Beyond diagnosis: exploring coeliac disease incidence alongside clinical and laboratory characteristics of newly diagnosed children in Slovenia.

OBJECTIVE: Coeliac disease is characterized by a wide array of clinical presentations. The focus of our study was to comprehensively assess the clinical manifestations of coeliac disease in newly diagnosed children in Slovenia. Our objectives include estimating the incidence of the disease in children in 2022. METHODS: In this prospective study, Slovenian paediatric gastroenterologists were invited to provide patient data using medical records of children under 19 diagnosed with coeliac disease from March 2021 to October 2023. Patient data were collected through a dedicated web-based form adapted from the CD SKILLS project, including data on clinical manifestations and laboratory results. Furthermore, the study included an estimation of the incidence of coeliac disease in children and adolescents in Slovenia in 2022. RESULTS: Analysis involved data from 160 children and adolescents (median age: 8 years; 61.9% female). Overall, 16.9% were asymptomatic at diagnosis and 29.4% belonged to a high-risk group for coeliac disease. Among symptomatic cases (N = 133), abdominal pain was the leading symptom (44.4%), followed by anaemia (12.0%) and diarrhoea (10.5%). Malabsorption symptoms were more prevalent in very young children. Anaemia was found in 22.8 and 10.7% had abnormal alanine aminotransferase levels. The estimated incidence of coeliac disease in Slovene children in 2022 was 17.5/100 000. CONCLUSION: Abdominal pain emerged as the primary symptom of coeliac disease in children and adolescents, except in very young children where malabsorption symptoms were predominant. Our observation of a lower prevalence of abnormal liver function tests suggests subclinical coeliac disease may be less common in children. Moreover, the calculated coeliac disease incidence in Slovenia aligns with existing data.

Insights into coeliac disease diagnosis: a 2021-2023 overview of diagnostic approach and delays in children in Slovenia.

INTRODUCTION: Over the past decade, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) proposed the option of diagnosing coeliac disease (CD) in children without duodenal biopsy. The aim of our study was to assess the diagnostic approach in newly diagnosed children with CD in Slovenia. METHODS: In this prospective study, Slovenian paediatric gastroenterologists were invited to provide medical records of children under 19 years diagnosed with CD from March 2021 to October 2023. The analysis focused on tissue transglutaminase antibody (TGA) levels at diagnosis, diagnostic approach, adherence to ESPGHAN CD guidelines and diagnostic delays. RESULTS: Data from 160 newly diagnosed CD patients (61.9% female; median age 8 years; 16.9% asymptomatic) were available for the analysis. No-biopsy approach was used in 65% (N = 104) of children and the majority (N = 101) fulfilled all the criteria for the no-biopsy approach. Of 56 children diagnosed using duodenal biopsy, a further 10 (17.8%) would have also been eligible for the no-biopsy approach based on the very high levels of TGA. Median diagnostic delay from first symptoms to confirmation of diagnosis was 6 months (min 0 months, max 87 months). Use of the no-biopsy approach has risen significantly since 2016 (37.8% vs. 65.0%; p = 0.001) and diagnostic delays have shortened (6 vs. 7 months; p < 0.05). CONCLUSION: This prospective study highlights the frequent use of a no-biopsy approach for diagnosing CD in children in Slovenia, showing large adherence to ESPGHAN guidelines. Also, diagnostic delays have shortened over recent years, likely due to various awareness-raising projects on CD conducted during this period.

Safety beyond Sight: Handheld Metal Detectors as Diagnostic Allies in the Management of Children Suspected to have Ingested Foreign Bodies.

BACKGROUND: Foreign body (FB) ingestion remains a common cause of pediatric emergency department referrals, and the gold standard for detection is whole-digestive-tract radiographic examination. Our study explores whether handheld metal detectors (HHMD) can effectively identify the presence and location of ingested metal objects, potentially reducing the need for additional radiographic examination. METHODS: We collected medical data from children with suspected metal FB ingestion who were referred to our emergency department (October 2017-March 2023), focusing on object type and correlating metal detector findings with radiographic images. RESULTS: Data from 43 children (39.5% female; mean age: 4 y) referred to our emergency department were analyzed. Coins (32.6%), button batteries (18.6%), and hairpins (11.6%) were the most common ingested objects. Metal detectors detected the presence of FBs in 81.4% of cases (sensitivity: 89.7%; specificity: 100%). Radiographs, taken for 40 children, showed that the most common locations were the stomach (37%) and intestine (33%). The metal detector signals matched the radiography results in 69.8% of cases. According to HHMD, 34.9% of objects were accessible via endoscopy, contrasting with 51.2% via radiography (p < 0.05). CONCLUSION: While the findings obtained using handheld metal detectors often correlate well with radiograph findings in detecting metal FBs, for an important number of children, this confirmation is lacking, especially when determining the exact location of an object.

Evolving Landscape of Paediatric Inflammatory Bowel Disease: Insights from a Decade-Long Study in North-East Slovenia on Incidence, Management, Diagnostic Delays, and Early Biologic Intervention.

BACKGROUND: In the past decade, significant progress has been achieved in the care of children with inflammatory bowel disease (IBD). Our study concentrated on assessing the incidence and management of IBD in children in North-Eastern Slovenia over a 10-year period. METHODS: Medical data from children and adolescents diagnosed with IBD in North-Eastern Slovenia (2014-2023) was analysed. Disease incidence and management of children were assessed. Findings were compared between two periods (2014-2019 and 2020-2023, coinciding with the COVID-19 pandemic). RESULTS: 87 patients (median age 15.5 year; 50.6% male) with IBD (43.7% Crohn's disease (CD)), diagnosed between 2014 and 2023 were included. Extraintestinal manifestations were more common in CD than ulcerative colitis (UC) (15.8% vs. 2.4%, p < 0.05). Median delay from symptom onset to diagnosis was 2 months, lower in UC than CD (NS). Mean annual IBD incidence per 100,000 children aged 0 to 19 years was 6.4 (95% CI 4.4-8.3), slightly lower for CD than UC (2.8/100,000 vs. 3.1/100,000). In the second period, IBD incidence significantly rose (9.1 vs. 4.6, p < 0.05). During this period, 53% of CD patients transitioned to biological treatment within three months of diagnosis. CONCLUSION: IBD incidence rose among children in North-Eastern Slovenia over the past decade. Additionally, more children with CD underwent biological therapy in the second period.

Management of coeliac disease patients after the confirmation of diagnosis in Central Europe.

BACKGROUND: Recently published paediatric guidelines for diagnosing coeliac disease do not include recommendations on the follow-up of coeliac disease patients. GOAL: The aim of this study was to assess the management practices and experience of coeliac disease patients with their follow-up appointments in Central Europe. STUDY: Gastroenterologists and coeliac disease patients in five Central European countries were asked to complete the web-based questionnaire focusing on coeliac disease management practices. RESULTS: Answers from 147 gastroenterologists and 2041 coeliac disease patients were available for the analysis. More than half of the gastroenterologists (58.5%) schedule the first follow-up visit within 3 months after the diagnosis. At follow-up, tissue transglutaminase antibodies are checked in almost all patients (95.9%). Approximately two-thirds (60.7%) of gastroenterologists refer all of their patients to the dietitian at diagnosis. Similarly, 42.8% of coeliac disease patients reported that they had not been appointed to a dietitian. Almost one-third of coeliac disease patients (30.8%) reported that they had no follow-up appointments with gastroenterologist at all. CONCLUSIONS: Follow-up of coeliac disease patients is suboptimal in Central Europe. Many patients are not followed regularly. A lot of patients are not referred to a dietitian. The recommendations on the optimal follow-up of coeliac disease patients are needed in order to improve patient care.

The Knowledge About Celiac Disease Among Healthcare Professionals and Patients in Central Europe.

OBJECTIVES: Celiac disease (CD) remains undiagnosed for a long time in many adult and pediatric patients. We assessed the knowledge about CD among healthcare professionals (HCPs) and CD patients in Central Europe (CE). METHODS: HCPs and CD patients from 5 CE countries were asked to complete the web-based questionnaire about CD. The questions were divided into subsections on epidemiology, clinical presentation, diagnostics, treatment, and follow-up. Achieved scores of different specialists managing patients with CD were compared and regional differences in patients' knowledge were analyzed. RESULTS: Questionnaire was completed by 1381 HCPs and 2262 CD patients or their caregivers from Croatia, Hungary, Germany, Italy, and Slovenia. Mean score achieved by HCPs was 50.9%, and by CD patients 56.4%. Pediatric gastroenterologists scored the highest (69.4%; P < 0.001). There were significant differences in knowledge of patients from different CE regions with German participants scoring the highest (58.3%). Members of CD societies scored higher compared with nonmembers (mean score 58% vs 53.2%; P < 0.001) and patients diagnosed less than 5 years ago scored higher compared with those diagnosed more than 10 years ago (mean score 57.3% vs 54.6%; P < 0.001). CONCLUSIONS: The knowledge about CD among HCPs and CD patients is not satisfactory. Further awareness-raising and learning activities are needed to improve HCPs' knowledge and to minimize the number of unrecognized patients and unnecessary diagnostic delays. Patients should be better informed about their disease to reach higher compliance with the gluten-free diet.

Clinical Presentation in Children With Coeliac Disease in Central Europe.

OBJECTIVES: During the past decades, there has been a shift in the clinical presentation of coeliac disease (CD) to nonclassical, oligosymptomatic, and asymptomatic forms. We assessed clinical presentation of CD in children and adolescents in Central Europe. METHODS: Paediatric gastroenterologists in 5 countries retrospectively reported data of their patients diagnosed with CD. Clinical presentation was analyzed and the differences among very young (<3 years) and older children and adolescents were studied. RESULTS: Data from 653 children and adolescents (median age 7 years 2 months; 63.9% girls) from Croatia, Germany, Hungary, Italy, and Slovenia were available for the analysis. One fifth (N = 134) of all children were asymptomatic. In symptomatic children, the most common leading symptom was abdominal pain (33.3%), followed by growth retardation (13.7%) and diarrhoea (13.3%). The majority of symptomatic children (47.6%; N = 247) were polysymptomatic. Abdominal pain was the most common symptom in polysymptomatic (66.4%) as well as in monosymptomatic children (29.7%). Comparing clinical presentation of CD in very young children (younger than 3 years) with older children (3 years or older), we found that symptoms and signs of malabsorption were significantly more common in younger (P < 0.001), whereas abdominal pain and asymptomatic presentation were more common in older children and adolescents (both P < 0.001). CONCLUSION: In children with CD, abdominal pain has become the most common symptom. However, in younger children, symptoms of malabsorption are still seen frequently. This raises a question about the underlying mechanism of observed change in clinical presentation in favour of nonclassical presentation and asymptomatic disease at certain age.

The Use of Biopsy and "No-Biopsy" Approach for Diagnosing Paediatric Coeliac Disease in the Central European Region.

OBJECTIVES: The current European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines introduced the option to diagnose coeliac disease (CD) in children and adolescents without upper endoscopy if the defined criteria are met. The aim of our study was to evaluate how frequently paediatric gastroenterologists in Central Europe used the "no-biopsy" approach and how often the duodenal biopsy could have been omitted. METHODS: Medical records of patients aged < 19 years diagnosed with CD in 2016 from five European countries were analysed, focusing on levels of transglutaminase antibodies (TGA) at the time of diagnosis and on whether the diagnosis was confirmed using duodenal biopsy or "no-biopsy" approach. Clinical presentation and delays until final diagnosis were analysed according to diagnostic approach. RESULTS: Data from 653 children (63.9% female, median age: 7 years, range: 7 months-18.5 years) from Croatia, Hungary, Germany, Italy, and Slovenia were analysed. One fifth (n = 134) of included children were asymptomatic at diagnosis. Of 519 symptomatic children, 107 (20.6%) were diagnosed by the "no-biopsy" approach. Out of the remaining 412 children who underwent duodenal biopsies, 214 (51.9%) had TGA ≥ 10 times upper level of normal (ULN) and would have been eligible for the "no-biopsy" approach. Signs and symptoms of malabsorption were more frequent in children diagnosed without duodenal biopsies. There were no differences in diagnostic delays with respect to the diagnostic approach. CONCLUSION: In this cohort, about 60% of symptomatic CD patients could have been diagnosed without duodenal biopsies. The aim of the "no-biopsy" approach was to make the diagnostic procedure less challenging without compromising its reliability. However, this option was applied only in 20%, in spite of fewer burdens to the family and reduced costs. The reasons for this discrepancy are unknown. Physicians should be made more aware about the reliability of CD diagnosis without biopsies when the ESPGHAN guidelines for CD diagnosis are followed.

Diagnostic Delays in Children With Coeliac Disease in the Central European Region.

OBJECTIVES: Coeliac disease (CD) is a systemic autoimmune disorder affecting about 1% of the population. Many patients remain undiagnosed or are diagnosed with substantial delay. We assessed diagnostic delays in symptomatic CD children in Central Europe (CE). METHODS: Paediatric gastroenterologists in 5 CE countries retrospectively reported data of their patients diagnosed in 2016. Age at first CD-related symptom(s), first visit to paediatric gastroenterologist and confirmed diagnosis were used to determine diagnostic delays. RESULTS: Data from 393 children (65% girls, median age 7 years, range 7 months to 18.5 years) from Croatia, Hungary, Germany, Italy, and Slovenia were analysed. Median duration from first symptom(s) to visit to paediatric gastroenterologist was 5 months (range 0-10 years; preschool 4 months, school-aged 5 months), and further duration until final diagnosis was 1 month (range 0-5 years) with significant regional differences (P < 0.001). Median diagnostic delay was 6 months (range 0-10 years; preschool 5 months, school-aged 7 months). Type of clinical presentation had little, however, significant effect on delays. Reduced body mass in delays longer than 3 years compared with delays shorter than 1 year was found (z score -0.93 vs -0.39, P < 0.05). CONCLUSIONS: Time from first symptoms to CD diagnosis in children in 5 CE countries is slightly shorter compared with few other small paediatric studies, and significantly shorter than reported for adults. Nevertheless, delays of more than 3 years in 6.6% of children are worrisome. Raising awareness about the variable symptoms and implementation of reliable diagnostic tools will further reduce diagnostic delays.

Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and short-chain fatty acids.

BACKGROUND & AIMS: Celiac disease (CD) is an immune-mediated systemic disease, caused by ingestion of gluten in genetically predisposed individuals. Gut microbiota dysbiosis might play a significant role in pathogenesis of chronic enteropathies and its modulation can be used as an intervention strategy in CD as well. In this study, we aimed to identify correlations between fecal microbiota, serum tumor necrosis factor alpha (TNF-α) and fecal short-chain fatty acids (SCFAs) in healthy children and children with CD after administration of probiotic Bifidobacterium breve BR03 and B632. METHODS: A double-blind placebo-controlled study enrolled 40 children with CD (CD) and 16 healthy children (HC). CD children were randomly allocated into two groups, of which 20 belonged to the placebo (PL) group and 20 to the Probiotic (PR) group. The PR group received a probiotic formulation containing a mixture of 2 strains, B. breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) in 1:1 ratio for 3 months. Subsequently, for statistical analysis, blood and fecal samples from CD children (on enrolment - T0 and after 3 months, at the end of intervention with probiotic/placebo - T1) and HC children were used. The HC group was sampled only once (T0). RESULTS: Verrucomicrobia, Parcubacteria and some yet unknown phyla of Bacteria and Archaea may be involved in the disease, indicated by a strong correlation to TNF-α. Likewise, Proteobacteria strongly correlated with fecal SCFAs concentration. The effect of probiotic administration has disclosed a negative correlation between Verrucomicrobia, some unknown phyla of Bacteria, Synergistetes, Euryarchaeota and some SCFAs, turning them into an important target in microbiome restoration process. Synergistetes and Euryarchaeota may have a role in the anti-inflammatory process in healthy human gut. CONCLUSIONS: Our results highlight new phyla, which may have an important relation to disease-related parameters, CD itself and health.

Administration of Bifidobacterium breve Decreases the Production of TNF-α in Children with Celiac Disease.

BACKGROUND: Increasing evidence suggests that not only genetics, but also environmental factors like gut microbiota dysbiosis play an important role in the pathogenesis of celiac disease (CD). AIM: The aim of our study was to investigate the effect of two probiotic strains Bifidobacterium breve BR03 and B. breve B632 on serum production of anti-inflammatory cytokine interleukin 10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in children with CD. METHODS: The study was a double-blinded, placebo-controlled trial that included 49 children with CD on gluten-free diet (GFD) randomized into two groups and 18 healthy children in the control group. The first group (24 children with CD) daily received B. breve BR03 and B632 (2 × 10(9) colony-forming units) and the second group (25 children with CD) received placebo for 3 months. RESULTS: TNF-α levels were significantly decreased in the first group after receiving B. breve for 3 months. On follow-up, 3 months after receiving probiotics, TNF-α levels increased again. Children with CD who were on GFD for less than 1 year showed similar baseline TNF-α levels as children who were on GFD for more than 1 year. IL-10 levels were in all groups of patients below detection level. CONCLUSIONS: Probiotic intervention with B. breve strains has shown a positive effect on decreasing the production of pro-inflammatory cytokine TNF-α in children with CD on GFD.