Selective immunoglobulin A deficiency and celiac disease: let's give serology a chance.

Patients with selective immunoglobulin (Ig) A deficiency have a 10- to 20-fold increased risk of celiac disease. In these patients, serological diagnosis of celiac disease can be difficult, since specific IgA-based assays are usually negative and IgG-specific antibody tests are insufficiently reliable. We describe a girl with selective IgA deficiency who had a troublesome diagnosis of celiac disease that was established only after an unexpected positive test result for antitransglutaminase IgA and antiendomysium IgA. Our observation indicates that IgA-based serology should not be forgotten in patients with selective IgA deficiency, since positive results for antitransglutaminase IgA, antiendomysium IgA, or both can be observed at any time during diagnostic investigations.

Celiac disease and obesity: need for nutritional follow-up after diagnosis.

More than 20 years of serological approach to diagnosis of celiac disease (CD) has deeply changed the classical clinical presentation of the disease, and some reports indicate that CD and obesity can coexist in both childhood and adolescence. We reviewed clinical records of 149 children with CD followed in our institution between 1991 and 2007, considering weight, height and body mass index (BMI), both at diagnosis and after at least 12 months of gluten-free diet (GFD). In all, 11% of patients had BMI z-score >+1 and 3% were obese (z-score >+2) at presentation. In our population, there was a significant (P=0.008) increase in BMI z-score after GFD and the percentage of overweight (z-score >+1) subjects almost doubled (11 vs 21%, P=0.03). Our data suggest the need for a careful follow-up of nutritional status after diagnosis of CD, especially addressing those who are already overweight at presentation.

Early diagnosis and treatment of celiac disease in type 1 diabetes. A longitudinal, case-control study.

OBJECTIVES: Subjects with type 1 diabetes mellitus (DM) are at increased risk to develop celiac disease (CD). However, most of the published investigations on the association between type 1 DM and CD are cross-sectional ones. In this paper, longitudinal data are presented on the effects of gluten-free diet (GFD) on growth and metabolic control in children and adolescents with type 1 DM screened for CD. METHODS: Clinical records of 27 patients with type 1 DM+CD (7% of a population of 385 subjects with type 1 DM) were reviewed. The following variables were considered at the diagnosis of CD (T0) and after 24 (T24) and 48 (T48) months of GFD according to the length of available follow-up: weight, height, body mass index (BMI), Hb and HbA1c levels and per kg/day dose of insulin. Forty-three patients with type 1 DM alone, matched for sex, age and duration of diabetes were chosen as controls. RESULTS: In patients with type 1 DM+CD, mean (SD) age at type 1 DM diagnosis was 8 (3.3) years. Median time interval between diagnosis of type 1 DM and of CD was 1.8 years (range 0.1-23.9 years). At T0 (n = 23), height and BMI z-score, HbA1c levels and daily insulin dose were comparable in type 1 DM+CD and in control subjects. Mean Hb concentration was significantly lower in subjects with type 1 DM+CD (12.6 (1.3) vs. 13.3 (0.7) g/dl, p < 0.05). At T24 (n = 22) and T48 (n = 16), no difference was detectable in height, BMI, HbAlc and insulin dose and also Hb concentration was comparable in both groups. CONCLUSIONS: This study shows that, at diagnosis of CD, screened subjects with type 1 DM had only minor signs of malnutrition and metabolic disturbances were uncommon. Dietary treatment of CD can allow a growth and diabetes control comparable with subjects with diabetes alone.

[Primary ad secondary gastro-esophageal reflux in pediatric age]. / Reflusso gastro-esofageo primario e secondario in età pediatrica.

AIM: This study takes into consideration children traited for: a) "primary" gastro-esophageal reflux (GER); b) GER "secondary" to delayed gastric emptying; c) some congenital anomalies which can cause or favour GER in pediatric age. METHODS: During 2002, 21 infants or children operated on for "primary" or "secondary" GER and 62 patients operated on for esophageal atresia, diaphragmatic hernia or abdominal wall defect were followed-up to evaluate the frequency and the course of post-operative GER. RESULTS: Patients with "primary" GER had 14% relapses after partial or total fundoplication; all patients with "secondary" GER submitted to fundoplication, usually associated to pyloroplasty, had 0% relapses. One child, after Bianchi's operation, developed an erosive gastritis. Variable degrees of GER developed in 43% of patients operated on for esophageal atresia, in 25% for congenital diaphragmatic hernia and in 0% for abdominal wall defect. In 90% of GER occurred after treatment of esophageal atresia and in 100% of diaphragmatic hernia (predominantely "acquired") an exclusively medical therapy was successfully performed. CONCLUSION: The conclusion is drawn that: a) the relatively high percentage of relapses after fundoplication in "primary" GER may be related to an incorrect classification of a few number of cases ("secondary" GER considered--and treated--like "primary" GER in the '70s and '80s years?); b) fundoplication associated to a best gastric-emptying operation (pyloroplasty) may lead to excellent results in secondary GER; c) esophageal atresia and congenital diaphragmatic hernia (not including the abdominal wall defects) can cause GER in most cases responsive to simple medical therapy.

Screening of coeliac disease in north Italian children with type 1 diabetes: limited usefulness of HLA-DQ typing.

AIM: To determine the contribution of HLA-DQA1* and HLA-DQB1* genes to the risk of coeliac disease (CD) in a cohort of children with type 1 diabetes mellitus (T1DM) from northern Italy. METHODS: Three hundred and fifty-seven children with T1DM, attending the Childhood Diabetes Unit of the University of Verona, have been regularly tested for serum IgA endomysial antibodies (EMA). All patients with positive EMA underwent small bowel biopsy to confirm the diagnosis of CD. HLA typing was performed in subjects with T1DM and CD, and in a control group of 79 EMA-negative patients with T1DM. RESULTS: Of the 357 patients tested, 25 (7%) had CD. The frequency of HLA-DQA1*0501-DQB1*0201 (T1DM + CD 68% vs T1DM 62%) and of DQA1*0301-DQB1*0302 (T1DM + CD 40% vs T1DM 35%) haplotypes, between T1DM patients with and without CD, was statistically comparable. A trend towards a reduction of the risk of CD (p = 0.055, OR: 0.22, CI 0.05: 1.04) was observed in patients with T1DM (28% vs T1DM + CD 2%) who did not carry either the HLA-DQA1*0501-DQB1*0201 or the DQA1*0301-DQB1*0302 haplotype. CONCLUSION: A high prevalence of HLA-DQA1* and -DQB1* susceptibility haplotypes for CD was observed both in EMA-negative diabetics and in those with associated CD. The implementation of screening programmes of CD in a T1DM population, based on the identification of HLA susceptibility haplotypes, seems to be of limited usefulness. Serial serologic screening of diabetic patients remains the advisable strategy.

[Feeding neurologically disabled children with dysphagia: the role for gastrostomy]. / La nutrizione enterale in bambini con grave encefalopatia e disfagia: il ruolo della gastrostomia.

INTRODUCTION: Undernutrition and growth retardation are often observed in children with severe neurological disabilities. Our experience of feeding gastrostomy in children and adolescents with central nervous system (CNS) disease and dysphagia is reported. PATIENTS AND METHODS: A gastrostomy feeding tube was placed in 11 children who had severe impairment of swallowing and clinically evident food aspiration. Percutaneous endoscopic technique was preferred, unless operative placement was suggested by unfavourable anatomical conditions or concomitant abdominal surgery. Commercial formulas or natural food were used at home and the children were regularly followed-up at the outpatient clinic. RESULTS: Median age at the gastrostomy placement and median follow-up lenght were 5.9 years (range 1.8-16.7 years) and 15 months (3-66 months) respectively. Four of 11 patients had moderate (weight/height (W/H) ratio = 80%) and 3 severe (W/H ratio < 70%) malnutrition. Ten of 11 subject were exclusively gastrostomy fed. After 3 months of enteral nutrition a weight gain was observed in all patients as well as a significant increase of mean W/H ratio (81.2% vs. 87.2%, p = .002). Nutritional improvement was confirmed at follow-up, despite caloric intakes lower (< 50%) than recommended for age and weight. Micronutrients and vitamins were supplemented on the basis of calculated intakes. CONCLUSIONS: In children with severe CNS disease and dysphagia, long-term gastrostomy feeding is a safe and useful method that allows adequate nutritional and micronutrient intakes and prevents the risk of dystrophy.

Gluten sensitivity and 'normal' histology: is the intestinal mucosa really normal?

BACKGROUND: Early pathogenetic events of gluten intolerance may be overlooked in patients with serologic markers of celiac disease and normal intestinal mucosa by both conventional histology and immunohistochemistry. AIMS: To investigate if a submicroscopical damage of the absorptive cell surface was associated with developing gluten sensitivity. PATIENTS AND METHODS: Duodenal biopsies of seven subjects with positive anti-endomysial antibodies and normal histology underwent ultrastructural evaluation of the epithelial surface by means of both scanning and transmission electron microscopy. Specimens of intestinal mucosa of 14 children with non-celiac conditions were used as controls. RESULTS: In four patients, electron microscopy revealed alterations of the enterocyte brush border with a significant reduction of the height of microvilli. After several months, three of them had a second biopsy that eventually showed histological modifications suggestive of celiac disease. In the other three patients, no significant alteration of enterocyte ultrastructure was observed. One of them, rebiopsied after 12 months, still showed a normal duodenal histology. CONCLUSIONS: Gluten sensitivity can be associated with 'minimal' mucosal changes not detectable with conventional light microscopy. Such lesions, which primarily involve microvillous structure, may imply a reduction of intestinal absorptive surface already in the latent stage of the disease.

[Percutaneous endoscopic gastrostomy in children with ventriculoperitoneal shunt]. / La gastrostomia percutanea endoscopica in bambini con derivazione ventricoloperitoneale.

The complications of percutaneous endoscopic gastrostomy (PEG) placement or replacement or of home management of gastrostomy, must be taken in account in patients with hydrocephalus and ventriculoperitoneal shunt. In this report we describe four children with spastic quadriplegia and ventriculoperitoneal shunt who had a median follow-up of 15 months (range 4-32 months) after PEG placement. Intravenous antibiotic prophylaxis was always used during routine procedures and no shunt infection was observed. In a patient, during accidental PEG dislodgement, peritoneal infection developed that required temporary diversion of the catheter. A second dislodgement, in the same individual, determined a large amount of serous peritoneal fluid that needed to be evacuated but no shunt infection or malfunction. In nobody of our patients, the shunt, located in the upper left abdomen, interfered with gastrostomy placement. Our experience confirms that PEG is not contraindicated in patients with ventriculoperitoneal shunt, provided that the risks of catheter infection are known and prevented.

[Latent celiac disease in subjects with serum anti-endomysial antibodies and normal intestinal biopsy]. / Celiachia latente in soggetti con anticorpi antiendomisio positivi e biopsia intestinale normale.

OBJECTIVES: Data on the follow-up of a group of subjects with serum antiendomysial antibodies (EMA) and normal mucosal architecture at the intestinal biopsy are reported. Clinical problems concerning possible evolution of potential celiac disease (CD) towards gluten-induced histological damage are discussed. METHODS: Eleven patients belonging to high-risk groups for CD (5 with type-1 diabetes, 2 with familiarity for CD and 4 with symptoms suggesting CD) who had a normal intestinal biopsy, despite positive antiendomysial test, were followed-up. Antigliadin and antitransglutaminase antibodies (anti-tTG) and HLA genotyping were also assessed. According to clinical and serological data a second biopsy was performed in six of them. RESULTS: At the time of the first normal biopsy, all patients were positive for EMA and 5/8 for anti-tTG. Five of 6 subjects genotyped were HLA-DQ2+ or DQ8+. Six patients were rebiopsed after 1 to 4 years. Three had mucosal atrophy, 1 had mild increase of intraepithelial lymphocytes and 2 were morphologically normal. CONCLUSIONS: Subjects with antiendomysial antibodies and normal intestinal biopsy deserve clinical and serological follow-up to reduce the time of possible latency of CD. Although good predictors of progression of the disease are not still available, antiendomysial antibodies assessment and HLA genotyping may help to suggest individuals at higher risk to develop gluten-induced enteropathy. This study confirms that subjects with persistent signs of gluten sensitivity and normal biopsy should be re-examined.

Early bronchopulmonary involvement in Crohn disease: a case report.

BACKGROUND: Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. CASE PRESENTATION: A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. CONCLUSIONS: Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD.

FEF25-75 as a marker of airway obstruction in asthmatic children during reduced mite exposure at high altitude.

Sensitivity of forced expiratory flow between 25% and 75% of the vital capacity (FEF25-75) in detecting airway obstruction was investigated in 14 children with mild-moderate asthma, allergic to house dust mites, while at high altitude (1756 m). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEF25-75, and peak expiratory flow (PEF) were measured every 2 weeks for 12 weeks (total, 84 measurements). The presence or absence of wheezing at the chest auscultation was ascertained before each test. During the study period, a significant improvement of both mean (SD) FEF25-75 [61 (12)% vs. 68 (11)% of the predicted value, p = 0.005] and PEF [95 (16)% vs. 103 (13)%, p = 0.002] was observed. FEV1 changed only marginally [82 (7)% vs. 86 (6)%, p = 0.05]. Wheezing was present on 12/84 occasions. Wheezing was associated with abnormal FEF25-75 values on most occasions but not with abnormal FEV1 or PEF. FEF25-75 was decreased on 51% of days in which wheezing was absent. FEV1 and PEF were, respectively, normal in 69% (p < 0.0001) and 92% (p < 0.0001) of measurements in which FEF25-75 was abnormal. These results suggest that FEF25-75 may be considered a good indicator of airflow obstruction and a sensitive marker of respiratory improvement in asthmatic children during reduced antigen exposure.

Tannic acid supplemented fixation improves ultrastructural evaluation of respiratory epithelium in children with recurrent respiratory tract infections.

Samples of the respiratory mucosa of children with recurrent respiratory infections suspected of having primary ciliary dyskinesia are routinely fixed with glutaraldehyde before ultrastructural examination. This standard technique, however, may not be optimal for visualizing ciliary components or for preserving several cellular and extracellular structures during dehydration and embedding procedures. In this study, brushes of nasal (28 samples) and/or tracheal (9 samples) mucosa from 32 children with recurrent respiratory tract infections were examined. Twenty-nine samples were fixed with glutaraldehyde supplemented with tannic acid to determine if the ultrastructural analysis of respiratory epithelium and bronchial secretions could be improved. Eight samples were conventionally fixed with glutaraldehyde alone. Lesions of the cellular membrane and damaged cells were easily visualized using tannic acid supplemented fixation. Internal ciliary structures including individual microtubules and dynein arms were also more clearly observed. In addition, the internal structure of microvilli of the respiratory epithelium could be studied and the presence of phospholipid-rich surfactant-like material within nasal and tracheal secretions were visualized after tannic acid supplemented fixation. We suggest that addition of tannic acid during fixation is useful for accurate ultrastructural evaluation of respiratory mucosa in both clinical and experimental situations.

[Limits in the evaluation of bronchial reactivity in children with asthma]. / Limiti della valutazione della reattività bronchiale nel bambino con asma.

Bronchial hyperresponsiveness (BHR) reflects an exaggerated sensitivity of airways to pharmacologic and/or physical stimuli. Patients with symptomatic asthma often have a higher degree of BHR than nonasthmatics, even though BHR shows a variable relationship with the clinical expression of the disease and with medication requirements. Methods of bronchial challenge, initially developed in adults, are increasingly employed also in children. The Authors discuss the clinical significance of the evaluation of bronchial responsiveness in the diagnostic approach and follow-up of children with asthma. Some methodological aspects and limits of bronchial challenging in childhood are expecially addressed.

Bronchial artery embolization in the management of hemoptysis in cystic fibrosis.

Massive hemoptysis and/or recurrent expectoration of measurable amounts of blood are common complications of chronic bronchopulmonary infections in cystic fibrosis (CF). When conservative treatment fails to control bleeding, surgery or bronchial artery embolization (BAE) is frequently considered. We present our experience and long-term follow up of BAE in 14 CF patients (age range 15-39 years) with massive (6 subjects) and/or recurrent (8 subjects) hemoptysis not responsive to medical treatment. Seven had chronic hypercapnic respiratory failure. After angiographic evaluation, polyvinyl alcohol particles (Ivalon) were injected to embolize obviously enlarged bronchial arteries. Seventeen procedures were performed in 14 patients and 36 bronchial arteries were embolized. All the patients stopped bleeding immediately upon BAE. Most of the patients had postembolization fever, dysphagia, and transient chest pain which were managed symptomatically. After a median follow-up period of 10.5 months (range 0.5-38 months), no recurrence of hemoptysis was observed in 8 patients who are still alive. In 3 patients hemoptysis recurred and they underwent reembolization after 3, 22, and 25 months, respectively. Three subjects died of respiratory failure within 5 months from BAE. Presently, 50% of patients studied had a > or = 1 year interval free of major hemoptysis after the first BAE. Our experience indicates that massive and/or recurrent hemoptysis in CF patients can be safety and effectively managed by BAE if the procedure is performed by a skilled practitioner. The procedure was well tolerated and resulted in prolonged and satisfactory bleeding control in most patients.

Peak expiratory flow variation and bronchial hyperresponsiveness in asthmatic children during periods of antigen avoidance and reexposure.

Changes of diurnal variation of peak expiratory flow rate (%PEF variation) and their relationship with bronchial hyperresponsiveness (BHR) to methacholine (PC20) were evaluated in 12 children with mild-to-moderate asthma and house-dust mite allergy, during successive periods of stay in a mite-free environment at high altitude (1756 m) and at their home at sea level. The children remained at the high altitude from October until the end of December; then they spent a 3-week period at home and returned to high altitude residence in January. PEF was measured daily, in the morning and in the evening, during the 3 months' stay at high altitude and them for 10 days after the return in January. PC20 was assessed in 8/12 children, once a month from October to December, and at the return in January. Mean absolute PEF values did not change significantly throughout the study. From October to December, patients showed a significant decrease of mean %PEF variation (P = 0.04), while PC20 showed an increase (P = 0.05). After the 3 weeks at home, both %PEF variation (P = 0.03) and PC20 (P = 0.05) significantly worsened. The correlation between PC20 values and mean %PEF variation in the 2 days before and after each methacholine test was r = -0.63 (P = 0.001). Our data suggest that there is a beneficial effect of a prolonged stay in a mite-free environment, on both PEF variability and BHR, also in asthmatic children with good pulmonary function. PEF variability and bronchial responsiveness to methacholine were significantly correlated also for small changes of the two variables.

Education in asthmatic children.

Several educational programmes have been developed for patients with asthma, in order to promote changes in behaviour and to improve health and quality of life. Such programmes are commonly termed "asthma self-management" programmes. First generation self-management programmes started in the early 1980s and were intended to develop the concept of "partnership" between physician, patient and family, and to teach children the skills necessary to manage asthma at home. As a result of participation in these programmes, children experienced a reduction of emergency room and unscheduled physician visits, and an improvement in their physical and social activities. The need to assess the long-term persistence of self-management skills led to the development of second generation programmes. These programmes will pay more attention to the within-subject assessment of acquisition and application of self-management techniques. Crucial issues, such as decision-making strategies and evaluation of quality of life should also have a prominent role.