Treatment of Helicobacter pylori in children with recurrent abdominal pain.

BACKGROUND: The role of Helicobacter pylori remains unclear in children with recurrent abdominal pain (RAP). In this study children with RAP were included in a double blind treatment study to elucidate whether symptoms disappear in children with a H. pylori infection and RAP, if the bacteria are eradicated. METHODS: Thirty-seven H. pylori-infected children aged 4.9-14.5 years (median 9.8 years) with RAP were included. H. pylori was identified by histology and culture. The children were treated with amoxicillin and metronidazole for 14 days. A re-endoscopy including biopsies for histology and culture was done at least one month after the end of treatment. Simple questions for symptoms were asked and blood for serology was repeated 3 and 6 months after the end of treatment. During the observation period the results of the re-endoscopy and the serology 3 and 6 months after the re-endoscopy were blinded for 23 patients and opened to 14 of the patients according to the choice of the families. RESULTS: The eradication rates were 81% (30/37) in the total group and 74% (17/23) in the blinded group. The IgG antibodies to H. pylori decreased significantly 3 (p =.03) as well as 6 months after end of treatment (p <.001) in children with successful eradication. The number of children with RAP decreased after examination and treatment and the well-being improved after 6 months in almost 95% of the children. However, no correlation was seen between eradication of H. pylori and disappearance of RAP, neither after 3 nor after 6 months' observation in the total group of patients (p =.94 and p =.90) or in the blinded group (p =.42 and p =.65). CONCLUSIONS: These results do not provide evidence for a causal relationship between RAP and H. pylori.

High prevalence rates of adult silent coeliac disease, as seen in Sweden, must be expected in Denmark.

AIM: To disclose the prevalence of adult "silent" coeliac disease in Denmark and Sweden. EXPERIMENTAL DESIGN: 1573 Danish and 1866 Swedish healthy blood donors were screened for the presence of serum anti-gliadin antibodies (AGA) by enzyme-linked immunosorbent assay. AGA-positive serum samples were further analysed for IgA anti-endomysium antibodies (EmA) by indirect immunofluorescence microscopy. MAIN RESULTS: The Danish donor population had a higher mean age than the Swedish (41.4 years versus 37.6 years) and a higher proportion of females (41% versus 32%), and had a lower mean level of AGA (17.3 units versus 20.6 units). Sixty-one (3.9%) Danish donors had AGA above the cut-off limit, and four of these also had positive EmA tests. Sixty (3.2%) Swedish donors had AGA above the cut-off limit, and five of these also had positive EmA. Coeliac pathology was proven by biopsy in all five coeliac disease-suspected Swedish donors. No small intestinal biopsy was performed in the coeliac disease-suspected Danish donors. CONCLUSIONS: Based upon the finding of EmA in AGA-positive serum samples, silent coeliac disease may be suspected in 1 per 394 Danish blood donors (2.5 per 1,000). A similar rate was proven in 1 per 373 Swedish blood donors (2.7 per 1,000), indicating no major differences in the prevalence of adult silent coeliac disease between the two neighbouring countries.

Different patterns of Helicobacter pylori adherence to gastric mucosa cells in children and adults. An ultrastructural study.

BACKGROUND: Infection with Helicobacter pylori in childhood may be the initiation of a lifelong coexistence between microorganisms and epithelial cells resulting in chronic inflammation. The adhesion pattern of H. pylori found in antral biopsies from a group of H. pylori-infected children with recurrent abdominal pain was compared with a group of H. pylori-infected adults suffering from dyspepsia, in an attempt to reveal differences in the type of adhesion. METHODS: The histology of antrum biopsies and the ultrastructure of adherent H. pylori in biopsies from 26 children (median age, 10.1 years) were compared with organisms in biopsies from 19 adults (median age, 54.4 years). RESULTS: More than 1000 adherent H. pylori were studied and divided into four types of adhesion: 1) contact to microvilli; 2) connection to the plasma membrane via filamentous material; 3) adhesive pedestal formation; and 4) abutting or making a depression in the plasma membrane. Contact to microvilli was significantly higher (69% versus 39%; P = 0.002) in children compared with adults and comprised two-thirds of all adherent organisms in children. The more intimate adhesion types as abutting or adhesive pedestals dominated in adults. CONCLUSIONS: These results indicate a change in contact types between H. pylori and gastric epithelial cells in adults compared with children and this may be a natural development in the lifelong infection of humans.

Interobserver variation in diagnosing coeliac disease. A joint study by Danish and Swedish pathologists.

There is an almost 40-fold difference in incidence rates of symptomatic coeliac disease between Denmark and Sweden. In an attempt to explain this difference, the present study focused on the interobserver agreement when pathologists were assessing small intestinal biopsy specimens from children suspected of suffering from coeliac disease. The study was performed on 90 biopsy specimens from 73 children. Most of the biopsies came from children who turned out not to suffer from coeliac disease after a clinical evaluation including small intestinal biopsy. Using the kappa methodology, the interobserver agreement between two Danish pathologists and one Swedish pathologist, all of whom were experienced, was "moderate" to "substantial" or 0.57-0.75. Kappa indices when the pathologists evaluated selected histological elements were in the interval from 0.24 to 0.67. A comparison of a previous routine diagnostic assessment of the 90 biopsies (14 pathologists) with the results of the experienced pathologists in the present study gave kappa indices of from 0.53 to 0.57. The study could prove no major differences in the histopathological assessment of small intestinal biopsy specimens made by Danish and Swedish pathologists. The difference in clinical presentation of coeliac disease in Denmark and Sweden does not relate to differences in the histopathological assessment of small intestinal biopsies.

[Inflammatory bowel diseases in children]. / Inflammatorisk tarmsygdom hos børn.

From an incidence cohort diagnosed during 1962-1987 we identified all patients with onset of IBD before the age of 15 in order to describe the course and to compare course and prognosis with adult onset IBD. The mean incidence of IBD among children below 15 years was 2.2/10(5), 2.0 for ulcerative colitis (UC), and 0.2 for Crohns disease (CD). At diagnosis, UC children had more extensive disease compared to adults (p < 0.05). Abdominal pains were also more frequent. The cumulative colectomy probability was 6% after one year and 29% after 20 years, not different from adults. Regarding disease activity, it was found that 60-70% of UC patients were in remission in the first 10 years of disease, for CD about 50% were in remission. One UC patient developed carcinoma of the sigmoid colon. Time between onset and development of carcinoma was 12 years. For CD no differences in clinical appearance at diagnosis and course between children and adults were found. No deaths occurred among CD patients. Three CD patients were found to have severe growth retardation already at diagnosis. In conclusion, the incidence of IBD is low in childhood. At diagnosis children with UC have more widespread disease than adults. Children with CD do not differ in clinical presentation, course or prognosis compared to adult onset CD. However, growth retardation is a problem among CD patients.

The prevalence and related symptomatology of Helicobacter pylori in children with recurrent abdominal pain.

The aim of the study was to assess and compare the IgG seroprevalence of H. pylori in children with recurrent abdominal pain with healthy children and to investigate the related symptoms. IgG antibodies against low-molecular weight H. pylori antigens were assessed in 438 children with recurrent abdominal pain and in 91 healthy controls. Sera with an ELISA unit-value above the cut-off level were confirmed by Western immunoblot. Only seropositive children with recurrent abdominal pain were examined by an oesophago-gastro-duodenoscopy. Symptomatology was recorded according to the localization of the abdominal pain, presence of pyrosis, nocturnal pain, relation of pain to meals and bowel irregularities. The seroprevalence was 21% (95% CI: 17-25%) in the children with recurrent abdominal pain and 10% (95% CI: 5-18%) in the healthy controls (p = 0.30). In seropositive children with RAP H. pylori was found in 46/66 by culture and histology. The presence of H. pylori was significantly associated with active or inactive chronic gastritis. The presence of H. pylori was associated with both parents being born in a country with a high prevalence and a low social class. Helicobacter pylori-positive children had more often pain related to meals than the H. pylori-negative children. No differences among the two groups were seen according to the levels of haemoglobin, leucocytes, thrombocytes, weight and height. In conclusion, the seroprevalence of H. pylori is comparable in children with recurrent abdominal pain and healthy children. No specific symptomatology was seen in H. pylori-positive children with RAP.

[Pediatric colonoscopy]. / Paediatrisk koloskopi.

The procedure and results of 50 colonoscopies performed over a three-year period on a group of 43 children (range: 0.3-16 yr; median: 9 yr) are described. The main indications were evaluation for, or control of already known, chronic inflammatory bowel disease (n = 38) and rectal bleeding (n = 8). Following verbal and written information the children were admitted one to two days before the procedure for bowel preparation. Children < 10 years old received general anaesthesia during the colonoscopy (n = 25) and most children > or = 10 years old received an intravenous sedation with pethidine and midazolam (n = 25). In only one case was intravenous sedation not successful. The coecum was visualised in 96% and the terminal ileum intubated in 77% (when intended) of the endoscopies. The most important results obtained were establishment of the diagnosis of inflammatory bowel disease in 21 of 30 suspected cases and the removal of a polyp in two cases. At the time of colonoscopy a "best guess" diagnosis of either ulcerative colitis or Crohn's disease often predicted the histological diagnosis, but endoscopy tended to underestimate the severity and extent of the inflammation as compared to microscopy. There were no complications. We conclude that colonoscopy performed according to our recommendations is a safe and informative procedure for evaluation of the large bowel and terminal ileum in children with intestinal disease.

Abdominal ultrasonography in the diagnostic work-up in children with recurrent abdominal pain.

UNLABELLED: We report on our experience with routine abdominal ultrasonography in 120 children (aged 3-15 years) with recurrent abdominal pain, in order to determine the diagnostic value of this investigation. Eight children (7%) revealed sonographic abnormalities: gallbladder stone (n = 2), splenomegaly (n = 1) and urogenital abnormalities (n = 5). The recurrent abdominal pain could be explained by these findings in only two (may be three) cases. CONCLUSION: The diagnostic value of abdominal ultrasonography in unselected children with recurrent abdominal pain is low. However, the direct visualization of the abdominal structures as being normal may be helpful to the parents and the child in their understanding and acceptance of the benign nature of recurrent abdominal pain.

[Esophago-gastro-duodenoscopy of pediatric patients]. / Osofago-gastro-duodenoskopi af paediatriske patienter.

In total 199 oesophago-gastro-duodenoscopies (OGD) were performed in 71 female and 71 male paediatric patients (three months-15 years, median 8 years 2 months). The endoscopy was performed in general anaesthesia in children less than five years old, and in an intravenous sedation in older patients. The indications for OGD were: recurrent abdominal pain and concomitant positive antibodies against Helicobacter pylori as a part of a scientific project, upper dyspepsia, upper gastrointestinal bleeding, failure to thrive, coeliac disease, suspicion of chronic inflammatory bowel disease and a percutaneous gastrostomy. Seventy-two OGD were carried out in general anaesthesia, 86 in intravenous sedation with midazolam and pethidine and 41 in intravenous midazolam sedation. Complications related to the sedation or to the endoscopy were not observed. Amnesia was reported in 94/95 children who were sedated intravenously with midazolam and pethidine or midazolam alone. Six endoscopies could not be carried out in intravenous sedation because of agitation. In the primary OGD endoscopy revealed a normal mucosa in 121/142 (85%), oesophagitis in four (3%), nodular mucosa in six (4%), gastritis in four (3%) and a duodenal ulcer in one (0.7%). Histology disclosed active or inactive chronic gastritis at the primary endoscopy in 35/69 (51%) of the children with recurrent abdominal pain and antibodies against H. pylori. In children with failure to thrive an avillous duodenal mucosa was seen in 3/32 (9%). A comparison between histological and stereomicroscopical evaluation of the duodenal biopsies revealed agreement in 41/47 (87%). We conclude that OGD is a safe and tolerable procedure in paediatric patients, in whom possible morphological changes are suspected. The indications for an OGD need further evaluation.

Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity, and mortality in a regional cohort.

BACKGROUND AND METHODS: In a geographically derived incidence cohort diagnosed from 1962 to 1987 we identified all patients with onset of inflammatory bowel diseases (IBD) before the age of 15 years, to describe the clinical course and to compare the course and prognosis with those of adult-onset IBD. RESULTS: The mean incidence of IBD among children below 15 years was 2.2/10(5), 2.0 for ulcerative colitis (UC) and 0.2 for Crohn's disease (CD). At diagnosis children with UC had more extensive disease than adults (P < 0.05). Abdominal pain was also more frequent. The cumulative colectomy probability was 6% after 1 year and 29% after 20 years, not different from that of adults. More females underwent colectomy. With regard to disease activity, apart from the year of diagnosis 60-70% of UC patients were in remission in each of the first 10 years of disease; for CD about 50% were in remission. One patient with UC developed carcinoma of the sigmoid colon. Time between onset of UC and development of carcinoma was 12 years. For CD no differences in clinical appearance at diagnosis and course between children and adults were found in relationship to surgery. No deaths occurred among CD patients. Three CD patients were severely growth-retarded already at diagnosis. CONCLUSION: The incidence of IBD is low in childhood. At diagnosis children with UC have more widespread disease than adults. Childhood-onset CD does not differ in clinical presentation, disease course, or prognosis from adult-onset CD. However, growth retardation is a problem among male CD patients.

Pancreatitis in a child after rectal administration of 5-aminosalicylic Acid.

: A case of 5-aminosalicylic acid (5-ASA)-induced pancreatitis in a 7-year-old girl with ulcerative colitis is described. Pancreatitis was first diagnosed after 7 months of treatment with 5-ASA by mouth. When she later received 5-ASA rectally, pancreatitis recurred after 2 weeks of treatment. She rapidly recovered after withdrawal of 5-ASA.

[Celiac disease in children on the two sides of the Sound]. / Morbus coeliacus hos børn på de to sider af Oresund.

Of 771 children (381 Swedish and 390 Danish) investigated during 1972-1989 because of suspected coeliac disease (CD), 179 proved to have the disease. Surprisingly only 24 CD patients were Danish whereas 155 were Swedish, despite the very similar ethnic, geographical, and cultural backgrounds of the two populations. The Danish CD children were diagnosed at an older age (mean 5.5 versus 1.5 years). Breastfeeding habits were comparable. The estimated content of gliadin in the officially recommended diets of the two countries in 1987 differed substantially, the Swedish diet containing more than 40 times more gliadin than the Danish (4400 mg versus 100 mg) at the age of eight months, and four times more (3600 mg versus 900 mg) at the age of 12 months. Compared to the Swedish diet, the Danish infant diet contained significantly larger amounts of rye flour, which is low in gluten. The earlier introduction of food items with a high gluten content in the Swedish as compared with the Danish diet could be a possible explanation for the great difference in incidence and symptomatology of CD between the two populations.

Striking differences in the incidence of childhood celiac disease between Denmark and Sweden: a plausible explanation.

Among 771 children (381 Swedish and 390 Danish) investigated between 1972 and 1989 because of suspected celiac disease (CD), 179 proved to have the disease. Surprisingly only 24 CD patients were found among the Danish children, compared with 155 in the Swedish group, despite the close ethnic, geographical, and cultural background of the two populations. The Swedish CD children were diagnosed at an earlier age than the Danish children (mean, 1.5 vs. 5.5 years). The symptoms of the Swedish patients were dominated by failure to thrive (93 vs. 71%), whereas a higher proportion of the Danish CD patients suffered from stomach pain (21 vs. 5%). Breast-feeding habits were comparable. The estimated content of gliadin in the officially recommended diets of the two countries in 1987 differed substantially, the Swedish diet containing more than 40 times more gliadin than the Danish (4,400 vs. 100 mg) at the age of 8 months, and 4 times more (3,600 vs. 900 mg) at the age of 12 months. The Danish infant diet differed significantly from the Swedish in containing a larger amount of the lower gluten-containing rye flour. The earlier introduction of food items with a high gluten content in the Swedish compared with the Danish diet seems to be an obvious explanation for the great difference in incidence and symptomatology of CD between the two populations.

Helicobacter pylori infection in children with recurrent abdominal pain.

Helicobacter pylori was cultured and Helicobacter-like organisms (HLO) were seen in 6 (16%) of 37 children with recurrent abdominal pain. Five children had concomitant histological inflammation, but none had endoscopic changes. All 6 children demonstrated positive serology. Compared with the total group, they were more often from developing countries, larger families and lower social groups. Treatment with phenoxymethyl penicillin and colloidal bismuth subcitrate did not result in side effects or elevated serum levels of serum bismuth. Three children demonstrated metronidazole-resistant strains and the treatment of these children remained an unsolved problem. Among the 31 H. pylori/HLO negative children 8 (26%) demonstrated histological changes, 5 (16%) endoscopic changes and 11 (35%) had positive serology. In conclusion, pathological findings at upper gastrointestinal endoscopy are common in children with recurrent abdominal pain. Because of disconcordance between endoscopy, histology and culture, we recommend that biopsies should always be taken to clarify the diagnosis.

Insulin-like growth factor-I in celiac disease.

To contribute to the description of the physiopathological mechanisms of celiac disease, changes in insulin-like growth factor I (IGF-I) were followed-up in 21 children suspected of suffering from celiac disease. Thirteen children were suffering from celiac disease according to the original criteria of the European Society of Paediatric Gastroenterology and Nutrition. Ten celiac children changing from a gluten-containing to a gluten-free diet presented a significant rise in IGF-I (+1.54 mM per month). In a group of eight celiac children challenged with gluten, seven had a significant decrease in IGF-I (-1.11 mM per month), and five celiac children returning to the gluten-free diet after challenge with gluten had a marked but not significant increase in IGF-I (+1.7 mM per month). Eight children not suffering from celiac disease, but challenged with gluten, had a significant increase in IGF-I (+0.29 mM per month), corresponding to the expected age-dependent increase. The significant changes in IGF-I described under the diagnostic dietetic phases of celiac disease reflect the extent of growth retardation caused by the disease. IGF-I may be a supplementary aid in the diagnosis of celiac disease in describing individual changes under the dietetic phases.

The humoral immune response to Helicobacter pylori infection in children with recurrent abdominal pain.

The systemic humoral immune response to Helicobacter pylori antigens was investigated in 36 children with recurrent abdominal pain (RAP). H. pylori was cultured and Helicobacter-like organisms (HLO) were seen in six children, three of whom had active and two inactive chronic gastritis. None of these children had endoscopic abnormalities. All sex children had increased IgG antibodies to heat-stable H. pylori antigens which were of the IgG1 and IgG3 subclasses. Using six other IgG tests, four of which were commercially available, two to five H. pylori-positive children were found seropositive. Five of six H. pylori-negative children with inactive chronic gastritis and no endoscopic abnormalities had increased IgM antibody levels in addition to increased or borderline increased IgG antibody levels to H. pylori, indicating activity in a chronic H. pylori infection. Five children without H. pylori and with no morphological changes, but with gastritis or duodenitis by endoscopy, had significantly lower IgG and IgA antibody levels compared to other groups. Six of nineteen children without H. pylori, and with no morphological or endoscopic changes had increased IgG and IgM antibody levels to H. pylori. All H. pylori-negative children were seronegative by the four commercial kits. Overall, 12 (33%) of 36 children with RAP were either H. pylori positive by culture and microscopy or had increased IgG antibody levels to H. pylori, which is significantly different from the 10-14% seropositive rate of asymptomatic children. H. pylori may therefore be a cause of RAP in one quarter to one third of the children with RAP in whom other etiologies of RAP are excluded. Further studies on a large number of children are needed for an extended evaluation of the humoral immune response to H. pylori and for further examination of commercial kits which seem to give a high number of false-negative results.

[Helicobacter pylori infection in children]. / Helicobacter pylori infektion hos børn.

Approximately 10 per cent of all schoolchildren have recurrent stomach pain, and 50 per cent of those referred to hospital for gastralgia can be expected to have persistent problems as adults. Some of these children might be helped by diagnosis and treatment. The lack of large controlled studies of the importance of H pylori in childhood needs to be remedied, with a view to diagnosis and treatment in the future.

[Giardiasis in children with chronic diarrhea. Incidence, growth, clinical symptoms and changes in the small intestine]. / Giardiasis hos børn med kronisk diaré. Incidens, voekst, kliniske symptomer og tyndtarmsforandringer.

During a six-year period, 29 children (aged 0.7-13.5 years, mean 3.3 years) suffering from chronic diarrhoea due to giardiasis were studied. The incidence of this illness was 81 per 1,000,000 per year among children aged 0- < 7 years. According to growth charts, relative height and weight of the patients decreased significantly (both approximately 0.5 SD) from before the onset of diarrhoea to the time of diagnosis and subsequently increased up to the end of catch-up growth. Small intestinal mucosal specimens were studied. Two patients had severe villous atrophy, 8 moderate abnormalities, 6 only slight changes and 13 biopsies were normal. D-xylose or lactose malabsorption was detected in 25% of the patients. The lactose malabsorption was due to hereditary low lactase levels. None of the patients with a Danish ethnic background showed lactose malabsorption. D-xylose absorption and the relative weight loss of the patients correlated with the degree of mucosal damage. Patients with persistent diarrhoea (n = 19) were younger and had a shorter duration of diarrhoeal illness and a more significant weight reduction than those with intermittent diarrhoea (n = 10). However, the age at onset of symptoms was similar in the two groups (medians 1.3 years). Seven patients contracted the disease abroad. They all developed persistent diarrhoea and had a more severe course of the illness than those who acquired the disease in Denmark.

The diagnostic value of the gliadin antibody test in celiac disease in children: a prospective study.

Serum gliadin antibodies (IgA/IgG) were determined in 191 consecutive children (median age, 2.75 years; range, 0.33-15.5 years) admitted for a small-intestinal biopsy on suspicion of celiac disease. The test was a diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA). Of these 191, 14 (7.3%) appeared to have untreated celiac disease. Depending on the choice of cut-off value of the test (combined determination of IgA and IgG), the sensitivity was 86-100%, the specificity was 97-99%, and the positive/negative predictive values were 70-92% and 99-100%, respectively. No variation according to age was found. Gliadin antibodies were determined in 47 children who had well-treated celiac disease. Fourteen of these children were also investigated when challenged with gluten. Gliadin antibodies (IgA or IgG) decreased significantly in 13 of 13 cases when the patients shifted from a gluten-containing diet to a gluten-free one. During the gluten challenge, the IgG and IgA increased in 14 of 14 and 11 of 14 cases, respectively (two patients suffered from IgA deficiency). In eight patients who later appeared to be free of celiac disease, the gliadin antibodies were determined on gluten-free diet and during gluten challenge; no significant differences in gliadin antibodies were found. We conclude that this test is useful in selecting patients with symptoms suggesting celiac disease for a small-intestinal biopsy. The test seems to be of some value in monitoring the effects of a gluten-free diet and during gluten challenge.