Giuseppe Maggiore

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.

Lymphocytic gastritis : a positive relationship with celiac disease

Lymphocytic gastritis is characterized by lymphocytic infiltration of the surface and pit epithelium. Its cause has not been established, but an association with Helicobacter pylori infection or celiac disease has been suggested. We evaluated the histologic features of both gastric and duodenal biopsy specimens from 245 consecutive children and adolescents, and found chronic gastritis in 60 children and celiac disease in 25. Chronic gastritis was associated with H. pylori infection in 36 children and with celiac disease in 15. Lymphocytic gastritis was found in nine children with celiac disease. Children with lymphocytic gastritis had a mean of 40.64 lymphocytes per 100 epithelial cells, compared with a mean of 3.92 lymphocytes per 100 epithelial cells in children with H. pylori-associated gastritis and 5.15 lymphocytes in normal control subjects. Immunohistochemical studies showed that the intraepithelial lymphocytes in lymphocytic gastritis were T cells. No child with lymphocytic gastritis had serologic evidence of past H. pylori infection. We conclude that lymphocytic gastritis in children is associated with celiac disease. Dyspeptic symptoms are frequent; the endoscopic appearance is not characteristic.

Circulating levels of interleukin-6, interleukin-8, and tumor necrosis factor-α in children with autoimmune hepatitis

Circulating levels of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in 13 children with autoimmune hepatitis (AIH) (seven with type 1 and six with type 2). In untreated children with type 1 AIH, TNF-alpha, IL-6, and IL-8 levels were elevated when compared to those of healthy controls (p < 0.005, p < 0.02, p = 0.06, respectively), whereas in children with type 2 AIH, cytokine levels were normal in all except one sample. A significant decrease in circulating IL-6, IL-8, and TNF-alpha was observed when patients were evaluated during a subsequent remission. We found no significant correlation of cytokine levels with alanine aminotransferase (ALT) activity, total serum gamma-globulins, or prothrombin activity. In patients with cirrhosis, serum IL-8 and IL-6 levels were higher (significantly in the case of IL-8) than those of patients without cirrhosis. In conclusion, activation of the in vivo production of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha appears to be associated with type 1 but not with type 2 AIH.

MEMBRANOUS GLOMERULOPATHY AND CHRONIC SMALL‐INTESTINAL ENTEROPATHY ASSOCIATED WITH AUTOANTIBODIES DIRECTED AGAINST RENAL TUBULAR BASEMENT MEMBRANE AND THE CYTOPLASM OF INTESTINAL EPITHELIAL CELLS

ABSTRACT. A child with an immune‐mediated disease is described, who presented two very rare clinical manifestations, a membranous glomerulopathy with circulating anti‐renal tubular basement membrane antibody and a small‐intestinal enteropathy with circulating antibody directed against the cytoplasm of intestinal epithelial cells. Steroid treatment was followed by complete resolution of the renal but not the intestinal manifestations.

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.

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.

Chronic viral hepatitis B in infancy

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A defect in neutrophil motility in two siblings with recurrent infections and a remarkable family history.

SummaryTwo siblings with recurrent infections were found to have impaired neutrophil motility. The same association of infections (otitis media, bronchitis, chronic diarrhoea) has caused seven fatalities in the paternal side of the family, suggesting genetic implications.ZusammenfassungBei zwei Geschweistern mit wiederholten Infektionen ist ein wahrscheinlich genetischer Schaden der Granulocyten-Chemotaxis gefunden worden. Durch Häufung von Infekten (Mittelohrentzündung, Bronchitis, chronischer Durchfall) sind sieben Geschwister in der väterlichen Familie in jungem Alter gestorben.

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

Barretts esophagus is a gastrointestinal metaplasia of the esophageal epithelium occurring frequently in adults with long-standing peptic esophagitis. Recent reports of Barretts 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 Barretts epithelium has never been described in children. We report here a child with Barretts esophagus and GER, treated with H2 blockers, who showed a Barretts 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 Barretts epithelium may have an important role in determining its inflammation and possibly ulceration.

Central nervous system hyperintensity on magnetic resonance imaging in children with cholestatic liver disease.

Sir: Ballauff et al. [1] described three children with chronic liver disease of different aetiology without hepatic encephalopathy in whom MRI revealed bilateral and symmetrical hyperintensity of the globus pallidus in T~-weighted images. Two patients had an inflammatory liver disease of autoimmune aetiology and one a cryptogenic cirrhosis. The hyperintensity seems to correlate with neither the duration of the liver disease nor the activity, since the serum aminotransferase level was within the normal range in two of the three children. In the patient with auto-immune hepatitis with circulating anti-liver-kidney microsomal antibody, a complete regression of CNS hyperintensity was documented 8 months after the start of an immunosuppressive therapy while in complete remission. We recently observed two patients with a chronic cholestatic disorder and MRI hyperintensity of the basal ganglia; one also showed hyperintensity in the pituitary gland. The first patient is a 15-year-old girl with sclerosing cholangitis and biliary cirrhosis in the context of a Langerhans cell histiocytosis. Biliary cirrhosis was diagnosed at age 6. First MRI performed at age 10 because of central diabetes insipidus evidenced absence of a posterior pituitary bright spot and a thick pituitary stalk with no other pathological findings. MRI follow-up 2 years later, at age 12, revealed normalisation of pituitary stalk size and hyperintensity of both pituitary gland and basal ganglia. In 1994 the hyperintensity of the pituitary gland was still present while the signal of the basal ganglia was increased (Fig. 1). Anterior pituitary function was conserved. Neurological examination and school performance were normal. Liver function evaluation showed a total bilirubin level of 5.5 mg/dl with 3.2 mg/dl of conjugated bilirubin, alanine aminotransferase activity was 4 times the upper limit of normal, y-glutamyl transFig.1 a Sagittal section of hypothalamicpituitary MRI T~-weighted image of patient 1 with sclerosing cholangitis. The hyperintensity involves the whole pituitary gland (arrow). b Coronal section of MRI brain of the same patient revealing bilateral hyperintensity of the basal ganglia (arrows)