Gastrointestinal Comorbidities Associated with Atopic Dermatitis-A Narrative Review.

The current understanding of atopic dermatitis (AD) seems to be extending beyond a skin-confined condition frequently associated with allergic comorbidities, as in a number of epidemiological studies, the prevalence rate of a range of illnesses has been determined to be greater in patients with AD, or inversely. In most cases, the reasons for this are vague. A subset of these conditions are gastrointestinal disorders, including food sensitization (FS) and food allergy (FA), eosinophilic esophagitis (EoE) (it is of mixed background, both IgE-dependent and independent), food protein-induced enterocolitis syndrome (FPIES) (it exemplifies an IgE-independent food allergy), Crohn's disease (CD), colitis ulcerosa (CU), celiac disease, irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD). In this review, we performed a comprehensive search of the literature using the PubMed database. We addressed the epidemiology of the increased co-occurrence of these diseases with AD and discussed potential causes for this subject. Multiple gastroenterological comorbidities appear to be more common in patients with AD, according to our review. The mechanisms that underlie this phenomenon are largely unknown, highlighting the need for further study in this field.

Mediator-Related Symptoms and Anaphylaxis in Children with Mastocytosis.

Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier's sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.

Molecular Background, Clinical Features and Management of Pediatric Mastocytosis: Status 2021.

Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline mutations in the KIT proto-oncogene are detected in most patients. Cutaneous mastocytosis is the most common form of the disease in children. In the majority of cases, skin lesions regress spontaneously around puberty. However, in few patients, mastocytosis is not a self-limiting disease, but persists into adulthood and can show signs of systemic involvement, especially when skin lesions are small-sized and monomorphic. Children with mastocytosis often suffer from mast cell mediator-related symptoms. Severe hypersensitivity reactions can also occur, mostly in patients with extensive skin lesions and blistering. In a substantial number of these cases, the triggering factor of anaphylaxis remains unidentified. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers, treatment with H1 and H2 histamine receptor blockers, and equipment of patients and their families with epinephrine auto-injectors for use in severe anaphylactic reactions. Advanced systemic mastocytosis occurs occasionally. All children with mastocytosis require follow-up examinations. A bone marrow investigation is performed when advanced systemic mastocytosis is suspected and has an impact on therapy or when cutaneous disease persists into adulthood.

Before-and-after online community survey on knowledge and perception of COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic impacts many communities worldwide. In this study the Poles' knowledge about COVID-19 as well as people's behaviours, attitudes and fears during the pandemic were assessed. Changes in these between the outset of the pandemic and the imposition of the strictest lockdown measures in Poland were investigated. METHODS: Physicians, nurses, students of medicine-oriented faculties, non-medical professionals, students of non-medicine-oriented faculties and secondary school students were surveyed by an anonymous online questionnaire two times: at the onset of the pandemic and in the second week of the strictest lockdown. Statistical analyses were performed using non-parametric tests - Pearson Chi Square, Kruskal-Wallis tests. RESULTS: In total 2618 responses were collected. At the beginning people knew that the respiratory system was attacked (97.9%); correctly identified the major symptoms of COVID-19 (95.0%) and ways to prevent infection: hand washing (99.8%), covering mouth (85.9%) and the need to call sanitary-epidemiological services if one experienced COVID-19-like symptoms (92.1%). The biggest changes between the first and second phase of the study concerned behaviours: more people wearing facial masks (+ 37.5%) and staying at home (+ 66.1%). Respondents in the second wave of the survey were also more scared of the pandemic (+ 19.6%), economic crisis (+ 64.1%), and worried about their families (+ 26.5%). However, they were less afraid of the quarantine (lockdown) (- 18.2%). Nurses and physicians were the most worried groups. CONCLUSIONS: The study showed that even at the outset of the pandemic Polish population had a good initial knowledge about symptoms, transmission, and preventive behaviours regarding COVID-19. People revealed more short-term concerns, such as the worries about coping with quarantine and isolation. After a month, the knowledge and the concerns among the respondents changed. A shift towards long-term pandemic management issues was observed. Respondents reported to experience more fears concerning the pandemic in general, as well as economic and healthcare crises. Medical professionals reported higher level of fear of the pandemic than other groups included in this study. This study uses before-and-after approach which highlights the changes in people's knowledge and perception of the COVID-19 pandemic during the pandemic's progression.

New Approach to Paediatric Mastocytosis: Implications of KIT D816V Mutation Detection in Peripheral Blood.

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Peripheral and Intestinal T-regulatory Cells are Upregulated in Children with Inflammatory Bowel Disease at Onset of Disease.

BACKGROUND/AIMS: To determine the proportion of T-regulatory cells (CD4+CD25highFOXP3+ cells) in peripheral blood and the number of FOXP3+ cells in intestinal mucosa of children with inflammatory bowel disease (IBD), and to verify whether these parameters correlate with the activity of the disease. MATERIAL AND METHODS: 24 patients newly diagnosed for IBD were included in the study: ulcerative colitis (UC; n = 13) and Crohn's disease (CD; n = 11). Seventeen healthy controls (HC) and 16 patients with irritable bowel syndrome (IBS) served as a control group for peripheral and intestinal Tregs assessment, respectively. The disease activity was assessed by Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn's Disease Activity Index (PCDAI). Quantification of regulatory T cells of CD4+CD25highFOXP3+ phenotype in peripheral blood was based on three-color flow cytometry. Mucosal Tregs represented by FOXP3+ cells were evaluated using immunohistochemistry. RESULTS: Median proportion of CD4+CD25highFOXP3+ cells among CD4+ T cells in peripheral blood (5.1%, range 1.7-84% vs. 4.3%, range 2-8.1%, p = 0.023) and median number of intestinal FOXP3+ cells (115.33 per high-power field, hpf, range 39.33-375.67 vs. 10.16 per hpf, range 5-30, p = 0.0001) were significantly higher in children with IBD than in the controls. The proportion of circulating Tregs and the number of intestinal FOXP3+ cells did not correlate with clinical activity of the disease, as well as with endoscopic and histopathologic scoring. No significant correlation was found between the percentage of peripheral CD4+CD25highFOXP3+ cells and the number of intestinal FOXP3+cells. CONCLUSIONS: Children with IBD likely do not present with a quantitative deficiency of circulating and intestinal Tregs at the moment of diagnosis.

Diagnosis of Mastocytosis in Children and Adults in Daily Clinical Practice.

Mastocytosis comprises a heterogeneous group of disorders characterized by clonal, neoplastic proliferation of mast cells accumulating in one or multiple organs. In the majority of cases skin involvement is the first clinical manifestation of the disease. Clinical work-up consists of a combination of morphological, immunohistochemical, flow cytometric immunophenotyping and molecular examination. Cutaneous mastocytosis predominates in children, whereas systemic mastocytosis is the most common form of the disease in adults. Therefore, different diagnostic algorithms have to be applied in adult patients and children with suspected mastocytosis. This comprehensive review presents currently defined variants of the disease and recommendations to facilitate diagnostic work-up in children and adults with suspected mastocytosis in daily clinical practice.

The Assessment of Comprehensive Care for Autistic Children Provided by Polish Primary Healthcare Physicians in Parental View.

Objectives. Important factor in caring for ASD patients is the successful cooperation between the physician and the parent. Methods. The online survey has been conducted. For statistical analysis the t-student test and the U-Mann Whitney test were performed to compare 2 variables, then the Kruskal-Wallis test or ANOVA as well as The Pearson correlation and Sperman's rank correlation were performed. Results. 80.5% of respondent's PHPs did not notice the child's developmental difficulties. 22.02% of respondents can speak to their PHP about a child's difficulties. PHPs take different strategies to make patient contact with the healthcare system easier. We discovered statistically significant differences in the assessment of PHPs' abilities depending on the physicians' specialty, the children's age, the age at ASD diagnosis. Conclusion. The care for autistic patients provided by Polish PHPs is insufficient and the topic needs to be addressed immediately.

Can Lactose Intolerance Be a Cause of Constipation? A Narrative Review.

Lactose intolerance and constipation are common in children and impact everyday life, not only for patients but also their families. Both conditions can be comorbid with other diseases or form a part of their clinical presentation, but constipation is not usually associated with lactose intolerance. The typical symptoms of lactose intolerance include abdominal pain, bloating, flatus, diarrhoea, borborygmi, and less frequently nausea and vomiting. In approximately 30% of cases, constipation can be a symptom of lactose intolerance. Constipation is characterized by infrequent bowel movements, hard and/or large stools, painful defecation, and faecal incontinence, and is often accompanied by abdominal pain. This paper provides a narrative review on lactose intolerance, its epidemiology, pathogenesis, the correlation between lactose intolerance and constipation in children, and potential mechanisms of such association.

Changes in Air Pollution-Related Behaviour Measured by Google Trends Search Volume Index in Response to Reported Air Quality in Poland.

Decreased air quality is connected to an increase in daily mortality rates. Thus, people's behavioural response to sometimes elevated air pollution levels is vital. We aimed to analyse spatial and seasonal changes in air pollution-related information-seeking behaviour in response to nationwide reported air quality in Poland. Google Trends Search Volume Index data was used to investigate Poles' interest in air pollution-related keywords. PM10 and PM2.5 concentrations measured across Poland between 2016 and 2019 as well as locations of monitoring stations were collected from the Chief Inspectorate of Environmental Protection databases. Pearson Product-Moment Correlation Coefficients were used to measure the strength of spatial and seasonal relationships between reported air pollution levels and the popularity of search queries. The highest PM10 and PM2.5 concentrations were observed in southern voivodeships and during the winter season. Similar trends were observed for Poles' interest in air pollution-related keywords. Greater interest in air quality data in Poland strongly correlates with both higher regional and higher seasonal air pollution levels. It appears that Poles are socially aware of this issue and that their intensification of the information-seeking behaviour seems to indicate a relevant ad hoc response to variable threat severity levels.

Histamine Intolerance in Children: A Narrative Review.

Histamine intolerance is defined as a disequilibrium of accumulated histamine and the capacity for histamine degradation. This clinical term addresses a non-immunologically mediated pathology when histamine ingested with food is not particularly high, however its degradation is decreased. This paper aims to provide a narrative review on etiopathology, epidemiology, possible diagnostic algorithms and diagnostic challenges of histamine intolerance in children. The clinical picture of histamine intolerance in children is similar to that observed in adults apart from male predominance found in paediatric patients. Both in children and adults, a histamine-reduced diet is typically the treatment of choice. Diamine oxidase supplementation offers another treatment option. There is no symptom or test pathognomonic for histamine intolerance. Nevertheless, manifestations of chronic gastrointestinal symptoms, measurements of diamine oxidase deficits, positive results of histamine provocation tests and improvement in symptoms with histamine-reduced diet considerably increase the probability of histamine intolerance diagnosis. These factors have been included in the proposed diagnostic algorithm for histamine intolerance. In children histamine intolerance most likely co-occurs with allergies and bowel diseases, which creates an additional diagnostic challenge. As the evidence for children is poor further research is needed the determine epidemiology, validate diagnostic algorithms and establish possible treatment options regarding histamine intolerance.

Does Informal Education Training Increase Awareness of Anaphylaxis among Students of Medicine? Before-After Survey Study.

Allergies are among the most common chronic diseases in Europe. The most serious complication is anaphylactic shock. Most cases occur outside the hospital; thus, knowledge of symptoms and first aid is crucial. This study aimed to evaluate the awareness of anaphylaxis and the ability to use adrenaline auto-injectors among medical students, and to determine an improvement after training based on non-formal education. The research was conducted among 364 medicine students (years 1-5) from the Medical University of Gdansk, with year-specific curriculum-based general medical knowledge. Training consisted of pre-test, practical training and post-test. Descriptive statistics were used to reveal the characteristics of students from different grades. A Mann-Whitney U test was used for statistical analysis. The tested students did not have sufficient knowledge to provide first aid in cases of anaphylaxis before training. There was an increase in knowledge (on average, 28.6%, p = 0.005) after training. Almost all (99.4%) of the respondents believed that they would be able to use an adrenaline auto-injector in case of emergency after the training. The training based on non-formal education was effective. The use of the subject-performed task method helped students to remember the stages of action in stressful situations.

[Blood culture analysis in children with central venous catheter]. / Analiza wyników posiewów krwi u dzieci z zalozonym cewnikiem centralnym.

We analyzed 99 blood cultures taken from 28 children with central venous catheter. Children were hospitalized in pediatric, pediatric surgery and pediatric intensive care department. All samples were collected from peripherial vein. Positive blood cultures were obtained more frequently from children with central venous catheter than from children without central venous catheter (57.5% vs. 7.4%). Staphylococcus epidermidis was the most frequently obtained bacteria. The other bacterial species were obtained less frequently. The highest percentage of multi resistant straines was isolated from blood samples collected from intensive care department patients. In each departments in which coagulase-negative Staphylococci were isolated, metycillin-resistant straines dominated.

Peripheral regulatory T cells and anti-inflammatory cytokines in children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a chronic, heterogenous inflammatory disease of unclear pathogenesis. JIA is hypothesized to be linked to a defective immune regulation. Anti-inflammatory cytokines belong to the best known regulatory factors. T-regulatory cells are a crucial cellular component of immune tolerance. One of their functions is synthesis of interleukin 10 (IL-10) and transforming growth factor beta1 (TGF-ß1). The aim of this study was to determine the proportion of T-regulatory cells (CD4+CD25highFOXP3+) in peripheral blood, and serum levels of TGF-ß1 and IL-10 in patients with JIA. METHODS: The study included 25 patients with newly diagnosed JIA: oligoarthritis (n=17) and polyarthritis (n=8). The control group was comprised of 17 healthy children. CD4+CD25highFOXP3+ T cells in peripheral blood were quantified by means of three-color flow cytometry. Serum concentrations of TGF-ß1 and IL-10 were estimated with ELISA. RESULTS: The proportion of peripheral CD4+CD25highFOXP3+ cells in patients with JIA was significantly higher than in the controls (p=0.04). The two groups did not differ significantly in terms of their TGF-ß1 and IL-10 concentrations. CONCLUSIONS: At the time of diagnosis, children with JIA presented with an elevated proportion of T-regulatory cells (CD4+CD25highFOXP3+) in peripheral blood. Anti-inflammatory cytokines, IL-10 and TGF-ß1, are not upregulated in the serum of patients with JIA, and therefore should not be considered as biomarkers of this condition.

Immune response against HtrA proteases in children with cutaneous mastocytosis.

Mast cells play an important role in both, the innate and adaptive immunity, however, clonal proliferation of abnormal mast cells in various organs leads to mastocytosis. A skin variant of the disease, cutaneous mastocytosis (CM) is the most frequent form of mastocytosis in children. HtrA proteases are modulators of important cellular processes, including cell signaling and apoptosis, and are related to development of several pathologies. The above and the observation that mast cells constitutively release the HtrA1 protein, prompted us to investigate a possible involvement of the HtrA proteins in pediatric CM. Levels of the serum autoantibodies (IgG) against the recombinant HtrA proteins (HtrA1-4) in children with CM (n=36) and in healthy controls (n=62) were assayed. Anti-HtrA IgGs were detected using enzyme linked immunosorbent assay (ELISA) and Western-blotting. In the CM sera, levels of the anti-HtrA1 and anti-HtrA3 autoantibodies were significantly increased when compared to the control group, while the HtrA protein levels were comparable. No significant differences in the anti-HtrA2 IgG level were found; for the anti-HtrA4 IgGs lower levels in CM group were revealed. In healthy children, the IgG levels against the HtrA1, -3 and -4 increased significantly with the age of children; no significant changes were observed for the anti-HtrA2 IgG. Our results suggest involvement of the HtrA1 and HtrA3 proteins in pediatric CM; involvement of the HtrA4 protein is possible but needs to be investigated further. In healthy children, the autoantibody levels against HtrA1, -3 and -4, but not against HtrA2, increase with age.

Association between uridin diphosphate glucuronosylotransferase 1A1 (UGT1A1) gene polymorphism and neonatal hyperbilirubinemia.

OBJECTIVE: To assess the prevalence of UGT1A1*28 and UGT1A1*60 polymorphisms of UGT1A1 gene and their association with hyperbilirubinemia. STUDY DESIGN: The study was performed at a single centre - at the Department of Obstetrics of the Medical University of Gdansk in Poland. DNA was isolated from Guthrie cards of 171 infants. Only full term newborns (gestational age 38-42 weeks) were included in the study. Fluorescent molecular probes were used for UGT1A1 promoter variation analysis. The presence of UGT1A1*28 polymorphism was detected with a dual-probe system, and UGT1A1*60 with a SimpleProbe™. RESULT: Homozygous UGT1A1*28 and UGT1A1*60 genotypes were detected in 14.6% and 20.5% of the newborns, respectively. Homozygous (G/G) genotypes of UGT1A1*60 polymorphism were found in all of the UGT1A1*28 (i.e. (TA)7/(TA)7) homozygotes. More than 80% (55/66) of the children with "wild" type UGT1A1*28 genotype (where no polymorphism was detected) (i.e. (TA)6/(TA)6) carried the "wild" (T/T) genotype of UGT1A1*60 as well. The UGT1A1*28 polymorphism was detected more often among neonates with elevated bilirubin. Hyperbilirubinemia was diagnosed more frequently in boys. CONCLUSION: Polymorphisms of the UGT1A1 gene frequently co-exist in neonates. The presence of UGT1A1*28 polymorphism and male gender seem to predispose to neonatal hyperbilirubinemia.

[Prevalence of ESBL strains in urinary tract infections in children in 1996 and 2004]. / Wystepowanie szczepów ESBL w zakazeniach ukladu moczowego u dzieci w latach 1996 i 2004.

Ethiological agents in urinary tract infections and prevalence of bacterial strains producing extended spectrum of beta-lactamases isolated from urine of children with urinary tract infections were compared. Patients were hospitalized in Department of Pediatry, Pediatric Gastroenterology and Oncology of Medical University of Gdansk in 1996 and 2004. Seventy bacterial strains isolated from urine in 1996 and 113 strains isolated in 2004 were analyzed. In both years Enterobacteriaceae were the most frequently encountered with Escherichia coli predominance. Proteus spp. (10.9%), Enterobacter spp. (7.1%), Klebsiella spp. (4.4%), and Enterococcus spp. (9.3%) were isolated rarely. Among bacteria isolated in 1996 there were no ESBL strains while in 2004 ESBL strains accounted for 11.5% of all urinary bacteria. Klebsiella oxytoca (25%) and Klebsiella pneumaniae (20%) produced ESBL most frequently. ESBL production was less frequent in Escherichia coli (13.2%) and Proteus mirablilis (10%). In conclusion, among bacteria isolated from urine of children with urinary tract infections G(-) strains producing ESBL were encountered only in recent years.

Coexistence of type 1 diabetes mellitus and spinal muscular atrophy in an 8-year-old girl: a case report.

The spinal muscular atrophy is a rare autosomal recessive genetic disease characterized by the progressive loss of muscular strength. In its natural course the disease leads to death. Diabetes mellitus type 1 is an autoimmune metabolic disorder characterized by the disturbed insulin synthesis. This is a case report of an 8-year-old girl suffering from Werdnig Hoffman disease in whom DM1 was diagnosed. The unspecific clinical manifestation and diagnostic difficulties are presented in this paper. To the authors' knowledge, this is the first publication concerning the co-existence of these two medical conditions.

Evaluation of clinical usefulness of serum neopterin determination in children with bacterial infections.

UNLABELLED: Neopterin (NPT) (6-D-erythro-trihydroxypropyl pteridin) is one of the indicators of the immune system activity. Elevated neopterin concentration occurs in diseases mostly involving stimulation of cellular immunity. The determination of neopterin concentration, usually in blood serum and urine but also in many other bodily fluids, has already been applied in many areas of medicine, such as transfusiology, transplantology, oncology, infectious diseases and autoimmunological diseases. OBJECTIVE: The aim of this work is to evaluate clinical usefulness of serum neopterin determination in children with urinary tract infections of confirmed bacterial etiology. MATERIAL: The study involved 56 children with bacterial urinary tract infections - patients of the Clinic of Paediatrics, Paediatric Gastroenterology, Hepatology & Paediatric Nutrition of Medical University of Gdansk in the years 2012-2013. The control group included 105 healthy children. RESULTS: The values of NPT concentration in blood serum obtained in the group of children with urinary tract infections did not significantly differ from the values obtained in the control group. CONCLUSIONS: The determination of neopterin concentration in children with bacterial urinary tract infections is not a clinically useful parameter.

Fecal lactoferrin, a marker of intestinal inflammation in children with inflammatory bowel disease.

The aim of this study was to analyze the usefulness of fecal lactoferrin in the diagnosis and monitoring of inflammatory bowel disease (IBD) in children. The study included 52 children with IBD (24 with Crohn's disease and 28 with ulcerative colitis) aged between 0.92 and 18 years, and 41 IBD-free controls of similar age. Fecal concentration of lactoferrin was determined with a quantitative immunoenzymatic test. Fecal concentration of lactoferrin in children with IBD was significantly higher than in the controls. The cut-off value of fecal lactoferrin concentration optimally distinguishing between the children with IBD and the controls was identified as 13 µg/g. The sensitivity and specificity of this cut-off value equaled 80.7% and 92.7%, respectively, and its positive and negative prognostic values were 96.8% and 63.3%, respectively. Patients diagnosed with moderate Crohn's disease had significantly higher fecal concentrations of lactoferrin than children with the mild or inactive disease. Similarly, children with moderate ulcerative colitis showed significantly higher fecal concentrations of lactoferrin than individuals with the mild condition. No significant relationship was found between the fecal concentration of lactoferrin and the severity of endoscopic lesions. Patients with IBD and a positive result of fecal occult blood test were characterized by significantly higher concentrations of lactoferrin than the individuals with IBD and a negative result of this test. In conclusion, fecal concentration of lactoferrin seems to be a useful parameter for diagnosis and monitoring of IBD in children.