A significant increase in anthropometric indices during long-term follow-up of pediatric patients with celiac disease, with no endocrine disorders.

Celiac disease (CeD) is likely to be associated with growth impairment and poor weight gain. However, long-term growth patterns following diagnosis are poorly characterized. We evaluated long-term anthropometric changes in a large cohort of pediatric patients with CeD. A retrospective chart review of patients diagnosed with CeD between 1999 and 2018 was conducted. Demographic and clinical data were collected, and anthropometrics were analyzed from diagnosis and throughout follow-up. The study included 500 patients (59.8% females, median (IQR) age at diagnosis 5.7 (3.7-8.9) years), with a mean follow-up of 5.5 (range 1.5-16.2) years. Weight, height, and BMI Z-score-for-age (WAZ, HAZ, and BMIZ) increased significantly from a mean (± SD) of - 0.82 (± 1.21), - 0.73 (± 1.16), and - 0.32 (± 1.11) at diagnosis to - 0.41 (± 1.23), - 0.45(± 1.16), and - 0.17 (± 1.14) at last follow-up, respectively (p < 0.001 for WAZ and HAZ and p = 0.002 for BMIZ). The largest improvements were observed in patients diagnosed before 3 years of age (p < 0.01). Patients for whom the final adult height was available (n = 86) improved from HAZ mean (± SD) - 0.89 ± 1.37 at diagnosis to - 0.51 ± 1.28 at adulthood measurement, p < 0.05. Wasting was present in 19.7% and stunting in 16.4% of the cohort at diagnosis and normalized in 77.3% and 64.8%, respectively, within a median (IQR) time of 0.79 (0.42-4.24) and 2.3 (0.72-6.02) years, respectively. Gluten-free diet adherence and frequency of visits were not associated with normalization of wasting or stunting in all age groups.  Conclusion: Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. Younger age at diagnosis is associated with greater improvement in weight and linear growth, emphasizing the importance of early diagnosis of CeD. What is Known: • Celiac disease (СeD) is likely to be associated with growth impairment and poor weight gain. • Long-term changes in anthropometric indices after diagnosis of CeD are not well characterized. What is New: • Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. • Young age at diagnosis is associated with larger improvement in weight and linear growth.

Gluten Immunogenic Peptides Are Not Correlated With Reported Adherence to Gluten-Free Diet in Children With Celiac Disease.

OBJECTIVE: There is no gold standard to assess adherence to gluten-free diet (GFD) among patients with celiac disease (CeD). Gluten immunogenic peptides (GIPs) in urine and stool were suggested as novel markers for evaluating adherence to GFD. Our aim was to assess the presence of GIP in pediatric patients with CeD, and to compare the results with alternative methods for evaluating GFD adherence. METHODS: Pediatric patients diagnosed with CeD, who were on GFD for at least 1 year, were enrolled and followed prospectively between November 2018 and January 2021. Study visits included clinical assessment, a dietitian interview, Biagi score, food questionnaires, anthropometric and laboratory measurements, and urine and stool samples obtained for laboratory GIP analysis. RESULTS: The study included 74 patients (63.5% females), with median (interquartile range, IQR) age of 9.9 (7.8-11.7) years, and median (IQR) duration on GFD of 2.5 (2-5.5) years. Good GFD adherence, assessed by Biagi score, was reported in 93.1% of cases. GIP was evaluated during 134 visits, with GIP detected in 27 of 134 (20.1%) of the visits (16.3% of stool samples and 5.3% of urine samples). Positive GIP results were significantly more common in males compared to females (30.6% vs 14.1%, respectively, P < 0.05). Detection of positive GIP was not associated with dietary assessment of GFD adherence, celiac serology results, or reported symptoms. CONCLUSIONS: Stool and urine GIP can be detected in children with CeD, even when dietary assessment indicate good adherence to GFD. The role of GIP testing in clinical practice should be further explored.

Age-Dependent Trends in the Celiac Disease: A Tertiary Center Experience.

OBJECTIVES: Celiac disease (CD) is a common intestinal autoimmune disorder with diverse presenting features. We aimed to determine age-dependent patterns in CD presentation, diagnosis and management at a large tertiary referral center. METHODS: A retrospective review of electronic medical records of pediatric patients diagnosed with CD between January 1999 and December 2018 at Schneider Children's Medical Center of Israel. We compared demographics, clinical and laboratory parameters between four age groups at CD presentation. RESULTS: A cohort of 932 children was divided into four groups by age (in years) at diagnosis: 0-3 (17.9%), 3-6 (31.8%), 6-12 (34.5%), 12-18 (15.8%). The youngest age group presented more frequently with diarrhea, weight loss, abdominal distention, vomiting and lower weight z scores, P < 0.01. Hypoalbuminemia and zinc deficiency were also more frequent in this age group, compared to older patients (P < 0.05, each). Rates of anemia were higher in younger age groups (0-3 and 3-6 years), compared to older age groups, P < 0.05. Patients in the younger age groups (0-3 and 3-6 years) presented more frequently with tissue transglutaminase (TTG) levels above 10 times the upper limit of normal (ULN; P < 0.05), and more often normalized their CD serologies by 24 months of gluten-free diets (GFD) compared to older age groups (P < 0.05). CONCLUSION: There is an age-dependent variation in CD presentation during childhood. Younger patients present more often with malabsorptive features, and higher TTG levels, yet normalize TTG while on GFD more rapidly than older patients. Clinicians should be aware of the diversity in CD presentation and course at the various presentation age.

Intestinal Fatty Acid Binding Protein Levels in Pediatric Celiac Patients in Transition From Active Disease to Clinical and Serological Remission.

Celiac disease (CD) is increasingly diagnosed without endoscopy. As such, the need for accurate serological markers to aid in the diagnosis and follow-up of CD has increased. Intestinal fatty acid binding protein (I-FABP) is a cytosolic protein present in enterocytes, whose blood levels reflect mucosal damage in a reliable and quantifiable way. The aim of this study was to compare I-FABP levels in newly diagnosed patients with CD and to examine changes in levels following 6 months of gluten-free diet (GFD). Methods: A prospective observational case control study of pediatric patients diagnosed with CD, with measurements of tissue transglutaminase IgA (TTG-IgA) and I-FABP levels at diagnosis and after 6 months of gluten free diet were compared to a control group of nonceliac patients. Results: This study included 35 patients and 32 controls. The CD group had higher I-FABP levels at diagnosis compared with the control group (median 641.7 pg/mL versus 334 pg/mL; P < 0.05). I-FABP levels significantly differed between patients presenting with TTG-IgA level 3-10 times the upper limit of normal (ULN) compared with those presenting with values >10 times ULN (median 432.2 pg/mL versus 796.2 pg/mL; P < 0.05). Patients with CD had a significant decrease in median I-FABP levels after 6 months of GFD (median 268.2 pg/mL), paralleling a decrease in TTG-IgA and GFD adherence. Conclusions: I-FABP levels are increased in patients with CD at diagnosis compared with controls and decrease significantly while patients adhere to GFD.

Two decades of pediatric celiac disease in a tertiary referral center: What has changed?

BACKGROUND: Celiac disease (CD) is common worldwide with increasing prevalence and changing presentation. AIMS: To evaluate changes in the presentation and management of CD over the last two decades. METHODS: Retrospective chart review of pediatric patients with CD between 01.1999 to 12.2018 was performed. Comparisons were made between an early (1999 to 2008) and late (2009 to 2018) decade, regarding clinical and laboratory parameters at presentation and follow-up. RESULTS: In a cohort of 932 patients (early decade n = 316, late decade n = 616), patients from the late decade presented with lower rates of weight loss and abdominal distention (24.2% vs 34.7% and 6% vs 11%, respectively p < 0.01), and with higher rates of abdominal pain or asymptomatic presentation (41.4% vs 27.4%, p < 0.01, and 18% vs 13%, p < 0.05, respectively). Good adherence to gluten-free diet was reported more often in the late decade (64% vs 50.6%, p < 0.001), and fewer patients were lost to follow-up. During the late decade, significantly higher rates of celiac serology normalization were achieved during the first two years of follow-up. CONCLUSION: In recent years, children with CD were diagnosed with milder symptoms, showed better adherence and demonstrated earlier normalization of celiac serology.

Long-term Extent Change of Pediatric-Onset Ulcerative Colitis.

BACKGROUND: Data describing extent change (progression or regression) in pediatric-onset ulcerative colitis (UC) are scarce. GOAL: We aimed to describe extent change in pediatric-onset UC during long-term follow-up and to assess predictors of extent change. STUDY: Medical charts of pediatric-onset UC patients with at least 5-year follow-up were analyzed retrospectively. Disease extent was determined using the Paris classification. It was examined at diagnosis and during follow-up at different time points. The impact of possible predictors on extent change including age at diagnosis, gender, clinical manifestations, disease, severity indices, and different therapeutic regimens during disease course was assessed. RESULTS: Patients (n=134, 55% males) were followed for a median duration of 13.1 (range, 5 to 28) years. Median age at diagnosis was 13.1 (range, 2 to 17.8) years. Of 134 patients, 40.5% had extensive or pancolitis, 33.5% left-sided colitis, and 26% had proctitis at diagnosis. On follow-up (n=117), 45% had unchanged disease extent, 35% experienced extent progression, whereas 20% experienced regression of disease extent. The multivariate Cox models demonstrated that among children with left-sided disease at diagnosis, presence of extraintestinal manifestations (hazard ratio, 5.19; P=0.022), and higher pediatric UC activity index (hazard ratio, 8.77; P=0.008) were associated with extent progression to extensive disease. Predictors of extent regression have not been identified. CONCLUSIONS: Disease extent changes significantly over time in pediatric-onset UC. In our cohort, presence of extraintestinal manifestation and higher pediatric UC activity index score at diagnosis were associated with progression from limited to extensive disease during follow-up.

Predictors of pouchitis after ileal pouch-anal anastomosis in pediatric-onset ulcerative colitis.

OBJECTIVES: Few studies have reported on the incidence and risk factors for pouchitis following colectomy and ileal pouch-anal anastomosis (IPAA) in patients with pediatric-onset ulcerative colitis (UC). We aimed to determine clinical predictors for the development of pouchitis following IPAA in this population. PATIENTS AND METHODS: We performed a retrospective chart review of all pediatric UC cases that were diagnosed at the Schneider Children's Medical Center of Israel between 1981 and 2013 and who underwent colectomy during disease course. Potential predictors for pouchitis and chronic pouchitis including various demographic, clinical, endoscopic, and histological variables at diagnosis and at the time of surgery were assessed. RESULTS: Of 188 patients with pediatric-onset UC, 33 (18%) underwent colectomy and IPAA surgery. During a median postsurgical follow-up of 7.6 (range: 1-21.5) years following IPAA, 20/33 (60%) patients developed pouchitis including 11/33 (33%) patients who developed chronic pouchitis. Kaplan-Meier survival estimates of the cumulative probability for pouchitis were 9% at 1 year and 36 and 55% at 5 and 10 years, respectively. Multivariate Cox models showed that older age at colectomy (hazard ratio: 0.86, P=0.024) was a protective factor, whereas preoperative vitamin-D deficiency (≤20 ng/ml) (hazard ratio: 4.4, P=0.021) increased the risk for pouchitis. Age at diagnosis, sex, disease extent, and preoperative therapeutic regimens did not affect the risk of pouchitis. CONCLUSION: Long-term risk for pouchitis is significantly high in pediatric-onset UC after IPAA. Vitamin-D deficiency and younger age at colectomy may increase the risk for pouchitis.

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.

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 Children's 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 α 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.

The natural history of pediatric-onset IBD-unclassified and prediction of Crohn's disease reclassification: a 27-year study.

OBJECTIVES: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) in patients who were initially diagnosed as inflammatory bowel disease-unclassified (IBDU) remains challenging. Our aims were to describe the natural history of pediatric-onset IBDU patients during prolonged period of follow up and to identify associated predictors for CD reclassification among them. MATERIALS AND METHODS: In this retrospective single center study, out of 723 patients with pediatric onset IBD, we identified 53 patients (7.3%) diagnosed with IBDU at the Schneider Children's Medical Center of Israel between 1986 and 2013. Potential predictors for CD reclassification including age at diagnosis, gender, clinical manifestations, disease extent and laboratory findings were assessed. RESULTS: The median follow-up was 6.8 (± 6.7) years. Reclassification to CD was observed in 24/53 (45%) of patients. The median interval from diagnosis to CD reclassification was 9.4 years. In 58% of these patients, CD reclassification occurred within 5 years from diagnosis. Multivariate Cox models showed that familial history of CD and hypoalbuminemia at diagnosis were significantly associated with CD reclassification (HR 11.3, p = .02 and HR 5.3, p = .03, respectively). All other assessed clinical, laboratory and endoscopic parameters did not serve as predictors for CD reclassification later on. CONCLUSIONS: In our cohort, a substantial high proportion of pediatric onset IBDU patients were later re-diagnosed as CD. Only a family history of CD and hypoalbuminemia could predict reclassification among IBDU patients.

Evolution of disease phenotype in pediatric-onset Crohn's disease after more than 10 years follow up-Cohort study.

BACKGROUND: Pediatric-onset Crohn's disease (CD) is a heterogeneous disorder which is subjected to progression and complications in a substantial proportion of patients. AIMS: We aimed to assess the progression in pediatric-onset CD phenotype on long term follow up. METHODS: Medical charts of pediatric onset CD patients with at least 10 years follow-up were analyzed retrospectively. Disease phenotype was determined at diagnosis and during follow up at different time points. Phenotype was determined according to the Paris classification. The impact of possible predictors on phenotype progression was assessed as well as the association between different therapeutic regimens during disease course and phenotype progression. RESULTS: Progression of disease location, behavior, and perianal involvement was observed in 20%, 38% and 20% of patients, respectively, after a median follow-up of 16.4 (±4.4) years. Microscopic ileocolonic disease at diagnosis was significant predictors for progression of disease extent. Treatment with anti tumor necrosis factor-ɑ agents and number of flares per years of follow-up were associated with progression of disease extent, behavior and perianal involvement. CONCLUSION: Disease extent, behavior and prevalence of perianal disease change significantly over time in pediatric-onset CD. In our cohort, most clinical, laboratory and endoscopic parameters do not serve as predictors for long-term disease progression.