Vol 22, No 1 (2025)

BACKGROUND: Anaphylaxis is the most severe manifestation of immediate systemic hypersensitivity reactions. In recent years, there has been an increase in the number of reported cases of anaphylaxis. Given the variety of clinical manifestations behind the diagnosis of “anaphylaxis”, one of the most urgent issues at present is the task of phenotyping and endotyping of patients with this life-threatening pathology as part of implementation of the individual approach, both during treatment in the acute period and diagnosis in the period of recovery.

AIM: To find the main clinical phenotypes of patients with immediate hypersensitivity reactions, which will further allow stratifying patients by risk groups bringing therapeutic and diagnostic algorithms to the modern level of personalized medicine.

MATERIALS AND METHODS: The study was conducted based on retrospective stepwise analysis of patient medical record data from 2019 to 2022. To identify relatively homogeneous groups of patients based on clinical, agglomerative clustering was performed on 56 variables followed by 2 principal component extraction using the dimensionality reduction method with t-distributed stochastic neighbor embedding. Agglomerative clustering divided patients into 4 major clinical phenotypes, and each patient was assigned a corresponding phenotype.

RESULTS: Based on this analysis, 4 phenotypes of patients with severe immediate-type hypersensitivity reactions were identified.

CONCLUSION: A new classification based on the use of phenotypes, endotypes and biomarkers is currently being developed to broaden our understanding of anaphylactic reactions. Given the limitations of the study (patients were not subjected to additional examinations in the current study), it is not possible to reliably identify endophenotypic differences in different clusters. Additional studies are needed to identify the correlation between anaphylactic reaction phenotypes and its pathophysiological mechanisms of development.

Eosinophilic esophagitis is a T2 disease characterized by eosinophilic infiltration of the esophageal mucosa, subepithelial and submucosal fibrosis, and progressive dysphagia. Early diagnosis and appropriate treatment of eosinophilic esophagitis can prevent the development of strictures and other complications. The treatment of eosinophilic esophagitis includes the use of elimination diets, pharmacological therapy, and endoscopic dilation or bougienage of the esophageal strictures. The most effective drugs for achieving clinical and histological remission in eosinophilic esophagitis are proton pump inhibitors, topical glucocorticosteroids, and biological agents represented by monoclonal antibodies. Over time, the advantages of systemic monoclonal antibody therapies (anti-interleukin 4/13) over proton pump inhibitors and topical glucocorticosteroids have become evident, particularly in terms of their impact on mucosal inflammation and on remodeling of the esophageal wall. Currently, the only approved anti-interleukin drug for eosinophilic esophagitis is dupilumab, which has demonstrated high efficacy and safety in clinical trials and is approved for use in children aged 1 year and older, as well as in adults. Endoscopic dilation or bougienage is performed in patients with eosinophilic esophagitis who have esophageal strictures and stenosis (with an esophageal diameter <13 mm) following a course of pharmacotherapy. To this day, numerous questions remain regarding maintenance therapy, its duration, and predictors of disease progression. With the emergence of new biologic therapies for eosinophilic esophagitis, their accessibility, long-term efficacy, and safety have become critically important considerations.

The article systemizes existing data on the treatment strategies for patients with eosinophilic esophagitis.

The article provides an overview of the latest concepts regarding the role of specific exposomal factors in atopic dermatitis in children and adults. As is known, specific factors include: air pollutants (external, internal), air humidity, metals, water hardness, detergents, pollen and other allergen, diet, human lifestyle factors. In this work, the main attention is paid to all the above factors, except for the role of allergy in the etiopathogenesis of atopic dermatitis (a separate publication will be devoted to this issue). Based on the data of systematic reviews, meta-analyses and recent studies, the role of specific factors is analyzed: air pollutants (external and indoor), diet for pregnant women and during lactation; various dietary supplements, etc. — in the development of atopic dermatitis. It is shown that these (and other exposomal) factors can also participate in the worsening of clinical manifestations of atopic dermatitis (for example, detergents). However, the leading role of any specific factor (factors) in the etiopathogenesis of atopic dermatitis (including allergies) has not been reliably proven to date. This also applies to nutritional factors (for example, adherence to a hypoallergenic diet by the mother during pregnancy and lactation, use of vitamin D and probiotics in the pre- and postnatal periods, etc.). In all likelihood, the external exposome is involved as a risk factor in the development of atopic dermatitis and worsening of the severity of the disease. Nevertheless, measures aimed at improving environmental factors can only be useful, especially in combination with anti-inflammatory drugs.

Hereditary angioedema with normal C1 esterase inhibitor is a rare genetic disorder characterized by periodical and unpredictable angioedema without quantitative and qualitative deficiency of C1-inhibitor. According to the modern classification, this disease can present as two different endotypes: bradykinin-mediated and endothelium dysfunction-associated. Diagnosis of this disease is complicated by the need to perform genetic screening because available laboratory tests (C1-inhibitor, its functionality, and C4 protein in blood plasma) are within normal values, functional molecular tests are not available, clinical data are limited to few cohorts and, for some genetic defects, to single clinical observations. Genetic examination of patients with recurrent angioedema expands the cohort of patients with hereditary angioedema and normal C1 esterase inhibitor.

The article describes 17 patients with hereditary angioedema with normal C1 esterase inhibitor who underwent treatment at a specialized center in Moscow. The bradykinin-mediated angioedema endotype was found in 13 patients (9 with mutation in PLG, 2 with mutation in FXII, and 2 with mutation in KNG1), and endothelium dysfunction-associated angioedema was diagnosed in 4 patients with mutation in MYOF (2 asymptomatic carriers). Currently, data on the clinical presentation, diagnosis, and therapy of patients are limited to single clinical cases and small clinical case series, thus further data collection is needed.

The publication contains unique data on the algorithm of diagnosis and selection of therapy in patients with angioedema and normal C1-inhibitor level.

The article describes a clinical case of a patient with primary immunodeficiency. Initially, the patient presented symptoms of febrile temperature, recurrent respiratory infections, hematological changes in the form of anemia, neutropenia, thrombocytopenia, elevated liver transaminases, episodes of nose bleeds and was observed by an infectious disease doctor.

When lymphadenopathy was revealed, the patient was referred to an oncologist and diagnosed with follicular lymphoma. Splenectomy was performed and 1 course of chemotherapy was administered resulting in stabilization of the patient’s condition for 6 months. Dynamic observation of lymph node biopsies at a federal hematological center ruled out the diagnosis of follicular lymphoma. Concurrently, hypergammaglobulinemia was diagnosed, lymphadenopathy persisted, and the patient was referred to an immunologist. The patient underwent molecular genetic testing, and mutations in STAT3 and RIPK1 genes were detected with undetermined clinical significance. The patient was diagnosed with primary immunodeficiency with immune dysregulation, lymphoproliferative and autoinflammatory syndromes. The patient was kept under observation of an immunologist and a hematologist, was regularly examined by a gastroenterologist and a rheumatologist. The patient received immunosuppressive rituximab therapy and filgrastim for severe neutropenia, was administered preventive antibiotics, antifungal medications, antiviral medications after diagnosis of cytomegalovirus and Epstein–Barr virus. Additionally, plasmapheresis was performed several times. The patient received consultations at the leading immunological, hematological, rheumatological centers. He was also administered anticytokine therapy with an anti-interleukin-1 monoclonal antibody with no significant clinical effect.

Due to insignificant clinical effect during rituximab therapy, the patient was prescribed ruxolitinib. This treatment resulted in normal neutrophil count, decreased intensity of fever, rare episodes of nasal bleeding and ulcerative stomatitis but lymphoproliferation syndrome persisted. In addition, the patient developed pain and swelling in the joints so low-dose oral prednisolone was also prescribed in combination with ruxolitinib. This treatment resulted in improvement of clinical and laboratory parameters of the patient.

This clinical case demonstrates the complexity of diagnosis and treatment of a patient with primary immunodeficiency, the necessity of interdisciplinary approach in management of such patients.

Birch pollen allergy is widespread globally and ranks among the leading allergic diseases in Russia. Cross-reactive food allergy, often observed in patients with birch pollen allergy, is an underestimated issue that exacerbates the course of pollinosis. The presence of cross-reactive food allergy significantly impacts the quality of life of patients with pollinosis. Unlike reactions to pollen, reactions to plant foods can occur year-round and may sometimes have severe, even life-threatening manifestations (e.g., angioedema of the lips and tongue, laryngeal edema, urticaria, anaphylaxis). In many patients, сross-reactive food allergy symptoms first appear during or immediately after the pollen season. According to existing scientific data, this may be due to an increase in the levels of specific immunoglobulin E during the flowering season, both to the causative pollen allergens and to cross-reacting food allergens.

The article presents two clinical cases of development of oral allergy syndrome after consuming raw apple during the birch flowering season, demonstrating possible differences in the mechanisms of cross-reactive food allergy to apple in patients sensitized to birch pollen allergen.