Vol 18, No 2 (2021)
- Year: 2021
- Articles: 12
- URL: https://rusalljournal.ru/raj/issue/view/106
- DOI: https://doi.org/10.36691/RJA.18.2
Full Issue
Original studies
Hereditary Angioedema (HAE) with a mutation in the plasminogen gene: a retrospective study of a cohort of 14 patients from Russia
Abstract
BACKGROUND: In 2018, a new form of hereditary angioedema without C1-inhibitor deficiency — hereditary angioedema with a mutation in the plasminogen gene — was identified. The world scientific literature describes a small number of patients with this form of the disease and, therefore, new research is relevant.
AIMS: To identify the sociodemographic and clinical features of patients with hereditary angioedema with plasminogen gene mutation; to evaluate the treatment efficacy; to conduct a comparative analysis in a group of patients with hereditary angioedema type I/II.
MATERIAL AND METHODS: 14 patients (1 male and 13 females, mean age 51.64±13.55 years) with hereditary angioedema with c.988A>G mutation in the plasminogen gene (p.Lys330Glu; K330E) were enrolled in a retrospective study. The comparison group included 194 patients with hereditary angioedema type I/II (56 males and 138 females, mean age 37.03±16.23 years).
RESULTS: The average age at disease onset in patients with hereditary angioedema with a mutation in the plasminogen gene is 25.07±10.46 years, which is significantly higher than in patients with hereditary angioedema type I/II — 11.58±8.92 years (p <0.001). Peripheral angioedema was reported in 21.4% of patients with hereditary angioedema with a mutation in the plasminogen gene, abdominal attacks in 28.6%, which is less common than in patients with hereditary angioedema type I/II (peripheral edema 97.4%, p <0.001; abdominal attacks 86.6%, p <0.001). Face and neck angioedema was observed in all patients with hereditary angioedema with a mutation in the plasminogen gene (100%) and in 72.2% of patients in the group of hereditary angioedema type I/II (p=0.023). 85.7% of patients with hereditary angioedema with a mutation in the plasminogen gene had edema of the tongue. A decrease in the severity and duration of 28 out of 29 attacks by an average of 71.4% was reported by 4/5 of patients who used icatibant (Firazyr); 3/4 of patients reported a decrease in the frequency of attacks during treatment with tranexamic acid.
CONCLUSIONS: The disease’s manifestation in adulthood, the predominance of face and tongue angioedema are common features of hereditary angioedema with a mutation in the plasminogen gene. The efficacy of tranexamic acid and icatibant was demonstrated in the observed cohort of patients.
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Anti-inflammatory activity of the antiallergic drug 7-[4-(4-benzhydrylpiperazinyl-1)butyl]-3-methylxanthine succinate (theoritin)
Abstract
BACKGROUND: Many antagonists of histamine (H1) receptor, in addition to antihistamine action, suppress allergic inflammation by inhibiting the formation and secretion of proinflammatory cytokines. The new antiallergic drug benzhydrylpiperazinyl butylmethylxanthine succinate (theoritin), which has an antihistamine activity comparable to the known second generation H1-antihistamines, surpasses them in the ability to suppress the allergic inflammatory reaction, which allows this drug to have additional anti-inflammatory properties associated with the inhibition of the formation of proinflammatory cytokines.
AIM: This study aimed to determine the effect of theoritin on the induced release of proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in cell culture in comparison with the action of the inverse agonist of H1 receptor cetirizine and a known inflammation inhibitor glucocorticosteroid dexamethasone.
MATERIALS AND METHODS: U937 cells differentiated toward macrophage-like cells were used. Cytotoxicity of the substances used was assessed in the methyltetrazolium test at different incubation times (up to 24 h). Cells were stimulated with lipopolysaccharide (LPS). The tested compounds (theoritin and cetirizine) were evaluated at concentrations from 0.001 to 100 μM and dexamethasone at 10 μM was tested when added to cells 1 h before (prophylactic effect) or 1 h after (therapeutic effect) the addition of LPS. The presence of IL-6, IL-8, and TNFα in the supernatants was determined by enzyme immunoassay.
RESULTS: For cetirizine and theoritin, no cytotoxic action was found in the tested concentrations and time points. Dexamethasone inhibited the formation of IL-6 and TNFα to the initial level and IL-8 to 50%–60%. Theoritin led to a significant concentration-dependent decrease in the LPS-induced production of IL-6, IL-8, and TNFα, and at a concentration of 100 μM, the effect of theoritin was comparable with that of dexamethasone at a concentration of 10 μM. The “prophylactic” test scheme for theoritin was more effective in suppressing LPS-induced production of proinflammatory cytokines than the “curative” one. The described effect of theoritin on LPS-induced production of proinflammatory cytokines exceeded that of the reference drug cetirizine.
CONCLUSION: In addition to its antihistaminic action, theoritin, a new antiallergic agent, inhibits LPS-induced production of proinflammatory cytokines, which may be of clinical importance in suppressing allergic inflammation.
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Features of the fungal spectrum in the air environment in the Rostov region according to the results aeropalynologic monitoring 2019
Abstract
BACKGROUND: In recent decades, there has been an epidemic growth of allergic diseases, in which fungi along with other allergens significantly play a role in their etiology. Spores of a number of micromycetes are present in the air. Aeropalynology environmental monitoring enables examination of the composition of airborne microorganisms, their dynamics, and role in the formation of allergic diseases. The Rostov region has climatic and geographical features that affect the qualitative and quantitative compositions of the fungal spectrum in the air environment.
AIM: This study aimed to investigate the composition and features of the fungal spectrum of the air environment in Rostov-on-Don, to assess the dynamics of the concentration of fungal spores during the monitoring period (March to October), and to make a calendar of plant pollination and fungal spore production for this region.
MATERIALS AND METHODS: In this longitudinal, observational, single-center study, aeroallergens were detected using a volumetric Burkard trap. Identification of plant pollen and fungal spores was performed by microscopy of colored slides obtained from a sticky tape covered with a special mixture.
RESULTS: Results of aeropalynological monitoring in 2019 in the air environment of Rostov-on-Don revealed the presence of pollen taxa and fungal spores, represented by the mold fungi Cladosporium herbarum and Alternaria alternata in high increasing concentrations. Their dynamics were recorded throughout the observation period (March to October). The specific weight of fungal sensitization in patients with seasonal allergic rhinitis was 11.6%.
CONCLUSIONS: This study identifies the regional features of the fungal spectrum of air allergens, and a calendar of dusting and sporulation was compiled for the city of Rostov-on-Don.
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Analysis of the prevalence of food hypersensitivity and food anaphylaxis in the children’s population of Ekaterinburg
Abstract
BACKGROUND: In recent decades, the number of patients experiencing food allergies and food anaphylaxis has been increasing worldwide. However, at present, epidemiological data on this problem are unclear. Anaphylaxis is an acute, potentially life-threatening pathological reaction of systemic hypersensitivity with various clinical symptoms, which can be coded under different diagnoses and conditions. Its acute onset and transient nature make it difficult to obtain prospective data. Thus, it appears realistic to conduct retrospective studies using a questionnaire analysis to identify children who have undergone such reactions for further examination and observation.
AIM: This study aimed to investigate the prevalence of food hypersensitivity and food anaphylaxis in the pediatric population of Ekaterinburg.
MATERIALS AND METHODS: A total of 5,000 parents with children aged 2–17 years were surveyed. The children attend preschool or school general educational institutions (children’s education institution (ChEI) of the city. ChEIs were randomized, and the parent survey was anonymous and voluntary. Respective parents were asked to complete the questionnaire, which asks them whether their children have skin lesions, wheezing, and clinical presentations of allergic rhinitis or food allergy. The developed questionnaire was based on the ISAC questionnaire translated into Russian. In the questionnaires, the parents gave only those symptoms that arose in children against the background of somatic health at normal body temperature.
RESULTS: A total of 2,400 questionnaires were analyzed: 1,196 questionnaires were filled by parents of boys (49.9%) and 1,204 questionnaires by parents of girls (50.1%) aged 2–17 years (average age 10.31 ± 0.30 years). Data collected from questionnaire revealed that skin rashes in 17% of the children were associated with products: most often, these were obligate allergens and histamine liberators. Additionally, 6.8% of the parents noted that persistent rhinitis in their children was associated with consumption of milk/fish/fruit/nuts. Symptoms of respiratory obstruction after eating fish/cow’s milk/nuts were described by parents of 2.7% of the children. Association of urticarial manifestations with food was noticed by parents of 194 (8.1%) children. Moreover, 0.96% of children experienced symptoms of anaphylaxis to food, 0.3% to cow’s milk, 0.12% to chicken eggs and fruit, and 0.08% to wheat, nuts, and fish.
CONCLUSIONS: Epidemiological studies help understand the spread and nature of allergic diseases in a region. Moreover, identification of children who have had episodes of food-borne anaphylaxis helps prevent recurrent cases by conducting case follow-up of these patients.
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Reviews
Developmental adaptations of neonatal neutrophils (review)
Abstract
Neutrophils are crucial components of the innate immunity. Differences exist in the physiological, phenotypic, and functional characteristics between neonatal and adult neutrophils. The severity of these changes is inversely proportional to gestational age, which indicates the dynamic development of these cells throughout pregnancy. Therefore, functional insufficiency of neonatal neutrophils is associated with an extremely high risk of developing neonatal infections and sepsis in infants born premature. Neonatal neutrophils are adapted to conditions that prevent unwanted triggering of proinflammatory factors. In addition, suppression of neutrophil functions is necessary to create a healthy microbiome in the postpartum period; however, it can be inhibit the development of a response to pathogenic organisms. Mechanisms underlying the normal transition of functionally limited neutrophils, capable of fully resisting pathogenic microorganisms, have not been established. This review presents features of neutrophil ontogenetic adaptation to intrauterine conditions and early neonatal period and their potential role in neonatal pathology.
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Modern H1- antihistamines in the treatment of allergic rhinitis: focus on bilastine
Abstract
The second generation of H1-antihistamines is approved for the stepwise treatment of seasonal and perennial allergic rhinitis in adults and children by international and national guidelines. They reduce the severity of nasal and ocular symptoms of rhinitis and improve the quality of life of patients.
Bilastine, a piperidine derivative, is a novel H1-antihistamine. It has a potent and selective effect on H1- receptors and a rapid onset and long duration of action and substantially reduces nasal and ocular symptoms of seasonal and perennial allergic rhinitis. Bilastine has no clinically substantial hepatic metabolism and has a high safety profile: it has no sedative effect, does not affect cognitive functions, has no cardiotoxic effects, and does not interact with alcohol and benzodiazepines in normal and high doses. Tachyphylaxis does not develop despite long-term (up to 1 year) use.
Bilastine is registered for clinical use in adults and children aged >12 years. The results of clinical and experimental studies have demonstrated that bilastine has many of the features of modern H1-antihistamines recommended by international guidelines.
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Help to the practitioner
Hereditary angioedema. Clinical guidelines. (D84.1)
Abstract
Hereditary angioedema is a rare, potentially life-threatening genetic disease that manifests with skin and mucous/submucosal swelling that occurs under the influence of bradykinin. The clinical guidelines for hereditary angioedema (code for the International Statistical Classification of Diseases and Related Health Problems D84.1) were developed in December 2020 by the Russian Association of Allergology and Clinical Immunology, Association of Medical Geneticists, National Association of Experts in the Field of Primary Immunodeficiencies, Union of Pediatricians of Russia. In December 2020, the project was approved at a meeting of the Scientific and Practical Council of the Ministry of Health of the Russian Federation (December 10, 2020 No. 743/12).
The clinical guidelines are devoted to optimizing the clinical care of patients with hereditary angioedema. The topic is relevant owing to the under-diagnosis of hereditary angioedema and insufficient awareness of doctors of various specialties about this problem, as well as the difficulties in managing this category of patients. The clinical guidelines contain information about the epidemiology, etiology, classification, pathogenesis, and common clinical manifestations of hereditary angioedema. Thus, the paper described actual diagnostic approaches and differential diagnosis of hereditary angioedema and established its diagnostic criteria. Medical care algorithms to patients with hereditary angioedema at the prehospital and hospital stages are also described. The principles of pharmacotherapy, including long-term prophylaxis, short-term prophylaxis, and acute therapy, for hereditary angioedema are also presented. Treatment regimens are stratified according to patients’ age and gender. Non-drug measures for the prevention hereditary angioedema attacks are considered. Sections were also added in the edition of the new clinical guidelines of hereditary angioedema. Clinical guidelines for hereditary angioedema are intended for practicing doctors of all specialties, students and teachers of medical universities, residents, graduate students of medical universities.
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Case reports
Case report of the dupilumab applying in atopic dermatitis child
Abstract
In recent years, there has been a clear trend towards an increase in the number of patients with severe atopic dermatitis. In most cases, patients are dissatisfied with the previous therapy, which requires hospital treatment to relieve acute manifestations of atopic dermatitis and the selection of pharmacological agents aimed at achieving long-term control under the of the disease symptoms
The article presents the features of the atopic dermatitis therapy of at the present stage, the experience of using the new biological drug dupilumab in a 7-year-old child.
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Patient with polymorbid pathology. Possibilities of therapy with monoclonal antibodies
Abstract
With the widespread increase in the number of patients with allergic pathology, doctors in clinical practice increasingly have to observe the simultaneous development of several nosological forms in the same patient. Frequent occurrence of a combination of lesions of the skin and respiratory tract in patients with atopy (atopic dermatitis, allergic rhinitis, and atopic bronchial asthma) is traditionally considered within the framework of comorbidity and suggests a number of therapeutic interventions given the similarity of the pathogenesis. However, phenotypic or endotypic differences exist between patients (e.g., triggers, age, persistence of manifestations, degree and type of inflammation, severity of symptoms, and response to treatment), for which it is more correct to use the term multimorbidity. The strategy of precision medicine for patients with several immune-mediated diseases should focus on identifying not only the general features of the disease, but also the pathogenetic mechanisms in the target organs. Because of these differences, the sensitivity to therapeutic interventions by target organs can vary. Herein, a clinical case of a patient with comorbid pathology ― chronic spontaneous urticaria, allergic rhinitis, and bronchial asthma ―was analyzed. Respiratory manifestations (rhinitis and asthma) were mild to severe. Chronic urticaria had the most severe disease course and resistant to antihistamines, which are considered first and second lines of drugs according to federal and international clinical guidelines that required the use of monoclonal antibodies. Anti-IgE therapy with omalizumab had a rapid and complete effect on urticaria symptoms, but respiratory symptoms were less responsive to treatment. In patients with multimorbid pathology, therapy should be individualized in terms of targeted drugs and their dosage.
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Challenges of differential diagnosis of mediators-induced and bradykinin-induced angioedema shown by a clinical case series
Abstract
Angioedema is caused by a local increase in vascular permeability induced by bradykinin or mast cell mediators. The main challenge of the differential diagnosis of angioedema lies in the fact that different pathophysiological processes may lead to a very similar clinical picture. Moreover, verification of the type of angioedema is crucial for selection of appropriate therapy. In 2020, a school for doctors “Chronic urticaria: scientific and medical accomplishments and practical aspects of patient management” was held on the basis of the National Research Center Institute of Immunology of the FMBA of Russia as part of the work of the reference center that provides expert assistance to patients with urticaria (GA²LEN UCARE). A clinical case series of related patients with hereditary angioedema due to a mutation in the PLG gene was presented to demonstrate the challenges of the differential diagnosis between types of angioedema. This article focused on the description of this series.
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«Possibilities of a unified approach to the treatment of IgE-associated respiratory diseases. Clinical Experience exchange».
Abstract
Inflammatory diseases of the upper and lower respiratory airways, such as allergic rhinitis, nasal polyposis, bronchial asthma have common proinflammatory mechanisms, mediated by IgE-dependent cascade of inflammation. Concurrent existence of asthma and allergic rhinitis and/or nasal polyposis increases clinical symptoms severity, disease course aggravation and eventually disease control loss for the patient. Anti-IgE-therapy is pathogenetically justified effective and safe therapeutic option for various patient groups. Today principles of interdisciplinary approach are in practice to target upper and lower respiratory diseases management, which determines the success of biological therapy. ENT, pulmonology and allergy specialists define patient management tactics in close collaboration taking into consideration diseases manifestation. The proven efficacy and safety of оmalizumab makes this drug a universal tool to achieve IgE-associated diseases control and an alternative solution for surgical intervention and therapy with systemic corticosteroids.
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Obituary
Vera Nikolaevna Fedoseeva: in memory of outstanding scientist, teacher, person
Abstract
On May 12, at the age of 83, a famous Russian scientist in the field of allergology, academician of the Russian Academy of Natural Sciences in biomedical sciences, doctor of biological sciences, professor Vera Nikolaevna Fedoseeva passed away. Vera Nikolaevna was one of the founders of the national, now internationally recognized Association of Allergists and Clinical Immunologists, a student of the founder of Russian allergology, Academician Andrei Dmitrievich Ado.
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