Vol 20, No 4 (2023)
- Year: 2023
- Published: 02.12.2023
- Articles: 14
- URL: https://rusalljournal.ru/raj/issue/view/119
- DOI: https://doi.org/10.36691/RJA.20.4
Original studies
Cationic peptides as promising compounds for the treatment of bacterial complications in atopic dermatitis: Antibacterial activity assessment
Abstract
BACKGROUND: The decrease in the effectiveness of antibiotics against the background of resistance of microorganisms aggravates the therapy of atopic dermatitis complicated by bacterial infection and actualizes the development of new antimicrobial agents.
AIM: To develop, synthesize, and evaluate the antibacterial activity of cationic peptides and an aqueous solution of fullerene C60 to create drugs based on them that will have a spectrum of biological activity, including anti-inflammatory, antiallergic, and antibacterial activities.
MATERIALS AND METHODS: This study analyzed the developed linear and dendrimer cationic peptides, whose structure was confirmed by matrix-assisted laser desorption ionization–time of flight mass spectrometry. An aqueous solution of fullerene C60 was obtained using a uniquely developed and patented technology. Antibacterial activity was assessed by diffusion into agar using disks (screening) and serial dilution, which was used to determine the minimum bactericidal concentration of the studied compounds.
RESULTS: Moreover, 42 cationic peptides with various structures were developed and synthesized. The molecular weight of the peptides did not exceed 5,000 Da. They contained 7–25 amino acids with charges from +5 to +16. Screening was carried out through diffusion into agar using disks and revealed 15 peptides that showed activity against Escherichia coli Dh5a. Thus, using the method of counting colonies, the peptides AB-14, AB-17, and AB-18 showed bactericidal activity relative to E. coli Dh5a in concentrations of 0.03, 0.15, and 0.74 mM, respectively, which exceeded that of ampicillin (0.74 mM) several times. Analysis of an aqueous solution of fullerene C60 did not reveal its antibacterial activity.
CONCLUSIONS: The antibacterial activity of the resulting peptides makes them promising for the development of antibacterial therapeutic agents.
Clinical predictors of antihistamine resistance in patients with chronic spontaneous urticaria
Abstract
BACKGROUND: Сhronic spontaneous urticaria is characterized by itchy wheals and/or angioedema on the skin for ≥6 weeks. A large-scale international AWARE study by Russian researchers indicated the ineffectiveness of therapy with standard doses of second-generation antihistamines in >50% of patients with chronic spontaneous urticaria. Clinical predictors of antihistamine resistance include low quality of life based on CU-Q2oL, baseline urticaria activity score for 7 days (UAS7) >16, combination with chronic inducible urticaria, and autoimmune comorbidity. Currently, research into the clinical predictors of antihistamine resistance, including body mass index, in patients with chronic spontaneous urticaria is ongoing.
AIM: To examine the degree of symptom control based on body mass index and physical activity in patients with chronic spontaneous urticaria treated with second-generation antihistamines.
MATERIALS AND METHODS: The examination of patients with сhronic spontaneous urticaria (n=34) included the clinical history and use of the following international questionnaires: UAS7, urticaria control test, dermatology quality of life index, and global physical activity questionnaire of the World Health Organization. The questionnaires were analyzed in subgroups of patients with controlled and uncontrolled chronic spontaneous urticaria and subgroups of patients with chronic spontaneous urticaria having normal weight, overweight, and obesity.
RESULTS: Uncontrolled symptoms were observed in 24 (70.6%) patients with chronic spontaneous urticaria, including 11 (45.8%) with resistance to fourfold doses of second-generation antihistamines. In 52.9% of patients with chronic spontaneous urticaria, the body mass index exceeded normal values. In this study, an inverse correlation was found between the body mass index and the degree of control of chronic spontaneous urticaria symptoms.
CONCLUSIONS: Owing to the negative correlation between body mass index and the degree of symptom control, further research into the role of body mass index as a clinical predictor of antihistamine-resistant chronic spontaneous urticaria is needed. In the future, personalized therapy for chronic spontaneous urticaria may consider the degree of disease control, clinical predictors of antihistamine resistance, and proinflammatory biomarkers.
Levels of eosinophils and interleukin-5 and severity of atopic dermatitis in the presence of psychosocial stress
Abstract
BACKGROUND: Skin damage in atopic dermatitis is caused by the participation of several immune cells and their inflammatory mediators. However, data on correlations between the severity of atopic dermatitis, combined with and without food allergies (severity of atopic dermatitis (SCORAD) index, etc.), and the levels of eosinophils and interleukin-5 are scarce and contradictory. No studies have compared the frequency of eczematous reactions occurring at different times or immediate allergic reactions in the above patients. Moreover, no studies or certain studies have reported results on the frequency of the combination of atopic dermatitis and food allergies, its various degrees of severity depending on these indicators, levels and relationships of the concentration of eosinophils, and interleukin-5 in the presence of psychosocial stress.
AIM: To study the frequency and severity of the course, skin reactions in patients with atopic dermatitis, with and without food allergies, and levels and correlations of interleukin-5 and eosinophils in the presence of psychosocial stress in patients in the Donbass region.
MATERIALS AND METHODS: A total of 165 patients with atopic dermatitis were examined. Questionnaire survey, anamnesis collection, and general clinical and specific allergological examinations were performed, and the levels of interleukin-5, absolute quantity, and percentage of eosinophils in the peripheral blood were determined. Two subgroups of patients with atopic dermatitis were analyzed: 1) those with food allergies and 2) those without food allergies. Persons living in areas with high and low shelling intensities were also identified. Data were statistically processed using the domestic program Medstat (Donetsk).
RESULTS: In patients with atopic dermatitis, randomly selected from those who applied for an appointment with allergists-immunologists, this disease was combined with food allergy in 81.2% of cases. The severity of atopic dermatitis and eosinophil levels were significantly higher in the group with food allergies. Stable direct reliable correlations of varying strength have been established between the severity of atopic dermatitis (SCORAD index and its indicators) and the absolute quantity, percentage of eosinophils, and interleukin-5 level, as well as between the above laboratory parameters. Differences were found in the frequency of recording eczematous and immediate skin reactions. The residence of patients with atopic dermatitis with and without food allergies in areas that differed in shelling intensity was associated with the severity of atopic dermatitis and the level of eosinophils and interleukin-5.
CONCLUSION: In most patients, atopic dermatitis is combined with food allergy, and the severity of its combination with food allergy increases. Therefore, reliable correlations of the SCORAD index with blood eosinophilia and interleukin-5 levels are revealed. The severity of atopic dermatitis and biomarkers in both subgroups increased when they lived in areas with high intensity of shelling.
Cutaneous mastocytosis and allergic diseases in children: A cross-sectional study
Abstract
BACKGROUND: Mastocytosis is a heterogeneous group of diseases characterized by abnormal accumulation of clonal mast cells in one or more organs. Comorbidities in patients with mastocytosis include IgE-dependent allergies, psychiatric or psychological disorders, and vitamin D deficiency. Despite the clinical similarities between allergies and mastocytosis, only a few European studies have considered these comorbidities.
AIM: To analyze the frequency of concomitant-allergic diseases in children with cutaneous mastocytosis.
MATERIALS AND METHODS: Data of 248 children aged 6 months to 17 years who were diagnosed with cutaneous mastocytosis and received outpatient treatment and observation at the Moscow Scientific and Practical Center for Dermatovenereology and Cosmetology between March 2022 and June 2023 were analyzed. Serum levels of total and allergen-specific IgE were analyzed in children with and without allergic diseases. In addition, a positive history of allergy was analyzed in close relatives of children with cutaneous mastocytosis.
RESULTS: Every third child (36.7%) with cutaneous mastocytosis had a concomitant allergic disease. Relatives of 27.4% of the examined children had allergic diseases. The process was significantly more often accompanied by allergic diseases in children with mastocytomas than in those with maculopapular cutaneous mastocytosis (χ2=45.46; p=0.001). The level of total IgE was not a statistically significant sign of the presence of allergic diseases in cutaneous mastocytosis (χ2=1.161; p=0.3). Allergen-specific IgE was detected in 47.2% of the children with allergic diseases. Among children without signs of food allergy and pollinosis, asymptomatic low and moderate sensitization to any plant product and birch was detected in 26.5%. Sensitization to respiratory allergens was found in 8% of children with cutaneous mastocytosis without allergic diseases.
CONCLUSIONS: In Russia, this study demonstrated for the first time a high incidence of allergic diseases in children with cutaneous mastocytosis. The results showed that all clinical forms of mastocytosis in children, including cutaneous mastocytosis, should be subjected to interdisciplinary observation and examination. The timely detection of comorbid allergic diseases contributes to the development of individual techniques for the treatment and prevention of complications and anaphylaxis.
Targeted Therapy for Severe Asthma: Switching Biological agents in Real Clinical Practice — Causes and Consequences
Abstract
BACKGROUND: The complexity of choosing a genetically engineered biological drug for the treatment of severe bronchial asthma is due to the intersection of disease endotypes and phenotypes. Mistakes in biological choice lead to the discontinuation and/or switching of the drug because of insufficient effectiveness of therapy.
AIM: To determine the reasons for stopping targeted therapy and biological switching effectiveness in patients with severe bronchial asthma in clinical practice.
MATERIALS AND METHODS: Patients with severe bronchial asthma (n=116) from the Sverdlovsk region register were divided into three groups: (1) continuous, (2) stoppers, and (3) switchers. Predictors of biological withdrawal and switching, reasons for the first biological stopping, switching schemes, therapy effectiveness after switching according to the asthma control test (ACT), asthma quality of life questionnaire (AQLQ), 22-item sinonasal outcome test [SNOT-22], forced expiratory volume in the first second, need for systemic glucocorticosteroids, and achievement of strong asthma control were determined.
RESULTS: Of the 116 patients in the registry, 17.2% were stoppers and 12.1% were switchers. Stoppers suffered from chronic rhinosinusitis with nasal polyps less often and had an earlier asthma onset. Switchers had higher blood eosinophil levels. Therapy was canceled for personal reasons in 45% of the patients. The ineffectiveness of therapy in severe bronchial asthma and/or chronic rhinosinusitis with nasal polyps was the main reason for switching (92.8%) from omalizumab and benralizumab. The drug of choice for switching was dupilumab. Indicators improved, namely, ACT by 86.4%, AQLQ by 52.5%, SNOT-22 by 48%, and forced expiratory volume in the first second by 21.2%), and the need for systemic glucocorticosteroids decreased to 0 in 12 months after switching. Strong control was achieved in 62.5% of the patients when excluding the forced expiratory volume in the first second, and 50% of patients when including the forced expiratory volume in the first second.
CONCLUSION: Careful selection of targeted therapy patients minimizes the failures of the starting drug to 12.1%. Switching the starting genetically engineered biological drug, aimed only at blocking eosinophils or only at blocking IgE, because of its inefficiency, to a drug with a dual mechanism of action leads to a significant improvement in ACT, AQLQ, SNOT-22, forced expiratory volume in the first second, and absence of systemic glucocorticosteroids.
Spectra of sensitization to aeroallergens in patients with allergy from the upper chirchik district of the Republic of Uzbekistan
Abstract
BACKGROUND: Allergic airway diseases caused by hypersensitivity to aeroallergens are the most common manifestation of atopy in children and adults. However, sensitization in the population primarily depends on the allergenic composition of the air environment. Identification of sensitization is a prerequisite for successful treatment of allergic diseases, although the structure of sensitization may have regional characteristics.
AIM: To study the spectrum of sensitization in people with allergic diseases, namely, allergic rhinitis, bronchial asthma of varying severity, and atopic dermatitis, in the Upperchirchik district of the Tashkent region, which is characterized by a long period of flowering of weeds (wormwood, saltwort, and quinoa, from the end of August to the end of November), cereals (timothy, foxtail, rye, and bluegrass), and herbs (from the end of February to the end of July); the duration of flowering is associated with the peculiarities of climatic and geographic conditions.
MATERIALS AND METHODS: From January to May 2022, a clinical and allergological examination was conducted on 100 patients with allergic diseases; of these, 38 were children aged 2–18 years (including 20 children with allergic rhinitis, 12 with bronchial asthma, 6 with atopic dermatitis) and 62 were adults (including 32 patients with allergic rhinitis, 13 with bronchial asthma, 17 with atopic dermatitis). To study the total IgE in the blood serum, allergen-specific IgE and standard diagnostic allergens were used for skin testing.
RESULTS: Among all examined patients, the most frequent were intermittent and persistent forms of allergic rhinitis in 52 (52%), bronchial asthma in 25 (25%), atopic dermatitis in 23 (23%), combination of allergic rhinitis + bronchial asthma in 13 (13%), allergic rhinitis + atopic dermatitis in 12 (12%), and atopic dermatitis + bronchial asthma in 9 (9%) patients. Combined sensitization to pollen and household and food allergens was detected in 90% of the patients, monosensitization to allergens of cereal grasses (meadow Timothy and meadow bluegrass) in 6% and to allergens of weeds (wormwood and quinoa) in 4%. Sensitization to house dust (h1) was detected in 29 children and 51 adults. The frequency of sensitization to food allergens was higher in children than in adults: to cow’s milk allergens in 28.9% of children and 8.1% of adults; to egg allergens in 44.7% of children and 24.2% of adults; and to nut allergens in 38.7% of children and 34.2% of adults.
CONCLUSION: The spectrum of sensitization to allergens in patients with allergic diseases in the Upperchirchik district of the Tashkent region is characterized by a predominance of sensitization to pollens and household allergens in children and adults, with a significant proportion of polysensitized patients in all age groups.
Characteristics of the molecular sensitization profiles in patients with birch pollen allergy and cross-reactive food allergy to PR-10 proteins
Abstract
BACKGROUND: Birch pollen allergy is widespread and is the main allergic disease in Russia. Cross-reactive food allergy, often found in patients with birch pollen allergy, is an underestimated problem that complicates the course of pollinosis and requires further study to improve the quality of diagnosis and personalized recommendations for such patients.
AIM: To study the features of the molecular sensitization profile of adult patients with birch pollen allergy and cross-reactive food allergy to PR-10 proteins.
MATERIALS AND METHODS: Twenty-five adult patients with confirmed birch pollen allergy, with or without cross-reactive food allergy, were included in an open single-center interventional prospective controlled nonrandomized study. Specific IgE to 112 allergens was determined by multiplex analysis using ImmunoCAP ISAC (ThermoFisher, Sweden). Patients with cross-reactive food allergy completed a validated questionnaire on cross-reactive food allergy symptoms and causative allergens. The primary endpoint of the study was the assessment of the sensitization profile to Bet v 1 and PR-10 proteins (Mal d 1, Ara h 8, Cor a 1.0101, Cor a 1.0401, Act d 8, Api g 1, Pru p 1, and Gly m 4) and the clinical characteristics of the sensitized patients. The secondary endpoint was the comparison of patients with and without cross-reactive food allergy and the evaluation of how sensitization to Bet v 1 and PR-10 homologs can affect clinical manifestations of cross-reactive food allergy in patients.
RESULTS: The study included 25 patients aged 18–55 years, from which two comparable groups were formed: group 1 consisted of 13 patients with cross-reactive food allergy symptoms and group 2 (without cross-reactive food allergy) consisted of 12 patients who had never experienced cross-reactive food allergy symptoms. Analysis of the sensitization profile to PR-10 allergens revealed similar patterns in both groups; however, sIgE concentrations to all allergens were significantly higher in group 1. A strong correlation was found between the number of triggering products and total IgE level with PR-10 proteins (r=0.81; p=0.001). The severity of cross-reactive food allergy symptoms correlated with the total level of IgE to PR-10 proteins (r=0.97; p <0.0001). The cutoff level for total sIgE to food PR-10 proteins, equal to 70 ISU-E, allowed us to distinguish patients with only oral allergic syndrome from those with systemic manifestations of cross-reactive food allergy.
CONCLUSION: The results of the study are applicable in clinical practice and have prognostic value in determining the severity of cross-reactive food allergy.
Quantitative and species changes in the local microbiota of the upper respiratory tract in allergic rhinitis
Abstract
BACKGROUND: The role of local microflora in the pathogenesis of allergic rhinitis has not been sufficiently studied; therefore, the study of changes in the nasal microbiome is of interest from a scientific and practical point of view.
AIM: To evaluate changes in the local microbiota of the nasal mucosa in patients with seasonal and year-round allergic rhinitis before and after pharmacological and allergen-specific therapy.
MATERIALS AND METHODS: An observational retrospective single-center case-control study was conducted, which included 182 patients with allergic rhinitis. The groups were randomized according to the diagnosis (seasonal and year-round allergic rhinitis) and the therapy used: basic pharmacotherapy and allergen-specific (sublingual) immunotherapy.
RESULTS: In total, 182 patients completed the study, of which 50 had seasonal allergic rhinitis, 51 had seasonal allergic rhinitis + atopic asthma (aged 7–42 years), and 81 had year-round allergic rhinitis, which included 29 aged 12–54 years and 52 with year-round allergic rhinitis + atopic asthma, aged 12–39 years. Patients with allergic rhinitis were divided into two subgroups: those who received basic therapy to achieve remission and those who received allergen-specific (sublingual) immunotherapy. After basic therapy, the abundance of Staphylococcus aureus in the local microbiota of the upper respiratory tract in patients with seasonal allergic rhinitis decreased by 1.4 times; in the allergen-specific (sublingual) immunotherapy group, its abundance more significantly decreased (3.9 times; p <0.05). In the group with year-round allergic rhinitis, the same pattern was noted. In the group with seasonal allergic rhinitis and year-round allergic rhinitis and the group with both allergen-specific (sublingual) immunotherapy and atopic asthma who received a full course of allergen-specific (sublingual) immunotherapy, the activation index of blood basophils by rSplA-proteinase S. aureus was reduced by 1.2–1.5 compared with the value in those who received basic pharmacotherapy.
CONCLUSION: Patients with allergic rhinitis exhibited quantitative and qualitative significant changes in the microbiome of the upper respiratory tract mucosa, one of the consequences of which is the development of IgE-mediated sensitization to S. aureus products. Allergen-specific immunotherapy for patients with allergic rhinitis leads to decreased colonization of the nasal mucosa with S. aureus and decreased sensitization to rSplA proteinase.
Reviews
IgE mediated food allergy and celiac disease: An updated review
Abstract
Celiac disease is a chronic autoimmune disorder that affects the small intestine. It is triggered in genetically predisposed individuals by consumption of gluten, a protein found in wheat, barley and rye. Celiac disease typically manifests in young pediatric patients as malabsorption of nutrients, gastrointestinal symptoms, and other health complications, which is associated with partial or total villous atrophy of the proximal small intestine. Food allergy, on the other hand, is an abnormal immune response to a specific food protein that causes inflammation and a range of symptoms, from mild hives to life-threatening anaphylaxis.
Although the mechanisms behind celiac disease and food allergy are different, both conditions involve an immune response to food proteins. The current study revealed the possibility of IgE-A coexistence in celiac disease and food allergy screening should be considered for people with celiac disease, especially when symptoms persist even after implementing a gluten-free. However, the relationship between celiac disease and food allergy is not fully understood, and more research is needed to explore this link.
This review aims to examine the available literature for the occurrence of food allergy in subjects with celiac disease.
Severe anaphylaxis in children: Definitions, etiology, and preventive approaches
Abstract
Anaphylaxis is a generalized allergic reaction, and its severe course has a potential risk of fatal outcome. The course of each episode of anaphylaxis is the result of a complex interaction between the patient and some internal and external factors (concomitant diseases, profile and level of sensitization, features of allergen exposure, intercurrent infections, etc.). Currently, the clinical and biological features of severe anaphylaxis are not well characterized; however, arterial hypotension and/or loss of consciousness are usually observed in these patients, possibly without typical symptoms from the skin, whereas the outcome of the disease is associated with the possibility of timely emergency medical care. The lack of generally accepted reliable individual prognostic predictors for determining this group of patients is a serious problem. Very little data are available on subfatal/fatal anaphylaxis in pediatric patients, and approaches to it are often based on clinical experience in other age groups. This article presents a systematization of data in the context of severe and subfatal/fatal anaphylaxis in pediatrics to understand the etiology, risk factors, and markers of severe life-threatening allergic reactions in children and the possibilities of their prevention.
Diagnostic verification and routing of children with bronchial asthma using the current information system capabilities
Abstract
Asthma is a heterogeneous, chronic, and recurrent inflammatory lung disease that also affects children. In recent decades, the incidence of bronchial asthma has been steadily increasing. In 2021, asthma affected 0.89% and 1.87% of Russian children aged 0–14 and 15–17 years, respectively; however, the prevalence of asthma according to official statistics is lower than the real data. Therefore, a significant proportion of patients do not receive proper treatment, which ultimately affects the quality of life of these patients and their parents. Early and accurate diagnosis of bronchial asthma and identification of children with an uncontrolled disease course will provide an opportunity to select/change therapy to achieve remission, thereby preventing possible negative consequences of the disease. In Moscow, according to Order No. 947n of the Ministry of Health of Russia, to improve the quality of medical services, including outpatient care, the Unified Medical Information and Analytical System (UMIAS) has been implemented, which has improved the availability and quality of medical services of public healthcare institutions in the city. This study proposes simple algorithms, and their integration into the UMIAS system will facilitate diagnosis verification for pediatricians and provide allergologists with tools for timely and structured routing of patients with uncontrolled bronchial asthma.
Diagnostic and prognostic value of biomarkers in atopic dermatitis for assessing its endotypes, phenotypes, and treatment efficacy
Abstract
Atopic dermatitis is a highly heterogeneous disease that usually requires a tailored approach to therapy. Recent studies have described a variety of biomarkers linked to diverse pathophysiological aspects of atopic dermatitis. Furthermore, they have provided encouraging evidence supporting high clinical importance of these biomarkers as promising tools for personalized diagnosis, assessment of disease severity, and monitoring of treatment efficacy. This review aims to provide a comprehensive summary of research progress on atopic dermatitis biomarkers, their diagnostic and prognostic value, as well as the benefits they might potentially offer not only for determining the disease endotype, but also for developing novel management strategies. The implementation of easily accessible and simple methods to measure atopic dermatitis biomarkers into clinical practice is an ambitious task for allergologists and dermatologists. A detailed overview of currently available data will allow us to identify the most important trajectories for future research in this area that will promote the concept of personalized atopic dermatitis therapy, reduce the disease burden, and improve the quality of life of patients.
Case reports
Development of cofactor-dependent anaphylaxis in a patient with cross-reactive food allergy
Abstract
Anaphylaxis is a severe life-threatening systemic IgE-dependent hypersensitivity reaction that develops rapidly and can be fatal. As a rule, an anaphylactic reaction develops in response to food, insect stings, and medicine drugs. Sometimes, cofactors can modulate anaphylaxis and significantly reduce the required allergen dose for the development of an anaphylactic reaction. In such cases, anaphylaxis is considered cofactor-dependent. Alcohol consumption is a leading factor in cofactor-dependent anaphylaxis. This article presents a clinical case of cofactor-dependent anaphylaxis. Skin testing with extracts of inhalation allergens and molecular allergy diagnostics using the ImmunoCAP ISAC allergochip (112 allergy components) performed at the Institute of Immunology (Moscow) showed positive results with pollen allergens of deciduous trees and meadow grasses and an increase in the level of specific immunoglobulin E (sIgE) to the main inhalation allergens — birch, hazel, alder, Timothy, pigweed, and wormwood pollen, and to cross-reacting components of allergens from the PR-10 protein group, such as soya bean, kiwi, apple, peach, celery, peanut, and hazelnut. Based on the results of molecular allergy diagnostics, a personalized elimination diet was prepared and recommendations were made to the patient.
Editorial
Moisturizers for the treatment and prophylaxis of atopic dermatitis exacerbations
Abstract
Atopic dermatitis is a global problem with increasing prevalence. Genetic predisposition to allergies, epidermal barrier dysfunction, and T2 immune response underlie atopic dermatitis. Xerosis, itchy skin, and exacerbation are the main atopic dermatitis symptoms, leading to increased permeability of allergens and microbes through the damaged epidermis and to the development of sensitization. The main purpose of atopic dermatitis therapy is to achieve long-term remission and improve quality of life. Topical treatment includes glucocorticosteroids, topical calcineurin inhibitors, and emollients to reduce inflammation, xerosis, and infection prevention. Daily use of effective emollients as basic skin care can improve epidermal barrier function, provide skin hydration, and reduce the need for topical glucocorticosteroids.