Vol 17, No 3 (2020)

Topical calcineurin inhibitors (TCI) have emerged from the shadow of topical corticosteroids as another first-line remedies for treating acute flares of atopic dermatitis (AD). The effectiveness of TCI in maintenance therapy is also undeniable. The wider use of TCI increases the relevance of the issue of their safety. The adherence of physicians and their patients to the treatment with TCI is constrained by a controversial FDA black box warning against these drugs based on the theoretical risk of skin tumors, especially lymphoma. This warning, formulated in 2005, has been repeatedly refuted. However, there have been studies that at least partially supported cautious use of TCI. In recent years, the results of large cohort prospective studies clarifying the issue of oncological safety of TCI have been published. The review highlights the results of various studies with optimistic, pessimistic and balanced conclusions regarding the safety of TCI, primarily their effect on tumorigenesis, in order to better inform physicians about the benefit/risk balance when using these drugs in AD patients. The data presented in this review indicate that there is no increased risk of melanoma and other forms of skin cancer in TCI users, but these data do not completely rule out the risk of skin lymphoma. However, the very low level of potential risk to an individual patient gives physicians the right to neglect this risk when choosing TCI as a treatment option for AD.

This article is dedicated to the main characteristics of severe bronchial asthma (SBA) and its heterogeneity. In particular, it describes T2 asthma and the role of the main cytokines involved in T2 inflammation. It focuses on the role of IL-4 and IL-13 in the pathogenesis of asthma and other T2-associated diseases, as key cytokines in the initiation and maintenance of T2 inflammation. The article presents the results of experimental studies proving that the activation of IL-4/IL-13 can cause significant hyperresponsiveness of the human airway smooth muscles and the combined blockade of the activity of these cytokines using a human monoclonal antibody against the common IL-4/13 receptor á-subunit-dupilumab-determines the clinical efficacy not only in relation to exacerbations and control of asthma symptoms, but also an improvement of the lung function and a reduction in bronchial hyperresponsiveness. When type 2 helper cells (Th2) interact with antigen-presenting cells, IL-4 and IL-13 are simultaneously released, therefore, blocking IL-4Rá is more effective than blocking each of the ligands separately, which explains the high efficacy of dupilumab not only in T2 asthma, but also other T2-associated diseases: atopic dermatitis and chronic rhinosinusitis with nasal polyps. In addition to asthma and atopic dermatitis, a new indication for dupilumab, chronic rhinosinusitis with nasal polyps, has recently been approved.

According to the recommendations of the European Academy of Allergy and Clinical Immunology (EAACI) for the biological therapy of SBA 2020, dupilumab is recommended as an add-on maintenance therapy in adults and children aged 12–17 years old with uncontrolled severe T2 asthma, including asthma with the allergic and eosinophilic phenotype, as well as mixed (when there are signs of both phenotypes) and steroid-dependent asthma. At the same time, dupilumab is well tolerated.

BACKGROUND: Allergic diseases and gastrointestinal tract diseases can influence on the natural course of each other.

AIM: To study the sensitization profile in patients with comorbidity of seasonal allergic rhinitis (SAR) and upper gastrointestinal tract inflammatory diseases (UGITID).

MATERIALS AND METHODS: 112 adult residents of Volgograd city suffering from SAR but without perennial symptoms and sensitization to indoor allergens have been included in the study. 31/112 patients had H. pylori­-negative and 38/112 H. pylori­-positive UGITID. Control group consisted of 43/112 patients without gastrointestinal diseases. Skin prick-­testing with 3 groups of pollen allergens have been carried out.

RESULTS: 75.9% of patients were sensitized to weed pollen; sensitization to grass pollen was in 1.5–3 times less, and 10.5% of patients (4/38) had positive tests with birch pollen. The sensitization to quinoa and ragweed in SAR and H. pylori«–»­-UGITID patients was comparable with control group but less common with wormwood, sumpfweed allergens. The sensitization in SAR patients and H. pylori«+»­-UGITID was similar to the control group, but positive SPT with sunflower and corn allergens were rare then in control group.

CONCLUSION: Weed pollen allergens prevail in sensitization spectrum of adult Volgograd residents with SAR. Sensitization to goose-foot and ragweed is common less in SAR patients and H. pylori«–»­-UGITID but to graminea grass and birch pollen is more often. It may be supposed that the UGITID are predisposing factors to the sensitization to cross-­reacting plant food allergens. At the same time supposed immunomodulating action of H. pylori make the differences between AR patients with H. pylori«+»­-UGITID or H. pylori«–»­-UGITID minor.

BACKGROUND: Urticaria is one of the most common dermatoses and affects 15–25% of the population; chronic spontaneous urticaria occur in 1.8% of adults and in 0.1–3% of children. Second generation antihistamines are effective only in 45–77% of patients. The next steps of treatment include increase antihistamines dose and their combination with omalizumab.

AIM: To analyze own clinical experience and assess effectiveness of omalizumab in severe chronic spontaneous urticaria.

MATERIALS AND METHODS: Effectiveness of biological treatment with omalizumab was analyzed in 14 patients with severe chronic spontaneous urticaria.

RESULTS: The prescription of omalizumab in the basic therapy of patients with severe chronic spontaneous urticaria (CSU) allowed to reduce significantly the severity of clinical symptoms in 78.6% of patients, to abandon the use of systemic glucocorticosteroids and to achieve partial or complete control of the disease. It should be noted, that 28.5% of patients during the immunobiological therapy stopped taking second-generation antihistamines and the dosage was reduced to therapeutic in 35.7% of patients.

CONCLUSION: Omalizumab is a highly effective in patients with severe chronic spontaneous urticaria.

Over the last years, high attention is given to the hereditary angioedema (HAO). Practitioners can identify the disease by clinical manifestations and family history even before specific laboratory testing. More than 95% of HAO cases are associated with C-1­inhibitor deficiency/dysfunction caused by a mutation in SERPING1 gene. In 25% of patients without C1-inhibitor deficiency HAO is associated with heterozygous mutations in gene F12 coding Hageman XII factor. In 2017–2018 years two more genes responsible for normal C1-inhibitor HAO were discovered: genes PLG and ANGPT1. In clinical practice patients do not always meet typical HAO diagnosis criteria. Diagnostic difficulties appear when clinical picture is not confirmed by related genetic testing results, for example, mutations in genes not described earlier are detected. It should be noted that app. 25% of patients do not have any HAO family history, i.e. have so called de novo mutations. Normally HAO onset takes place within 2 first life decades. 40% of patients have disease progress before the age of 5, and 75% of patients – before the age of 15 y.o. However, it can appear in elderly age, which means certain diagnostic difficulties. It is important to analyze thoroughly patient’s comorbidity and make differential diagnosis with a secondary angioedema.

Severe combined immunodeficiency (SCID) is the most life-threatening form of primary immunodeficiency, fatal within the first years of life if hematopoietic stem cell transplantation (HSCT) is not performed. Early diagnosis is crucial for prevention of multiple life-threatening complications, which in turn allows for successful HSCT. Current publication contains clinical recommendations for diagnosis of SCID and its complications, complex treatment, including HSCT, prenatal diagnostics and genetic family counselling.

In many countries of the world and in Russia, in particular, the pharmacological use of antagonists of cysteinyl receptors LT1 (CysLTR) is a long­-proven and well­-proven pharmacotherapy of bronchial asthma (BA) and allergic rhinitis (AR) in adults and children.

Among antileukotriene drugs the most commonly used medication for the treatment of these diseases is the original montelukast, which is considered a safe drug associated with the appearance of only a few adverse reactions, usually not differing in type and frequency from those that occur with placebo. Currently, there are a large number of generics of montelukast, therefore, practitioners have many questions regarding the benefits and risks of montelukast therapy for patients with BA and AR.

In 2020 FDA (Food and Drug Administration USA) analyzed the risk of adverse events during Montelukast treatment and indicated them on the packaging of the drug (original montelukast and its generics). This contributed to the creation of an expert commission to study this issue and form an expert opinion, which is demonstrated in our publication.

To the 85th anniversary of the birth