Hereditary angioedema (HAE) is a rare but potentially life-threatening disease characterized by episodic swelling due to excessive bradykinin production. This review discusses the main pathogenetic mechanisms of the disease and analyzes the main differences between types of HAE with C1-inhibitor deficiency (types I and II) and with normal C1-inhibitor levels. The paper summarizes and systematizes the main biomarkers with diagnostic significance for hereditary angioedema, including the level and functional activity of C1-inhibitor, the concentration of complement system components (C4, C1r, C1s), as well as molecular genetic markers that allow verifying the disease type. Modern therapeutic strategies are presented, focusing both on the rapid relief of acute attacks using drugs that target the kallikrein-kinin system, and on preventive approaches that reduce the frequency, severity, and duration of recurrences. An important part of the review is the analysis of existing in vitro and in vivo models of HAE, including cell systems and transgenic animal models used for the preclinical evaluation of the efficacy and safety of new therapeutic agents, as well as for a deeper understanding of the molecular and cellular mechanisms underlying the disease. The presented analysis highlights the importance of integrating fundamental and applied research to develop personalized approaches for HAE management and to improve patient prognosis.

BACKGROUND. With the remarkable growth of research on the mechanisms of asthma development, it is becoming evident that the field of intercellular communication and auxiliary messengers represents a promising research sector. The accumulated experience presented in the literature emphasizes the importance of ion channels, defining them as possible key elements of asthma pathogenesis in terms of molecular complexes and intercellular disorders. Their significance lies not only in the direct regulation of immunocompetent cells, but also in the activity of others involved in asthma pathogenesis, including epithelial cells and smooth muscle cells of the airways. However, additional studies are needed to fully elucidate their role in the pathophysiology of asthma, in particular, the functional role of gap junction connexins in intercellular communication, their participation in maintaining cellular and tissue homeostasis at asthma. AIMS: to analyze Cx43 levels in the blood serum of children with asthma of varying severity. MATERIALS AND METHODS: A single-center prospective continuous study was conducted for the period from 2023 to 2024 using laboratory, statistical, analytical research methods, ongoing observation and desk research. 125 children with an established diagnosis of bronchial asthma and 30 children of health groups I and IIa included in the control group were examined. Clinical examination included anamnesis and physical examination of the study participants. To determine laboratory parameters, blood was taken from the cubital vein in this group. Quantitative determination of the connexin level in the blood serum was carried out by enzyme-linked immunosorbent assay using the SEA277Hu kit, Cloud-Clone. Corporation, Wuhan, China. Statistical processing of the results was carried out using Statistica 12.0 for Windows software package. RESULTS: It was found that in patients suffering from bronchial asthma the Cx43 levels in the blood serum of 0.24 [0.19; 0.34] ng/ml exceed the results established in the control group of 0.16 [0.13; 0.19] ng/m3 (p= 0.0002). Moreover, the values ​​recorded in the group of patients with severe course of the disease are higher than in the group of patients with mild manifestations of bronchial asthma [p 0.0001]. It was shown that in bronchial asthma patients with polyvalent sensitization, the concentration of Cx43 in the blood serum is higher (0.39 [0.36; 0.42] ng/ml) compared to patients who note an allergic reaction to one type of allergen (0.20 [0.17; 0.25] ng/ml) [p 0.0001]. CONCLUSIONS: It has been shown that Cx43 plays an important role in the pathogenesis of bronchial asthma, and the study of changes in the concentration of this cytokine in patients with varying severity of bronchial asthma manifestations is of great scientific and practical interest.

BACKGROUND: Bronchial asthma (BA) and allergic rhinitis (AR) often concomitant to form a single clinical and pathogenetic syndrome based on the activation of T2 inflammation. Important biomarkers of this type of inflammation are eosinophils and total immunoglobulin E (IgE). Prolonged course of AR in patients with asthma can lead to the development of chronic rhinosinusitis with polypoid-hyperplastic changes (PHC) in the sinonasal mucosa. The effect of PHC on the severity of clinical manifestations and the level of systemic biomarkers of T2 inflammation in patients with a combination of asthma and AR in the pediatric population cannot be considered established. AIMS: Сomparаtive the clinical manifestations (assessed by TNSS and SNOT-22 scales) and the content of systemic biomarkers of T2 inflammation between groups with the presence and absence of PHC in children and adolescents with combined course of BA and AR. MATERIALS AND METHODS: The single-stage, single-center observational study included patients with asthma and AR aged 6-17 years. All patients underwent clinical and laboratory examinations, rhino endoscopy and computed tomography of the nose and paranasal sinuses according to indications. RESULTS: Totally, 268 patients were examined: 203 boys (75,75%) and 65 girls (24,25%). PHC was detected in 31,84% of patients. Clinical symptoms (assessed using the TNSS and SNOT-22 scales) were more pronounced in children with PGSS compared to those without PHC (p0,001), but there was no significant difference between boys and girls in terms of these symptoms. At the same time, TNSS scores were statistically significantly higher for girls than for boys (p=0,045), and SNOT22 scores were significantly higher in both groups (p 0,05). Higher levels of eosinophils and total IgE were also recorded by children with PHC (p 0,01 and 0,5 respectively), indicating a significant role for systemic T2 inflammation in this CONCLUSIONS: The presence of PHC by children and adolescents with asthma and AR correlates with increased clinical symptoms and increased levels of eosinophils in blood and total serum IgE, especially in girls. The results obtained indicate the potential involvement of systemic T2-inflammation in the processes of pathological remodeling and the formation of structural disorders of PHC

One of the leading problems in modern allergology is drug hypersensitivity. There is an increase in allergic reactions to medications that are commonly used in routine practice. The article presents a clinical case of a patient who developed anaphylaxis following the simultaneous administration of local anesthetics and chlorhexidine. Data on drug allergy (DA) to antiseptic agents are discussed. As a part of diagnostic workup in vitro and in vivotesting with suspected drugs was conducted, resulting in confirmation of DA to chlorhexidine, which led to the prohibition of its use and ruled out allergy to local anesthetics.

BACKGROUND: Anaphylaxis is a severe, life-threatening systemic allergic reaction. Currently, the only biomarker of anaphylaxis recommended for use in Russian and international consensus documents is tryptase, with very limited data on the efficacy of its use in real clinical practice in children. AIMS: To determine the frequency of measurement and diagnostic significance of tryptase level estimation in children with anaphylaxis within the recommended time frame in real clinical practice, as well as its relationship with the age of patients and the severity of symptoms. METHODS: The observational single-center prospective study included 128 patients aged 0 to 18 years who were hospitalized urgently in the State Budgetary Institution “Morozov Children's Hospital of Moscow” due to an episode of anaphylaxis in the period from May 2022 to April 2025 and were included in the Pediatric Moscow Anaphylaxis Register. The diagnosis of anaphylaxis was verified by an expert allergist-immunologist based on clinical criteria for anaphylaxis. Serum tryptase levels were measured in patients admitted to the hospital within 3 hours of the onset of symptoms of acute allergic reaction. The patients' clinical and laboratory parameters were entered into an online registry questionnaire and processed using a computer program, which is a system for data recording and analysis. RESULTS: Of the 128 children, 52 (40.6%) had their tryptase levels measured within 3 hours of symptom onset. Among these, 15 (28.8%) showed elevated tryptase levels. For the 76 children who were not assessed (due to delayed hospitalization), a higher frequency of mild anaphylaxis was observed compared to those assessed for tryptase levels (31.6% vs 15.4%, p=0.037). No correlation was found between age and tryptase levels, though there was a trend toward older patients (median 12 years vs. 10 years, p=0.052) being within the timeframe for tryptase measurement. Severity of reaction did not affect tryptase concentrations. CONCLUSIONS: In clinical practice, tryptase levels can be measured within 3 hours of symptom onset in less than half of patients, with only one third showing elevated levels. Delayed hospital arrival in patients with mild anaphylaxis is likely to delay diagnosis and treatment.

BACKGROUND: Dupilumab, a monoclonal antibody targeting the alpha subunit of the interleukins 4 and 13 receptor, has fundamentally transformed the approach to treating atopic conditions such as atopic dermatitis, bronchial asthma, and chronic rhinosinusitis. However, its increasing use has drawn heightened attention to several adverse ocular events — conjunctivitis, blepharitis, keratitis, corneal ulcers, and cicatricle conjunctivitis — that remain underrecognized and often underestimated in clinical practice. These manifestations frequently occur in patients with atopic dermatitis and vary in severity, posing diagnostic and therapeutic challenges. AIM: To study the efficacy and safety of anti-IL-4,13 therapy in Andogsky syndrome. MATERIALS AND METHODS: The study included patients with moderate-to-severe atopic dermatitis and cataracts who had experienced insufficient efficacy from conventional treatment over a period of at least 3 months. The decision to prescribe dupilumab was made by a medical commission based on the assessment of the SCORAD index and the previous volume of therapy. Patients were monitored dynamically for 16 weeks. Follow-up visits were conducted at weeks 4 and 16. During these visits, an assessment of atopic dermatitis symptom control was performed using the SCORAD, DQLI, and POEM scales. Additionally, monitoring of adverse events and their timing was conducted. RESULTS: The study included 5 patients with Andogsky syndrome. Four of them had a history of surgical treatment for cataracts, and initiation of anti-IL-4,13 therapy for severe atopic dermatitis was performed more than 5 years after cataract surgery. One patient with severe atopic dermatitis and progressive cataracts started therapy prior to surgical intervention. The initiation of systemic therapy allowed for successful cataract treatment and preservation of visual acuity without development of adverse events related to dupilumab. No adverse events, including those related to the visual organs, were recorded in this cohort of patients during the entire observation period (52 weeks). CONCLUSION: The therapeutic potential of dupilumab in the treatment of Andogsky syndrome is of particular interest, given the complex nature of the disease and the involvement of various body systems. Suppression of T2 inflammation through inhibition of interleukins 4 and 13 leads to a reduction in the severity of skin manifestations, a decrease in the intensity of the inflammatory process, and improvement in ophthalmological parameters. Further study of the efficacy of dupilumab in Andogsky syndrome will allow: to determine the optimal duration of therapy, evaluate the impact on disease progression and develop personalized treatment approaches.

Bronchiolitis obliterans is a rare severe complication of Stevens–Johnson syndrome and toxic epidermal necrolysis. The article presents an observation of a fatal histologically confirmed bronchiolitis obliterans in a 16-year-old patient developed as a delayed complication of Stevens–Johnson syndrome after the use of lamotrigine and nonsteroidal anti-inflammatory drugs. The diagnosis of bronchiolitis obliterans was established based on the development of severe bronchoobstructive syndrome, confirmed by a study of the external respiratory function, chronic respiratory failure 2 months after Stevens–Johnson syndrome, characteristic computed tomography signs (foci of mosaic perfusion, bronchiectasis). Bronchiolitis obliterans therapy, in addition to commonly used drugs, included the janus kinase inhibitor tofacitinib. To discuss clinical observation, a systematic review of the world literature over 45 years was conducted. 43 cases of post-Stevens–Johnson syndrome/toxic epidermal necrolysis were selected from 187 publications with an analysis of the etiology, timing of onset, spirometric and radiological signs, features of therapy and course. According to the analysis, the main triggers of Stevens–Johnson syndrome/toxic epidermal necrolysis were antibiotics (50 %) and nonsteroidal anti-inflammatory drugs (40 %), infection caused by Mycoplasma pneumoniae (12 %), and less often anticonvulsants. The average age of children with bronchiolitis obliterans was 7 years, and the average age of adults was 28 years. In 50 % of cases, the manifestation of bronchiolitis obliterans occurred 1–3 months after the start of Stevens–Johnson syndrome/toxic epidermal necrolysis. Most patients (35 %) had severe bronchoobstructive syndrome, and characteristic computed tomography signs included mosaic perfusion (75 %) and bronchiectasis (49 %). Systemic (77 %) and inhaled (35 %) glucocorticosteroids, bronchodilators (63 %), and macrolide antibiotics (26 %) formed the basis of bronchiolitis obliterans therapy. Mortality in the analyzed cases reached 30 %, complete recovery was observed in only 33 %, and 35 % of patients retained persistent bronchoobstructive syndrome.

Atopic dermatitis is one of the most common inflammatory skin diseases, affecting 10–21 % of the population and accounting for up to 50–60 % of allergic disorders. The classical concept of the atopic march suggests a sequential progression from atopic dermatitis in infancy to bronchial asthma in early childhood and allergic rhinitis in school-age children. However, recent data demonstrate that only 3.1 % of patients follow this strict sequence, while the majority exhibit a heterogeneous combination of atopic diseases, including food allergy and eosinophilic esophagitis. The key mechanisms underlying the atopic march include epidermal barrier dysfunction (filaggrin mutations), transcutaneous allergen sensitization, systemic T2 inflammation, and genetic predisposition. Other contributing factors include microbiome disturbances, lifestyle factors, and environmental triggers. Preventive strategies involve the use of emollients from birth, early introduction of allergenic foods (e.g., peanuts) to induce tolerance, microbiome modulation, and targeted therapies (e.g., dupilumab) aimed at suppressing interleukin 4/13-mediated inflammation. However, no universal approach exists, highlighting the need for personalized strategies tailored to individual immunological and genetic profiles. Thus, the modern understanding of the atopic march has evolved from a linear model to a concept of multimorbidity, requiring a comprehensive approach to diagnosis, prevention, and treatment. Further research should focus on developing predictive biomarkers and individualized therapeutic algorithms.