Marina Dalgatovna Shakhnazarova

Hereditary angioedema with normal C1 inhibitor (HAE-nC1INH) lacks validated biochemical biomarkers, complicating diagnosis and interpretation of rare genetic variants, particularly in children. To improve molecular characterization of pediatric HAE-nC1INH, we studied 23 children with recurrent non-histaminergic angioedema, normal C4 and C1 inhibitor levels, and no pathogenic SERPING1 variants. All 23 patients underwent whole-exome sequencing, followed by integrated in silico assessment of candidate variants. A rare heterozygous MYOF p.Arg1590Gln variant was identified in one patient and classified as a VUS, with computational analyses suggesting potential functional relevance. Homozygous F12 p.Ala207Pro was identified in two unrelated patients; however, its high population frequency and benign ClinVar classification do not support a causative role. Four HS3ST6 missense variants were detected in five patients; p.Pro199Leu showed the strongest computational evidence of potential functional relevance, whereas the clinical significance of the remaining variants remains uncertain. These findings expand the molecular spectrum of pediatric HAE-nC1INH and support combining sequencing with prioritization of variants in relevant genes. Functional studies are required to confirm causality before clinical implementation.

Background. Inflammatory bowel disease (IBD) and allergic diseases (ADs) share some pathogenetic mechanisms. The intersection of IBD and ADs is increasingly discussed within the scientific community. However, pediatric data on the relationship between IBD and allergy remain limited, particularly in the Russian literature, warranting this study. Aim. To determine the prevalence and characteristics of allergic disorders in children diagnosed with IBD, and to compare these findings with a control group of children with juvenile idiopathic arthritis (JIA). Materials and methods. The main group comprised 54 children diagnosed with IBD, with a mean age of 13.2±3.8 years, including 32 patients (59.3%) diagnosed with Crohn's disease and 22 patients (40.7%) diagnosed with ulcerative colitis. The comparison group included 34 patients with JIA, with a mean age of 11.9±4.3 years. All participants were observed at the Clinic of Children's Diseases of the Sechenov Center for Motherhood and Childhood. Diagnoses were confirmed in accordance with the current clinical guidelines issued by the Ministry of Health of Russia. The study evaluated the family history of ADs, the frequency of adverse perinatal events, feeding practices, and the frequency and types of allergic manifestations (including asthma, atopic dermatitis, allergic rhinitis, and food and drug allergies) in each group with a comparative analysis of the collected data. Statistical analyses were performed using Stata software, employing the Shapiro–Wilk test, Student's t-test, Mann–Whitney test, Pearson's χ² test, Fisher's exact test, and logistic regression to calculate odds ratios and 95% confidence intervals. Differences were considered statistically significant at p 0.05. Results. Among the children diagnosed with IBD, 59.3% reported allergic disorders, with 25.9% exhibiting two or more allergies. The most prevalent allergies included atopic dermatitis (18.5%) and food allergies (27.8%), with drug allergies observed in 14.8% of children in this group. Perinatal complications were noted in 44.4% of these patients. 47.4% of patients had been breastfed for over six months, and a family history of ADs was documented in 25.9% of the children. In contrast, allergic manifestations were reported in 38.2% of the JIA group; the most common manifestations included atopic dermatitis (20.6%) and food or drug allergies (11.8% each), with asthma and allergic rhinitis being less common (2.9% each). A complicated early medical history was recorded in 50.0% of JIA patients, with 29.4% having been breastfed for more than six months, and 14.7% showing a family history of ADs. Conclusion. The prevalence of ADs in children diagnosed with IBD is significantly higher than in the general population. Although the prevalence of allergies in children with JIA is also higher compared to the overall population data, the difference is not statistically significant. It remains lower than that observed in children with IBD (Fisher's exact test p=0.079). However, the probability of developing allergies in IBD patients was approximately 2.9 times greater than that of JIA patients, with the most pronounced trend in food allergy. The findings of this study suggest a probable association between IBD and the prevalence of allergic disorders.

Crohn’s disease (CD) in children with juvenile idiopathic arthritis (JIA) is frequently diagnosed late due to overlapping symptoms and non-specific biomarkers. We hypothesized that longitudinal cytokine profiling could identify a pre-symptomatic signature predictive of CD conversion in pediatric JIA patients. Ninety pediatric participants (JIA, CD, psoriatic arthritis, healthy controls) underwent serum cytokine profiling (IL-1α, IL-1β, IL-36α, IL-37, IL-6, IL-18, IL-27, IL-31) at baseline and 12 months. Statistical analysis used Mann–Whitney U tests for two-group comparisons, the Kruskal–Wallis test with Dunn’s post hoc for multi-group comparisons, Fisher’s Exact Test for categorical outcomes, and exploratory principal component analysis (PCA). Baseline screening identified a subgroup of JIA patients (N = 4) with significantly elevated IL-1α, IL-1β, and IL-36α. At 12 months, all four patients in this subgroup received a secondary CD diagnosis (4/4 converters vs. 0/21 non-converters; Fisher’s Exact Test: p < 0.0001). The longitudinal analysis at conversion revealed a broader pro-inflammatory shift, with marked increases in IL-18 and IL-31, alongside elevated IL-37, suggesting a compensatory regulatory response. PCA confirmed that converters clustered distinctly from both stable JIA and established CD. A baseline IL-1 family signature may represent a preliminary predictive signature for CD onset in pediatric JIA. Although constrained by the small converter subgroup (N = 4), these data support cytokine profiling for earlier diagnosis in high-risk populations.

Background. Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, are immune-mediated inflammatory diseases with a complex pathogenesis. In addition to the involvement of the intestinal wall in the pathological process, systemic extraintestinal manifestations are observed in Crohn's disease and ulcerative colitis, and there is also often an association with psoriasis and psoriatic arthritis. Objective. Purpose of the study was to analyze the nature of the articular syndrome in children with inflammatory bowel diseases associated with juvenile psoriatic arthritis. Materials and methods. A retrospective analysis of the nature of the articular syndrome was carried out in a group of children with inflammatory bowel diseases associated with juvenile psoriatic arthritis (20 patients, mean age 12.7 years (95% CI [11.01; 14.29]). The diagnosis of juvenile psoriatic arthritis was established according to the Vancouver diagnostic criteria (1989). The diagnosis of Crohn's disease was established in accordance with Clinical recommendations for Crohn's disease for pediatric patients, 2025. The diagnosis of ulcerative colitis was established in accordance with Clinical guidelines for ulcerative colitis for pediatric patients, 2025. Statistical processing was performed using parametric methods and exact formulas for percentages. Results. 17/20 (85%) of our patients were diagnosed with Crohn's disease, inflammatory form, 3/20 patients (15%) – ulcerative colitis. The diagnosis of definite juvenile psoriatic arthritis, according to the Vancouver diagnostic criteria, was made in 11/20 patients (55%), probable – in 9/20 (45%). Boys predominated in the group – 14/20 (70%). The mean disease duration was 5.0 years (95% CI [3.21, 6.79] years). 13/20 (65%) patients had relatives 1 and 2 degrees of relatives suffered from psoriasis. All children with definite psoriatic arthritis (11/20 children) had plaque (vulgar) psoriasis. In 15/20 (75%) patients, the onset of articular syndrome was asymmetrical oligoarthritis. At the height of the disease, the oligoarticular variant was observed in 10/20 (50%) children, rheumatoid-like (polyarticular) in 3/20 (15%), spondyloarthritis with damage to peripheral joints in 7/20 (35%). The most commonly affected joints were the knee (15/20 (75%)), ankle (5/20 (25%)), and hip (8/20 (40%)) joints. Conclusions. The articular syndrome in inflammatory bowel diseases associated with juvenile psoriatic arthritis is characterized by a frequent onset of the disease with joint damage (in 40%), asymmetric oligoarthritis at the onset and at the height of the disease, while isolated juvenile psoriatic arthritis is characterized by a pattern of development of the articular syndrome from oligo- to polyarthritis. The association of inflammatory bowel diseases and juvenile psoriatic arthritis is characterized by a high percentage of spondyloarthritis with damage to peripheral joints (35%). The most common joints involved are the knee and hip joints (75% and 40%), with a high incidence of enthesitis (55%), while in isolated juvenile psoriatic arthritis the knee and ankle joints are most often affected. The course of inflammatory bowel diseases against the background of psoriatic arthritis requires an individual approach to patient management and selection of therapy aimed at the common links in the pathogenesis of these conditions.

Background: Takayasu’s arteritis (TA) is a systemic vasculitis that primarily affects the aorta and major arteries. Despite aggressive treatment with glucocorticoids (GCs) and non-biological disease-modifying antirheumatic drugs (nbDMARDs), about 30% of patients experience resistance to therapy or relapse. This study aimed to identify risk factors associated with refractory and relapse TA in pediatric patients. Methods: A retrospective, open-label, case–control study was conducted with 56 pediatric patients with TA diagnosed between February 2011 and October 2022. Fourteen patients were excluded due to insufficient data in their medical records, leaving 42 for further analysis. The patients were divided into two groups: Group 1 (18 patients) with no evidence of relapse and Group 2 (24 patients) with relapse despite first-line treatment at the end of the follow-up period. Clinical, laboratory, and instrumental data were collected and analyzed using R v4.2 and Python v3.10. Results: The median time to relapse was 18 [IQR: 13; -] months according to the Kaplan–Meier curve. Patients with ITAS.A with a diagnosis of TA ≥ 12 had a higher probability of relapse, according to the log-rank criterion (p = 0.006). Symptoms of critical ischemia, such as limb claudication, were more common in Group 2 at diagnosis (p = 0.047), and a trend toward a longer diagnostic delay was observed (p = 0.067). Conclusions: Pediatric patients with an initial ITAS.A score above 12 have a higher risk of relapse when treated with a combination of GCs and nbDMARDs as first-line treatment. Further research is needed to identify high-risk patients more accurately and optimize therapeutic strategies.

Introduction. The relevance of studying community-acquired pneumonia in children is associated with its high prevalence, despite timely prevention and effective approaches to the treatment of respiratory diseases. Factors influencing the severity of pneumonia are diverse and include comorbid pathology, early age of the child, the state of the immune system, etc.Objective. To identify and rank risk factors for severe community-acquired pneumonia in infants and preschool children.Materials and methods. This article presents the results of a retrospective analysis of 291 medical histories of children from 3 months to 7 years with community-acquired pneumonia. 83 children had severe CAP, of which 63 patients were hospitalized in the ICU.Results and discussion. The average age of a patient with community-acquired pneumonia was 33 months. Children from families with two or more children fell ill more often. On average, children were hospitalized for 4–5 days of illness. Concomitant diseases in children with CAP were quite common and often complicated the course of pneumonia. According to the results of our study, more than 70% of children were not vaccinated against pneumococcus, Haemophilus influenzae and influenza. We established significant linear relationships between the presence of bronchial obstruction and complications of CAP such as respiratory failure and transfer to the ICU (odds ratio (OR) 7.1; Cramer coefficient 0.40; relationship 0.005). It was shown that patients who received outpatient antibiotic therapy were less likely to require transfer to the ICU.Conclusion. Risk factors for severe community-acquired pneumonia and hospitalization in the ICU were: male gender, age under 2 years, lack of vaccination against pneumococcus, Haemophilus influenzae and influenza, combination of bronchial obstruction with CAP, presence of ENT pathology, lack of antibacterial therapy during prehospital stage, as well as the presence of a serious condition already upon admission.

Foreign body aspiration (FB) is one of the leading causes of death from accidents among preschool children. Every year, up to 8% of children worldwide die as a result of foreign body aspiration. In developed countries, the mortality rate is lower, but the problem remains no less urgent due to the high attendance at emergency departments. Longstanding foreign bodies deserve special attention. The absence of an aspiration episode in the anamnesis of the disease, nonspecific respiratory symptoms, “X-ray negative” foreign bodies, as well as organic FB can complicate the diagnostic search. The article presents data from domestic and foreign literature on epidemiology, risk factors, clinical features, as well as modern approaches to the diagnosis and treatment of foreign body aspiration. The authors present their own clinical observation of a long-standing foreign body in the bronchus in a 7-year-old child. Prolonged cough and repeated episodes of bronchial obstruction for 4 years were regarded as the onset of bronchial asthma. The lack of effect from ongoing bronchodilator and anti-inflammatory therapy with high doses of inhaled glucocorticosteroids dictated the need to expand the diagnostic search, and therefore the child was sent for examination in a hospital to the pulmonology department of the Children’s Clinical Hospital I.M. Sechenov. During endoscopic examination, a metal spiral spring (7 mm in size) was found in the child and simultaneously removed, which was presumably within 4 years in the right bronchus. Over the next 6 months, bronchial obstruction did not recur, there were no complaints.

Aim. To study the characteristics of resistance/sensitivity to normobaric hypoxia in 50 children with bronchial asthma (BA) from 9 to 12 years old, 24 of them after a previous coronavirus infection СOVID-19. Materials and methods. A normobaric hypoxic test (HT) was carried out by creating hypoxemia (threshold level SpO2 80%) during mask inhalation of a gas mixture with 1011% O2 by a child using a ReOxy Cardio apparatus (Ai Mediq S.A., Luxembourg). The data obtained were compared with the results in a group of healthy children the same age. Results. It was found that the integral level of hypoxic resistance of children with BA was generally lower in comparison with the group of healthy children, which was manifested in lower values of the hypoxic index (3.11.4, in the group of healthy children 4.92.8, p=0.005), a significantly increased level of tachycardia and a hypotonic response to dosed hypoxia. Conclusion. When typing reactions to HT, it was found that in children with BA, the type of low resistance to hypoxia is more common (to a greater extent in children with BA after a coronavirus infection), which confirms the need to involve such children in comprehensive rehabilitation programs.

Objective. To evaluate the efficacy and safety controlled hypoxic stimulation in children after coronavirus infection, including those with BA. Patients and methods. This study included 72 children aged 9–12 years who had had COVID-19 at least 1.5–2 months before the enrollment; of them, 24 patients had mild to moderate BA. Study participants were randomized into two groups: ‘intermittent hypoxic training’ (IHT, n = 31) and ‘intermittent hypoxic-hyperoxic training’ (IHHT, n = 41). Before the procedures, we assessed hypoxic resistance of children using a hypoxic test. The following parameters were measured before and after the course, which included 10 procedures: hypoxic resistance (hypoxic index, time to desaturation, and reoxygenation time), spirometry parameters (forced expiratory volume in 1 second, peak expiratory flow, and airway resistance), changes in systolic/diastolic pressure, heart rate variability, tolerability of procedures (using a visual analog scale), and anxiety level (CMAS test). Results. We found no significant differences between BA and non-BA children in their spirometry parameters and hypoxic resistance. We observed good tolerability of the procedures in children from different groups. After the course of IHT/IHHT, patients demonstrated a significant increase in their resistance to hypoxic stimulation. IHHT procedures were more effective and safer than IHT according to spirometry parameters (RINTexp), tolerability, and anxiety level. Conclusion. Hypoxic conditioning procedures can be recommended as a part of comprehensive rehabilitation in BA children who had had COVID-19. Key words: intermittent hypoxic training, new coronavirus infection, bronchial asthma, children, rehabilitation

Williams syndrome (WS), also known as Williams–Beuren syndrome, is a rare genetic disorder affecting many organs and caused by hemizygous deletions of the long arm of chromosome 7 (7q11. 23). In this article, we describe typical pathological changes in the cardiovascular, endocrine, urinary, digestive, and nervous systems, as well as phenotypic characteristics and psychological aspects of this disease. We also cover a correlation between clinical manifestations of WS and genes in the remote area. The article contains a summary of the main recommendations for the treatment of individual manifestations, i.e. pathological conditions associated with this syndrome. Key words: children, Williams syndrome, cardiovascular disorder, hypercalcemia, hypothyroidism, growth retardation, mental retardation