Long-Term Follow-Up and Outcome of Pediatric Acute Pancreatitis: A Multicenter Study.

OBJECTIVE: Over the past decades, the incidence of acute pancreatitis is increasing, but the progression of acute recurrent pancreatitis and chronic pancreatitis is still not well documented in children. The aim of this multicenter study is to delineate the changes that occur in a certain time period in the course of childhood pancreatitis. MATERIALS AND METHODS: The data of consecutive patients hospitalized with acute pancreatitis between 2010 and 2017 in 4 different pediatric gastroenterology units were reviewed. The clini- cal characteristics of the disease were defined. RESULTS: A total of 165 patients (55.2% female) were included. Over the years, the rate of acute pancreatitis admissions increased while the duration of hospitalization decreased (P < .05). Nearly two-thirds of the patients with acute pancreatitis resolved spontaneously, 30.9% and 4.3% of the cases developed acute recurrent pancreatitis and chronic pancreatitis, respectively. Furthermore, 27.4% patients with acute recurrent pancreatitis progressed to chronic pancre- atitis, and eventually, 12.7% of cases developed chronic pancreatitis within 3-4 years. Local complications developed in 13.3% of the patients with pancreatitis in this cohort. CONCLUSION: The result of this study confirmed the increased incidence of acute pancreatitis in recent years. Conversely, the length of hospital stay decreased over the years. Patients with pancreaticobiliary abnormalities or genetic risk factors had a higher rate of progression to acute recurrent pancreatitis or chronic pancreatitis. Therefore, genetic testing and radiological imaging should be considered early in the follow-up of patients with acute pancreatitis having risk factors for progression to acute recurrent pancreatitis/chronic pancreatitis.

Characteristics of Siblings With Celiac Disease Diagnosed by Family Screening.

OBJECTIVES: The aim of this study was to evaluate the features of asymptomatic siblings of index celiac patients who were diagnosed with celiac disease (CD) at the initial screening. METHODS: We reviewed hospital records of 210 children with CD. The characteristics of sibling celiacs (n=24) were compared with index celiacs (n=186). RESULTS: At diagnosis, sibling celiacs were older than index celiacs (mean (SD) 10.4 (2.7) vs 8.2 (4.3) years; P=0.02). There were no significant differences between sibling and index celiacs in terms of serum anti-tTG IgA titer (≥10xULN, 83.3% vs 85%), and most of the patients had moderate/severe villous atrophy in both groups. The rates of iron deficiency anemia, folic acid deficiency, wasting and stunting were comparable between sibling and index celiac patients. CONCLUSIONS: Siblings with CD were older than index children with CD at diagnosis, and their characteristics were similar to symptomatic index children with CD, despite not having any complaints.

Phenotypic Pattern of Early Versus Later-Onset Pediatric Inflammatory Bowel Disease in a Eurasian Country.

OBJECTIVES: It is not clear whether the characteristics of pediatric inflammatory bowel disease (IBD) differ between Eastern and Western countries. The aim of this study was to analyze the characteristics of PIBD in Turkey, according to the age at diagnosis. METHODS: The data of 176 children with IBD who were followed in our center were analyzed. Patients were divided into early (EO-IBD, onset at 2 to <10 years) and later-onset (LO-IBD, 10 to ≤17 years) IBD according to the age at diagnosis. Patients' data with ulcerative colitis (UC) and Crohn's disease (CD) were compared. RESULTS: Of 176 patients, 47 (26.7%) were diagnosed with EO-IBD. Patients with early-onset ulcerative colitis (EO-UC) had the highest rate of family history of IBD (17.6%). Pancolitis was the most common form of UC regardless of the age at onset. The rate of moderate-severe disease activity in later-onset UC (62.5%) was higher than in EO-UC (37.5%). A higher rate of extraintestinal manifestations was observed in EO-IBD patients, particularly in EO-UC (38.2%) than in LO-IBD patients. Patients with early-onset CD (EO-CD) had predominantly colonic involvement and nonstricturing, nonpenetrating disease behavior. The rate of perianal disease in patients with later-onset CD (LO-CD) (64.5%) was noticeably higher than those with EO-CD (23%). CONCLUSIONS: Our results suggest that patients with EO-UC represented a distinct phenotype with a mild disease activity, high rate of extraintestinal symptoms, and a high proportion of family history. The analysis of our IBD cohort also demonstrated remarkably high rate of perianal disease, particularly in patients with LO-CD.

Evaluation of mucosal status in the follow-up of pediatric patients with celiac disease: the role of serology.

Recent guidelines suggest non-biopsy serology-based approach for the diagnosis of celiac disease; however, there is no evidence-based data regarding noninvasive follow-up of mucosal healing. The aim of this study is to investigate the efficacy of serology in reflecting mucosal status in the follow-up of pediatric patients with celiac disease. This is a validation study conducted at a university hospital. Patients who had biopsy proven celiac disease (Marsh III) at diagnosis, and had been followed-up for at least 12 months, were prospectively evaluated with duodenal biopsies. tTG-IgA and EMA tests were performed on the day of endoscopy. One hundred four patients with a mean age of 7.4 ± 4.02 years were included in the study. The sensitivity and specificity of tTG-IgA were 85.2% and 61% respectively, with a high negative predictive value (NPV) of 92.2% but a very low positive predictive value (PPV) of 43.4%. We found that a cutoff value of 68.5 U/mL for tTG-IgA had a sensitivity, specificity of 85.2% and 85.7% respectively. The AUC was 0.891. The sensitivity and specificity of EMA was 77.8% and 87% respectively, with a high NPV of 91.8% but low PPV of 67.7%. CONCLUSION: This study suggests that negative tTG-IgA and/or EMA can be used as an indicator of mucosal improvement in the follow-up of pediatric patients with celiac disease. However, positive serology (i.e., < 10 × ULN) may be misleading in reflecting mucosal status in the follow-up of pediatric patients with celiac disease. WHAT IS KNOWN: • The tissue transglutaminase IgA (tTG-IgA) and endomysium IgA (EMA) tests are widely used, sensitive and reliable diagnostic tests, but their role in monitoring adherence to dietary treatment in celiac patients has not yet been demonstrated. • There is still no reliable and non-invasive marker of persistent villous atrophy or mucosal recovery. WHAT IS NEW: • Negative celiac serology detected in the follow-up of pediatric patients with celiac disease was successful in demonstrating histopathological mucosal healing. • Positive celiac serology, which is highly reliable in the diagnosis of celiac disease, has not been successful in reflecting mucosal status when used in the follow-up of pediatric patients with celiac disease.

Low Titer Tissue Transglutaminase Antibodies: A Link to Helicobacter pylori Infection?

INTRODUCTION: Low serum titer of anti-tissue transglutaminase (tTG) has been described in various conditions without any evidence of celiac disease (CD). Infectious agents have been suggested to trigger autoimmunity and promote the production of anti-tTG. The aim of this study was to investigate if there is a link between a positive celiac serology and concomitant Helicobacter pylori infection in children. METHODS: The data of 178 pediatric patients who underwent upper gastrointestinal endoscopy due to positive celiac serology were compiled. The patients whose histopathologic findings were not consistent with CD were followed on gluten-containing diet. The changes in the serum level of anti-tTG IgA on the follow-up were compared between H. pylori-infected and noninfected patients after the eradication of H. pylori. RESULTS: Of 155 patients who met the inclusion criteria, 119 (group 1) were diagnosed as CD, and duodenal histopathology of the remaining 36 children (group 2) was not compatible with CD. In group 2, 11 out of 36 (30.5%) patients were infected with H. pylori. After the eradication of H. pylori, anti-tTG IgA level either decreased or dropped below cutoff value in 9/11 (81%) patients while it was 20% in those who were not infected with H. pylori in the 6th month of the follow-up (p = 0.001). CONCLUSION: Our results suggest that H. pylori infection may be the cause of false or transient positive celiac serology. Thus, a positive celiac serology should be carefully interpreted in the presence of H. pylori infection before confirming the diagnosis of this life-long disease.

Outcomes of Pediatric Fistulising Perianal Crohn's Disease.

BACKGROUND: Perianal disease is reported more widely in pediatric Crohn patients than in the past, and has been stated as an independent modifier of the disease behavior. In this study, we aimed to analyze the clinical characteristics and outcomes of fistulising perianal Crohn's disease (fpCD) in the pediatric age group. METHODS: A total number of 149 children with an established diagnosis of inflammatory bowel disease who have been diagnosed before 18 years of age and followed in our tertiary center were revised. Clinical, endoscopic, laboratory, and radiologic data of 50 patients with CD, who had at least 18 months follow-up data, were compiled. RESULTS: Of 50 patients, 26 (52%) were diagnosed as fpCD (38% at onset). More than half of the patients without any notable external orifices around the perianal area were diagnosed as fpCD by an magnetic resonance imaging (MRI). Pediatric fpCD patients had a higher disease activity score and platelet count, lower serum albumin level, and a higher rate of granuloma in the biopsy samples, compared with non-fistulising patients. A considerably high rate of surgical interventions (i.e., seton placement 46% and abscess drainage 15%) was performed in combination with infliximab. CONCLUSION: Fistulising perianal Crohn's disease seems to be more common than previously reported in the pediatric age group. A severe course of the disease might serve as a warning for the development of fpCD. A careful physical examination and use of perianal MRI with a high index of suspicion may increase the likelihood of fistula detection, hence may change the treatment strategy.

Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.

Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.

IgG4 related disease in a seven year old girl with multiple organ involvement: A rare presentation.

Autoimmune pancreatitis has been described as a pancreatic manifestation of immunoglobulin G4-related disease, which is characterized by typical histopathologic, radiologic, and clinical features. Immunoglobulin G4-related disease is usually accompanied by elevated serum immunoglobulin G4 level, and can involve multiple organ/systems. Immunoglobulin G4-related disease has rarely been reported in pediatric population. There are few reports of inflammatory bowel disease in association with immunoglobulin G4-related disease. We describe a 7-year-old girl who presented with pancreatitis and concurrent sclerosing cholangitis, and developed bloody diarrhea during follow-up. An endoscopic examination revealed inflammatory bowel disease, and later lacrimal gland involvement was also recognized. She was diagnosed as having immunoglobulin G4-related disease, and her clinical signs and symptoms improved dramatically after steroid treatment. Hence, awareness of the clinical picture is important and early diagnosis can prevent fibrosis and organ damage.

Helicobacter pylori infection in children with celiac disease: Multi-center, cross-sectional study.

BACKGROUND: An inverse association has been suggested between celiac disease (CD) and Helicobacter pylori (Hp) infection in children; however, there are inconsistent data. The purpose of this multi-center study is to evaluate the association between Hp and CD in childhood. METHODS: Children who underwent endoscopy between July 2016 and November 2017 in four pediatric gastroenterology centers were included in the study. Patients with a history of previous Hp eradication, antibiotic or acid-suppressive drug therapy in the last 4 weeks, and any underlying chronic disease were excluded. The presence of Hp infection was confirmed by both histopathology and the rapid urease test. The ones who had the diagnosis of CD were compared with the children who underwent endoscopy during the same period and had another diagnosis. Duodenal histopathology of children with CD was categorized according to the modified Marsh classification. RESULTS: Of 3056 endoscopies performed in the study period, 2484 cases were eligible for the study. A total of 482 CD patients (mean age: 9.71 ± 4.63 years, 58.5% girls) and 2060 controls (mean age: 9.92 ± 4.66 years, 54.6% girls) were included in the study. The rate of Hp infection was significantly lower in CD group (26.3% vs 50.1%, P < .01). The difference was prominent even in children younger than 6 years old (P < .01). There was no correlation between Hp infection and the modified Marsh scores in CD (P > .05). CONCLUSION: In this cross-sectional study, where Hp infection is common even in the pediatric population, the frequency of Hp infection was significantly lower in children with CD compared with the controls. Systematic cohort studies are necessary to clarify causal association between Hp infection and the development of celiac disease.

Gastrointestinal sarcoidosis presenting with malabsorption at an early age.

Sarcoidosis is a chronic multisystemic granulomatous disease that predominantly involves the thoracic lymph nodes and lungs and primarily occurs in young adults. Isolated extrapulmonary localization is uncommon in adults, and exceptionally rare in the pediatric age group. A 4-year-old male patient with chronic diarrhea and abdominal distention for the last 8 months is presented. Endoscopic biopsies, obtained during gastroscopy and colonoscopy, revealed noncaseating granulomas in all segments of the gastrointestinal tract. A noncaseating granuloma was also demonstrated in the liver biopsy. Granulomatous inflammation of both the gastrointestinal system and liver along with elevated serum angiotensin-converting enzyme were consistent with sarcoidosis. The peculiarity of our pediatric sarcoidosis was the involvement of whole gastrointestinal system, which is exceptionally rare in all age groups. Furthermore, this is the youngest case in the literature with gastrointestinal and hepatic sarcoidosis in the absence of pulmonary involvement at onset.

Gastrointestinal Manifestations in Children with Primary Immunodeficiencies: Single Center: 12 Years Experience.

BACKGROUND: It has been reported that 5-50% of patients with primary immune deficiencies (PID) may present with or develop gastrointestinal (GI) manifestations. OBJECTIVE: This study was aimed at analyzing GI and related endoscopic, histopathological findings in children with PID. METHODS: Children with PID who were evaluated by endoscopy between 2005 and 2016 were enrolled in this study. Demographic data, growth parameters, signs and symptoms at diagnosis were obtained. RESULTS: Of 425 children with PID, 195 had GI manifestations. Forty-seven of 195 children required endoscopic investigation, 30 (63.8%) were male, and the mean age was 7.7 ± 5 years. The rate of consanguinity was 61.7%, and the most common symptom was chronic diarrhea (57.4%). Seventy-two percent of the patients were malnourished. Giardia intestinalis was detected in 4, and Helicobacter pylori was confirmed in 8/45 (17.7%) patients. Non-celiac villous flatting was discovered in 15.5% of patients. Twelve patients were diagnosed as having immunodeficiency associated inflammatory bowel disease (IBD)-like colitis. CONCLUSIONS: PID may present with GI manifestations or develop during the course of the disease. Investigating immunodeficiency in patients with atypical GI symptoms can provide an appropriate therapeutic option, and an improved quality of life, particularly in populations with a high rate of consanguinity.

A Rare Complication of Giardiasis in Children: Protein-losing Enteropathy.

Protein-losing enteropathy may develop as a complication of a wide spectrum of diseases. Three cases of giardiasis that presented with acute onset of hypoalbuminemia were documented, and resolution of protein loss after treatment was also confirmed. Thus, chronic enteric infections should be considered as an etiology of severe intestinal protein loss, particularly in children.