(1) Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design—a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%—TEN. In total, 30% were pediatric SRs, 21.2%—SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level.

BACKGROUND: Bullous pemphigoid is known to be an autoimmune, life-threatening blistering skin disorder characterized by subepidermal blister formation. In bullous pemphigoid activation of B-cell immunity depends on the interaction between T-cell receptors and classic HLA II molecules. Similar interrelation has been revealed in a vast variety of studies on severe allergic reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. It was also suggested that Stevens-Johnson syndrome and toxic epidermal necrolysis might be associated both with HLA I and II classes. AIM: To assess the prevalence of HLA-DRB1 and DQB1 alleles at a low and high-resolution levels in patients with bullous pemphigoid and Stevens-Johnson syndrome / toxic epidermal necrolysis. MATERIALS AND METHODS: 29 Bullous pemphigoid, 14 Stevens-Johnson syndrome / toxic epidermal necrolysis patients and 92 health volunteers were included in the study. HLA-DRB1 and DQB1 alleles were assessed by polymerase chain reaction using specific primers. RESULTS: At a low-resolution level, HLA-DRB1*4 (p 0.02) and DRB1*14 (p 0.0015) alleles were statistically significantly revealed in bullous pemphigoid patients compared to health controls. Additionally, at the high-resolution level the predisposing to bullous pemphigoid HLA-DRB1*04:02 allele was also identified (p 0.01). At the low-resolution level of HLA-DQB1 typing we displayed protective and predisposing to bullous pemphigoid alleles HLA-DQB1*1 (p 0.01) and HLA-DQB1*2 (p 0.039) respectively. At the low-resolution level of HLA-DQB1 typing, the chances to obtain DQB1*03:02 allele were 3.71 times higher compared to healthy volunteers (p 0.01). In patients with Stevens-Johnson syndrome / toxic epidermal necrolysis, HLA-DRB1*4 allele was shown to be predisposing (p 0.03). For all other types of HLA alleles (DRB1 and DQB1) at the high-resolution level no any statistically significant results have been observed in these patients. CONCLUSION: We identified HLA-DRB1*4, DRB1*14, DRB1*04:02 alleles predisposing to the development of bullous pemphigoid, with the HLA-DQB1*1 allele being protective for the development of bullous pemphigoid and HLA-DRB1*4 allele predisposing to the development of severe drug reactions of Stevens-Johnson syndrome / toxic epidermal necrolysis. No any protective alleles in Stevens-Johnson syndrome / toxic epidermal necrolysis patients were detected.

Background. Bullous dermatoses are severe life-threatening antibody-induced organ-specific multifactorial diseases resulting from a genetic predisposition. Systemic glucocorticosteroids are the first-line therapy for many bullous dermatoses. However, there is a small though significant proportion of patients who are resistant to basic therapy with systemic glucocorticosteroids. Although studies of the steroid resistance have been performed at the level of receptors and genes in the serum of patients, no studies of this mechanism have been carried out at the level of blister fluid locally in the area of blister formation.Objectives. To estimate cytokine (interleukin 10, 15, 4, tumor necrosis factor alpha), chemokine (eosinophil chemotactic protein, interleukin 8) profiles and granulysin levels in patients with bullous dermatoses in serum and blister fluid, as well as their possible relationship with steroid resistance.Methods. The observational cohort controlled study included 67 patients with bullous dermatoses hospitalized between January 2020 and December 2023 in the V.A. Rakhmanov Clinic of Skin and Venereal Diseases of the University Clinical Hospital No. 2 of the I.M. Sechenov First Moscow State Medical University (Sechenov University) and the Department of Allergology and Immunology of the Municipal Clinical Hospital No. 24 of the Moscow City Health Department. The patients were classified into three groups by diagnosis. The first group included patients with pemphigus vulgaris (n = 43), the second was patients with bullous pemphigoid (n = 11), and the third consisted of patients with Stevens — Johnson syndrome and toxic epidermal necrolysis (n = 13). The control group consisted of 43 healthy donors, whose biological material was obtained from the Blood Center of the I.M. Sechenov First Moscow State Medical University (Sechenov University). After a 3-week course of systemic glucocorticosteroids, the groups of patients with bullous dermatoses were stratified into steroid-resistant and steroid-sensitive subgroups, respectively: with pemphigus vulgaris 18/25 patients; with bullous pemphigoid 3/8; with Stevens — Johnson syndrome and toxic epidermal necrolysis 1/12. Due to the small number of patients, the data of steroid-resistant and steroid-sensitive patients with Stevens — Johnson syndrome and toxic epidermal necrolysis were not statistically analyzed. The main indicators of the study comprised interleukins 10, 15, 4, tumor necrosis factor alpha, eosinophil chemotactic protein, interleukin 8, and granulysin levels in serum and blister fluid of patients depending on the presence or absence of steroid resistance. Statistical processing of data was performed using Statistica 10.01 software package (StatSoft, USA), Microsoft Excel 2010 (Microsoft, USA) and IBM SPSS 24.0 software (IBM, USA). Differences were considered statistically significant at p < 0.05.Results. The concentrations of tumor necrosis factor-α, interleukin 10, granulysin, as well as chemokines — interleukin 8 and eosinophilic protein — were statistically significantly higher in serum in patients with pemphigus vulgaris, Lever’s bullous pemphigoid, and Stevens — Johnson syndrome and toxic epidermal necrolysis compared to the control group (p < 0.001). Significantly lower levels of tumor necrosis factor-α, particularly in blister fluid as opposed to serum, correlated with steroid resistance in patients with pemphigus vulgaris (p < 0.05). Reduced levels of the key neutrophil chemoattractant may indicate impaired recruitment of immune cells to the lesion, thus being a potential biomarker of the refractory course of the disease. Meanwhile, steroid-resistant patients with bullous pemphigoid had statistically significantly high levels of interleukins 4, 8, 15, and granulysin in their blister fluid compared to steroid-sensitive patients (p < 0.05). Due to this, differences in inflammatory marker profiles associated with insensitivity of patients to hormone therapy are emphasized. Importantly, most patients with bullous pemphigoid responded adequately to therapy (8/11) with systemic glucocorticosteroids compared to the pemphigus vulgaris group. In patients with Stevens — Johnson syndrome and toxic epidermal necrolysis, the level of granulysin (median 12,105 ng/mL) in blister fluid was statistically significantly higher compared with pemphigus vulgaris (median 10,842 ng/mL; p = 0.024) and bullous pemphigoid (median 10,335 ng/mL; p = 0.048). The findings suggest that analysis of this biomarker in blister fluid can be applied to the diagnosis as well as differential diagnosis of bullous dermatoses.Conclusion. This study identified potential predictors of response to therapy with systemic glucocorticosteroids in the blister fluid of patients with pemphigus vulgaris and bullous pemphigoid. In the long-term, the analysis of blister fluid can be used complementary to the histologic method as an express diagnostic test, differential diagnosis of severe bullous dermatoses, real-time monitoring of response to therapy, and prognosis of the severity of the course of these diseases. Additionally, a timely administration of adjuvant therapy to patients’ refractory to systemic steroids would assist in minimizing the risk of complications and side effects.

Background/Objectives: Cutaneous adverse drug reactions (CADRs) represent the most common manifestations of drug-induced allergy, with most unfavorable clinical outcomes seen in severe cutaneous adverse reactions (SCARs). To manage SCARs immediate cessation of the offending drug is needed; therefore, it is crucial to identify the list of medications associated with SCARs in real-world clinical practice. The objective of this study was to evaluate the structure of drugs associated with SCARs and to analyze drug-induced SCAR signals by calculating the reporting odds ratio (ROR) and proportional reporting ratio (PRR) based on spontaneous reports extracted from the Russian national pharmacovigilance database. Methods: A retrospective, descriptive pharmacoepidemiological analysis of spontaneous reports (SRs) registered in the pharmacovigilance database from 1 April 2019 to 31 March 2025. Results: A total of 7011 SRs with SCARs were finally revealed, with 907 identified drug triggers. The most frequently reported were antibacterial drugs for systemic use (22.8%), antineoplastic agents (17.8%), and antiepileptics (6.0%). The top five drugs involved in SCARs were dupilumab (2.14%, n = 244), piperacillin and beta-lactamase inhibitor (2.0%, n = 227), pembrolizumab (1.98%, n = 225), levofloxacin (1.95%, n = 222), and linagliptin (1.93%, n = 220). The strongest signals were detected for linagliptin (PRR = 15.37, 95% CI: 13.54–17.44; ROR = 17.24, 95% CI: 14.95–19.88), followed by clindamycin (PRR = 12.44, 95% CI: 10.89–14.21; ROR = 13.62, 95% CI: 11.77–15.77) and by piperacillin and beta-lactamase inhibitor (PRR = 10.02, 95% CI: 8.86–11.43; ROR = 10.81, 95% CI: 9.42–12.40). Conclusions: Pharmacovigilance databases facilitate the identification of diverse phenotypes of SCARs and the list of culprit drugs. The accumulated data serve as a valuable tool to enhance clinical practice outcomes and strengthen overall healthcare monitoring.

Atopic dermatitis is a chronic inflammatory skin disease characterized by a recurrent course, difficulty in individual selection of therapy, especially in patients with severe course. When examining and treating such patients, one of the routine diagnostic methods is to determine the level of total immunoglobulin E in the blood serum. The article is devoted to the analysis of available world practice data on published clinical cases of the use of biological therapy with dupilumab in real clinical practice in patients with severe atopic dermatitis, in whom high and very high levels of immunoglobulin E. The appointment of biological therapy for this cohort of patients often raises significant concerns. However, the use of a monoclonal antibody against IL-4/IL-13 proved effective, did not lead to serious adverse reactions in such patients and was accompanied by a decrease in the level of immunoglobulin E during treatment. It was noted that immunosuppressive treatment prior to biological therapy led to the development of adverse events in these patients. A separate group of patients with genetically determined hyper-IgE syndrome and severe atopic dermatitis is described, in which the positive experience of using dupilumab is also noted. The author presents his own clinical case of a patient with severe atopic dermatitis and a high level of immunoglobulin E receiving successful targeted therapy after a preliminary thorough examination except for lymphoproliferative and autoimmune diseases. Against the background of dupilumab therapy, there was a pronounced clinical regression of skin symptoms, a decrease in the level of immunoglobulin E, an increase in the patient’s quality of life, and the absence of side effects.

Introduction. Smoking, as one of the significant modifiable risk factors, is being actively studied in the context of asthma. Aim. To assess the effect of electronic cigarettes and electronic tobacco heating devices on the course and control of bronchial asthma, as well as changes on inflammatory profiles. An important aspect is to assess the profile of the patient using smoking devices in order to optimize the therapy selection and patient management strategies. Materials and methods. An open-label observational clinical trial including medical history assessment, physical examination, completion of the Asthma Control Questionnaire (ACT) and the Asthma Quality of Life Questionnaire (AQLQ), clinical functional examination, and venous blood sampling for biomarker analysis. The study included patients aged 18–45 years with a confirmed diagnosis of bronchial asthma for at least 12 months. Results. 84 patients were included in the study (82 men and 2 women), with a mean age of 21.99 ± 2.38 years. Of these, 32 patients were non-smokers, while 52 reported using various nicotine and tobacco products. Among the smokers, 30 (57.7%) used two or more types of smoking devices. Passive smoking exposure was reported across all groups, with 69 patients (82.1%) indicating regular exposure to environmental tobacco smoke from their surroundings. Smokers were more frequently exposed to passive smoking. The average age of smoking initiation is 16 years. In both groups, according to ACT data, the lack of asthma control in smokers is 18.1 ± 4.2, non-smokers 16.8 ± 3.4. ACT score distribution curves showed a broader spread among smokers, with a more pronounced secondary peak corresponding to partial asthma control. Correlation analysis of peripheral blood eosinophil levels revealed a narrower distribution among smokers, while non-smokers exhibited a longer right-tail distribution, indicating a higher proportion of individuals with elevated eosinophil counts. Conclusion. The use of electronic nicotine delivery devices and electronic tobacco heating devices affects the course and control of bronchial asthma. Further research is needed to optimize therapy and management of patients using smoking devices