Vol 20, No 2 (2023)

In February 2023, a meeting of the Council of Experts was held, attended by leading specialists in the fields of allergology, pediatrics and dermatology.

The Working Group discussed the problem of sensitization to pollen allergens in patients with atopic dermatitis and exacerbation of the disease during the pollination season of plants, as well as the formation of epicutaneous sensitization through a damaged epidermal barrier. The experts comprehensively considered the criteria that a modern emollient used for the care of atopic dermatitis patients' skin should meet, discussed the role of moisturizers in preventing seasonal exacerbations of atopic dermatitis based on previously conducted research, and developed unified recommendations on the principles of managing this type of patients.

Suggestions were made for further informational and organizational measures aimed at expanding the knowledge of patients and medical specialists about the problem of epicutaneous sensitization to aeroallergens in atopic dermatitis patients, their role in the development of seasonal exacerbations of atopic dermatitis, and the possibility of their prevention using modern emollients.

BACKGROUND: Ebastine is widely used in medical practice for treating urticaria and allergic rhinitis. This compound is an antiallergic drug that belongs to the second generation of H₁ histamine receptor blockers. The effectiveness of ebastine can be observed when it is orally administered. As a part of the registration of the trade name Allergostin, a clinical study of its bioequivalence with Kestin was conducted involving 26 healthy volunteers.

AIM: To summarize the results of the clinical study of the comparative pharmacokinetics and bioequivalence, safety, and the tolerability of Allergostin (film-coated tablets, 20 mg; NTFF POLYSAN LLC, Russia) and Kestin (film-coated tablets, 20 mg; Almirall S.A., Spain) among healthy volunteers after a single oral dose on an empty stomach.

MATERIALS AND METHODS: To confirm bioequivalence, we conducted an open, randomized, two-period crossover study of comparative pharmacokinetics and bioequivalence of drugs with a single oral administration on an empty stomach in healthy male and female volunteers aged ≥18. During the study, blood plasma samples were collected from volunteers. Each sample was tested using a validated high-performance liquid chromatography with tandem mass spectrometry method, and the concentrations of ebastine and the active metabolite carabastin were determined. Based on the obtained data, pharmacokinetic and statistical analyses were carried out, and 90% confidence intervals were calculated for the ratio of the geometric mean values of the pharmacokinetic parameters C_max and AUC_0-72 for carabastin.

RESULTS: Based on the results of statistical analysis, the pharmacokinetic parameters of the test (Allergostin) and reference (Kestin) drugs were characterized by high similarity. For the estimated pharmacokinetic parameters of carabastin, the 90% confidence intervals ranged from 80% to 125% for AUC_0-t and C_max.

CONCLUSION: Therefore, in accordance with the applied criteria, the drugs are recognized as bioequivalent.

BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency is a rare disease caused by a deficiency and/or a decrease in the functional activity of the C1 inhibitor. The primary symptom of this condition is recurrent angioedema of various localizations. According to the modern concept of treatment, the therapy aims to stop emerging angioedema and prevent death as well as achieve complete control of the disease and a high quality of life. Lanadelumab is a modern medicine developed and used to prevent attacks in patients with hereditary angioedema aged ≥12 years.

AIM: A retrospective study (IISR-2021-200085) was conducted to evaluate the efficiency and safety of lanadelumab in real-life practice in Russia.

MATERIALS AND METHODS: In all, 16 patients with hereditary angioedema and C1 inhibitor deficiency were enrolled at the initiation of lanadelumab treatment. The patients were predominantly female (81%; 13/16). The average age of patients was 29.9 years; 19% (3/16) of the patients were adolescents. The effectiveness was evaluated by comparing the patient-reported attack rates. The following PROs for the adults only were assessed initially and during the treatment: angioedema activity score, angioedema control test (AECT), angioedema quality of life questionnaire (AE-QoL), and hereditary angioedema activity score. The incidences of adverse events were evaluated.

RESULTS: Before lanadelumab, 69% (11/16) of the patients received alternative long-term prophylaxis, which was canceled after the start of lanadelumab treatment. The average number of attacks per month and treated attacks per month prelanadelumab were 10 and 4.7 per patient, respectively. After 6 months of treatment, these values were 0.26 and 0.09, respectively (10 patients were symptom free at 6 months after the initiation of the treatment). After 3 months of treatment, the mean AECT values improved from 5.6 to 14.2 (p <0.001), and all patients showed adequate disease control. After 6 months of treatment, AE-QoL decreased from 58 to 19 (p <0.001). No serious adverse events related to lanadelumab were observed.

CONCLUSION: Our study demonstrated that the composite effect of lanadelumab minimizes the attack rate and improves the quality of life in patients with hereditary angioedema. A good safety profile of lanadelumab is shown.

Allergen-specific immunotherapy is the primary pathogenetically substantiated method for treating allergic diseases.

This treatment decreases the severity of clinical symptoms, has disease-modifying effects, and prevents disease progression, asthma development, and the spread of sensitization. A complex interaction between various cells of innate and adaptive immunity mediates immunological tolerance driven by allergen-specific immunotherapy. Although the primary mechanisms of allergen-specific immunotherapy have been described to date, the understanding of these processes becomes more detailed at the cellular, molecular, and epigenetic levels each year. As a result, deep insights into the mechanisms underlying the development and maintenance of tolerance to allergens during allergen-specific immunotherapy can help reveal the predictive biomarkers of efficacy. These biomarkers can streamline the selection of patients via the identification of responders to allergen-specific immunotherapy.

This review presents the current concepts of allergen-specific immunotherapy mechanisms at various stages of the allergic process. Furthermore, the predictive biomarkers of the efficacy are described, with consideration of promising directions of research in this area.

Drug allergy is one of the most common problems in clinical medicine including ophthalmology. The frequency and severity of drug-induced eye lesions continuously increase as the arsenal of active drugs increases.

Among the common causes of eye contact allergy, along with traditionally noted antibiotics and anesthetics, an expanded list of the most remarkable drug allergens, including mydriatics (tropicamide and phenylephrine), beta blockers, dorzolamide, latanoprost, and topical corticosteroids, have been registered recently. In addition to active ingredients, ophthalmic preparations contain various auxiliary substances, such as benzalkonium chloride, chlorhexidine, and thiomersal, which possess sensitizing properties.

This study presents a clinical case of a patient suffering from cataracts who developed an acute local allergic reaction during the introductory period of lens replacement surgery, resulting in the cancelation of surgical intervention. In addition, several drugs are used simultaneously, each of which can cause allergies and excipients in their composition. Approaches to specific diagnostics including the choice of skin tests are described depending on the clinical phenotype of drug allergy. After determining the cause of allergy, recommendations are given to the patient and ophthalmologist for further treatment, enabling the subsequent performance of the operation without complications.

Hereditary angioedema is a rare genetically determined disease characterized by the recurrent angioedema of various localizations with no response to systemic glucocorticosteroids, antihistamines.

In the majority of hereditary angioedema cases C1-inhibitor level or it’s functional activity is decreased due to a mutation in the SERPING1 gene. In recent years, the expansion of genetic diagnostic recourses significantly changed our understanding of the pathogenesis of hereditary angioedema without of C1-inhibitor deficiency with previously unknown mutations. Currently mutations in six different genes have been identified as causing hereditary angioedema: factor XII (F12), plasminogen (PLG), angiopoietin 1 (ANGPT1), Kininogen 1 (KNG1), Myoferlin (MYOF), and heparan sulfate (HS)-glucosamine 3-O-sulfotransferase 6 (HS3ST6). Moreover, the last 3 of them are referred to a separate phenotype ― intrinsic endothelial dysfunction.

In 2020 a series of clinical cases in patients with MYOF gene mutation in an Italian family were published. This type is exceptionally rare ― only 3 female relatives from the same family are described.

This article presents a review of the actual international literature and describes the first clinical case of a male patient with a mutation in the myoferlin gene confirmed by genetic testing.

Nasal symptoms such as nasal congestion, rhinorrhea, and cough are especially common in children. Despite symptomatic treatment (various nasal sprays, physiotherapy, antibiotics and topical glucocorticosteroids), nasal congestion can persist for a long time. In such cases, several diseases are most likely: adenoids, allergic rhinitis, various anomalies in the structure of intranasal structures and sinuses (for example, curvature of the nasal septum), rhinosinusitis (acute, subacute). If a child has two main symptoms ― congestion and discharge from the nose ― and such additional symptoms as a headache with predominant localization in the paranasal sinuses and a deterioration in smell (possibly also the taste of food) for more than 3 months, it is necessary to exclude the diagnosis of chronic rhinosinusitis, which can be combined with a nasal polyp.

The purpose of this article is to analyze clinical cases of chronic rhinosinusitis with nasal polyp in two preschool children, including one of them with intolerance to non-steroidal anti-inflammatory drugs, and to raise physicians' awareness of this nosology.

In children with symptoms such as prolonged nasal congestion, rhinorrhea, possibly impaired sense of smell, headache, intolerance to non-steroidal anti-inflammatory drugs, in the absence of sensitization and immunodeficiency, a computed tomography scan of the paranasal sinuses is recommended to exclude nasal polyp.