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Lactose malabsorption and lactose-induced symptoms are poorly correlated, as shown by breath tests and various symptom assessment methods. Validated assessment is the key to overcome the limitations of biased symptom measurements. We characterized lactose-induced symptoms with the population-specific, validated paediatric carbohydrate perception questionnaire (pCPQ) and their correlation with the history of symptoms (HoS).A total of 130 patients with functional gastrointestinal symptoms underwent a lactose hydrogen breath and tolerance test (LBTT) allowing for a diagnosis of malabsorption (M+) and lactose sensitivity (S+). HoS indicative of lactose-induced symptoms (abdominal pain, nausea, bloating, flatulence, diarrhoea) in the 4 weeks preceding the test was determined using a validated questionnaire. The pCPQ was used to score lactose-induced symptoms.The LBTT revealed 41 children (31.5%) with lactose malabsorption (M+), 56 (43.1%) with lactose sensitivity (S+) and 24 (18.5%) were M+/S+. Sensitivity correlated with HoS (P0.001), regardless of whether malabsorption was detectable. Malabsorption status did not correlate with HoS (NS). The odds of lactose sensitivity significantly increased when abdominal pain [odds ratio (OR) 3.5, confidence interval (CI) 1.6-7.8], nausea (OR 2.3, CI, 1.1-4.9) and flatulence (OR 3.1, CI 1.4-6.8) were reported in the 4 weeks preceding the LBTT. Symptoms after the lactose load were similar for M+/S+ and M-/S+, except for flatulence, which was more frequent in malabsorbers (P0.01).Our findings fit well with the emerging view of the important role of a validated symptom assessment after a lactose load. The determination of symptoms may be more relevant than malabsorption for the clinical outcomes of paediatric patients with lactose-related gastrointestinal symptoms.

Autoimmune pancreatitis is a rare, distinct and increasingly recognized form of chronic inflammatory pancreatic disease secondary to an underlying autoimmune mechanism. We report on a 14-year-old boy who developed autoimmune pancreatitis, while he was under treatment with eltrombopag for chronic immune thrombocytopenia. Therapy with corticosteroids resulted in complete remission of both. This is the first report on the co-occurrence of autoimmune pancreatitis and chronic immune thrombocytopenia in childhood, and clinicians should be aware of this rare association, because early diagnosis and therapy of autoimmune pancreatitis may prevent severe complications.

Aim Anti‐tumour necrosis factor (TNF)‐α drugs are effective treatments for the management of moderate/severe Crohn's disease (CD), but treatment failure is common. In the treatment of paediatric CD, there are no data about the use of a third introduced subcutaneous TNF antibody golimumab. Methods We evaluated the efficacy of golimumab for adolescents with moderate/severe CD. Retrospective analyses were done in all 7 (5 girls) adolescents who received golimumab at a median age of 17 years for a median of 7.2 months. Paediatric Crohn's disease activity index (PCDAI), full blood count, inflammatory markers, use of corticosteroids and adverse events were recorded. Results With golimumab, 5 of the 7 children were PCDAI responders and 2 entered remission (PCDAI

Therapy of children with post‐transplantation lymphoproliferative disorder (PTLD) after hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) can be challenging. In this retrospective study, we investigated PD‐L1 and PD1 expression in all PTLD categories of childhood and adolescence to see whether checkpoint inhibition with PD‐L1/PD1 inhibitors may serve as a therapy option. We included 21 patients aged 19 years or younger (at date of transplant) with PTLD following SOT or HSCT having adequate tumor samples available (n = 29). Using immunohistochemistry, we evaluated PD‐L1/PD1 expression on both tumor cells and cells of the microenvironment in all samples. Availability of consecutively matched tumor samples during 6 of 21 patients' disease courses also allowed an intra‐individual assessment of PD‐L1/PD1 expression. We observed lower PD‐L1 and higher PD1 expression in non‐destructive lesions, and higher PD‐L1 and lower PD1 expression in polymorphic and, in particular, in monomorphic PTLD, mostly diffuse large B‐cell lymphomas (DLBCL, n = 10/21). The amount of PD‐L1‐ and PD1‐positive cells changed in the opposite way in sequential biopsies of the same individual correlating well with the PTLD category. This is the first comprehensive pediatric study assessing PD‐L1 and PD1 expression on tumor cells and in the microenvironment of PTLD including not only monomorphic, but also non‐destructive early lesions. PD‐L1 expression of the tumor cells inversely correlated with PD1 expression in surrounding tissues, with the highest expression in DLBCL. Since PTLD can be therapeutically challenging, our results indicate a potential efficacy of checkpoint inhibitors if standard immune‐ and/or chemotherapy fail or are impossible. We therefore recommend routine staining of PD‐L1 and PD1 in all PTLD categories.

Purpose Gd-EOB-DTPA-enhanced liver MRI is frequently compromised by transient severe motion artifacts (TSM) in the arterial phase, which limits image interpretation for the detection and differentiation of focal liver lesions and for the recognition of the arterial vasculature before and after liver transplantation. The purpose of this study was to investigate which patient factors affect TSM in children who undergo Gd-EOB-DTPA-enhanced liver MRI and whether younger children are affected as much as adolescents. Methods One hundred and forty-eight patients (65 female, 83 male, 0.1–18.9 years old), who underwent 226 Gd-EOB-DTPA-enhanced MRIs were included retrospectively in this single-center study. The occurrence of TSM was assessed by three readers using a four-point Likert scale. The relation to age, gender, body mass index, indication for MRI, requirement for sedation, and MR repetition was investigated using uni- and multivariate logistic regression analysis. Results In Gd-EOB-DTPA-enhanced MRIs, TSM occurred in 24 examinations (10.6%). Patients with TSM were significantly older than patients without TSM (median 14.3 years; range 10.1–18.1 vs. 12.4 years; range 0.1–18.9, p Conclusion TSM in Gd-EOB-DTPA-enhanced liver MRI do not appear in children under the age of 10 years.

Background Management of pediatric post‐transplantation lymphoproliferative disorder (PTLD) after hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) is challenging. Aim This study of 34 PTLD patients up to 19‐years old diagnosed in Austria from 2000 to 2018 aimed at assessing initial characteristics, therapy, response, and outcome as well as prognostic markers of this rare pediatric disease. Methods and results A retrospective data analysis was performed. Types of allografts were kidney (n = 12), liver (n = 7), heart (n = 5), hematopoietic stem cells (n = 4), lungs (n = 2), multi‐visceral (n = 2), small intestine (n = 1), and vessels (n = 1). Eighteen/34 were classified as monomorphic PTLD, with DLBCL accounting for 15 cases. Polymorphic disease occurred in nine, and non‐destructive lesions in six cases. One patient had a non‐classifiable PTLD. Thirteen/34 patients are surviving event‐free in first remission (non‐destructive, n = 4/6; polymorphic, n = 4/9; monomorphic, n = 6/18). Fourteen/34 patients lacked complete response to first‐line therapy, of whom seven died. Four/34 patients relapsed, of whom two died. In 3/34 patients, death occurred as a first event. The 5‐year overall and event‐free survival rates were 64% ± 9% and 35% ± 9% for the whole cohort. Among all parameters analyzed, only malignant disease as the indication for transplantation had a significantly poor influence on survival. Conclusions This study shows PTLD still to be a major cause of mortality following SOT or HSCT in children. A continued understanding of the molecular biology of the disease shall allow to decrease treatment intensity for lower risk patients and to identify patients who may benefit from newer therapy approaches to improve outcome and decrease morbidity.

OBJECTIVES The relevance of methane measurement in breath tests for the detection of carbohydrate malabsorption in children is controversial. The need for correction for poor sample collection is disputed. We evaluated the relevance of methane/CO2 measurements for the diagnosis of paediatric carbohydrate malabsorption. METHODS A total of 132 breath tests (fructose: n = 54; lactose: n = 78) were performed in 91 children/adolescents with functional abdominal complaints. Breath samples were collected and analysed for hydrogen, methane, and CO2. Malabsorption was defined by a net increase over baseline of ≥20 parts per million (ppm) for hydrogen, ≥5 to ≥12 ppm for methane, and ≥10 to ≥15 ppm for hydrogen-plus-methane. The diagnosis was made before and after the use of a CO2-based correction factor (5.5% as the numerator). Hydrogen-based test results were compared with results obtained with other cut-off values. RESULTS Fifty-eight positive tests were obtained by hydrogen measurement (without CO2 correction). The addition of methane measurements did not significantly influence the test results (P > 0.05). Only under the use of extraordinary cut-offs (combined hydrogen-plus-methane smaller than ≥18 ppm) did the rate of malabsorbers increase significantly (P

Background Inducing and maintaining clinical remission in children with Crohn’s disease (CD) is associated with treatment with antibody to tumor necrosis factor (TNF)-α such as infliximab or adalimumab. In the treatment of paediatric CD, there are no data about the use of a third introduced subcutaneous TNF-antibody, golimumab, Methods We evaluated the efficacy of golimumab for adolescents with moderate/severe CD. Retrospective analyses were done in all 7 (5 girls) adolescents who received golimumab at a median age of 17 years for a median of 7.2 months. Paediatric Crohn’s disease activity index (PCDAI), full blood count, inflammatory markers, use of corticosteroids and adverse events were recorded. Results With golimumab, 5 of the 7 children were PCDAI responders and 2 entered remission (PCDAI

This Executive summary of the Guideline on pediatric gastrointestinal endoscopy from the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) refers to infants, children, and adolescents aged 0 - 18 years. The areas covered include: indications for diagnostic and therapeutic esophagogastroduodenoscopy and ileocolonoscopy; endoscopy for foreign body ingestion; endoscopic management of corrosive ingestion and stricture/stenosis; upper and lower gastrointestinal bleeding; endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography. Percutaneous endoscopic gastrostomy and endoscopy specific to inflammatory bowel disease (IBD) have been dealt with in other Guidelines and are therefore not mentioned in this Guideline. Training and ongoing skill maintenance will be addressed in an imminent sister publication.

Background Vedolizumab is safe and effective in adult patients with Crohn’s disease (CD) and ulcerative colitis (UC); however, data in children with inflammatory bowel disease (IBD) are scarce. Therefore, we evaluated vedolizumab use in a cohort of Austrian paediatric patients with IBD. Methods Twelve patients (7 female; 7 CD; 5 UC), aged 8–17 years (median, 15 years), with severe IBD who received vedolizumab after tumour necrosis factor α antagonist treatment were retrospectively analysed. Clinical activity scores, relevant laboratory parameters, and auxological measures were obtained at infusion visits. Results In the CD group, 1/7 patient discontinued therapy due to a severe systemic allergic reaction; 1/7 and 2/7 patients achieved complete and partial response, respectively, at week 14; and 3/7 patients discontinued therapy due to a primary non-response or loss of response. In the UC group, complete clinical remission was achieved at weeks 2, 6, and 14 in 2/5, 1/5 and 1/5 patients respectively; partial response was observed in one patient at week 2. CD activity scores did not significantly change from baseline to week 38 (median 47.5 vs. 40 points, p = 1,0), while median UC activity scores changed from 70 to 5 points (p

Immune responses need to be controlled tightly to prevent autoimmune diseases, yet underlying molecular mechanisms remain partially understood. Here, we identify biallelic mutations in three patients from two unrelated families in differentially expressed in FDCP6 homolog (DEF6) as the molecular cause of an inborn error of immunity with systemic autoimmunity. Patient T cells exhibit impaired regulation of CTLA-4 surface trafficking associated with reduced functional CTLA-4 availability, which is replicated in DEF6-knockout Jurkat cells. Mechanistically, we identify the small GTPase RAB11 as an interactor of the guanine nucleotide exchange factor DEF6, and find disrupted binding of mutant DEF6 to RAB11 as well as reduced RAB11

Objectives Patients suffering from celiac disease (CD) have a higher risk of developing disturbed eating behaviour. Method In a multi-centre study, 259 female adolescents with CD and without a chronic condition were analysed regarding their eating disorder (ED) status, depression, personality, coping strategies and quality of life. Results Patients with CD and comorbid EDs were older and more often non-compliant with their diet and had a higher body mass index (BMI) and higher levels of depression. Differences in personality features disappear when controlling for age and depression. Higher ill-being and lower joy in life were reported by patients with CD and ED compared with patients without EDs, even when controlling for age and depression levels. No differences between patients (with CD) with and without EDs in coping strategies were found. BMI and lower self-directedness predicted ED status. Conclusions Early identification of EDs in patients with CD is suggested and should include BMI and personality factors. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

This guideline refers to infants, children, and adolescents ages 0 to 18 years. The areas covered include indications for diagnostic and therapeutic esophagogastroduodenoscopy and ileocolonoscopy; endoscopy for foreign body ingestion; corrosive ingestion and stricture/stenosis endoscopic management; upper and lower gastrointestinal bleeding; endoscopic retrograde cholangiopancreatography; and endoscopic ultrasonography. Percutaneous endoscopic gastrostomy and endoscopy specific to inflammatory bowel disease has been dealt with in other guidelines and are therefore not mentioned in this guideline. Training and ongoing skill maintenance are to be dealt with in an imminent sister publication to this.

Celiac disease (CD) is an inflammatory affliction of the small bowel caused by an immunological hypersensitivity to ingested wheat antigens affecting almost 1 % of the population. The gliadin fraction of wheat has been shown to contain the pathogenic antigens which react with antibodies and T cells. However, there is only limited knowledge regarding the precise nature of the wheat antigens recognized by IgA antibodies from CD patients and diagnostic tests based on the gliadin fraction have been demonstrated to give frequently false positive results. The aim of this study was the characterization of wheat antigens specifically recognized by IgA antibodies of CD patients. We developed a combined biochemical, biophysical, and immunological approach for the identification of celiac disease-specific wheat antigens. It is based on sub-fractionation of the wheat gliadin fraction using two ion exchange chromatography steps, the localization of CD-specific antigens by immunoblotting with IgA antibodies from CD patients, subsequent digestion followed by electro spray ionization-liquid chromatography/mass spectrometry (LC-ESI-MS/MS) and N-terminal sequencing by Edman degradation. Through the sub-fractionation procedure it was possible to separate CD-specific IgA-reactive wheat antigens from other wheat antigens which were also recognized by IgA antibodies of individuals without CD or by CD patients on gluten-free diet. Analysis by LC-ESI-MS/MS and N-terminal sequencing of the sub-fractions and the proteins specifically recognized by CD patients identified certain γ-gliadins with molecular mass of 37,000 and 45,000 as CD-specific wheat antigens. The CD-specific γ-gliadins with the molecular mass of 37,000 and 45,000 should be useful to study pathomechanisms of the disease and to improve the specificity of diagnostic tests for CD.

CLTA4 is relevant for FOXP3(+)Treg cells, and the link between skewed X chromosome inactivation (XCI) and autoimmunity is recognized. The observation of immune dysregulation polyendocrinopathy enteropathy X-linked syndrome and multiorgan endocrine autoimmune phenomena in various members of one family, associated with a CTLA4 polymorphism and skewed XCI, provides an in vivo model of how mechanisms of immune dysregulation may cooperate.

Objectives: Autosomal recessive, congenital chloride diarrhea (CLD) is a form of persistent secretory diarrhea, presenting with polyhydramnios and intractable diarrhea from birth. CLD is caused by mutations in the SLC26A3 gene, encoding a Na + -independent Cl ― /HCO 3 - exchanger. The diagnosis is generally made on the basis of high fecal chloride concentration in patients with serum electrolyte homoeostasis corrected by salt substitution. We aimed to evaluate the role of diagnostic genetic testing in CLD. Patients and Methods: Clinical and laboratory data were collected from 8 unrelated children diagnosed as having or suspected to have CLD. The evaluation included physical examination, routine clinical chemistry, and SLC26A3 mutation analysis by direct sequencing of DNA extracted from buccal swabs or peripheral leukocytes. Results: CLD was initially diagnosed on high fecal chloride concentrations in 7 patients, and by mutation analysis in 1 patient. In 3 of these patients the correct diagnosis was made more than 6 months after birth. We identified SLC26A3 mutations on both alleles in all 8 patients with CLD, including 3 novel missense and 4 novel truncating mutations. We present a compilation of reported SLC26A3 mutations and polymorphisms. Conclusions: The diagnosis and therapy of CLD were considerably delayed in 3 of 8 patients from this series, highlighting the potential of misdiagnosing CLD. We add 7 novel mutations, including 3 missense changes of highly conserved residues to a total of 41 mutations in this gene. Molecular analysis is efficient and should be considered as a means of early diagnosis of CLD, especially if the clinical diagnosis remains uncertain.

Background: Increase of antibiotic resistance is a worldwide problem. Within the 4 years before the turn of the millennium Helicobacter pylori strains isolated in children living in Vienna, Austria, showed a primary clarithromycin and metronidazole resistance of 20% and 16%, respectively. The aim of this retrospective follow-up survey was to assess the further development and current antimicrobial resistance status. Methods: Children having undergone upper endoscopy between March 2002 and March 2008 at the same two co-operating pediatric gastroenterology units which had also been collaborating on the prior assessment were included. H. pylori infection was diagnosed by rapid urease test, histology, and culture. If the latter was positive, susceptibility testing to amoxicillin, clarithromycin and metronidazole by E-test followed. From March 2004 onwards, susceptibility to levofloxacin, tetracycline and rifampin was additionally assessed. Results: Out of 897 children, 153 had a proven infection with H. pylori and no history of prior eradication treatment. Their median age was 11.5 years (range 0.5–20.9 years). Primary resistance to clarithromycin and metronidazole were 34% and 22.9%, respectively; dual resistance was found in 9.8% of the strains; 0.9% was resistant to tetracycline and rifampin, respectively. No case of amoxicillin resistance was detected. The only independent risk factor for clarithromycin resistance turned out to be the origin of a child from Austrian parents. Conclusions: In the last decade, the rate of primary resistance of H. pylori to clarithromycin continued to rise. No significant change was found regarding primary resistance to metronidazole or dual resistance to metronidazole and clarithromycin, respectively.

Die Hepatitis B ist die haufigste chronische Virusinfektion der Leber. Sie betrifft zumindest geschatzte 350 Millionen Menschen weltweit und ist die haufigste leberbedingte Todesursache. In der letzten Zeit gab es dramatische Entwicklungen sowohl in der Diagnostik als auch in der Medikamentenentwicklung der chronischen Hepatitis B. Heute ist die chronische Hepatitis B in der uberwiegenden Mehrzahl der Patienten eine gut behandelbare Erkrankung und die wichtigste Herausforderung bleibt die rechtzeitige Identifikation der betroffenen Patienten, bevor diese eine fortgeschrittene Lebererkrankungen mit den assoziierten Komplikationen erleiden. Die rasche Entwicklung der medikamentosen Therapie verlangte nach einer Neufassung der Osterreichischen Konsensusempfehlungen zur Behandlung der Hepatitis B, welche bisher nach den Versionen von 1994 und 1998 in ihrer dritten Version von 2005 vorlagen. Alle Kapitel des 3. Konsensus-Statements von 2005 wurden uberarbeitet, mit Ausnahme des Kapitels uber die Leberbiopsie, welches weiterhin in der Version von 2005 Gultigkeit hat. Im Speziellen spielen nun virologische Parameter fur Behandlungsentscheidungen eine zentrale Rolle, die HBV-Genotypisierung wird nun fur die Wahl des Therapeutikums vermehrt in Betracht gezogen und die orale Erstlinientherapie fur die chronische Hepatitis B hat sich verandert. Dieser Konsensus-Bericht beinhaltet die entscheidenden Fortschritte der Behandlung der Hepatitis B und verandert das klinische Management von Patienten mit Hepatitis B in Osterreich entscheidend.

Limited valid data are available regarding the association of fructose-induced symptoms, fructose malabsorption, and clinical symptoms.To develop a questionnaire for valid symptom assessment before and during a carbohydrate breath test and to correlate symptoms with fructose breath test results in children/adolescents with functional abdominal pain.A Likert-type questionnaire assessing symptoms considered relevant for hydrogen breath test in children was developed and underwent initial validation. Fructose malabsorption was determined by increased breath hydrogen in 82 pediatric patients with functional abdominal pain disorders; fructose-induced symptoms were quantified by symptom score ≥2 and relevant symptom increase over baseline. The results were correlated with clinical symptoms. The time course of symptoms during the breath test was assessed.The questionnaire exhibited good psychometric properties in a standardized assessment of the severity of carbohydrate-related symptoms. A total of 40 % (n = 33) had malabsorption; symptoms were induced in 38 % (n = 31), but only 46 % (n = 15) with malabsorption were symptomatic. There was no significant correlation between fructose malabsorption and fructose-induced symptoms. Clinical symptoms correlated with symptoms evoked during the breath test (p 0.001, rFructose-induced symptoms but not fructose malabsorption are related to increased abdominal symptoms and have distinct timing patterns.

Objectives Patients suffering from a chronic condition such as coeliac disease (CD) need to develop coping strategies in order to preserve emotional balance and psychosocial functioning while adhering to their obligatory life-long gluten free diet (GFD). However, this can be particularly challenging for adolescents and may lead to dietary transgressions. Little is currently known about the influence of coping strategies and personality factors on dietary compliance. This study aims to explore these factors for the first time in adolescents with biopsy-proven CD. Study design We included 281 adolescents with CD and 95 healthy controls. We classified patients according to their GFD adherence status (adherent vs. non-adherent) and assessed coping strategies using the KIDCOPE and personality traits using the Junior-Temperament and Character Inventory (J-TCI). Results Adolescents with CD adherent to GFD used less emotional regulation and distraction as coping strategies than non-adherent patients. In terms of personality traits, adherent patients differed from non-adherent patients with respect to temperament, but not with respect to character, showing lower scores in novelty seeking, impulsivity and rule transgressions and higher scores in eagerness with work and perfectionism compared to non-adherent patients. No differences were found between healthy controls and adherent CD patients across these personality traits. Conclusions Coping strategies and personality traits differ in adolescent patients with CD adherent to GFD from those not adherent, and may therefore relate to risk or protective factors in adherence. Targeting coping and temperament using psychological interventions may therefore be beneficial to support adolescents with CD and optimise their adherence to GFD.

Reactivation of persistent human adenoviruses (HAdVs) is associated with high morbidity and mortality in paediatric haematopoietic stem cell transplant (HSCT) recipients. Although invasive HAdV infections mainly arise from the gastrointestinal (GI) tract, the specific sites of HAdV persistence are not well characterised. We prospectively screened biopsies from 143 non-HSCT paediatric patients undergoing GI endoscopy and monitored serial stool specimens from 148 paediatric HSCT recipients for the presence of HAdV by real-time PCR. Persistence of HAdV in the GI tract was identified in 31% of children, with the highest prevalence in the terminal ileum. In situ hybridisation and immunohistochemistry identified HAdV persistence in lymphoid cells of the lamina propria, whereas biopsies from five transplant recipients revealed high numbers of replicating HAdV in intestinal epithelial cells. The prevalence of HAdV species, the frequencies of persistence in the GI tract and reactivations post transplant indicated a correlation of intestinal HAdV shedding pre-transplant with high risk of invasive infection. HAdV persistence in the GI tract is a likely origin of infectious complications in immunocompromised children. Intestinal lymphocytes represent a reservoir for HAdV persistence and reactivation, whereas the intestinal epithelium is the main site of viral proliferation preceding dissemination. The findings have important implications for assessing the risk of life-threatening invasive HAdV infections.

Summary Background: Patients with gluten sensitivity, i. e. celiac disease and dermatitis herpetiformis have anti-endomysial antibodies recognizing transglutaminases, which are usually detected on appropriate tissue sections. It would be desirable to have available a reliable, tissue-independent serological diagnostic tool. We compared disease-specificity and sensitivity of tTG versus eTG-based detection systems for the diagnosis of anti-endomysial IgA-antibodies. Patients and Methods: We examined 204 serum samples in duplicates with commercial human ELISA-kits: 54 healthy blood donors, 20 celiac disease, 29 dermatitis herpetiformis and 101 with other autoimmune dermatoses. Results: The tTG-based ELISA proved to be very disease-specific (100 %) and sensitive for the diagnosis of gluten sensitivity (95 % celiac disease; 96.6 % dermatitis herpetiformis). The eTG-based ELISA was also perfectly specific (100 %), but only 15 % of celiac disease-sera and 44.8 % of dermatitis herpetiformis-sera yielded positive results. Conclusions: The human tTG-ELISA fulfills all criteria of a screening test and, because of being investigator-independent, inexpensive and highly reproducible, compares favorably with the current diagnostic gold standard (indirect immunofluorescence and biopsy) of celiac disease and dermatitis herpetiformis. The low sensitivity of the eTG-ELISA may have technical reasons, but could theoretically also be linked to disease activity or indicate the existence of an as yet undefined disease subset. Studies are currently under way to address these issues. Zusammenfassung Hintergrund: Da die sichere Diagnose der beiden glutensensitiven Erkrankungen Zoliakie und Dermatitis herpetiformis Duhring Gewebsschnitte erfordert, ist eine verlassliche Methode zur serologischen Diagnose wunschenswert. Deshalb testeten wir komparativ kommerzielle ELISA-Kits mit humanem Antigen auf ihren diagnostischen Wert bezuglich Krankheitsspezifitat und Sensitivitat zur Detektion von anti-endomysialen IgA-Autoantikorpern gegen einerseits Gewebs- bzw. andererseits epidermale Transglutaminase. Patienten und Methodik: Wir untersuchten in Doppelbestimmung Seren von 204 Personen (54 Gesunde, 20 Zoliakie, 29 Dermatitis herpetiformis, 42 Pemphigus, 38 Bulloses Pemphigoid, 17 Lupus erythematodes, 2 Lichen ruber pemphigoides, 1 Epidermolysis bullosa acquisita, 1 Pemphigoid gestationis). Ergebnisse: Der tTG-ELISA erwies sich als ideal spezifisch (100 %) sowie hoch sensitiv fur die Diagnose von Zoliakie (95 %) und Dermatitis herpetiformis (96,6 %). Auch der eTG-ELISA erreichte eine ideale Spezifitat (100 %), jedoch waren nur 15 % der Zoliakie-Seren bzw. 44,8 % der Dermatitis herpetiformis-Seren positiv. Schlussfolgerungen: Der humane Anti-tTG-ELISA erfullt alle Kriterien einer Screeningmethode. Verglichen mit dem bisherigen diagnostischen Goldstandard, der Immunfluoreszenz und der Biopsie, ist dieser Untersucher-unabhangige, preisgunstige und leicht reproduzierbare Test als eine vollig gleichwertige, wenn nicht uberlegene Methode zur hoch sensitiven Diagnostik von Zoliakie und Dermatitis herpetiformis einzustufen. Die Grunde fur die niedrige Sensitivitat des eTG-ELISA konnten technischer Natur sein, aber auch in Bezug zur Krankheitsaktivitat stehen oder auf eine noch nicht definierte Auspragungsform der Glutensensitivitat hinweisen. Untersuchungen dieser Theorien sind im Gange.

Background: Dietary intake of wheat can cause two distinct immunologically mediated diseases with severe gastrointestinal manifestations, coeliac disease (CD) and IgE-mediated food allergy. The pathomechanisms underlying these diseases are different, but the profile of the target antigens in wheat has not been compared for the two diseases. Methods: We compared IgA- and IgE-reactive antigens in wheat using sera from patients with coeliac disease (n = 35) and food allergy to wheat (n = 16) by one- and two-dimensional immunoblotting. Furthermore, the IgG subclass (IgG1–IgG4) reactivity to wheat antigens was studied by enzyme-linked immunosorbent assay. Results: IgA antibodies from CD patients and IgE antibodies from allergic patients recognised distinct profiles of wheat antigens. Furthermore, the IgG subclass responses to wheat antigens were different in CD and wheat-allergic patients. Conclusion: This study thus demonstrates that wheat contains antigens/epitopes which are preferentially recognised by CD patients, whereas others elicit IgE-mediated food allergy. This finding suggests that the nature of a food antigen may influence the quality of the pathological immune response in the gut and has implications for the diagnosis and therapy of hypersensitivity to wheat.

The prevalence of celiac disease (CD) in children with diabetes mellitus type 1 (DM) is significantly higher than in the nondiabetic population. Most patients with DM and associated CD do not experience typical gastrointestinal symptoms of CD. There is no agreement on the necessity of screening and management of silent CD for patients with DM or on the time scale for screening. Only few data on follow-up evaluation of children with DM and CD-related antibodies are available.One hundred fifty-seven patients with DM (mean age, 14.8 years; range, 4-21 years; male, 83) were screened with endomysial antibodies (EMA) between 1993 and 2001. A follow-up period of at least 3 years, with at least 2 EMA measurements, was possible. Group 1 comprised 37 patients whose first measurement was at the onset of DM. Group 2 comprised 120 patients whose first measurement was during the course of the disease. In patients with positive EMA, small bowel biopsy was performed. Thyroid peroxidase (TPO), thyroglobulin (TgA), glutamate decarboxylase (GAD), antiinsulin (IAA), and islet cell antibodies (IA2) were measured in all patients.EMA was positive in 16 patients, in 5 at onset of DM and in 11 during the course of DM (mean duration, 33.6 months; range, 11-105 months). Biopsy results showed normal mucosa in seven patients, increased intraepithelial lymphocyte counts in one, and flat mucosa in eight. There was no significant difference between EMA-positive and EMA-negative patients regarding height, weight, HbA1c level, frequency of hypoglycemia or hyperglycemia, TPO, TgA, GAD, IAA, or IA2.This study emphasizes the high prevalence of CD in patients with DM. Although several patients already had positive EMA titers at the onset of DM, seroconversion may also occur during the course of the disease. Screening for CD with EMA or tissue transglutaminase should be included in the initial investigation of DM, but should also be repeated over time to detect late seroconversion.

Background: The authors evaluate the prevalence of Helicabacter pylori resistance in 117 children and demonstrate the changes over a 4-year period. Methods: In 117 children and adolescents, H. pylori-positive gastritis was revealed by diagnostic upper endoscopy. Biopsies from the antrum and body of the stomach were tested by histology, urease test, and culture. H. pylori was isolated using standard culture techniques, and susceptibility to amoxicillin, clarithromycin, and metronidazole was tested using the E-test (AB-Biodisk, Sweden). Results: Endoscopy revealed gastric ulcers in 2 of 117 subjects, duodenal ulcers in 6 of 117, and erosive gastritis or duodenitis in 23 of 117. Almost all patients showed antral nodularity. Histology always showed chronic gastritis with different degrees of activity. During the 4-year study period, the authors noticed an increase of primary clarithromycin-resistant H. pylori strains, from 14.3% to 27.6% (mean, 20.3%). Metronidazole resistance varied between 5% and 25%. No resistance to amoxicillin was found. Conclusion: Eradication of H. pylori should take place only after testing of susceptibility. The general use of clarithromycin in children should be restricted to better-defined indications. Resistance to clarithromycin of H. pylori may also become a future problem for the treatment of adults.

In most patients with cystic fibrosis (CF), pulmonary symptoms are the first sign of presentation. Another predominant feature is maldigestion, frequently starting in early childhood. Pancreatic exocrine dysfunction causes maldigestion, characterised by failure to thrive, diarrhoea, hypoproteinaemia, oedema and anaemia. Dermatitis may be the initial manifestation in just a few patients with CF. We report on a patient presenting with refractory dermatitis resembling acrodermatitis enteropathica as the first sign of CF at the age of 4 months, but without pulmonary symptoms. Laboratory findings demonstrated anaemia, hypoproteinaemia and zinc deficiency. Peroral zinc substitution resulted in resolution of the dermatitis within a few days. A further work-up revealed a positive sweat test and homozygosity for the ΔF-580 mutation. Conclusion: in rare cases, acrodermatitis enteropathica-like dermatitis is the first symptom of cystic fibrosis.

In Celiac disease (CD), cytoskeletal integrity of intestinal cells is disrupted by gliadin exposure. This study investigates the role of heat shock protein (Hsp)70 during cytoskeletal recovery in CD by assessing its induction and effects on junctional proteins. Using an in-vitro model of CD, cytoskeletal injury and recovery was assessed in gliadin-exposed Caco-2 cells by measuring cellular distribution of ezrin, E-cadherin, and Hsp70 by differential centrifugation. Effects of Hsp70 were tested by an in-vitro repair assay, based on the incubation of injured or recovered cytoskeletal cellular fractions in noncytoskeletal supernatants containing low or high levels of Hsp70, or by transient transfection of Caco-2 cells with Hsp70. Cytoskeletal disruption of ezrin and E-cadherin was demonstrated in gliadin-exposed Caco-2 cells by their significant shift from the cytoskeletal pellet into the noncytoskeletal supernatant fraction. Recovery from gliadin exposure was associated with induction and cytoskeletal redistribution of Hsp70. The in-vitro repair assay delineated direct evidence for HSP-mediated repair by stabilization of junctional proteins by Hsp70. Overexpression of Hsp70 resulted in significantly increased cytoskeletal integrity. Our results establish an essential role of HSP-mediated cytoskeletal repair in Caco-2 cells during recovery from in-vitro gliadin exposure.

We report on the rare case of a 4-year-old boy with patent ductus venosus and pulmonary hypertension presenting with progressive fatigue, tachypnoea at rest and tachycardia. Cardiac catheterisation revealed suprasystemic pressure in the pulmonary arteries with severely elevated pulmonary vascular resistance. In order to reduce the diameter of the ductus venosus, a stent was implanted interventionally, which closed, as expected, spontaneously 2 years later. Pulmonary arterial pressure and pulmonary vascular resistance decreased significantly and the general condition of the boy improved dramatically. Conclusion To the best of our knowledge, this represents the first report of successful interventional stent occlusion of a patent ductus venosus associated with severe pulmonary hypertension. The future will tell whether this intervention is curative or represents a bridging procedure for subsequent liver transplantation.

Unrecognized celiac disease (CD) may be found in a substantial proportion of patients with type I diabetes mellitus.A cohort of 403 Austrian children and adolescents with type I diabetes mellitus (210 males and 193 females; age range, 1-22 years) was screened for celiac disease using the IgA anti-endomysium antibody test (EMA) and the immunoglobulin (Ig)G anti-gliadin (AGA-IgG) and IgA anti-gliadin (AGA-IgA) antibody test.Twelve patients' sera (2.98%) yielded positive EMA results and two patients' sera (0.49%) with IgA deficiency had high AGA-IgG values. All but one of these patients underwent intestinal biopsy. Six (1.49%) had clear histologic evidence of CD (flat mucosa), whereas three (0.74%) showed minor histologic changes (increase in intraepithelial lymphocytes) and four (0.99%), including the EMA-negative patients with IgA deficiency, had a normal mucosa. When the cases with silent and potential CD were combined, the overall prevalence in the current cohort was 2.98%. There was no difference in the hemoglobin (Hb)A1c level between antibody-positive and -negative patients, and subsequent gluten-free diet did not change this metabolic parameter.The prevalence of clinically unrecognized CD, found by EMA screening, is much higher in Austrian children with diabetes than in a comparable population without diabetes. The prevalence of CD in diabetic children in Austria is distinctly lower, however, than in several other countries.

ZusammenfassungUnter einer funktionellen Diarrhö (Synonyme: toddler’s diarrhoea, chronisch unspezifische Diarrhö, irritables Kolon des Kleinkindes) versteht man entsprechend den Rom-III-Kriterien Durchfälle mit einer Dauer von länger als 4 Wochen, mehr als 3 Stühlen am Tag mit zumeist breiiger bis flüssiger Konsistenz sowie vermehrtem Stuhlvolumen. Die Durchfälle treten ausschließlich tagsüber auf und sind ohne Begleitsymptome. Des Weiteren findet man häufig Schleim und unverdaute Nahrungsreste im Stuhl. Bei adäquater Kalorienzufuhr gedeihen die Kinder gut. Der Beginn liegt meist zwischen dem 6. und 36. Lebensmonat und sistiert zumeist im Schulalter spontan. Es gibt weder Hinweise auf organische noch biochemische Pathomechanismen. Als mögliche Ursachen werden erhöhte intestinale Transitzeiten bei Genuss von großen Mengen an Fruchtsäften (Sorbitol, Fruktose), hoher Kohlenhydratgehalt und niedriger Fettgehalt sowie Überfütterung genannt. Bezüglich der Therapie lässt sich oft mit einer entsprechenden Diätumstellung durch Reduktion der Kohlenhydratanteile sowie durch Reduktion von Fruchtzucker und Sorbitol, bei gleichzeitiger Erhöhung des Fettanteils in der Nahrung auf 40% der Gesamtkalorienzufuhr eine Besserung erzielen. Zusätzlich sollte eine Steigerung ballaststoffreicher Ernährung gefördert werden.

Aim This study determined the prevalence of cholelithiasis and/or cholecystectomy in Rett syndrome, described gallbladder function in a clinical cohort, and identified recommendations for assessment and management of gallbladder disease. Method The incidence of cholelithiasis/cholecystectomy was estimated from data describing 270 and 681 individuals with a pathogenic MECP2 mutation in the Australian Rett Syndrome Database and the International Rett Syndrome Phenotype Database respectively. Gallbladder function in 25 females (mean age 16y 5mo, SD 20y 7mo, range 3y 5mo–47y 10mo) with Rett syndrome (RTT) was evaluated with clinical assessment and ultrasound of the gallbladder. The Delphi technique was used to develop assessment and treatment recommendations. Results The incidence rate for cholelithiasis and/or cholecystectomy was 2.3 (95% confidence interval [CI] 1.1–4.2) and 1.8 (95% CI 1.0–3.0) per 1000 person-years in the Australian and International Databases respectively. The mean contractility index of the gallbladder for the clinical sample was 46.5% (SD 38.3%), smaller than for healthy individuals but similar to children with Down syndrome, despite no clinical symptoms. After excluding gastroesophageal reflux, gallbladder disease should be considered as a cause of abdominal pain in RTT and cholecystectomy recommended if symptomatic. Interpretation Gallbladder disease is relatively common in RTT and should be considered in the differential diagnosis of abdominal pain in RTT.

Aim Children with inflammatory bowel disease (IBD) have a high prevalence of growth retardation and low bone mineral density (BMD). This retrospective study investigated whether the start of infliximab treatment (IFX) was associated with improvement of growth and bone health. Methods Anthropometry, BMD and bone markers were measured 1 year before and after the start of IFX treatment in 33 patients (51% males), with a median age of 13.5 years at baseline. Outcomes were growth with treatment and indicators of improved bone health. Results Twenty-one children (64%) experienced a positive catch-up growth after IFX. Height standard deviation scores (SDS) were significantly higher in children in remission. Treatment with IFX was associated with a statistically significant increase in 25-hydroxycholecalciferol (25-OHD, p = 0.01). IFX had no influence on BMD. Children with low BMD

We report the case of a 7-month-old child with failure to thrive. Celiac disease was suspected because of highly raised antigliadin IgA and IgG antibodies and subtotal villous atrophy. In peripheral blood mononuclear-cells cellular proliferation was found in response to birch pollen, rye pollen and hazelnut extract. Born in June 1992 the infant had not yet experienced a birch pollen season. He had been fed with birch pollen allergy-associated carrot, apple and potato beginning at 6 weeks of life. In the serum, specific IgG, IgM and IgA to birch pollen and profilin, rye pollen and hazelnut antigens were detectable, indicating possible in utero sensitization or T cell cross-reactivity due to early sensitization with related food antigens.

Increase of antibiotic resistance is a worldwide problem. Within the 4 years before the turn of the millennium Helicobacter pylori strains isolated in children living in Vienna, Austria, showed a primary clarithromycin and metronidazole resistance of 20% and 16%, respectively. The aim of this retrospective follow-up survey was to assess the further development and current antimicrobial resistance status.Children having undergone upper endoscopy between March 2002 and March 2008 at the same two co-operating pediatric gastroenterology units which had also been collaborating on the prior assessment were included. H. pylori infection was diagnosed by rapid urease test, histology, and culture. If the latter was positive, susceptibility testing to amoxicillin, clarithromycin and metronidazole by E-test followed. From March 2004 onwards, susceptibility to levofloxacin, tetracycline and rifampin was additionally assessed.Out of 897 children, 153 had a proven infection with H. pylori and no history of prior eradication treatment. Their median age was 11.5 years (range 0.5-20.9 years). Primary resistance to clarithromycin and metronidazole were 34% and 22.9%, respectively; dual resistance was found in 9.8% of the strains; 0.9% was resistant to tetracycline and rifampin, respectively. No case of amoxicillin resistance was detected. The only independent risk factor for clarithromycin resistance turned out to be the origin of a child from Austrian parents.In the last decade, the rate of primary resistance of H. pylori to clarithromycin continued to rise. No significant change was found regarding primary resistance to metronidazole or dual resistance to metronidazole and clarithromycin, respectively.

Hepatitis B is the most common chronic viral infection of the liver. Chronic hepatitis B is estimated to affect at least 350 million people worldwide and is the leading cause of death from liver disease. There have been dramatic developments both in the diagnostic field and in drug treatment of chronic hepatitis B. Today, chronic hepatitis B is a well manageable disease in the vast majority of cases and the main challenge remains the detection of affected patients at an early enough disease stage to prevent end-stage liver disease and its complications. The rapid pace of drug development mandated an update of the Austrian guidelines on the treatment of hepatitis B, which after 1994 and 1998 were now dating back to 2005 in their third version. All chapters from the 3. consensus statement from 2005 were renewed except for the chapter on liver biopsy, which is still valid in its 2005-version. In particular, virologic parameters take now center stage for treatment decisions, HBV-genotyping is now being considered for the choice of treatment, and the oral first line treatment for chronic hepatitis B has been changed. Overall this consensus statement accounts for the major advances in the management of hepatitis B and significantly changes clinical management of patients with hepatitis B in Austria.

To assess the influence of gluten-free diet (GFD) compliance on the quality of life (QOL) of adolescents with coeliac disease (CD), and the impact of patient's age at time of diagnosis.Participants included 365 subjects: 283 adolescents (10-20 years old) with biopsy-proven CD and 82 adolescents without a chronic condition matched for age, sex, education, and social status. Their subjective QOL-comprising physical, mental, and social dimensions as defined by the World Health Organization-was measured and has been analyzed according to compliance status and age at CD diagnosis.Adolescents noncompliant with GFD reported a lower general QOL, more physical problems, a higher burden of illness, more family problems, and more problems in leisure time than adolescents who are compliant with GFD. More frequent GFD transgressions were associated with poorer QOL. Higher problem anticipation and higher feelings of "ill-being" were found in the noncompliant group. No differences between compliant patients with CD and adolescents without any chronic condition were found in all QOL aspects. Adolescents with a late CD diagnosis showed more problems at school and in social contact with peers, as well as worse physical health and higher CD-associated burden.Compliance with GFD is an essential factor to obtain optimal QOL. Psychosocial and educational support should be provided for patients having difficulties strictly adhering to GFD. Early CD onset and diagnosis is associated with better physical health, lower CD-associated burden and fewer social problems, indicating the importance of the earliest CD diagnosis possible.

Background: Celiac disease (CD), treated by a gluten-free diet, may represent a nonspecific trigger for the development of eating pathology, particularly in adolescence. Objective: The authors sought to perform a systematic study on eating pathology in CD. Method: CD patients were assessed for eating disorders by questionnaire, and body mass index was recorded. Results: There was a higher rate of eating pathology in CD patients than would be expected, especially, a higher rate of bulimia nervosa. This subgroup reported more noncompliance with the gluten-free diet and had higher scores on most eating-related questionnaires. In most cases, diagnosis of CD preceded the onset of eating pathology. Conclusion: The authors recommend asking earlyadolescent CD patients whether they are also dieting for aesthetic reasons. (Psychosomatics 2008; 49:399–406)

In der sinusoidalen Membran beginnt die Gallebildung. Rezeptoren und Transporter erleichtern die Aufnahme und den Eintritt von Gallensauren, Bilirubin, Fettsauren und anderen Gallekomponenten in die Leberzelle. Diese enthalt Rezeptoren fur Glykoproteine, Asialoglykoprotein, Immunglobulin A (Ig A), vasoaktives intestinales Peptid (VIP), Insulin, Glukagon und „epidermal growth factor“ (EGF). Ein primar aktiver Transport erfolgt durch die Na+-K+-ATPase, die einen Ionengradienten an der Zellmembran aufbaut und innerhalb der Zelle ein negatives elektrisches Potenzial erzeugt (wodurch die Diffusion erleichtert wird). Dieser Ionengradient ermoglicht die Arbeit anderer Carrier gegen das Konzentrationsgefalle, z. B. von NTCP (Natrium-Taurocholsaure-Kotransport-Polypeptid), das auch fur zahlreiche Medikamente, Ostrogene und zyklische Oligopeptide spezifisch ist. Transporter fur organische Anionen (OATP1) und anorganische Ionen wurden ebenfalls nachgewiesen.

Background: Dietary intake of wheat causes hypersensitivity reactions in patients suffering from IgE-mediated food allergy and coeliac disease. Aim: To study the expression of IgE- and IgA-reactive antigens during wheat seed maturation and in different wheat cultivars. Methods: Summer wheat was grown in a glasshouse and seeds were harvested at defined maturation stages. Mature seeds were obtained from 13 different defined cultivars. Protein extracts were prepared from different maturation stages and cultivars with a standardized procedure based on seed weight and analysed by IgE and IgA immunoblotting using sera from clinically defined patients suffering from wheat allergy or coeliac disease. Results: With a few exceptions the expression of IgE- and IgA-reactive wheat antigens increased during wheat seed maturation. Wheat cultivars could be identified in which the expression of certain IgE- and IgA-reactive components was strongly reduced or not detectable. Conclusions: The expression of IgE- and IgA-reactive antigens depends on wheat seed maturation and varies in different wheat cultivars.

To study whether adalimumab (ADA) was associated with improvement in growth, bone mineral density (BMD) and bone metabolism.In children with Crohn's disease (CD) there is a high prevalence of growth failure and reduced BMD. Treatment with infliximab is associated with an improvement in growth. Anthropometry, paediatric CD activity index (PCDAI), bone markers and BMD was measured in 18 patients (72% females) one year before and after start of ADA with a median age of 14.4 years (range: 5-19 years) at treatment start. Outcomes were indicators of growth with treatment as well as interval growth.Eleven (61%) children experienced catch-up growth after ADA. PCDAI significantly decreased from 52.1 ± 16 to 30.4 ± 23 (P ≤ 0.001). Post ADA, body mass index (BMI) standard deviation score (SDS) 0.1[range: 2.7-(-0.8)] vs -1 [range: 0.1-(-3.6)], P = 0.04 and ∆BMI SDS in children 0.3 [range: 0.7-(-0.2)] vs -1.1 [range: 1.2-(-2.3)], P = 0.01 in remission were significantly higher compared to those with moderate to severe inflammation. The main predictors for growth were 25-hydroxycholecalciferol and for bone mineralisation weight and height SDS. ADA had no significant influence on bone markers and BMD.Next to improvement of PCDAI, half of the children achieved a positive catch-up growth. A better nutritional status with improvement in BMI and weight is positive predictor for improved growth and bone mineralisation.

BACKGROUND. Allogeneic organ transplantation has become a common procedure in acute and chronic organ failure. The major limitation, rejection of the allograft by the host's immune system, can be limited by various immunosuppressive drugs that target the adaptive T-cell response. Most of these drugs are used in the treatment of allergic diseases as well, suggesting that transplant recipients under long-term immunosuppressive therapy should not develop any sensitizations or at least not show any clinical signs of allergy. Surprisingly, organ-transplanted children and adults do report symptoms of type 1 allergies, such as allergic rhinoconjunctivitis, bronchial asthma, and food allergies. Thus far, mainly case reports and series on the occurrence of allergy after orthotopic liver transplantation exist. OBJECTIVE. Our purpose with this study was to evaluate in a cross-sectional design the prevalence of immunoglobulin E-mediated sensitizations and type 1 allergies in solid organ–transplanted children and adolescents and to identify risk factors. METHODS. Seventy-eight organ-transplanted subjects (50 kidney, 9 lung, 19 liver; mean age: 14.06 ± 5.94 years; range 1.42 to 24.25 years) were studied by standardized interviews (modified International Study of Asthma and Allergies in Childhood [ISAAC] criteria), skin-prick tests, and measurement of specific and total serum immunoglobulin E. RESULTS. Nineteen patients (24.4%) were found to be sensitized to ≥1 common inhalant or food allergens, as reflected by elevated specific immunoglobulin E levels and/or positive skin-prick test results, and 8 subjects (10.3%) additionally reported a corresponding present history of atopic diseases. No severe anaphylactic reactions were reported. No statistically significant associations with gender, kind of transplanted organ, distinct immunosuppressive therapies, and age at time of transplantation or age at investigation were found (χ2 test, Fisher's exact test, and Wilcoxon rank-sum test, respectively). Multiple logistic-regression analysis did not identify any independent risk factor either. CONCLUSION. This study demonstrates that therapeutic immunosuppression does not control sensitizations and clinical manifestation of type 1 allergies in organ-transplanted children and adolescents.