One of the target drugs for plaque psoriasis treatment is apremilast, which is a selective phosphodiesterase 4 (PDE4) inhibitor. In this study, 34 moderate-to-severe and severe plaque psoriasis patients from Russia were treated with apremilast for 26 weeks. This allowed us to observe the effectiveness of splitting patient cohorts based on clinical outcomes, which were assessed using the Psoriasis Area Severity Index (PASI). In total, 14 patients (41%) indicated having an advanced outcome with delta PASI 75 after treatment; 20 patients indicated having moderate or no effects. Genome variability was investigated using the Illumina Infinium Global Screening Array. Genome-wide analysis revealed apremilast therapy clinical outcome associations at three compact genome regions with undefined functions situated on chromosomes 2, 4, and 5, as well as on a single single-nucleotide polymorphism (SNP) on chromosome 23. Pre-selected SNP sets were associated with psoriasis vulgaris analysis, which was used to identify four SNP-associated targeted therapy efficiencies: IL1β (rs1143633), IL4 (IL13) (rs20541), IL23R (rs2201841), and TNFα (rs1800629) genes. Moreover, we showed that the use of the global polygenic risk score allowed for the prediction of onset psoriasis in Russians. Therefore, these results can serve as a starting point for creating a predictive model of apremilast therapy response in the targeted therapy of patients with psoriasis vulgaris.

Objective — Assessment of phosphodiesterase-4 inhibitor (apremilast) therapy’s influence on skin cytokine levels in patients with moderate-to-severe and severe psoriasis. Material and Methods — An open, uncontrolled study was conducted. 16 patients with plaque psoriasis (13 men, 3 women; mean ± standard deviation (SD) age 35.1±9.7 years, range 21-60) were enrolled. The mean Psoriasis Area and Severity Index (PASI) was 20.7±8.93 (range 10-47). All patients were prescribed apremilast 30 milligrams (mg) per os (PO) Bis In Die (BID). The efficacy of therapy was evaluated by PASI at 14 and 26 weeks of therapy. Lesional skin samples were collected at baseline and weeks 14 and 26. Levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL -33, interferon (INF)-γ, Soluble CD40-ligand (sCD40L), tumor necrosis factor (TNF)-α were measured by microsphere-based suspension array technology (Luminex® xMAP™ system). Results — Levels of cytokines (except IL-4 and IL-33) in lesional skin samples were found to have decreased at week 14 compared with those at baseline. Similar decreases were seen for IL-23, IL-25, IL-31, sCD40L at week 26. In contrast, the levels of other cytokines increased again at week 26, in comparison with baseline. Levels of IL-4 and IL-33 rose throughout the follow-up period. Cytokine levels in lesional skin samples were compared with those of healthy controls both at baseline and during therapy. Conclusion — The results of our study show that administering apremilast therapy to patients with psoriasis can bring the levels of cytokines involved in the IL-23/IL-17 axis in the lesional skin to the level of cytokine in non-lesional skin and to the levels in the skin of healthy individuals.

Background.Psoriasis is a widespread skin disorder characterized by cytokines as the main modulators of skin inflammation. A promising psoriasis therapy approach is targeted on cytokine networks by inhibiting the phosphodiesterase 4 (PDE-4). The efficacy and safety of the PDE-4 inhibitor apremilast in psoriasis confirmed in multicenter controlled studies, which, however, are accompanied by reports of unsuccessful therapy cases.Aims to determine early immunological predictors for PDE-4 inhibitor (apremilast) therapy efficacy based on skin lesions cytokines analyzes in patients with moderate to severe psoriasis.Methods.An open, uncontrolled prospective clinical study was performed. Efficacy of apremilast was analyzed by PASI, BSA, sPGA and DLQI. The outcomes at 26 therapy week were compared with the cytokine levels in skin biopsies selected before starting therapy and analyzed using xMAP technology. The multiparameter prognostic model for apremilast therapy effectiveness was developed based on a heterogeneous sequential recognition procedure.Results.The 34 patients with moderate to severe psoriasis were included in the study. According to the clinical outcomes, two comparison groups were formed: high (75% reduction in PASI score or more; n=14) and insufficient (50% reduction in PASI score or less; n=20) apremilast efficiency. Cytokines analyses showed an inverse relationship between the initial anti-inflammatory IL-10 level and the PASI reduction (r=0.37; p0.025). On the other hand, the relationships between pro-inflammatory cytokines IL-1 and IL-6 levels and PASI score at the 26th week of therapy were characterized by positive correlation: r=0.31 (p0.05) and r=0.37 (p0.025), respectively. Based on the data obtained, a predictive model for the apremilast therapy efficiency was developed. The expected predictive values of this model were 86% for a high therapy effectiveness and 60% for an insufficient effectiveness, respectively.Conclusions.The study results for the first time describe the cytokine profiles in the skin lesions in patients, who responded differently to PDE-4 inhibitor therapy. These dada allows to predict the treatment efficacy and give a chance to personalize apremilast usage for the moderate and severe psoriasis treatment.

Mycosis fungoides is a primary epidermotropic T-cell lymphoma of the skin, characterized by the proliferation of small and medium-sized T-lymphocytes with cerebriform nuclei. Mycosis fungoides accounts for 60.6% of the total number of all cases of primary T-cell lymphomas of the skin. Diagnosis of mycosis fungoides remains a big challenge in dermatology: the average time for diagnosis from the onset of the disease is 5 years. The difficulty of differential diagnosis with chronic inflammatory dermatosis is due to the similarity of their clinical characteristics, especially in the early stages of the mycosis fungoides. The search for new methods aimed at early diagnosis of skin T-cell lymphoma is one of the most important tasks in dermatooncology. A number of morden studies aimed at assessing the capabilities of dermatoscopy as an additional method for diagnosing mycosis fungoides. Specific dermoscopic pattern of mycosis fungoides were identified: fine short linear vessels, orange-yellowish patchy areas and vascular structure resembling spermatozoa. Description of this dermoscopic pattern can influence the accuracy of diagnosis and timeliness of diagnosis, the prescription of effective methods of therapy in the early stages of the disease, improving the quality and increasing the life expectancy of patients. The article provides an overview of the most up-to-date information on the dermoscopic pattern of mycosis fungoides.

Psoriatic arthritis often leads to the development of severe outcomes ankylosis, deformities of the affected joints with severe impairment of their functions and disability. Early identification of patients with psoriasis with an increased risk of developing psoriatic arthritis for the purpose of its timely diagnosis and early initiation of therapy can prevent the development of severe disease outcomes. It is believed that the genes of the HLA system make the greatest individual genetic contribution to the formation of a predisposition to hereditary diseases with polygenic inheritance. The literature review considers the polymorphisms of the genes of the HLA system, associated with the development of psoriatic arthritis, in patients with psoriasis. The HLA alleles that contribute to the development of psoriatic arthritis and its individual forms have been identified. HLA alleles have been identified, which have a protective effect against the development of psoriatic arthritis.

Background. Psoriatic arthritis is a chronic inflammatory disease of the joints, spine and entheses that can occur in patients with psoriasis. The prevalence of psoriatic arthritis is 19.7%. In 70% of cases, psoriasis precedes the development of arthritis. It has been proven that a delay in the diagnosis of psoriatic arthritis even by 6 months is associated with a deterioration in long-term radiological and functional results, leading to disability. The problem of early diagnosis of joint damage can be solved by identifying predictors of the risk of developing psoriatic arthritis in patients with psoriasis. Aims. To determine possible predictors for the development of psoriatic arthritis in patients with psoriasis. Methods. The open, uncontrolled, prospective study enrolled 250 patients. The main group consisted of 190 patients diagnosed with plaque psoriasis. The control group consisted of 60 patients with psoriatic arthritis. In order to identify associations of clinical and genetic (HLA-B27 carriage) parameters with the development of psoriatic arthritis, we compared the frequency of occurrence of these parameters in patients with psoriatic arthritis and without. Results. Among 190 patients with plaque psoriasis 128 (67.4%) men, 62 (32.6%) women, aged 18 to 84 years (40.30 ± 15.56), the average duration of psoriasis was 10.09 ± 11.08 years (0–57). Among 60 patients with psoriatic arthritis 39 (65%) men, 21 (35%) women aged 18 to 86 years (44.43 ± 14.15), the average duration of psoriasis was 20.47 ± 13.22 years (2–57), the average duration of psoriatic arthritis was 7.97 ± 9.95 years (0–47). Сlinical predictors for the development of psoriatic arthritis in patients with psoriasis: nail psoriasis (OR = 2.244 [95% CI: 1.245–4.045]); severe psoriasis (PASI ≥ 20) (OR = 2.148 [95% CI: 1.161–3.975]); arterial hypertension (OR = 1.982 [95% CI: 1.031–3.812]); duration of psoriasis over 25 years (OR = 3.365 [95% CI: 1.676–6.756]), р 0,05. Conclusions. The joint consideration of informative predictors will allow us to develop an original multi-parameter mathematical model for calculating the risk of developing psoriatic arthritis in patients with psoriasis.