Takayasu arteritis in an adolescent with Crohn's disease.

Crohn's disease (CD) and Takayasu arteritis (TA) are two distinct clinical entities. Τhe likelihood of both diseases coexisting is low, and although CD co-occurs with all types of vasculitis, TA is the most common subtype. Herein, the case of a 15-year-old female, diagnosed with TA following an initial diagnosis of CD, is reported. A review of the literature, including a systemic review of the case reports and case series of children and adolescents up to the age of 21, with both CD and TA, follows the case description. In total, 28 cases of TA and CD were retrieved. The median age of patients was 14.8 years, they were mostly females (72%) and the median time between the two diagnoses was 3.7 years. In the majority of cases, CD was diagnosed first and TA followed. Computed tomography angiography and magnetic resonance angiography were the preferred imaging modalities to assist diagnosis.

Inflammatory fibroid polyp of the anus in a 12-month-old girl: Case report and review of the literature.

Inflammatory fibroid polyp (IFP) is a rare, usually solitary and intraluminal polypoid benign tumour that can affect any part of the gastrointestinal (GI) tract. Its aetiology is unknown and clinical presentation depends on the site of involvement. We present the case of a 12-month-old girl with IFP and review all reported cases of IFP in children and adolescents <18 years. A 12-month-old girl presented with rectal bleeding. The patient underwent colonoscopy which revealed an anus polyp. Surgical resection was performed and histopathological examination of the specimen showed features of IFP. A literature review of 20 cases (including ours) between 1966 and January 2022 is also presented. To our knowledge, this is the youngest reported patient with IFP and the first in the anal area.

Seroprevalence of Hepatitis C in Children Without Identifiable Risk-Factors: A Systematic Review and Meta-Analysis.

OBJECTIVES: Hepatitis C virus (HCV) remains a major public health burden for >30 years since its discovery. It is estimated that >80 million people have been already infected. Direct-acting antiviral (DAA) treatment is now approved for young children over the age of 3 years. Treating children before the development of high-risk behaviors is optimal. Thus, assessing the current epidemiology of HCV in children becomes important and may promote awareness. METHODS: Articles describing the prevalence of hepatitis C in children, were systematically reviewed. To assess HCV infection prevalence in the general population, studies discussing high-risk groups alone were excluded. RESULTS: Data from 58 studies were analyzed. National data was scarce. An overall prevalence of HCV in children of 0.87% was found, ranging from 0.34% in Europe to 3.02% in Africa. Prevalence of viremic infection is important and data synthesis from available data indicated that HCV viremia was detected in 56.8% of children. The prevalence of HCV according to sex was described in 25 studies but no difference between sexes was detected. HCV prevalence was significantly higher in children older than 10 years (0.97%) when compared to those ages under 10 years old (0.75%, P < 0.001). CONCLUSIONS: Considering probable underdiagnosis of HCV infection in children, this information reveals that prevalence is substantial. One may argue that future strategies aiming towards HCV elimination, may need to include antiviral treatment of pre-adolescent children as well.

Mutations in Myosin 5B in Children With Early-onset Cholestasis.

OBJECTIVES: Mutations in Myosin 5B (MYO5B) are known to be associated with microvillous inclusion disease (MVID) a genetic cause of neonatal intractable diarrhoea. More recently, they have been reported in children with cholestasis but without typical gastrointestinal symptoms of MVID. We describe our series of children with cholestasis and mutations in MYO5B. METHODS: Clinical, laboratory, and histological data were collected from patients with cholestasis and pathogenic mutations in MYO5B, found by next generation sequencing (NGS) but with minimal gastrointestinal disease. RESULTS: Six patients (3 boys) were identified. Median age at presentation was 19 months (range, 3-92). Presenting features were jaundice, pale stools, pruritus, and failure to thrive. Patients 5 and 6 had intractable diarrhoea until the age of 3 and 7 years, respectively, but currently are on full enteral diet with no intestinal symptoms. Median values for serum total bilirubin were 55 µmol/L (2-500), alanine aminotransferase 73I IU/L (32-114), γ-glutamyltransferase 7 IU/L (7-10), and serum bile acids 134 µmol/L (18-274). Three patients underwent 1 or more types of biliary diversion for symptom control. Median follow-up was 5 years (2-22). At most recent follow-up, they all reported pruritus while on antipruritics. Patient 1 had a liver transplant. CONCLUSIONS: We identified 6 patients, with mutations in MYO5B, early-onset cholestasis and pruritus, with variable response to biliary diversion without typical MVID.

Non-Nutritive Sweeteners and Metabolic Health Outcomes in Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically assess and quantitatively synthesize the literature regarding the association of consumption of non-nutritive sweeteners (NNS) during childhood with negative metabolic health outcomes. STUDY DESIGN: Following the PRISMA guidelines, published literature was systematically reviewed. Eligible studies (N = 13) were identified through the screening of over 2500 publications. Random-effects meta-analyses were conducted on the association of NNS consumption with body mass index (BMI) increase. Sensitivity and subgroup analyses by sex were also undertaken. RESULTS: Consumption of NNS during childhood and adolescence was associated with an increase in BMI (OR 1.15, 95% CI 1.06-1.25); the OR was similar in sensitivity analyses. The associations were positive but marginally significant in subanalyses by sex. The qualitative assessment of existing literature showed nonsignificant associations with other components of metabolic disease, such as waist circumference, fat mass accumulation, and type 2 diabetes. CONCLUSIONS: Systematic assessment of observational studies showed no association of NNS intake during childhood with fat mass accumulation and waist circumference and a small, but statistically significant association with BMI increase. Inherent methodological weaknesses of to-date published investigations, including mainly underpowered size to explore the hypothesis, call for more research.

Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases.

BACKGROUND: Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin). OBJECTIVE: We sought to characterize the genetic cause and clinical spectrum of Hz/Hc. METHODS: Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA. RESULTS: Thirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p.E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 ± 1300 µg/mL) compared with those with PAPA syndrome (116 ± 74 µg/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1. CONCLUSION: Mutations resulting in charge reversal in the y-domain of PSTPIP1 (E→K) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family.

Chronic Nonbacterial Osteomyelitis in Inflammatory Bowel Disease.

Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn's disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use and suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves a genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes.

Ileal bypass for pruritus relief in a 3-year-old boy with advanced progressive familial intrahepatic cholestasis: how effective is it?

Progressive familial intrahepatic cholestasis (PFIC) is a group of liver disorders that manifest in early childhood with cholestasis and pruritus resulting progressively in liver failure. We present a case of a 3-year-old boy with advanced PFIC from refractory pruritus. In order to offer an effective treatment of pruritus, our patient underwent ileal bypass and after a 2-month period free of symptoms, unexpectedly relapsed after a Rota viral infection. Finally, the child underwent orthotopic liver transplantation. Patients with advanced PFIC do not seem to benefit from nontransplant invasive interventions regarding the relief of pruritus.

Identifying Microbiome Dynamics in Pediatric IBD: More than a Family Matter.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects both children and adolescents. Symptoms can significantly affect a child's growth, development, and quality of life, making early diagnosis and effective management crucial. This study focuses on treatment-naïve pediatric IBD patients and their immediate families to identify the role of the microbiome in disease onset. METHODS: Nine families with pediatric IBD were recruited, comprising seven drug-naïve Crohn's disease (CD) patients and two drug-naïve ulcerative colitis (UC) patients, as well as twenty-four healthy siblings/parents. Fecal samples were collected for 16S ribosomal RNA gene sequencing and bioinformatics analysis. RESULTS: We identified patterns of dysbiosis and hallmark microbial taxa among patients who shared ethnic, habitual, and dietary traits with themselves and their families. In addition, we examined the impact of the disease on specific microbial taxa and how these could serve as potential biomarkers for early detection. CONCLUSIONS: Our results suggest a potential role of maternal factors in the establishment and modulation of the early life microbiome, consistent with the current literature, which may have implications for understanding the etiology and progression of IBD.

Measuring Children's Stress via Saliva in Surgical and Endoscopic Procedures and Its Measurement Intention in the Community: Reality-Future Prospects.

(1) Background: Children who undergo surgical or endoscopic procedures display high levels of stress, and various means are applied to reduce their anxiety. Salivary cortisol (S Cortisol) and salivary alpha-amylase (SAA) are often used as a valid biomarker of stress. The primary purpose of the study was the investigation of stress levels through S Cortisol and S amylase after intervention in surgical or endoscopic procedures (gastroscopy-colonoscopy). The secondary outcomes were the investigation of the intention to adopt new methods of saliva sampling. We collected saliva samples from children subjected to invasive medical procedures, with the aim of applying the Theory of Planned Behavior (TPB) as an intervention means to provide information and education to both parents and children undergoing stressful situations, and assess its efficacy in reducing stress levels. We also aimed at acquiring a better understanding of the acceptability of noninvasive biomarker collection in community settings. (2) Methods: The sample of this prospective study comprised 81 children who underwent surgical or endoscopic procedures at the Attikon General University Hospital, Athens, Greece and 90 parents. The sample was divided into two groups. The first, 'Group Unexplained', was not provided any information or education about the procedures, while the second, 'Group Explained', was informed and educated based on TPB. Thereafter, 8-10 weeks after intervention, the Theory of Planned Behavior questions were re-completed by the 'Group Explained'. (3) Results: Significant differences were detected in cortisol and amylase values between the two groups postoperatively after applying the TPB intervention. Saliva cortisol was reduced by 8.09 ng/mL in the 'Group Explained' while in the 'Group Unexplained' it was reduced by 4.45 ng/mL (p < 0.001). Salivary amylase values decreased by 9.69 ng/mL in the 'Group Explained' after the intervention phase of the study, while in the 'Group Unexplained' they increased by 35.04 ng/mL (p < 0.001). The regression explains 40.3% (baseline) and 28.5% (follow-up) of parental intention. The predictive factor of parental intention (baseline) is attitude (p < 0.001) and follow-up is behavioral control (p < 0.028) and attitude (p < 0.001). (4) Conclusions: Providing proper education and information for parents has a positive effect on reducing children's stress levels. Changing parental attitudes towards saliva collection plays the most important role, since a positive attitude can influence intention and ultimately participation in these procedures.

Benign anorectal disease in children: What do we know?

Benign anorectal disease refers to a diverse group of frequent anorectal complaints that cause considerable discomfort, disability, and often constitute a significant problem for the child and his or her family. Hemorrhoids, fissures, rectal prolapse, and perianal abscess and fistulas are the most common anorectal disorders in pediatric population and their appearance may be age-specific. Although they generally follow a benign course, a careful examination must be performed in order to exclude other serious and complicated underlying pathology. Their diagnosis is based on the patient's medical history, physical examination, endoscopy, and imaging. Moreover, the management of these disorders includes medical and surgical treatment options, and if they are treated promptly and properly may be limited and short lived. This review presents the currently available data in the literature on the diverse aspects of these disorders, including the definition, epidemiology, clinical presentation, pathogenesis, diagnosis, indications for surgery, and long-term outcomes.

Is Hepatobiliary Scintigraphy Sufficient to Diagnose Rotor Syndrome in a 3-Year-Old Boy?

Rotor syndrome (RS) is a benign, inherited, commonly misdiagnosed cause of conjugated hyperbilirubinemia whose identification prevents unnecessary invasive investigations. We present the case of a 3-y-old boy with phenotypic and laboratory findings of RS but negative genetic test results, whose diagnosis was confirmed by hepatobiliary scintigraphy.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

Disease impact on the quality of life of children with inflammatory bowel disease.

AIM: To assess the impact of disease characteristics on the quality of life (QOL) in children with inflammatory bowel diseases (IBD). METHODS: This was a cross-sectional study conducted at the First Department of Pediatrics of the University of Athens at the "Aghia Sophia" Children's Hospital. Children diagnosed with Crohn's disease (CD) or ulcerative colitis (UC), who were followed as outpatients or during a hospitalization, participated, after informed consent was obtained from their legal representative. QOL was assessed by the IMPACT-III questionnaire. Demographic data and disease characteristics were also collected. Statistical analyses included parametric (Student's t-test and Pearson's r) and non-parametric (Mann-Whitney test, Fisher's test and Spearman's rho) procedures. RESULTS: Ninety-nine patients (UC: 37, 73.0% females, CD: 62, 51.6% females), aged 12.8 ± 2.6 years were included. Overall, as well as, sub-domain scores did not differ between UC and CD (overall score: 73.9 ± 13.3 vs 77.5 ± 11.2, respectively, P = 0.16). In the entire sample, total score was related to physician's global assessment (PGA, patients classified as "mild/moderate" active disease had, on average, 14.8 ± 2.7 points lower total scores compared to those "in remission", P < 0.001) and age at IMPACT completion (Pearson's r = 0.29, P = 0.05). Disease activity assessed by the indices Pediatric Ulcerative Colitis activity index, Pediatric Crohn's disease activity index or PGA was significantly associated with all subdomains scores. Presence of extraintestinal manifestations had a negative impact on emotional and social functioning domains. CONCLUSION: Disease activity is the main correlate of QOL in children with IBD, underlining the importance of achieving and sustaining clinical remission.