Vol 21, No 2 (2024)

BACKGROUND: The main mechanism of drug hypersensitivity to non-steroidal anti-inflammatory drugs is associated with inhibition of cyclooxygenase type 1, which leads to cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs from various subgroups of different chemical structures. Clinically, cross-hypersensitivity usually manifests in the form of urticaria and/or angioedema.

AIM: To characterize a group of patients with cross-hypersensitivity to non-steroidal anti-inflammatory drugs manifesting as urticaria / angioedema / anaphylaxis.

MATERIALS AND METHODS: To achieve this aim a prospective single-center study was conducted. Patients with a presumptive diagnosis of drug hypersensitivity to non-steroidal anti-inflammatory drugs (n=307) were consulted. A group of patients (n=237) with high probability of such reactions was identified, of which cross-hypersensitivity manifested as urticaria / angioedema / anaphylaxis was observed in 127 patients. This group was divided into 2 phenotypes: a group with concomitant chronic urticaria (n=67) and without it (n=60). We assessed demographic data, drug triggers, clinical manifestations, concomitant atopy, and compared these indicators between both groups. Selected patients underwent a drug provocation test with selective or predominantly selective non-steroidal anti-inflammatory drugs and paracetamol.

RESULTS: Cross-hypersensitivity reactions manifested as urticaria / angioedema / anaphylaxis is the most common phenotype of immediate-type drug cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs (75.6%). Women develop this condition 2.5 times more frequently than men, and are more likely to develop cross-drug hypersensitivity with concomitant chronic urticaria with the onset of approximately 16 years later than men. Mild manifestations of cross-hypersensitivity (urticaria/angioedema) develop more frequently than severe ones (anaphylaxis). Angioedema in children, urticaria in adults with concomitant chronic urticaria and angioedema in adults without concomitant chronic urticaria are it's main manifestations. The most frequent non-steroidal anti-inflammatory drugs triggers are metamizole, acetylsalicylic acid and propionic acid derivatives. Non-steroidal anti-inflammatory drugs with the lowest risk of developing drug hypersensitivity are coxibs, paracetamol, and to a lesser extent ― meloxicam, nimesulide.

CONCLUSION: The data obtained allowed us to expand our understanding of cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs presenting as urticaria/angioedema or anaphylaxis. Selective cyclooxygenase type 2 inhibitors and paracetamol are drugs with the highest safety profile.

BACKGROUND: Diagnosis and treatment of COVID-19 in patients with primary immunodeficiency, or inborn errors of immunity, are often challenging.

AIM: Description of the COVID-19 course and therapy of adult patients with primary immunodeficiency treated in medical organizations of Moscow Healthcare Department.

MATERIALS AND METHODS: We analyzed a cohort of 68 patients over 18 years (median ― 35 years) with primary immunodeficiency; 91% of patients have primary immunodeficiency with predominantly antibody deficiencies. Altogether 90 cases of the new СOVID-19 were analyzed: in 68 cases infection occurred for the first time, in 22 cases it recurred. The duration of the disease ranged from 3 to 80 days. Duration of PCR-positivity ranged from 0 to 59 days, median 8 days.

RESULTS: Patients with Wuhan and Delta strains had more severe inflammatory signs according to C-reactive protein and lactate dehydrogenase, in patients with Wuhan lung involvement on CT-scam was larger. In demonstrated group of patients higher C-reactive protein correlated with larger lung involvement, longer duration of the disease and PCR-positivity, significant lymphopenia also correlated with higher C-reactive protein. To our data regularity of intravenous immunoglobulin therapy and IgG trough level didn’t correlate with infection severity and duration of the disease and virus-carriage.

Indirectly, the change in the spectrum of medicine used in patients of the analyzed group coincided with the virus strain evolution. Anti-inflammatory therapy was mainly presented by dexamethasone and antagonists to interleukin 6 or its receptor (anti-IL-6): 55% and 73% for Wuhan, 63% and 50% for Delta, 17% and 39% for Omicron. Then, preference was gradually given to the target anti-cytokine medicine. Etiotropic antiviral therapy was more often used to treat infection caused by Wuhan and Delta strains ― 32% and 38%, respectively (in 17% for Omicron). With shifting toward immunotherapy by specific against COVID-19 immunoglobulins and monoclonal antibody to SARS-CoV-2: 5% and 9% for Wuhan, 0% and 75% for Delta, 48% and 83% for Omicron, respectively. Immune and etiotropic therapy was not carried out in Wuhan in 39%, in Delta in 43%, in Omicron in 41% of cases. The overall mortality rate from COVID-19 in the analyzed group was 3%.

CONCLUSION: Patients with primary immunodeficiency represent a vulnerable group to the SARS-CoV-2 virus with a high risk of not only severe, but also a protracted and undulating course of infection, what must be taken into account for the correct interpretation of the patient's condition and the timely administration of the appropriate therapy.

BACKGROUND: Association of alopecia areata and atopic diseases has been confirmed in clinical, epidemiologic, genetic and immunologic studies. The study of sensitization features and atopic diseases structure in alopecia areata patients makes it possible to phenotype patients with atopy and consider additional treatment options for alopecia areata.

AIM: To determine the sensitization spectrum and atopic diseases structure in alopecia areata patients considering the age and clinical form of alopecia.

MATERIALS AND METHODS: A comparative uncontrolled study was conducted. The data of 162 patients 5–51 years with alopecia areata, atopic dermatitis, asthma, allergic rhinitis/rhinoconjuctivitis for the period from April 2022 to May 2023 were used. The nature of sensitization and the structure of atopic diseases were analyzed. Clinical forms of alopecia areata were assessed by the hair-loss area.

RESULTS: The patients were divided according to alopecia areata status: the first group included 54 alopecia areata patients with atopic diseases, the second ― 108 atopic patients without alopecia areata. Subgroups were formed according to age: in group 1 the mean age was 16.3±1.38 years, 57% were children (5–17 years), 43% were older 18 years; in group 2 the mean age was 17.1±1.43 years, 54% children and 46% adults. Among alopecia areata patients seasonal pollen sensitization prevailed (22/54 people); polyvalent sensitization was observed in 13/54 people, 6 of whom had severe forms of alopecia areata, 6 ― ophiasis. Comparison of the sensitization spectrum between the groups revealed no differences. In group of adult alopecia areata patients isolated respiratory allergies were significantly less frequent (OR 0.21; CI 0.07–0.60; p=0.004), but combined atopic diseases were more frequently observed (OR 4.71; CI 1.43–15.58; p=0.012). Most patients with severe alopecia areata were children (8/12) with polyvalent sensitization and respiratory and combined atopic diseases.

CONCLUSION: The comorbidity of alopecia areata and atopy is manifested by an increased incidence of severe alopecia in childhood and a tendency to progression of allergic inflammation, realized as combined atopic diseases. The spectrum of sensitization in patients with and without alopecia areata does not differ and characterized by the predominance of the most common allergens (plant pollen). These results indicate the need for timely phenotyping of alopecia areata patients with allergic predisposition, especially with early onset and progressive alopecia.

BACKGROUND: Hereditary angioedema is a rare disease with high frequency for orphan diseases. The autosomal dominant type of inheritance leads to a significant number of affected patients in families. Angioedema attacks significantly impair the quality of life. hereditary angioedema causes life-threatening conditions which depend on edema’s localization.

AIM: To evaluate the efficacy and safety of lanadelumab for long-term prophylaxis in hereditary angioedema in routine practice.

MATERIALS AND METHODS: 16 patients with hereditary angioedema were enrolled in the observational single-center study. The data were researched: sex, patients age, age of symptoms onset, efficacy of previous methods of therapy, type of hereditary angioedema, genetics of the disease, contraindications for other prophylaxis methods. The efficacy of therapy was evaluated according to the duration of the course, the frequency of administration, the number of attacks of edema during the period of observation, and the improvement of the quality of life according to the AAS28 scale. Safety of use was evaluated by the presence of adverse events during the investigation.

RESULTS: The long-term prophylaxis with lanadelumab was effectively and safety for all of 16 patients. Single attacks during of therapy were provoked by the influence of significant triggers. Life-threatening attacks were not registered. The frequency of lanadelumab injections was reduced after 12 months of usage for 50% of patients. The improvement of the quality of life (from 6 to 38 according to AAS28 scale) was confirmed for all patients. Adverse events weren’t registered during the period of treatment.

CONCLUSION: The long-term prophylaxis of edema in hereditary angioedema with lanadelumab usage was approved as efficiently and safety.

Chronic spontaneous urticaria is a fairly common disease with an unpredictable course, burdensome symptoms and a significant negative impact on patients` quality of life. Despite the established stepwise approach to treatment with antihistamines in standard and increased dosages, anti-IgE therapy, there remains a portion of patients with unsatisfactory control of urticaria symptoms, with the need to develop drugs that target new therapeutic targets. Mast cells, basophils and B cells are key cells involved in the pathogenesis of urticaria; activation, differentiation, proliferation, cytokine secretion and degranulation in all three types of cells is regulated via Bruton's tyrosine kinase signalling pathway through FcεRI and BCR receptors respectively. Inhibition of Bruton's tyrosine kinase is being developed as a new therapeutic strategy for chronic spontaneous urticaria.

Here we present overview of the current understanding of chronic spontaneous urticarial`s pathogenesis, the role of Bruton's tyrosine kinase, the history of medical use of Bruton's tyrosine kinase inhibitors, as well as clinical data on the use of new Bruton's tyrosine kinase inhibitors in patients with chronic spontaneous urticaria who have not achieved adequate disease control with antihistamines.

Molecules of the excretory-secretory product arising as a result of co-evolution of a host and a parasite are able to inhibit the type 2 immune response, while activating the type 1 and the type 17 responses. The ability to alter the immune response can be used to inhibit inflammation in allergic diseases. In this regard, a search for helminth-associated molecules both with an immunomodulatory effect and immunogenicity and low toxicity is represented as a topical task.

Hemozoin being a dark brown insoluble biocrystal is an excretory product of a number of hematophagous parasites (Schistosoma mansoni, Plasmodium falciparum and Opisthorchis felineus). This substance as a compound of parasitic origin with explicit immunomodulatory properties has prospects for deep research.

Lots of relevant literature has been studied carefully before developing a concept about Opisthorchis felineus hemozoin and its unique properties.

Thus, the current review presents an analysis of the accumulated data regarding the effect of Opisthorchis felineus trematode on the host immune system. Also the data on the immunomodulatory effect of hemozoin of various origins is analyzed. The current knowledge on the immune mechanisms of inflammasome activation and the possible role of hemozoin in reducing allergic inflammation through this mechanism is represented in this article.

According to the systemized research results the excretory-secretory molecule of the liver fluke is a product of parasitic origin with an explicit immunomodulatory effect which is promising for prospective scientific study. Opisthorchis felineus extract increases the expression of T-regulatory cells and inhibits the Th2-immune response.

Hemozoin produced by Opisthorchis felineus, like one produced by Plasmodium falciparum, may be involved in reducing the activity of allergic inflammation through activation of the inflammasome. Comprehension of the mechanism of how hemozoin interacts with the host immune system can be applied for correction of conditions associated with Th2-polarization of the immune response, which primarily include atopic diseases.

Studying the mechanism of inflammation will help by the search for a biological target to create a vaccine to prevent the spread of atopic diseases, including bronchial asthma.

Atopic dermatitis is a systemic multifactorial genetically determined inflammatory skin condition characterized by an impairment of the epidermal barrier and Type 2 inflammation. Atopic dermatitis is highly prevalent, especially among children. Many authors consider atopic dermatitis as the initial stage of the atopic march, which typically manifests in the first year of life. Topical agents such as topical glucocorticosteroids and topical calcineurin inhibitors are the first-line treatments for atopic dermatitis. In recent years, there has been an increasing use of modern systemic anti-inflammatory agents, such as monoclonal antibodies and Janus kinase inhibitors.

Therapy of patients with atopic dermatitis is aimed at relieving itching, improving skin barrier function, reducing inflammation, preventing skin infection and exacerbations. The effectiveness of treatment lies not only in improving the symptoms and quality of life of patients with atopic dermatitis, but also in preventing them from developing chronic or severe symptoms.

Modern topical glucocorticosteroids and their combinations, have a proven high safety profile. However, available data on adverse events associated with their use often lead patients and their parents to develop a negative, phobic attitude towards treatment with these drugs. Zinc pyrithione, an activated form of zinc, is a safe and highly effective medication with anti-inflammatory, antifungal, and antibacterial properties.

This article presents two clinical cases of moderate to severe atopic dermatitis in children, demonstrating the effectiveness of using activated zinc pyrithione in comprehensive therapy for this condition.

More than 20% of people worldwide suffer from allergic diseases. The high prevalence and wide range of provocative factors, which are increasing daily, complicate the diagnostic search. On the one hand, this leads to inadequately extensive dietary and lifestyle restrictions that reduce the quality of life for patients; on the other hand, it results in the failure to identify life-threatening allergens. The discovery of immunoglobulin E over 60 years ago initiated the search for specific biomarkers to etermine the causes of allergic diseases. Traditional methods of allergen diagnostics have several limitations that hinder the search for potential allergic disease triggers.

The article discusses modern laboratory approaches to multicomponent molecular allergen diagnostics, describes its differences from traditional diagnostic methods, and analyzes the advantages, prospects, limitations, and shortcomings of this method. It also presents a comparative characterization of the test systems available today.

The article presents four clinical cases that demonstrate the capabilities of the multicomponent ALEX 2 test system in diagnostics, choice of therapy tactics, and in forming further personalized recommendations for patients suffering from various allergic diseases.