EDITORIAL
REVIEW
Introduction. The study of the effectiveness and safety of allergen-specific immunotherapy remains relevant due to the emergence of a personalized approach in allergology and new dosage forms. Adverse reactions during sublingual allergen-specific immunotherapy are the leading reason of treatment discontinuation. Understanding the mechanisms of side effects and knowing how to overcome them allows us to achieve better tolerability of allergen-specific immunotherapy and maintain patient compliance.
The aim of the review is to combine the available literature data on the frequency, nature, and pathogenetic basis of adverse events during sublingual allergen-specific immunotherapy and to consider options for their prevention and treatment.
Relevance. The review examines modern ideas about the immunomodulatory effect of allergen-specific immunotherapy in relation to increasing resistance to infectious pathogens. The information presented will allow clinicians to take a more conscious approach to the process of planning therapy for bronchial asthma, considering allergen-specific immunotherapy not only as a tool for pathogenetic treatment of causally significant sensitization, but also as a tool for immunomodulatory therapy against respiratory viral infections.
Purpose of the work: systematization of accumulated experience in order to provide information for the practicing physician.
Allergen-specific immunotherapy is based on the development of induced tolerance in patients. Natural extracts are most often used as therapeutic allergens worldwide.
The article presents new approaches to biological standardization of subcutaneous administered allergens. It is established that own standard allergens have specific allergenic activity, which was determined on sensitized patients-volunteers. The Russian Federation uses its own units — EAA (Units of Allergenic Activity). 100 000 EAA/mL corresponds to the size of wheal in prick test equal to 8 mm. The internal reference material (RM) of allergenic activity of pollen allergens ”Microgen“ have different specific activity depending on the type of allergen. The most common series have allergenic (specific) activity in the range of 150,000 — 200,000 EAA/mL.
The control of the specific activity of allergen drugs is carried out in accordance with the current certified standard samples of the company’s standards. A method of competitive enzyme-linked immunosorbent assay using specific sera containing specific IgE antibodies is used for this purpose.
In addition, the specific activity of allergen preparations is certified through three additional characteristics: total protein content (using the Bradford method), protein profile (through electrophoresis in a polyacrylamide gel with sodium dodecyl sulfate under reducing conditions), and authenticity through the presence of major specific components, which is determined by the Western blot method using sera containing IgE antibodies specific for the corresponding allergen.
Currently, in the Russian Federation, the standardization of therapeutic and diagnostic allergens is conducted simultaneously according to two indicators: protein nitrogen content, expressed in Protein Nitrogen Units (PNU), and allergenic (specific) activity expressed in units of allergenic activity per milliliter (EAA/ml). While the PNU indicator partially reflects the allergenic properties of the drug, it does not fully capture these properties, making it necessary to remove PNU from the list of quality indicators for allergen medicines. This would require changes to regulatory documentation and instructions for allergens.
When evaluating the allergenic activity of allergens, it is now recommended to focus on units of EAA. The consistency of the protein composition and presentation in the drug ensures increased safety and efficacy of therapy, as well as allows for comparison between drugs.
Allergen-specific immunotherapy is a method of treatment and prevention of respiratory allergic diseases. Carrying it out changes and improves the course of allergic diseases. One of the promising and new approaches is the combination of allergen-specific immunotherapy with one of the biological drugs, omalizumab. Currently, few such studies have been carried out in the world. 14 works were selected from international databases (eLibrary.ru, PubMed, Embase, Cochrane, Web of Science). Their results were analyzed and summarized. The characteristics of these studies and their design are given. The results of the safety and effectiveness of the combined use of allergen-specific treatment and anti-IgE therapy are described. It was shown that in most cases (13 out of 14), omalizumab therapy precedes allergen-specific immunotherapy. However, the duration of combination treatment, drug regimens, and patient monitoring vary significantly. All studies have established a variety of positive effects of the combined use of omalizumab and allergen-specific immunotherapy (improvement of the course of diseases, increased possibility of treatment with allergens, good tolerability of drugs, etc.). These studies are very promising. Their continuation is required. It is necessary to clarify the most rational schemes for the combined use of anti-IgE and allergen-specific immunotherapy.
ORIGINAL ARTICLES
Due to its widespread distribution, the problem of pollen allergy does not lose its relevance for practical healthcare: the variety of clinical forms, the possibility of polyvalent sensitization and pathogenetic treatment in the form of allergen-specific immunotherapy determine the importance of studying its clinical and epidemiological features.
Materials and methods. A retrospective analysis of 119 discharge summaries of children with diagnoses of “Allergic rhinoconjunctivitis”, “Bronchial asthma”, “Atopic dermatitis”, occurring with clinically significant pollen sensitization, was carried out in the period 2015–2022. The prevalence, clinical features, prevailing symptoms and atopic comorbidity of patients with pollen allergy living in the Nizhny Novgorod region were assessed.
Results. Pollen allergy is characterized by a variety of clinical manifestations, which are mainly represented by allergic rhinoconjunctivitis, bronchial asthma, and oral allergic syndrome. In the study, in the majority of patients, polyvalent sensitization was combined with a pronounced variety of products that provoke oral allergic syndrome. Manifestations of pollen allergies requiring seeking medical help are equally distributed among residents of Nizhny Novgorod and the region’s villages.
Conclusions. Clinical and epidemiological features of the course of pollen allergy are of great interest to the practicing physician. The variety of manifestations of pollen allergies determines the need for a clinically effective treatment method, which today is ASIT. One of the needs of modern healthcare is to increase the awareness of primary care physicians about atopic diseases, incl. pollen allergy, with the aim of timely referral of patients to a specialist. Currently, allergen-specific immunotherapy is the most effective method of treating manifestations of pollen allergies.
Relevance. There is a shortage of studies that would evaluate the effectiveness of allergen immunotherapy (AIT) in children with bronchial asthma (BA) and polysensitization.
The aim of the study: to evaluate AIT effectiveness with house dust mite (HDM) allergens in the treatment of BA in children polysensitized to perennial allergens, based on the dynamics of the symptoms and medications score.
Materials and methods. The open prospective controlled study included 36 children aged 9,6 [6,9; 12,3] years (from 6 years 1 months to 14 years 3 months) with moderate atopic asthma (21 children (58%) and mild asthma (15 children (42%) and polysensitization to household allergens. Each patient was observed in the study for 4 years: 1 year of preliminary observation and 3 years of sublingual AIT with D. pteronyssinus and D. farinae (Staloral, Stallergenes Greer, France). For each year of observation, asthma symptoms and medications used were assessed, and the combined Score was calculated. To confirm sensitization, a prick test was performed using a standard method with allergens: house dust, D. pteronyssinus, D. farinae, cat, dog, horse, pillow feather (Biomed, Russia).
Results. Over 2 years of AIT, the decrease in the symptom and medication Score was 46,9%, and at the end of 3rd year of therapy, 59,8% (р = 0,0001 from baseline). A decrease in the combined Score exceeding 34.9% compared to baseline was noted in all patients in the study.
Conclusion. Sublingual AIT with HDM allergens is highly effective in the treatment of asthma in children with domestic polysensitization, in terms of reducing symptoms of the disease, the need for pharmacotherapy and the combined Score of symptoms and medications. A significant positive effect was registered already from the first year of AIT and continues to increase over subsequent years of therapy.
Introduction. According to modern data, Oral Allergy Syndrome (OAS) is most often formed by patients sensitized to the birch family: up to 73% of patients allergic to birch experienced OAS. 86% of them experience their oral symptoms year-round, which significantly affects the quality of life of these patients. The effectiveness of AIT in the treatment of respiratory allergy symptoms is beyond doubt, while the effect on the manifestations of cross-food allergies requires additional study.
Objective. To study the clinical effectiveness of the formation of oral tolerance to fruits and vegetables under the influence of allergen-specific immunotherapy (ASIT) with the allergen Staloral® “Birch pollen allergen” (Stallergenes Greer, France).
Material and methods. The study (prospective open comparative longitudinal) included 184 patients with respiratory allergy to birch pollen aged 5 to 16 years with confirmed sensitization to the major molecule (Bet v 1). Children of the main group (n = 134, 7.0 [5.0; 9.0] years) had OAS. Children from the comparison group (n = 50, 7.0 [6.0; 10.0] years) did not have OAS. A clinical examination, general clinical and allergological examinations were carried out for each child. Component allergy diagnostics was performed using a multiplex panel (ISAC-112, ImmunoCAP) for children with OAS (n = 40) who had multiple manifestations of cross-food allergies. Patients of both groups (n = 184) received a three-year course of AIT with the allergen Staloral® “Birch pollen allergen”.
Results. In patients with OAS, it was possible to achieve the formation of oral tolerance (total or partial) to fresh vegetables and fruits in 88.81% (n = 119, p = 0.000). There was a decrease in the intensity and duration of respiratory allergy symptoms during the pollination season, and the need for pharmacotherapy after a three-year course of AIT Staloral® “Birch pollen allergen” in children of both groups.
Conclusions: three-year AIT with the allergen Staloral® “Birch pollen allergen” is able to form oral tolerance in children with cross food allergies to PR-10 proteins of vegetables and fruits.
MEDICAL CASES
Introduction. ASIT is characterized by a high safety profile, however, when prescribing ASIT, indications and certain contraindications should be taken into account, knowledge of which is mandatory for every practicing allergist. In recent years, clinical contraindications to ASIT have been revised due to the publication of the Position Paper of the European Academy of Allergy and Clinical Immunology (EAACI). The decision to prescribe ASIT is based on an assessment of the individual patient’s condition, analysis of indications, consideration of contraindications to ASIT, assessment of concomitant diseases, and their pharmacotherapy. The doctor must make the final decision when prescribing allergen treatment, weighing the risk-benefit ratio. Refusal to perform ASIT on a patient with must be clearly reasoned and justified.
Presentation of a clinical case. A child aged 11 years was observed with a diagnosis of allergic bronchial asthma, mild intermittent course. Allergic rhinitis, persistent course. Allergy to trees, cereals, weeds. Cross food allergy (peas, melon) with clinical manifestations in the form of oral allergic syndrome, acute urticaria, angioedema of the lips and tongue. Asperger’s syndrome. Congenital cataract. Despite the annual progression of respiratory allergies and the expansion of the spectrum of sensitization, the patient was not offered ASIT for a long time if there were indications for its implementation due to the presence of comorbid pathology. The presence of mental illness, according to the Position Document, is a relative contraindication to ASIT. ASIT with the therapeutic allergen Grazax is not accompanied by side effects and is characterized by high compliance, which led to a significant therapeutic effect.
Conclusion. This clinical observation clearly demonstrates a situation where the initial refusal to administer ASIT to a patient with an indication for this type of treatment was unfounded. Even in the case of complex comorbid pathology, ASIT can be performed effectively and safely.
Introduction. Allergy to birch pollen is a common allergic disease. The main allergen of birch pollen is Bet v 1. The Bet v 1 protein structure is the similar to proteins of hazel, alder and elm pollen, as well as fruits proteins (apples, apricots, peaches, cherries) and vegetables ones (carrots, celery). Therefore, children with an allergy to the Bet v 1 protein may experience oral allergy syndrome (OAS) and even anaphylaxis when eating these foods. Allergen-specific immunotherapy (ASIT) is the indication for the pollen allergy treatment.
Presentation of the clinical case. A 11 years old child was observed with a diagnosis of bronchial asthma, allergic form, moderate persistent clinical course. Pollinosis. Allergic rhinitis. Allergic conjunctivitis. Allergy to birch pollen (Bet v 1). Cross food hypersensitivity: oral syndrome (PR-10 proteins) and anaphylaxis (hazelnuts, peanuts). Systemic manifestations of pollen allergy limit immunotherapy due to the possible development of adverse reactions.
The child was prescribed sublingual immunotherapy (SLIT) with the medication “Staloral birch pollen allergen”. Baseline therapy was chosen for the child to achieve control of asthma and rhinitis, a hypoallergenic diet with the exclusion of significant food allergens was prescribed. Asthma and rhinitis exacerbation and OAS was observed during the 1st and 2nd treatment courses. Against the background of baseline therapy, SLIT was continued. The full maintenance dose was achieved during the 3rd SLIT course. Immunotherapy contributed to the reduction of symptoms of rhinitis and asthma, reduction of disease clinical course severity, reduction of baseline medications doses and OAS relief.
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