Effect of PUVA and NB-UVB Therapy on the Skin Cytokine Profile in Patients with Mycosis Fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. The aim of the present study was to produce up-to-date information on different phototherapy approaches on skin cytokines in patients with MF. METHODS: A total of 27 patients with mycosis fungoides were treated with phototherapy: NB-UVB (narrow-band ultraviolet B therapy) (10 patients) and PUVA (long-wavelength ultraviolet radiation of spectrum A with the use of skin-photosensitizing furocoumarins) therapy (17 patients). Evaluation of the effectiveness of treatment was carried out using BSA (body surface area) and the modified assessment of the severity of the skin lesions scale (mSWAT) used to quantify tumor mass in cutaneous T-cell lymphomas. Average numbers of procedures were 30.2 and 27.8 in the NB-UVB and PUVA groups, respectively. The median total dose of NB-UVB irradiation was 19.9 J/cm2 and PUVA therapy was 104.0 J/cm2. The overall response to therapy including complete and partial remission was 74.9% in the total group; 70% in the NB-UVB group, and 77.7% in the PUVA therapy group. In the obtained biopsies from lesions, surrounding tissue before treatment and skin samples of four healthy volunteers, the concentration of the IL-1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40L, and TNF-α cytokines was studied. An increase in IL-4 and TNF-α levels was shown in the lesional skin of patients compared to the skin of healthy controls. After the treatment, positive correlations of mSWAT with the levels of IL22, IL33, and TNF-α in the tumor tissue were found. The levels of IL10 and IFN-γ after PUVA treatment were increased in comparison to baseline. There was no difference in cytokine levels before/after NB-UVB therapy.

A Cross-sectional Study of Plasma Trace Elements and Vitamins Content in Androgenetic Alopecia in Men.

Androgenetic alopecia (AGA) is the most common variant of male pattern baldness in which occurrence and development of multiple genetic, hormonal, and metabolic factors are involved. We aimed to estimate plasma element content (Mg, Ca, Zn, Cu, Se, Fe), vitamin status (B12, D, E, and folic acid) in patients with AGA using direct colorimetric tests or atomic absorption spectrometry, and the influence of these parameters in the formation of various hair loss patterns. The study included 50 patients with I-IV stages of AGA divided into two groups with normal and high levels of dihydrotestosterone compared with 25 healthy individuals. The presence of two patterns of pathological hair loss in the androgen-dependent (parietal) and androgen-independent (occipital) areas of the scalp was confirmed. It was shown that all patients with AGA have a deficiency of elements (Zn, Cu, Mg, Se) and vitamins (B12, E, D, folic acid). However, the hair loss rate was not due to their content. А positive interrelation between quantitative trichogram parameters in the occipital region and iron metabolism in pairs "hair density vs Fe" and "hair diameter vs ferritin" was shown. In turn, in the parietal region, an inverse correlation of hair diameter with plasma Cu level was found, the most pronouncing in patients with high levels of dihydrotestosterone. The obtained results indicate the importance of multiple micronutrient deficiencies in the AGA occurrence accompanied by the existence of two different hair loss patterns, differently related to the content of certain trace elements and androgens in the blood.

Plasma Zinc Levels in Males with Androgenetic Alopecia as Possible Predictors of the Subsequent Conservative Therapy's Effectiveness.

Androgenic alopecia (AGA) is the most common type of progressive hair loss in man. The search for reliable predictors of the conservative treatment's effectiveness is an urgent problem today. Forty-eight patients with AGA, stages I-IV by the Norwood-Hamilton scale, were treated for 4 months with 5% topical minoxidil joints with corrections for trace element and vitamin imbalances. In most cases, the positive therapy's effect was shown in the parietal but not in the occipital area, whereas that effect was observed in others. The attempts to associate the therapy's effectiveness with initially defined genetic, hormonal, and metabolic parameters showed the absence of differences between groups with positive and negative outcomes. Among the studied nutrient parameters (Zn, Cu, Mg, Ca, Fe, and Se, as well as vitamins B12, E, D, and folic acid), differences between these groups was shown in zinc content only. The starting point from a zinc plasma level above 10 µmol/L likely provides the success of the subsequent conservative therapy and correlates with an increase in the hair density and diameter in the parietal area. The integral predictive value of the Zn plasma level was assessed as 72.3% (positive predictive value: -88%; and negative predictive value: -55%).

Apremilast Pharmacogenomics in Russian Patients with Moderate-to-Severe and Severe Psoriasis.

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: IL1ß (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.

Disease Burden and Treatment Patterns of Psoriasis in Russia: A Real-World Patient and Dermatologist Survey.

INTRODUCTION: Data regarding disease burden and quality of life (QoL) for patients with psoriasis from Russia are limited. The objective of this study was to describe the demographic and clinical characteristics, comorbidities, and treatment patterns of systemic therapy eligible psoriasis patients in Russia in order to assess the impact of psoriasis on the QoL and work productivity of the patients and to evaluate patient/dermatologist concordance on disease severity, signs/symptoms, and satisfaction with psoriasis treatment. METHODS: Data were collected by the Growth from Knowledge Disease Atlas global real-world evidence programme from nine countries. The data from the Russian population are presented here. Adult patients who had a current or prior history of moderate-to-severe psoriasis and were receiving prescription treatment at the time of the survey were included. Dermatologist-reported data on disease severity, symptoms, comorbidities, and treatment as well as patient-reported data on QoL and work productivity were collected. Descriptive analysis of the data was conducted. Patient/dermatologist concordance was assessed using Cohen's κ. RESULTS: A total of 300 patients from Russia were included. The mean Psoriasis Area and Severity Index score was 9.0 and the mean disease duration was 9.9 years. The proportion of patients with itch, skin pain, and comorbidities increased as current psoriasis severity increased. The disease had a negative impact on patients' QoL (mean Dermatology Life Quality Index score: 7.1) and work productivity (33.2% drop in work productivity), which further deteriorated as disease severity increased. A large proportion of the enrolled patients (60%) were treated with topical agents only. Overall, the level of concordance between patients and their dermatologists regarding psoriasis severity and satisfaction with overall disease control achieved was low. CONCLUSION: Results demonstrate a substantial disease burden on psoriasis patients in Russia, despite receiving treatment for their psoriasis, as well as low patient/dermatologist concordance of views on treatment outcomes. These findings also highlight a need to further incorporate the patient's views into treatment decision-making in Russia. FUNDING: Novartis Pharma AG, Basel, Switzerland.