Yael Mozer-Glassberg

Spontaneous Normalization of Anti-Tissue Transglutaminase Antibody Levels Is Common in Children with Type 1 Diabetes Mellitus

BackgroundThe prevalence of celiac disease among type 1 diabetes mellitus (T1DM) patients is 5–10 times higher than in the general population. Thus, evaluation of celiac serology is indicated at diagnosis of T1DM and on follow up.AimThis study was prompted by the observation that elevated anti-TTG antibody levels in diabetic children may spontaneously normalize despite continued consumption of gluten. The objective of the study was to investigate the prevalence of this phenomenon and associated factors.Materials and MethodsThe files of all children diagnosed with type 1 diabetes mellitus from 2003–2009 at a tertiary pediatric medical center were reviewed for those with elevated serum levels of anti-TTG antibody. Clinical, medical, laboratory, and treatment data were collected. Findings were compared between patients diagnosed with celiac disease and patients with initially elevated anti-TTG antibody levels that spontaneously normalized.ResultsForty-eight of the 738 patients with type 1 diabetes attending our center (6.5%) had elevated anti-TTG antibody blood levels. Celiac disease was diagnosed in 23, and anti-TTG antibody levels normalized in 17 (35.4%), all of whom consumed gluten. At one-year follow-up, there was no significant difference between the groups in HbA1c level or change in anthropometric measurements.ConclusionPhysicians treating children with type 1 diabetes and mildly elevated anti-TTG antibody levels might consider 12-month serologic follow-up on a gluten-containing diet rather than immediate duodenal biopsy.

Follow-up of children with celiac disease - lost in translation?

Background: Celiac disease (CD) is a prevalent condition with a broad spectrum of presentations requiring a lifelong gluten-free diet (GFD). Our aims were to examine the presentation and adherence to a GFD as well as the adequacy of follow-up of children diagnosed with CD at a tertiary referral center. Methods: A retrospective electronic chart review of pediatric patients suspected of CD (n = 581) who were seen at our institute between January 1999 and December 2008 was performed. Results: 387 children were diagnosed with CD (F/M ratio of 1.54, median age: 6.25 years). Presenting symptoms were iron deficiency anemia (n = 82, 34%), short stature (n = 59, 24.5%) and abdominal pain (n = 59, 24.5%). In 63 patients (16.3%) an associated autoimmune disease was recorded. Only 42.7% of the patients (165/387) had regular out-patient gastroenterologist visits; 22% (86/387) were followed by their primary care physician. Over 35% (136/387) were completely lost to follow-up. Negative serology on follow-up was present in 91% of the CD patients(150/165) followed at our center in comparison to 70% (60/86) in those followed up by their primary physician (p = 0.0002). Conclusions: At least in our referral center, follow-up of children diagnosed with CD is far from satisfactory. Initiatives aimed at improving adherence to regular follow-up are needed as this intervention is associated with a significant increase in patient compliance with a long-term GFD.

Pediatric Celiac Disease Patients Who Are Lost to Follow-Up Have a Poorly Controlled Disease

Background: Follow-up of celiac disease (CD) patients is recommended for gluten-free diet (GFD) adherence monitoring and complication detection. We recently showed that 35% of children with CD were lost to follow-up (LTFU). We aimed to characterize LTFU population, and thus identify compliance barriers to GFD and follow-up. Methods: 50 LTFU patients were investigated using a telephone questionnaire, regarding frequency of follow-up, serology testing, and adherence to GFD (using the validated Biagi score). Fifty two regular follow-up patients served as controls. Results: LTFU patients had poor adherence to GFD (average Biagi score of 2.0 ± 1.4) compared to controls (3.0 ± 1.0, p < 0.001). Only 22% of LTFU performed periodic celiac serology testing compared to 82% of controls (p < 0.001). LTFU had higher prevalence of positive celiac serology tests (50% compared to 25% of controls, p = 0.01). Fewer LTFU were National Celiac Association members (24%) compared with controls (44%, p = 0.05). Regression analysis showed positive relationships between LTFU and poor adherence to GFD (R2 = 0.26737, p = 0.001), older age at diagnosis (R2 = 0.30046, p = 0.03), and non-membership in a celiac association (R2 = 0.18591, p = 0.0001). Conclusion: LTFU is associated with non-adherence to GFD and positive serology. Risk factors for LFTU should be identified and addressed in order to improve patient care.

Food Intake Adequacy in Children and Adolescents With Inflammatory Bowel Disease

Objectives: Diet assessment is essential in the care of patients with inflammatory bowel disease (IBD). We aimed to study food intake in children with IBD and evaluated the relation of dietary intake with disease activity and nutritional status in these children. Methods: This cross-sectional study investigated 68 children and adolescents with IBD (57 Crohn disease, 11 ulcerative colitis). Evaluation included clinical, laboratory, and nutritional assessment including 3 days diet record. Results: Compared with recommended daily allowance, the intake of patients with IBD was significantly poor for carbohydrates (75%, P = 0.016), calcium (49%, P < 0.05), magnesium (76%, P < 0.05), vitamin A (72%, P < 0.05), vitamin E (57%, P < 0.05), and fiber (44%, P < 0.05) and higher for protein (175%, P < 0.05), iron (112%, P < 0.05), and water-soluble vitamins (118%–189% P < 0.05). Compared with the intakes of healthy children from National Nutritional Survey, the intake of IBD group was lower for calories (78%, P = 0.012), carbohydrates (61% P < 0.05), magnesium (67% P < 0.05), vitamin C (34%, P < 0.05), and fiber (54%, P < 0.05) and high for B12 (141%, P < 0.05). Fifty subjects ate ordinary diets, 7 of 68 children were on exclusive enteral nutrition and 11 of 68 consumed regular food with different polymeric formulas supplements. Compared with children without supplements, children on exclusive enteral nutrition and nutritional supplements (18/68) had significantly better intakes of energy (1870 ± 755 vs 2267 ± 432, P < 0.05), carbohydrates (223 ± 97 vs 292 ± 99, P < 0.05), and all minerals (P < 0.05) and micronutrients (P < 0.05). Dietary intake was not different by disease status (remission or relapse). Conclusions: In the absence of nutritional supplements, food intake is inadequate for many nutrients in many children with IBD.

Concomitant autoantibodies in newly diagnosed diabetic children with transient celiac serology or proven celiac disease.

Abstract Background: We previously demonstrated that children with Type 1 Diabetes Mellitus (T1DM) may have transiently elevated tissue transglutaminase antibodies (TTG) on a gluten-containing diet. This study aimed to examine if the presence of autoantibodies in newly diagnosed T1DM differs between patients with celiac disease and those with transient celiac serology. Methods: Forty children were identified who had been diagnosed with T1DM between 2003 and 2009 and who had elevated serum IgA-TTG antibody levels at diagnosis. Blood samples were collected for measurement of insulin (IA-2A) antibodies, islet cell antigen (ICA) antibodies, glutamic acid decarboxylase (GAD) antibodies, thyroglobulin (TgAb) antibodies, and thyroid peroxidase (TPO) antibodies. Children diagnosed with celiac disease (CD; group 1, n=23) and children in whom TTG antibody levels spontaneously normalized over time (group 2, n=17) were compared. Results: No significant differences in positivity rates between groups 1 and 2 were found for any of the autoantibodies tested. The respective findings were as follows: IA-2A 50% and 47.1% (p=0.855); ICA 77.3% and 76.5% (p=0.953); GAD 27.3% and 52.9% (p=0.102). Thyroid antibodies were found positive in a limited number of patients: TgAb 4.5% and 11.8%; TPO 4.5% and 11.8%. In addition, antibody titer levels did not differ significantly for all autoantibodies. Difference in occurrence of clinical or subclinical thyroid disease did not reach significance (4.3% vs. 29.4%; p=0.07). Age was positively correlated with the presence of thyroglobulin and thyroid peroxidase antibodies, and negatively correlated with the presence of insulin antibody. Conclusion: Neither the number of concomitant autoantibodies nor their titers in newly diagnosed T1DM differed between patients with proven CD and those with transient TTG serology.

Risk of Colectomy in Patients with pediatric-onset Ulcerative Colitis.

Objectives: Data describing the incidence and risk factors for colectomy in pediatric ulcerative colitis (UC) is inconsistent. Our aim was to describe the colectomy rate and to identify risk factors associated with colectomy in a large cohort of children with UC with long-term follow-up. Materials and Methods: We performed a retrospective chart review of pediatric UC cases that were diagnosed at Schneider Childrens Medical Center of Israel between 1981 and 2013. Potential predictors for colectomy including age at diagnosis, sex, disease extent, severity indices, and different therapeutic regimens during disease course were assessed. Results: Of 188 patients with pediatric onset UC, 34 (18%) underwent colectomy. Median follow-up was 6.9 years (range, 1–30). Kaplan-Meier survival estimates of the cumulative probability for colectomy were 4% at 1 year and 17% at 10 years from diagnosis. Multivariate Cox models showed that male sex (hazard ratio 4.2, P = 0.001) and severe disease at diagnosis reflected by Pediatric Ulcerative Colitis Activity Index score ≥65 (hazard ratio 8.9, P < 0.001) were associated with increased risk for colectomy. Age, disease extent, ethnicity, family history of inflammatory bowel disease, early introduction of immunomodulators, or treatment with antitumor necrosis factor &agr; agent did not affect the risk of colectomy. Conclusions: Male sex and higher Pediatric Ulcerative Colitis Activity Index score at diagnosis are independent risk factors for colectomy.

Children post liver transplantation hospitalized with fever are at a high risk for bacterial infections.

Although infections post liver transplantation are a main cause of morbidity and mortality, data are limited on transplanted children. The objective of this study was to investigate the incidence, etiology, and predictors of infection in pediatric liver transplant recipients (LTR) in the specific practical clinical setting of hospitalization for fever in order to elucidate the appropriate management of these patients.

Oesophageal eosinophilia in children with coeliac disease

Objectives An association between coeliac disease (CD) and eosinophilic oesophagitis (EoE)/oesophageal eosinophilia (EE) has been suggested. We sought to characterise children with CD+EE in-depth and assess the contribution of each condition to the clinical presentation and treatment response. Study design Medical records of children with both CD+EE, or isolated EoE diagnosed between 2000 and 2014, were retrospectively reviewed and compared with patients with isolated CD or epigastric pain. Frequency of EE was calculated from endoscopy results of patients with suspected CD or epigastric pain between 2011 and 2014. Missing data were obtained via a telephone questionnaire. Setting Single large, tertiary paediatric centre. Patients 17 CD+EE, 46 EoE, 302 isolated CD and 247 epigastric pain. Results The patients with CD+EE shared characteristics of both individual conditions. While age at diagnosis, family history of autoimmunity/CD and anaemia were similar to patients with CD, other characteristics such as male gender, personal/family history of atopy, peripheral eosinophilia and oesophageal white papules were more similar to patients with EoE. Combined patients (CD+EE) tended to present with CD-associated symptoms; the majority (63%) later developed typical EoE symptoms. Only a minority (21%) of combined patients had EE that resolved after a gluten-free diet; another 21% had normalisation of EE upon proton pump inhibitor treatment. The remainder required EoE-specific treatment. Conclusion Patients with CD found to have EE share characteristics with both isolated CD and EoE. It appears that these are two coexisting entities presenting in the same patient rather than eosinophilia associated with CD, and therefore, interventions separately addressing each condition may be considered.

Hypogammaglobulinemia in the early period after liver transplantation in children

Data, on the kinetic and serum levels of immunoglobulins in the immediate post‐liver transplantation (LTx) period, are sparse with existing studies limited to adults or case reports of children. The aim of this study is to describe the phenomenon of hypogammaglobulinemia (HGG) in the immediate post‐transplantation period among children undergoing LTx. A retrospective 10‐yr chart review was conducted of all children who underwent LTx at a fourth‐level pediatric medical center. Fifty‐seven, of the 76 children who underwent LTx, were included in the study. Seventeen (29.8%) (mean age, 6.8 ± 5.2 yr) had HGG (11‐IgG, 1‐IgG+IgA, 1‐IgG+IgM, 4‐IgG+IgA+IgM), detected at 2 to 25 d after transplantation. Abdominal fluid was drained for 5 to 42 d; the amount drained until detection of HGG measured 27–668 mL/kg. HGG was associated with increased infection rate 0.9 episodes/patient vs. 0.17 episodes/patient (p < 0.01) in children without detected HGG. In conclusion, HGG is not rare in the immediate post‐LTx period in children, and it may place patients at increased risk of infection. Further studies are needed to delineate the rate of occurrence, risk factors, and clinical implications of hypogammaglobulinemia in this patient population.

Primary infection with human herpes virus type 6, post-pediatric liver transplantation - a pathogen to remember

In recent years, liver transplantation (LT) has become a well‐accepted therapeutic modality for children with end‐stage liver disease, with transplantation surgery being performed at a younger age. Human herpes virus 6 (HHV‐6) infection occurs in most children within the first 2 years of life, therefore, data on primary HHV‐6 infection in pediatric liver transplant recipients is scarce.