Clinical Features and Natural History of Paediatric Patients with Ulcerative Proctitis: A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND AIMS: Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes. METHODS: This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020. RESULTS: We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5-16.0]), with a median follow-up of 2.7 years [IQR 1.7-3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20-35], but most patients exhibited moderate-severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression. CONCLUSION: Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.

Thiopurines Maintenance Therapy in Children With Ulcerative Colitis: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Thiopurines are an established treatment for pediatric ulcerative colitis (UC). However, data regarding safety and efficacy are lacking. We aimed to determine short and long-term outcome following thiopurines use in children with UC. METHODS: We conducted a retrospective review of children (2-18 years) with UC treated with thiopurines between January 2008 and January 2019 at 7 medical centers in Israel. The primary outcome was corticosteroid (CS)-free clinical remission at week 52 following thiopurines initiation without the need for rescue therapy (infliximab, calcineurin inhibitors, or colectomy). RESULTS: A total of 133 children were included [median age at diagnosis of 12.4 (interquartile range 11.0-15.8) years, 30 (23%) left-sided colitis, 113 (85%) with moderate or severe disease at diagnosis]. At diagnosis 58 patients (44%) were treated with 5-aminosalicylates and 72 (54%) with CS. Sixty patients (45%) received thiopurines as 1st line maintenance therapy. Seventy-four patients (56%) had CS-free clinical remission at week 52 without rescue therapy. Predictors of clinical remission were not identified. In a sub-analysis among patients with steroid-responsive moderate to severe UC, 59 (55%) patients achieved this outcome. The likelihood of remaining free of rescue therapy among thiopurines-treated patients was 83%, 62%, 45%, and 37% at 1, 2, 3, and 4 years, respectively. CONCLUSION: More than half of children with UC starting thiopurines without previous or concomitant biologic therapy have CS-free clinical remission at 52 weeks later without the need for rescue therapy. Thiopurines are effective in pediatric UC and could be considered prior to biologics.

Yield of Emergency Department Stool Culture Tests Among Children With Acute Gastroenteritis in Israel.

Previous studies have attempted to predict a positive stool culture in pediatric patients with acute gastroenteritis (AGE), but most of them are either from developing countries or are outdated. In all, 276 patients with AGE and 560 control patients were analyzed for differences in clinical factors including the presence of fever, highest recorded temperature, bloody diarrhea, number of bowel movements in 24 hours prior to presentation, and the presence of seizures, as well as laboratory parameters including leukocyte count and C-reactive protein (CRP). Positive stool sample rate was 13.7%. The most common bacterial pathogen was Campylobacter jejuni. Bacterial AGE was significantly associated with fever >37.9°C, bloody diarrhea, higher stool passing frequency, seizures, and CRP levels. For pediatric patients who present to the emergency department with AGE and present without bloody diarrhea, fever, frequent stool passing, or seizures, a stool culture test is of poor yield and may not be necessary.

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.

Effect of a Gluten Free Diet on Hepatitis B Surface Antibody Concentration in Previously Immunized Pediatric Celiac Patients.

PURPOSE: To evaluate the effect of gluten-free diet (GFD) on hepatitis B surface antibody (HBsAb) concentrations among previously immunized pediatric celiac disease (CD) subjects. METHODS: We retrospectively evaluated pediatric CD subjects in serological remission who were previously immunized for hepatitis B virus as infants. The temporal relationship between HBsAb concentration, the amount of time on a GFD, and age were evaluated. RESULTS: Overall, 373 CD subjects were analyzed: 156 with HBsAb sampled prior to GFD initiation and 217 after initiation of a GFD and in serological remission. Median age at HBsAb concentration measurement for those before and after GFD initiation was 5.3 years (interquartile range [IQR], 3.1-9.2 years) and 7.6 years (IQR, 5.4-10.9 years), respectively (p<0.001). There was no sex difference between the groups. The median time of HBsAb measurement was 2 months (IQR, 0-5.7 months) before and 12.8 months (IQR, 5.3-30.3 months) after initiation of GFD. The HBsAb concentration was low in 79 (50.6%) and 121 (55.7%) subjects before and after GFD initiation, respectively (p=0.350). Age was inversely associated with low HBsAb concentrations. Neither being on a GFD nor sex was associated with low HBsAb concentrations. CONCLUSION: Adherence to a GFD does not affect HBsAb concentration in children with CD. Age is inversely associated with HBsAb concentration.

The Effect of Gluten-free Diet on Cardiovascular Risk Factors in Newly Diagnosed Pediatric Celiac Disease Patients.

OBJECTIVES: Although gluten-free diet (GFD) is the only proven therapy for celiac disease (CD), its effect on cardiovascular disease (CVD) risk factors is still unclear. Our aim was to determine whether adherence to GFD affects CVD risk factors among newly diagnosed pediatric CD subjects. METHODS: We prospectively enrolled pediatric subjects undergoing upper gastrointestinal endoscopy for suspected CD. We collected anthropometric and laboratory parameters related to CVD risk factors at the time of CD diagnosis and 1 year after initiation of a GFD and evaluated changes in CVD risk factors. Paired t tests or Wilcoxon nonparametric tests were used, each when appropriate. RESULTS: One hundred ten newly diagnosed CD pediatric subjects were included in the analysis. There were 64 (58.2%) girls and the mean age at diagnosis was 6.8 ±â€Š3.4 years. Median body mass index z scores (P = 0.84), rates of underweight or overweight (P = 0.32), and rates of elevated blood pressure (P = 0.78) remained unchanged. Although median fasting insulin levels increased (1.9 vs 5.4 µU/mL, P < 0.001), insulin resistance as measured by homeostatic model assessment did not increase after 1 year of GFD (P = 0.16). Although rates of dyslipidemia remained unchanged, median high-density lipoprotein levels increased on GFD (47 vs 51 mg/dL, P < 0.001). CONCLUSIONS: In this pediatric CD cohort, GFD for 1 year was not associated with increased CVD risk factors. The long-term significance of these mild changes is yet to be determined.

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.

Clinical characterization of gastroenteritis-related seizures in children: impact of fever and serum sodium levels.

Gastroenteritis-related seizures have increasingly gained attention in recent years. Most cases follow a brief, benign course with very few episodes of seizure recurrence and without development of epilepsy. Published reports usually do not make a distinction between febrile and afebrile patients, and most authors include only nonfebrile convulsions in their reported series. This study evaluated the impact of fever in children presenting with seizures during a mild gastroenteritis episode and found that the presence or absence of fever did not affect seizure characteristics or duration. However, mild hyponatremia affected some seizure features, particularly seizure duration, as hyponatremic children sustained more prolonged seizures than patients with normal serum sodium levels, irrespective of body temperature.

Subcutaneous fat necrosis and hypercalcemia following therapeutic hypothermia--a patient report and review of the literature.

Subcutaneous fat necrosis (SCFN) of the newborn is an uncommon dermatologic disorder characterized by firm, palpable subcutaneous nodules or plaques with or without erythema. Despite its benign course, SCFN may become complicated by extracutaneous manifestations. Hypercalcemia is considered a rare complication, but it is potentially fatal if unrecognized. During the last several years therapeutic hypothermia (TH) became an essential new therapeutic modality for severe neonatal asphyxia. We report a neonate who presented with SCFN and hypercalcemia following hypothermia therapy for hypoxic ischemic encephalopathy (HIE) and provide a review of the contemporary literature on the topic. We believe that this is important since the use of TH is rapidly increasing, and therefore, the possible side effects including SCFN and hypercalcemia may also become more prevalent. This prompts the need for awareness by treating physicians for this complication.

Marked hypotonia in an infant of a mother with Devic disease.

A full-term female neonate was born with severe hypotonia and weakness. Her mother had been treated for neuromyelitis optica (Devic disease) for 6 years. Her previous son, born 10 years earlier and before she developed the disease, also had marked hypotonia that gradually improved over several weeks. A suspicion of neonatal myasthenia gravis arose, as a search of the literature revealed the occasional detection of anti-acetylcholine receptor antibodies in patients with Devic disease. A neostigmine test was mildly positive in the baby, but anti-acetylcholine receptor antibodies were elevated. Aquaporin 4 antibodies typical of neuromyelitis optica were not detected in the infant. Because of clinical deterioration, intravenous immunoglobulin was administered with substantial improvement. Anti-acetylcholine antibodies were markedly elevated in the mother's serum, although she showed no clinical signs of myasthenia gravis. It is very likely that her previous baby also had unrecognized transient myasthenia gravis.

Osteoporosis in children: pediatric and pediatric rheumatology perspective: a review.

It is increasingly recognized that osteoporosis affects children as well as adults both as a primary problem and as secondary to various diseases, medications, and lifestyle issues. In this review, we emphasize the correct diagnosis of osteoporosis in children as opposed to adults, etiology, and pharmaceutical and non-pharmaceutical treatments. We especially focus on rheumatologic conditions associated with osteoporosis and management issues.

Insertion of inferior vena cava filters in patients with the antiphospholipid syndrome.

BACKGROUND: The antiphospholipid syndrome (APS) is a disease with a high prevalence of thromboembolic events, especially pulmonary emboli (PE). These events may recur despite anticoagulation therapy. In such cases, placement of an inferior vena cava (IVC) filter may be considered to prevent propagation of a distal thrombus toward the pulmonary vessels. It is unclear whether the placement of such a filter is beneficial in patients with APS. OBJECTIVE: Retrospective evaluation of the value of IVC filter placement as prophylaxis against recurrent pulmonary emboli in patients with medically treated APS. METHODS: We identified 10 patients suffering from APS who, despite anticoagulation treatment, had recurrent thromboembolic events. All of them underwent placement of an IVC filter. We examined their medical files for further recurrences. RESULTS: Of the 10 patients in our study, only 1 had a documented PE following the intervention. The remaining patients had no evidence of PE after the filter insertion. Five of the 10 patients died, 2 of them suddenly. In those 2 patients, the cause of death is unknown, but PE cannot be excluded. CONCLUSION: IVC filters seem to be protective against recurrent PE in APS patients but the true extent of their efficacy requires further study.

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.