annual infection rates/10,000 hospital admissions were calculated. Logistic regression was used to investigate risk factors for recurrence. A total of 177 CDI episodes was reported in 148 children (83 males, median age 55.3 months), with a cumulative infection rate of 2.25/10,000 admissions, with no significant variability over time. The majority of children (60.8 %) had CA-CDI. Children with HA-CDI (39.2 %) had a longer duration of symptoms and hospitalization (p = 0.003) and a more common previous use of antibiotics (p = 0.0001). Metronidazole was used in 70.7 % of cases (87/123) and vancomycin in 29.3 % (36/123), with similar success rates. Recurrence occurred in 16 children (10.8 %), and 3 (2 %) of them presented a further treatment failure. The use of metronidazole was associated with a 5-fold increase in the risk of recurrence [odds ratio (OR) 5.18, 95 % confidence interval (CI) 1.1-23.8, p = 0.03]. Short bowel syndrome was the only underlying condition associated with treatment failure (OR 5.29, 95 % CI 1.17-23.8, p = 0.03). The incidence of pediatric CDI in Italy is low and substantially stable. In this setting, there is a limited risk of recurrence, which mainly concerns children treated with oral metronidazole and those with short bowel syndrome.

The use of ciclosporin in paediatric inflammatory bowel disease: an Italian experience.

AIM: To asses the efficacy and safety of ciclosporin in a paediatric population with inflammatory bowel disease. PATIENTS AND METHODS: Twenty-three Italian children treated with ciclosporin were studied retrospectively. The indications for treatment were severe unresponsive colitis, chronic active colitis or severe fistulizing Crohn's disease. The treatment duration, follow-up and causes of drug discontinuation were assessed. RESULTS: Sixteen patients were treated intravenously for a mean time of 10 +/- 7 days (1-24 days) and 19 orally for a mean time of 133 days (17-660 days). The mean follow-up of all patients was 13.2 months. Ciclosporin was totally ineffective, being discontinued for surgery, in nine of 23 patients (39%); it was discontinued for partial response in three patients (13%). During treatment, clinical remission was achieved in eight children (35%) and maintained after drug withdrawal in four (17%). In severe unresponsive colitis, urgent colectomy was avoided in 12 (85%) of 14 patients who tolerated the drug. Side-effects appeared in six of 23 patients (26%), and three (13%) required ciclosporin to be discontinued due to neurotoxicity. CONCLUSIONS: Ciclosporin shows disappointing long-term results in the treatment of refractory inflammatory bowel disease, but can play an important role in preventing urgent surgery in unresponsive severe colitis. Severe side-effects can occur.

Fecal chymotrypsin: a new diagnostic test for exocrine pancreatic insufficiency in children with cystic fibrosis.

The purpose of this report is to evaluate whether a new, simple, non-invasive method for chymotrypsin measurement in stools is useful for the diagnosis of exocrine pancreatic insufficiency in cystic fibrosis (CF). A hundred children aged from 2 months to 12 years were tested: 50 children had been admitted for chronic diarrhoea, 15 for cystic fibrosis and 40 acted as controls. Chymotrypsin in stools was assayed using a kinetic measurement with Succ-Ala-Ala-Pro-Phe-pNa as substrate in a simple photometric assay. In 13 of 15 children with cystic fibrosis, stool enzyme levels were always remarkably low, while all control subjects and all children not presenting cystic fibrosis had normal stool levels of chymotrypsin. Our data suggest that stool chymotrypsin measurement is a simple and reliable "tubeless" test for the evaluation of exocrine pancreatic insufficiency in children with cystic fibrosis.

MR imaging of CNS involvement in children affected by chronic liver disease.

BACKGROUND AND PURPOSE: MR imaging sheds new light on CNS involvement in the course of acquired chronic liver disease; however, the exact pathogenetic mechanisms of hepatic encephalopathy and associated MR abnormalities remain unclear. Our purpose was to relate MR signal intensity abnormalities of the CNS to clinical, biochemical, and pathologic features of childhood-onset chronic liver disease. METHODS: Twenty-one patients (12 male and nine female patients) were included in the study; two had Crigler-Najjar disease type 2, 17 had chronic liver disease of different causes, and two had idiopathic copper toxicosis. Twelve patients had histologically proved liver cirrhosis, with a median disease duration of 175 months at the time of MR study. None had clinical symptoms of hepatic encephalopathy. MR imaging was performed using spin-echo T1- and T2-weighted sequences. RESULTS: Eleven patients had abnormal MR imaging findings of the brain revealed by T1-weighted MR sequences; two of the 11 had idiopathic copper toxicosis. The affected sites were the hypothalamus and globus pallidus, presenting symmetrical and bilateral high signal intensities, or the pituitary gland, which appeared homogeneously hyperintense, or both findings. Eight of the 12 patients with cirrhosis had abnormal MR signals of the brain. In these, the median cirrhosis duration was shorter (169 months) than in the remaining four patients with normal MR signals (177 months). A significant correlation was found between abnormal MR signals of the brain and cirrhosis (P = .008) and factor V activity (P = .008). CONCLUSION: MR imaging confirms the presence of abnormal brain signals in the globus pallidus, hypothalamus, and pituitary gland in patients with childhood-onset liver disease in the absence of clinical symptoms of encephalopathy. Signal intensity abnormalities are likely caused by an as yet unidentified metabolic process partially correlated with the severity of liver disease.

Celiac disease and type I (insulin-dependent) diabetes mellitus in childhood: follow-up study.

To ascertain the specificity of IgA and IgG antigliadin (IgA-AGA, IgG-AGA), IgA-antireticulin (R1-ARA), and antiendomysial (AEA) antibodies for the diagnosis of celiac disease, we evaluated 133 type I diabetic children aged 1.4-28.4 years (mean 14.1 +/- 6.6), with diabetes from onset to 20.5 years. Fifty-three patients were considered at onset and 49 of these also during follow-up. IgA-AGA and IgG-AGA were determined by enzyme-linked immunosorbent assay (ELISA), R1-ARA and AEA by indirect immunofluorescence. IgA-AGA were positive in 20 of 133 (15%), IgG-AGA were positive in seven of 133 (5.26%), while R1-ARA and AEA were positive in three patients. At the onset of disease we found elevated IgA-AGA in 17 of 53 (32%) patients, IgG-AGA in four (7.55%) patients, three of them with IgA-AGA as well; R1-ARA and AEA were present in three (5.66%) patients, all with high IgA-AGA levels. During 1-10 year follow-up IgA-AGA decreased to within the normal range in 13 patients, with elevated IgA-AGA at onset but without R1-ARA and AEA; in four patients with high IgA-AGA at onset, IgA-AGA remained constantly elevated as did R1-ARA and AEA in three of them; and two patients, without IgA-AGA, R1-ARA, and AEA at onset, became positive for all three antibodies. Intestinal biopsy confirmed a diagnosis of celiac disease in five of these with IgA-AGA, R1-ARA, and AEA, but not in one patient with persistent IgA-AGA but no AEA and R1-ARA, suggesting that R1-ARA and AEA are more reliable markers for the screening of celiac disease in type I diabetic patients.

Clinical aspects of coeliac disease in children with insulin-dependent diabetes mellitus.

Coeliac disease (CD) is heterogeneous in its clinical presentation and pathological expression. Silent, latent and potential forms represent the submerged part of the so-called "coeliac iceberg". The association of insulin-dependent diabetes mellitus (IDDM) and CD has been widely reported. For the screening of CD in diabetic patients, anti-reticulin R1 (ARA-R1) and anti-endomysium (AEA) antibodies are more reliable markers than anti-gliadin (AGA) antibodies. Recent studies have reported an increased prevalence of CD in children with IDDM. In our experience intestinal biopsy confirmed a diagnosis of CD in 6 out of 172 diabetic patients, with a prevalence of 3.5%. Only occasionally does CD precede the onset of IDDM; more often CD is diagnosed shortly or sometimes years after the onset of diabetes. Typical gastrointestinal complaints of CD (such as diarrhoea, abdominal distension) are rare in IDDM patients, while atypical isolated signs or symptoms of CD are more common, in particular sideropenic anemia, short stature, delayed puberty, epilepsy, hypertransaminasemia, dyspeptic symptoms, herpetiform dermatitis, and recurrent aphthous stomatitis. It is recommended that all diabetic children, even those asymptomatic, should be screened yearly for CD, using a combination of AGA plus ARA-R1 and AEA.

Morphological evidence of Campylobacter pylori pathogenicity in chronic gastritis and peptic ulcer.

Campylobacter pylori (CP) were found in 84% of 384 patients with chronic gastritis and in none of 49 subjects without inflammation. CP were present in similar percentages among patients with active (90%) or healed peptic ulcer (84%), as well as in non-ulcerous dyspepsia complicated by gastritis (91%). Cytoplasmic vacuolization and swelling of foveolar-superficial cells with adhering bacteria, micropapillae and microerosions were commonly found in CP-infected mucosa. In 100 cases with gastritis both intraepithelial granulocytes and epithelial lesions were prominent features of heavily CP-infected antral mucosa. The occurrence of some cases with abundant, adhering CP but lacking epithelial lesions is in keeping with the different ability of various CP-strains to produce cytotoxins. In 16 of 19 children with type B chronic gastritis antibacterial therapy eradicated CP. This was followed by resolution or striking improvement of gastritis and disappearance of epithelial lesions. These data provide further morphological evidence of direct cytotoxic activity of CP toward gastric mucosal cells.

Defective neutrophil motility in children with chronic liver disease.

Neutrophil motility was assessed in 31 children with chronic liver disease to estimate the eventual increased susceptibility of these patients to bacterial infections. Twelve children had chronic hepatitis (seven with chronic persistent hepatitis and five with chronic active hepatitis), which was mostly related to hepatitis B virus (HBV) infection. Nineteen children had chronic intrahepatic or extrahepatic cholestasis. A total of six serious bacterial infections occurred in four of the 31 patients during the study. Twenty of the 31 children had a persistent defect of neutrophil chemotaxis. This defect was found in four types of childhood chronic liver disease: HBV-related chronic hepatitis and idiopathic intrahepatic cholestasis of infancy, in which the defect did not seem to predispose significantly to bacterial infection, and in Byler's disease and biliary atresia, in which this neutrophil defect was associated with an increased frequency of severe infections.

Idiopathic hepatic copper toxicosis in a child.

A 10-year-old Italian boy with chronic liver disease and copper overload is described. Biological and histopathological findings are similar to those described in children with Indian childhood cirrhosis. This report suggests that a disease akin to Indian childhood cirrhosis but different from Wilson disease can be found in non-Indian children probably representing a new, possibly inherited, disease of copper metabolism leading to copper overload in the liver.

Hepatitis B virus infection and Schönlein-Henoch purpura.

Sch onlein -Henoch purpura developed in two children in association with hepatitis B virus (HBV) infection. The first child, an 8-year-old boy, first had a clinical picture of Sch onlein -Henoch purpura and then was found to have HBV-related chronic persistent hepatitis. In the second child, a 6-year-old girl, characteristic skin lesions, arthralgia, and proteinuria developed during acute hepatitis B. Immunofluorescence demonstrated IgA deposition in the renal glomeruli of the first patient. We suggest that evidence of HBV infection should be sought in patients with Sch onlein -Henoch purpura.

Malignant small cell tumor of the thoracopulmonary region in childhood: a case report.

A case of malignant small cell tumor of the thoracopulmonary region in a 3-year-old boy is presented. The rarity of this tumor in children justifies the presentation of a new case. Differential diagnosis with other childhood neoplasms is discussed.

[Chronic HB virus hepatitis in children. A study of 29 cases]. / L'hépatite chronique à virus HB de l'enfant. Une étude de ving-neuf observations.

Clinical, biochemical and histological features of chronic hepatitis type B were studied in 29 children aged 8 months to 13 years. On entry into the study, all were known to have had hepatitis B surface antigen (HBsAg) with elevated serum transaminase levels for at least six months. A possible source of infection was found in 15 children. When they entered the study, all patients were anicteric and all but one asymptomatic. Hepatomegaly was detected in 15 patients and was associated with splenomegaly in two. Hypergammaglobulinemia was present in 4 children. Serological evaluation of hepatitis B virus markers showed evidence of complete viral replication (HBeAg positivity) in 24 cases and incomplete replication (anti-HBeAg positivity) in 5. Liver histology showed chronic persistent hepatitis (CPH) in 18 children, and chronic aggressive hepatitis (CAH) in 10 (3 moderately active and 7 with major signs of aggressivity ) associated with cirrhosis in 5. One patient had only minimal histological changes. Evaluation of clinical, biochemical and virological parameters did not strictly parallel the histological diagnosis in terms of "activity" of the disease. Follow-up for a mean period of 13 months showed good clinical tolerance to the disease in both CPH and CAH patients. Only 2 children with CAH were given corticosteroids and/or azathioprine for a short period. During follow-up no children with active disease developed liver insufficiency or evidence of portal hypertension. No significant difference in the percentage of children who had seroconversion to antiHBe was found between CPH and CAH groups. Only one child with CAH became HBsAg negative.(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of children with chronic hepatitis in the intrafamilial spread of hepatitis B virus infection]. / Rôle de l'enfant avec hépatite chronique dans la diffusion intrafamiliale de l'infection par le virus de l'hépatite B (VHB).

In order to evaluate the intrafamilial spread of hepatitis B virus (HBV) infection we studied the serological markers of HBV in 101 relatives of 35 children with chronic hepatitis B. Sixty per cent of relatives had markers of infection and 25% showed persistent HBs antigenemia. The high prevalence of HBeAg versus anti-HBe in chronically infected relatives suggests a close temporal relationship of the infection between adults and children. These results support the hypothesis that the child is the main carrier of HBV infection in his family.

Celiac disease presenting as chronic hepatitis in a girl.

A case of celiac disease presenting as an asymptomatic chronic persistent hepatitis in an 11-year-old girl is reported. Liver biopsy performed because of long-standing elevation of serum transaminase levels showed a mild portal fibrosis with mononuclear infiltrate. Immunofluorescence staining did not reveal deposits of immunoglobulins or complement in the liver specimen. Although the girl was totally asymptomatic, she had steatorrhea, a delayed bone age, and an abnormal D-xylose test. A jejunal biopsy showed villous atrophy and increased intraepithelial lymphocytes. On a gluten-free diet the level of transaminases fell to normal within 1 month and remained normal. According to biological remission, a second intestinal biopsy performed after 1 year of gluten-free diet revealed a normal intestinal mucosa. Our report suggests that an underlying chronic intestinal disorder, and particularly celiac disease, must be ruled out when evaluating a child with elevated levels of serum transaminase.

Serum immune response to Helicobacter pylori in children: epidemiologic and clinical applications.

Antibody responses to Helicobacter pylori were measured by a solid-phase whole-cell enzyme-linked immunosorbent assay in 150 children and adolescents; in 47 consecutive children undergoing upper gastrointestinal endoscopy, including 17 with H. pylori infection before and after antimicrobial treatment; and in 46 family members of the infected children. Abnormal levels of either IgG or IgA were found in 6% of the 150 children. In the latter group the prevalence of H. pylori seropositivity increased with age. Parents and siblings of the infected children had 94% and 71% seropositivity, respectively, suggesting intrafamilial spread. Abnormal levels of IgG or IgA against H. pylori identified infected children with 95% sensitivity and 84% specificity. Eradication of the infection was accompanied by a significant decrease in IgG and IgA titers, with normalization in 10 cured patients in 12 months or less. We conclude that the method described for evaluation of H. pylori-specific IgG and IgA antibodies gives helpful information on the epidemiology of the infection and represents a useful adjunct to diagnosis and management of chronic gastritis in children.

Omeprazole for severe reflux esophagitis in children.

BACKGROUND: Severe esophagitis is a rare complication of gastroesophageal reflux in children. In adults, omeprazole therapy of severe erosive esophagitis has become the gold standard short-term treatment of the disease. In children, data on its use are limited, and problems about the dosage are unresolved. The aim of this study was to evaluate the efficacy of a simplified, body-weight-based daily dosage of omeprazole in children with severe esophagitis. METHODS: Ten children (median age 75.6 months; range 25-109 months) with severe esophagitis were prospectively investigated. All patients were evaluated by endoscopy, histology, and 24-h pH-metry study before and after 3 months of omeprazole. The starting dose of omeprazole was 20 mg as a single daily dose in children weighing less than 30 kg, and 40 mg daily for those weighing over 30 kg. RESULTS: A significant improvement in all the children was demonstrated after 3 months of treatment by clinical, endoscopic, and pH-metry assessment. However, histologic study failed to show significant improvement of both inflammatory and hyperplastic findings. Relapse occurred in six of 10 patients after discontinuation of therapy. CONCLUSIONS: Omeprazole is effective in the short-term treatment of severe oesophagitis in children. The daily dose of the drug could be easily based on the body weight. The persistence of histologic features of esophagitis in spite of clinical and endoscopic healing could be an indicator of poor outcome.

Ultrasonographic prediction of the presence and severity of esophageal varices in children.

Twenty-eight consecutive children with either chronic liver disease or portal vein obstruction were investigated to study the presence of gastroesophageal collaterals due to portal hypertension by ultrasound and endoscopy. Sonographic measurements of the ratio of the lesser omentum thickness to aortic diameter (LO/Ad) and of portal vein diameter to body surface (Pv/m2) were significantly higher in children with esophageal varices than in those without varices. With a lower limit for the LO/Ad ratio of 1.3, no false negatives and only three false positives (91% predictive value of esophageal varices) could be detected. The combination of LO/Ad and Pv/m2 would exclude the possibility of detecting esophageal varices if the LO/Ad ratio is less than 1.8 and the Pv/m2 is less than 12 mm. All children with an LO/Ad ratio greater than 1.9 had varices. Even in the presence of an overlap between children with small and large varices, it is possible to identify with high probability a child with large varices if the LO/Ad ratio is greater than 2.5. This study confirms the value of ultrasound in the diagnosis and management of children with portal hypertension and suggests an algorithm to screen children with small and large varices.

Cell-mediated immunity in children with chronic cholestasis.

Cell-mediated immune response was evaluated in 14 children with long-lasting intra- or extrahepatic cholestasis. Cell-mediated immunity was clearly depressed in children with intrahepatic cholestasis while children with extrahepatic biliary obstruction had a more modest and variable degree of impairment. This finding may be related to the longer duration of cholestasis and the higher total bile acid level in the intrahepatic compared to the extrahepatic group. In particular, in children with Byler disease, long-lasting, severe intrahepatic cholestasis was associated with depressed cell-mediated immunity and recurrent severe infections.

Barrett's ulcer and Campylobacter-like organisms infection in a child.

Barrett's esophagus is a gastrointestinal metaplasia of the esophageal epithelium occurring frequently in adults with long-standing peptic esophagitis. Recent reports of Barrett's esophagus in children with gastroesophageal reflux (GER) showed that also at the pediatric age intestinal metaplasia of the esophagus may occur in association with peptic esophagitis. Recently a close association between Campylobacter-like organisms (CLOs) and gastritis has been found in the stomach of both adults and children with a variety of peptic diseases, but evidence of such infection in specimens of Barrett's epithelium has never been described in children. We report here a child with Barrett's esophagus and GER, treated with H2 blockers, who showed a Barrett's ulcer in association with CLO infection. The addition of amoxicillin to antireflux treatment was accompanied by healing of the ulcer, suggesting that bacterial infection of Barrett's epithelium may have an important role in determining its inflammation and possibly ulceration.