Pancreatic Involvement in the Course of Inflammatory Bowel Disease in Children-A Multi-Center Study.

The coexistence of inflammatory bowel disease (IBD) with pancreatic pathology is rare in children. A retrospective analysis of data from 1538 children diagnosed with IBD in 2014-2021 was conducted to determine the frequency and causes of pancreatitis and asymptomatic hyperlipasemia (HL) or hyperamylasemia (HA) in this group of patients. Among the 176 children (11.4%) with pancreatic involvement (PI), acute pancreatitis (AP) was diagnosed in 77 children (43.8%), and HA or HL was observed in 88 children (50.0%). Only a few patients were diagnosed with autoimmune or chronic pancreatitis (6.2%). PI was observed at the time of the IBD diagnosis in 26.1% of the cases. A total of 54.5% of the patients had moderate to severe IBD, and 96% had colonic involvement at the time of diagnosis of PI. Idiopathic PI was the most common (57%), followed by drug-induced PI (37%) and azathioprine (AZA). In patients with AZA-induced AP, the successful introduction of 6-mercaptopurine (6-MP) to therapy was noted in 62.5% of the children. Our results suggest that routine monitoring of pancreatic enzymes in patients with IBD should be performed, especially after the initiation of the AZA treatment. The presence of transient HA/HL in IBD does not necessarily indicate pancreatic pathology.

Etiology of IBD-Is It Still a Mystery?

Inflammatory bowel diseases (IBD), including colitis ulcerosa and Crohn's disease, are chronic diseases of the gastrointestinal tract for which the cause has not been fully understood. However, it is known that the etiology is multifactorial. The multidirectional network of interactions of environmental, microbiological and genetic factors in predisposed persons lead to an excessive and insufficiently inhibited reaction of the immune system, leading to the development of chronic inflammation of the gastrointestinal walls, the consequence of which is the loss of the function that the intestine performs, inter alia, through the process of fibrosis. Detailed knowledge of the pathways leading to chronic inflammation makes it possible to pharmacologically modulate disorders and effectively treatthese diseases. In this review, we described the primary and adaptive immune system response in the gut and the known immune pathogenetic pathways leading to the development of IBD. We also described the process leading to intestinal tissue fibrosis, which is an irreversible consequence of untreated IBD.

Selective Forms of Therapy in the Treatment of Inflammatory Bowel Diseases.

Selective interference with the functioning of the immune system consisting of the selective blockade of pro-inflammatory factors is a modern, promising, and developing strategy for the treatment of diseases resulting from dysregulation of the immune system, including inflammatory bowel disease. Inhibition of the TNF alpha pathway, group 12/23 cytokines, and lymphocyte migration is used in the treatment of severe or moderate ulcerative colitis and Crohn's disease. Intracellular signal transduction by influencing the phosphorylation of SAT (signal transducer and activator of transcription) proteins remains in clinical trials.

Endoscopic Ultrasonography in Children with Eosinophilic Esophagitis-A Review.

Endoscopic ultrasonography (EUS) is a diagnostic endoscopy of the upper gastrointestinal tract, during which ultrasound of nearby organs is also performed. It is also possible to perform a fine needle aspiration biopsy. Currently, EUS is performed more frequently in adults. Despite some limitations, this diagnostic method is also more and more often performed in pediatric patients. Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus, which also occurs in children, and leads to irreversible fibrosis of the esophagus wall, if left untreated. Traditional methods of diagnosing and monitoring EoE treatment have significant limitations, and the use of EUS and total esophageal wall thickness (TWT) assessment may bring measurable benefits. Several studies have shown an increased thickening of TWT in EoE in children compared to pediatric patients with gastroesophageal reflux disease, and a decrease in TWT in adults who responded to EoE treatment. These results suggest that EUS and TWT measurement may become an important test in diagnostics, monitoring the effectiveness of therapy, assessing disease progression, and in individualizing the method and duration of EoE treatment also in children.

The Incidence of Inflammatory Bowel Disease in the Paediatric Population in the District of Lower Silesia, Poland.

The incidence of IBD has been rising over the last decades. The trend applies not only to well-developed countries but also to the regions with limited number of cases so far, e.g., Asia or Middle East. AIM: The aim of the study was to determine the incidence of paediatric IBD in the district of Lower Silesia, Poland, between 2016 and 2018. METHODS: The number of newly diagnosed IBD per 100,000 children, living in the region, was calculated. The characteristics of the group were established. RESULTS: There were 81 cases of paediatric IBD diagnosed between the 1st of January 2016 and 31st of December 2018. The diagnosis of ulcerative colitis (UC) was made for 42 children. In the same period of time 39 cases of Crohn disease (CD) were recognised. The incidences were calculated as 2.57 for UC, and 2.38 for CD. The total incidence of IBD between 2016 and 2018 was 4.96/100,000/year which is rise in the last 20 years. CONCLUSION: An increase in incidence of IBD in the district of Lower Silesia has been observed.

Immunogenicity of Pertussis Booster Vaccination in Children and Adolescents with Inflammatory Bowel Disease: A Controlled Study.

BACKGROUND: There are limited data on antibody response to vaccination in patients with inflammatory bowel disease (IBD). In this study, we aimed to assess the immunogenicity of a booster dose of pertussis vaccine in pediatric patients with IBD and to compare their response with healthy controls. METHODS: We performed a multicenter, prospective, and controlled trial. Eligible for inclusion were children and adolescents (11-18 year olds), with no history of pertussis booster immunization after the age of 6 years or history of pertussis. Study population was divided into 4 groups: patients with IBD receiving no immunosuppressive therapy (group 1), those on thiopurines only (group 2), those on thiopurines and TNF-α agents (group 3), and healthy controls (group 4). Patients and controls received 1 dose of pertussis vaccine intramuscularly and were asked to record adverse effects for 3 days after vaccination. The primary outcome measure was adequate vaccine response, defined as the concentration of anti-Bordetella pertussis antibodies >11 µg/mL, measured between 4 and 8 weeks after the vaccination. RESULTS: In total, 138 subjects (111 patients and 27 controls) were enrolled in the study. Rates of adequate vaccine response did not differ among the 4 study groups (P = 0.11). Moreover, those patients with IBD who were on immunosuppressive therapy did not differ from those who were not (90.6% versus 88.2%, P = 0.37). No serious adverse effects in relation to the administration of vaccine were noted. CONCLUSIONS: Booster dose of pertussis vaccine was immunogenic and safe in pediatric patients with IBD.

Assessment of Clinical Symptoms and Multichannel Intraluminal Impedance and pH Monitoring in Children After Thoracoscopic Repair of Esophageal Atresia and Distal Tracheoesophageal Fistula.

BACKGROUND: Motility disturbances of the esophagus and gastroesophageal reflux disease (GERD) are observed frequently in children after repair of congenital esophageal atresia with distal tracheoesophageal fistula (EA/TEF). Recently, in many pediatric surgical centers, thoracoscopic repair was introduced, which theoretically would change the postoperative course. OBJECTIVES: The goal of the study was to assess physical development, disease symptoms, and GERD symptom frequency in children who underwent thoracoscopic surgery of congenital EA/TEF. MATERIAL AND METHODS: The study comprised 22 children (14 boys and 8 girls), aged 16 to 79 months (average age 47.3 months) after surgery of EA/TEF. Clinical symptoms and physical development were analyzed. In 19 children, multichannel intraluminal esophageal impedance connected with pH-metry (MII/pH) was performed. In 11 patients, esophagogastroduodenoscopy with a histological study of mucosa samples was done. RESULTS: The most frequent symptoms were dysphagia, belching, cough and recurrent bronchitis. In 31.5% of the children, body mass deficiency was observed and in 28.6%, low body mass and short stature. Prematurity was present in half of the patients. Depending on the result of the MII/pH study, the children were divided into two groups: 10 children with GERD and 9 children without diagnosis of gastroesophageal reflux. In the 10 with GERD, acid reflux was diagnosed in 9 and non-acid reflux was diagnosed in one. MII/pH demonstrated statistically significant differences in the number of reflux episodes, reflux index, bolus exposure index, mean time of esophageal exposure and acid exposure and mean acid clearance time in children with GERD in comparison to children without this disease. In 36.4% of children who underwent endoscopy, esophagitis was diagnosed, esophageal stricture in 18% and gastric metaplasia in 9.1%. CONCLUSIONS: In children who underwent corrective thoracoscopic surgery of EA/TEF, GERD caused by motility disorders of the esophagus was frequently observed. These children require constant monitoring and early treatment of the complication.

[Neurologic appearence of Behçet disease in 14-year old boy treated with adalimumab with good result]. / Postac neurologiczna choroby Behçeta leczona adalimumabem z dobrym efektem u 14-letniego chlopca.

Behçet disease is a multiorgan inflammatory vessel disorder of unknown etiology which only occasionally occurs in children. Here, we demonstrate a 14-year-old boy with Behçet disease diagnosed based on recurrent aphthous stomatitis, acneiform facial lesions, subpreputial erosions and extensive thrombosis involving sigmoid sinus, transverse sinus and right internal cervical vein. Treatment with low molecular weight heparins, systemic corticosteroids, and azathioprine only resulted in partial remission of clinical symptoms. Addition of adalimumab led to complete resolution of clinical and biochemical abnormalities and disappearance of thrombosis in central nervous system.

Metalloproteinase-3 and -9 as novel markers in the evaluation of ulcerative colitis activity in children.

OBJECTIVES: The enhanced activity of matrix endopeptidases (MMPs) involved in the degradation of connective tissue has been noted in tissue samples from the digestive tract in inflammatory bowel disease (IBD), however sera concentrations of MMPs, a potential tool for diagnostic tests in IBD patients, have not been established so far. The goal of the studies was to evaluate the concentrations of MMP-3 and MMP-9, in the sera of children suffering from ulcerative colitis (UC) in relation to disease activity. MATERIAL AND METHODS: The study was comprised of 31 children with UC (aged 3-18 years) and 37 children in the control group (aged 1-18 years). Disease activity was estimated using the Truelove-Witts scale. MMP-3 and -9 concentrations were determined using ELISA tests. RESULTS: Median MMP-3 concentrations were 18.4 ng/mL (95% CI: 12.5-24.3) for moderate and severe, 4.35 ng/mL (95% CI: 2.5-7.8) for the mild form of UC and 1.8 ng/mL (95% CI: 1.2-2.5) for the control group. Median MMP-9 concentrations were 18.0 ng/mL (95% CI: 2.83-36.6) for moderate and severe, 1.55 ng/mL (95% CI: 0.4-3.0) for the mild form of UC and 1.3 ng/mL (95% CI: 0.7-1.96) for the control group. Serum MMP-3 and MMP-9 concentrations in the moderate group were higher than those in the mild and control groups (p < 0.001). MMP-3 concentrations in the mild group also differed from those in the control group (p < 0.001). Among the parameters studied (MMP-3, MMP-9, CRP and ESR), MMP-3 had the highest discriminative value (AUC = 0.9, p < 0.001, sensitivity = 71%, specificity = 92%) in distinguishing patients with UC from healthy individuals. CONCLUSIONS: Elevation of MMP-3 and MMP-9 concentrations along with the disease activity suggests the possibility of their application in the evaluation of the clinical activity of UC.

Correlation of MMP-3 and MMP-9 with Crohn's disease activity in children.

BACKGROUND: Recently published data indicate that the inflammation in Crohn's disease (CD) may be accompanied by elevated levels of matrix metalloproteinases. AIMS: The goals of the present study were the estimation of MMP-3 and -9 concentrations in sera of children with Crohn's disease, the examination of correlation between the concentrations of MMP-3 and -9 and clinical activity of the disease in the relation to the control group and the evaluation of the utility of MMP-3 and -9 concentration measurements as markers of disease activity. METHODS: Serum concentrations of MMP-3 and -9 were estimated in 82 children (45 CD patients divided into severe, moderate and mild subgroups; 37 controls) and correlated with disease activity estimated by the Pediatric Crohn's Disease Activity Index (PCDAI), CRP, seromucoid and ESR. RESULTS: Mean MMP-3 concentrations were: 2.49 ng/ml (95% CI: 1.76-3.52) for mild, 16.44 ng/ml (95% CI: 10.34-26.15) for moderate, 5.25 ng/ml (95% CI: 2.73-10.11) for severe CD and 1.95 ng/ml (95% CI: 1.53-2.48) for the control group (differences between all three groups were statistically significant; P < 0.001). Median MMP-9 concentrations were: 2.14 ng/ml (95% CI: 0-8.9) for mild, 14.21 ng/ml (95% CI: 4.53-21.48) for moderate, 42.2 ng/ml (95% CI: 5.74-61.27) for severe CD and 1.3 ng/ml (95% CI: 0.7-2.18) for the control group. MMP-9 concentrations in moderate and severe CD differed from the concentrations in mild CD (P = 0.002) and control group (P = 0.0001). MMP-3 concentration significantly correlated with MMP-9, PCDAI and ESR, while MMP-9 concentration significantly positively correlated with MMP-3, PCDAI, and CRP. Diagnostic utilities of the tests were: MMP-3 accuracy 75%, positive likelihood ratio (LR+) = 4.11 and negative likelihood ratio (LR-) = 0.51, sensitivity 56%, specificity 87%, Youden index 0.43; for MMP-9, accuracy 73%, LR+ = 5.14 and LR- = 0.50, sensitivity 56%, specificity 89%, Youden index 0.45; and for CRP, accuracy 74%, LR+ = 8.56 and LR- = 0.54, sensitivity 49%, specificity 94%, Youden index 0.43. CONCLUSIONS: MMP-9 serum concentration increasing along with the activity of the disease, exhibiting high specificity and correlating well with the indices of inflammation might be of better usefulness in the prediction of CD activity status in children than MMP-3.

[Role of the matrix metalloproteinases activity in inflammatory bowel disease]. / Rola aktywnosci metaloproteinaz w nieswoistych zapaleniach jelit.

Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes participating in the metabolism of connective tissue. Imbalance between synthesis and degradation of MMPs can lead to pathological enhancement of synthetic or destructive processes causing ulceration or tissue fibrosis. The results of recent studies have been suggesting that inflammatory bowel disease may be accompanied by elevated levels of MMPs.

[Distinct clinical characteristics of inflammatory bowel disease in children younger than 5 years]. / Odrebnosci kliniczne nieswoistych zapalen jelit u najmlodszych dzieci do lat 5.

UNLABELLED: In the last decades an increase in morbidity of inflammatory bowel disease, particularly of Crohn disease, in children has been observed. OBJECTIVE: Assessment of clinical course and activity of inflammatory bowel disease in children younger than 5 years was the goal of the study. MATERIAL AND METHODS: The study comprised 21 children aged 2 to 5 years (13 boys and 8 girls) who were diagnosed with: Lesniowski-Crohn disease (7 children), ulcerative colitis (7 children) and indeterminate colitis (remaining 7 children). RESULTS: Among studied children boys prevailed (61.9%). In 6 children the disease started in the first and second year of life; the average age of disease onset was 26.9 months and the time between the onset of the disease and the diagnosis was 16.6 months. 46% of patients came from the cities with population above 100000 when only 23% lived in the country. Autoimmune diseases were diagnosed in the families of 6 children, food or pollen allergy in the families of 11 children. Abdominal pain, diarrhea, presence of blood and mucous in the stool, fever and lack of thrive were most apparent in the clinical picture. The pathological changes were present mainly in the large intestine and only in one case in the upper part of the alimentary tract and jejunum. The observed course of the disease was severe or moderate. In two children aged 3 years colectomy was performed. CONCLUSIONS: In children younger than 5 years severe and moderate course of the Lesniowski-Crohn disease and ulcerative colitis is apparent. Fever, abdominal pain, diarrhea, presence of blood and mucous in the stool and lack of appetite were the most often seen symptoms. Pathological changes in children younger than 5 years were present mainly in the large intestine and only in single cases in the upper part of the alimentary tract and jejunum. In children with inflammatory bowel disease a frequent occurrence of allergy, bronchitis, pneumonia and urinary tract infection, which required antibiotics, was observed.