The Association Between Iron Deficiency at Diagnosis, Female Sex, and Tissue Transglutaminase Antibody Normalization in Pediatric Celiac Disease.

BACKGROUND: Iron deficiency (ID) is one of the most common manifestations of Celiac disease (CD). We aimed to determine whether ID at CD diagnosis affects tissue transglutaminase antibody (TTG) normalization rate among pediatric CD patients adhering to a gluten-free diet (GFD). METHODS: We conducted a retrospective, observational cohort study that enrolled CD subjects aged 2-18y, diagnosed between Jan 2016 and Dec 2020. Demographic and laboratory data were collected at diagnosis and one year after adherence to GFD. ID was determined according to hemoglobin and ferritin levels. We compared CD subjects with and without ID at CD diagnosis in relation to TTG normalization at one year. RESULTS: Our cohort included 118 pediatric CD subjects. At diagnosis, 61 (51.7%) of CD subjects had ID, of whom 27 (44.3%) were female, compared to 46 (80.7%) females in the non-ID group (p<0.001). Median age at CD diagnosis was 5.7y (IQR 4-8.4, range 2-14) and 7.2y (IQR 4.7-10.8, range 0.9-16), and among those with and without ID, respectively (p=0.1). After one year of adherence to GFD, TTG normalization was achieved in 38 (65.5%) and 28 (53.8%) of those with and without ID at CD diagnosis, respectively (p=0.21). However, TTG normalization was achieved in 38 (79.2%) of males compared to 42 (49.4%) of females (p=0.001). CONCLUSIONS: ID at CD diagnosis was not associated with lower rates of TTG normalization at one year among pediatric patients adhering to GFD. However, TTG normalization at one year was significantly more frequent among male subjects compared to females.

Effect of Overweight and Obesity on the Response to Anti-TNF Therapy and Disease Course in Children With IBD.

BACKGROUND: This study aimed to evaluate the effect of overweight and obesity at the start of anti-TNF therapy on treatment response and relapse rate in children with inflammatory bowel disease (IBD). METHODS: This multicenter, retrospective cohort study included 22 IBD centers in 14 countries. Children diagnosed with IBD in whom antitumor necrosis factor (anti-TNF) was introduced were included; those who were overweight/obese were compared with children who were well/undernourished. RESULTS: Six hundred thirty-seven children (370 [58%] males; mean age 11.5 ±â€…3.5 years) were included; 140 (22%) were in the overweight/obese group (OG) and 497 (78%) had BMI ≤1 SD (CG). The mean follow-up time was 141 ±â€…78 weeks (median 117 weeks). There was no difference in the loss of response (LOR) to anti-TNF between groups throughout the follow-up. However, children in OG had more dose escalations than controls. Male sex and lack of concomitant immunomodulators at the start of anti-TNF were risk factors associated with the LOR. There was no difference in the relapse rate in the first year after anti-TNF introduction; however, at the end of the follow-up, the relapse rate was significantly higher in the OG compared with CG (89 [64%] vs 218 [44%], respectively, P < .001). Univariate and multivariate analysis revealed that being overweight/obese, having UC, or being of male sex were factors associated with a higher risk for relapse. CONCLUSIONS: Overweight/obese children with IBD were not at a higher risk of LOR to anti-TNF. Relapse in the first year after anti-TNF was introduced, but risk for relapse was increased at the end of follow-up.

Overweight and obese children with inflammatory bowel disease required more frequent dose escalations, but overall loss of response to anti-TNF therapy was not increased. Furthermore, in the long term, they tend to have a higher risk for relapse.

Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN.

OBJECTIVES: Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. METHODS: pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. RESULTS: A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children ( P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children( P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%). CONCLUSIONS: EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.

Monitoring Enables Progress: A Nationwide Quality Improvement Program in Children With Crohn Disease.

OBJECTIVES: In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation-wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country. METHODS: Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2-18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann-Kendall test, reporting τ (tau) values. RESULTS: The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ±â€Š3.1 years, median disease duration 1.8 years (interquartile range 0.69-4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti-tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 µg/mg (τ = 0.35; P = 0.015), and "resolution of inflammation" defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = -0.47; P = 0.001). CONCLUSIONS: Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators.

Practice Differences in the Diagnosis and Management of Eosinophilic Esophagitis Among Adult and Pediatric Gastroenterologists in Israel.

OBJECTIVES: Eosinophilic esophagitis (EoE) guidelines call for similar practices in adults and children with EoE. We compared the diagnostic and management practices of gastroenterologists treating adult and pediatric patients suspected of having, or diagnosed with, EoE. METHODS: A 19-question multiple-choice questionnaire was given to gastroenterologists treating either adults or children. Questions explored 4 areas of interest: physician demographics, diagnosis and tissue sampling practices, management, and the need for societal publications on EoE. RESULTS: Completed questionnaires were returned by 85/180 adult and 30/40 pediatric gastroenterologists (PGs). Compared to PGs, adult gastroenterologists (AGs) took esophageal biopsies significantly less frequently in the following scenarios: endoscopy without esophageal symptoms or macroscopic endoscopic findings (10% vs 57%; P < 0.001), dysphagia without macroscopic findings (83% vs 100%; P = 0.019), and gastroesophageal reflux symptoms with distal esophageal erythema (44% vs 100%; P < 0.001). Significantly fewer AGs reported taking gastric and duodenal biopsies when EoE was suspected (29% vs 90%; P < 0.001). AGs more often followed patients clinically (30% vs 0%; P < 0.001) rather than endoscopically, and were far less inclined to implement elimination diets compared to PGs (23% vs 68%; P < 0.001). CONCLUSIONS: Significant disparities exist between gastroenterologists treating adult and pediatric patients with EoE. These findings may impact rates of diagnosis, appropriate treatment, monitoring, long-term outcomes, and may affect negatively transition from pediatric to adult care.

Is there a connection between paediatric acute idiopathic scrotal oedema and intestinal worm infestation?

AIM: Based on our experience with acute idiopathic scrotal oedema (AISO) and observations of the incidence of intestinal worm infestation (IWI), we decided to test the hypothesis that IWI occurs more frequently among children with AISO than it does in the general population. METHODS: A retrospective questionnaire-based study was conducted comparing the frequency of IWI between children who had AISO and a matched control group who had inguinal hernia surgery in our Pediatric Surgery Department during 2003-2009. This second group was chosen to represent the incidence of IWI in the paediatric community in our region. Records of all patients admitted to the Department of Pediatric Surgery for AISO during 2003-2009 were reviewed. RESULTS: Seventeen out of thirty-eight (44.7%) AISO patients had a history of IWI compared with 5/38 (13.1%) in the control group (P= 0.0047). CONCLUSIONS: Our data clearly show that AISO in children is frequently associated with a history of IWI. Although well-documented, prospective studies are needed to establish these findings, we feel that this report provides a reasonable clue to a possible aetiology of AISO.

Antioxidants and smoking in autoimmune disease--opposing sides of the seesaw?

Autoimmune disorders carry significant morbidity and mortality. Reduction-oxygenation reactions and their byproduct reactive oxygen species have been suspected to influence the initiation and outcome of these disorders. It stands to reason that inhibition of these negative influences by the use of antioxidants would help control these entities. We reviewed the published works in relation to several autoimmune disorders and attempted to conclude what benefit can be achieved with the use of antioxidants. There are several reports which strengthen this notion. However, the number of interventional works is still to low for this to be unequivocal. Cigarette smoking, with its multitude of biological effects, is also implicated in the pathogenesis and course of these diseases. We tried to surmise what is the extent of its effect on the clinical and pathological course of these illnesses. Smoking was shown to increase morbidity and levels of markers for disease activity. It was also found to increase the risk of manifesting these diseases. The number of works needs to be expanded, though.

Prediction of neurological diseases by using autoantibodies: wishful thinking come true.

Medical screening is not a tangible existent tool in autoimmune disorders as it is in other illnesses. Numerous attempts are made to identify individuals destined to develop an autoimmune disease, including analysis of the genetic background, which along with the immunological profile, may assist in identifying those individuals. If these efforts turn out to be successful they could lead to proactive measures that might prevent the emergence of such disorders. This review will summarize the attempts made to pursue autoantibodies specific for the central nervous system as potential predictors of autoimmune neurological disorders.