Amra Osmancevic

Psoriasis is a chronic, immune-mediated inflammatory skin disorder that significantly impacts patients’ quality of life. While TNF-α inhibitors are frequently used to treat moderate-to-severe cases, not all patients respond adequately. Brodalumab, a monoclonal antibody targeting the IL-17 receptor A, has emerged as an alternative for individuals unresponsive to prior therapies. This prospective study investigated the effects of brodalumab on serum cytokine levels—specifically IL-6, IL-17A, IFN-α, IFN-γ, and TNF-α—and their correlation with disease severity as assessed by Psoriasis Area and Severity Index (PASI). Eighteen patients with moderate-to-severe psoriasis who were unresponsive to TNF-α inhibitors received brodalumab for 12 weeks. Cytokine concentrations were measured at baseline and week 12 using an automated immunoassay (ELLA), and clinical outcomes were evaluated using PASI. The results showed a significant increase in IL-17A levels, while changes in IL-6, IFN-α, IFN-γ, and TNF-α did not reach statistical significance. No significant correlations were found between changes in cytokine levels and PASI improvement. However, the small number of available serum samples at week 12 (n = 11) limited the statistical power to detect treatment-related changes in cytokine levels. These findings suggest that while brodalumab influences specific immune markers, the clinical response may not be directly reflected by serum cytokine levels. This highlights the multifactorial nature of psoriasis pathogenesis and underscores the need for further studies to clarify the role of cytokine biomarkers in treatment response.

Psoriasis is a chronic inflammatory skin disease marked by abnormal keratinocyte proliferation and immune dysregulation. The vitamin D receptor (VDR) plays a crucial role in regulating skin cell growth and immune responses, but its expression in psoriatic skin and modulation by treatment remain unclear. This study aimed to analyze VDR mRNA expression in psoriatic skin tissue before and after etanercept therapy using RNAscope, an RNA in situ hybridization technique that, to the best of our knowledge, has not previously been applied in psoriasis research. Two bio-naïve adult patients with moderate to severe plaque psoriasis received etanercept (50 mg weekly) for 12 weeks. Skin biopsies from lesional and perilesional areas were collected at baseline and post-treatment. VDR expression was assessed in different epidermal layers and the dermis using a semi-quantitative scoring system. In one patient, a statistically significant decrease in VDR expression was observed in the perilesional dermis after treatment (p < 0.001), though this preliminary finding warrants careful interpretation given the very limited cohort size. Both patients exhibited a non-significant trend toward increased VDR expression in the lesional epidermis post-treatment. These preliminary findings suggest that etanercept may modulate VDR expression in psoriatic skin, but individual variability and the small sample size preclude definitive conclusions. The study primarily demonstrates the feasibility of using RNAscope for VDR analysis in patients with psoriasis, an approach that may be novel in this context, and underscores the need for larger investigations to confirm these preliminary findings and further clarify the role of VDR in disease pathogenesis and treatment response.

Vitamin D plays an important role in psoriasis, but its involvement in pathogenesis remains unclear. This study aimed to evaluate vitamin D receptor (VDR) expression on peripheral blood mononuclear cells (PBMCs) in patients with psoriasis and healthy controls and to study the effects of the Etanercept treatment on VDR expression on PBMCs in patients with psoriasis. Twenty patients with moderate to severe psoriasis received treatment with Etanercept for 24 weeks. The age- and sex-matched controls did not receive any intervention. VDR expression on CD3⁺ lymphocytes and CD14⁺ monocytes, and serum levels of total and free 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)₂D) were analyzed at baseline, after 10–12 weeks, and after 24 weeks in both groups. VDR expression was analyzed using flow cytometry. We observed higher expression of the VDR on CD14⁺ monocytes in psoriasis patients compared to healthy controls at baseline. This difference was no longer significant after 24 weeks of the Etanercept treatment. The patients with psoriasis improved clinically. However, VDR expression was unaltered during the Etanercept treatment, and there was no correlation between VDR expression and disease severity.

The gut microbiota plays a critical role in immune system function, with dysbiosis linked to systemic inflammation, contributing to conditions like psoriasis and depression. Although biological treatments for severe psoriasis are known to impact gut bacteria, less is understood about their effects on fungi. This study aims to investigate fungal gut microbiota changes in psoriasis patients transitioning from TNF-α inhibitors to brodalumab. Fecal samples from 20 patients were analyzed using Illumina MiSeq sequencing of the ITS2 region of 18S rRNA. Microbial diversity was assessed through Bray–Curtis dissimilarity and the Shannon–Wiener index. Clinical outcomes were measured using clinical scores for psoriasis and depression severity, with statistical analysis performed via Wilcoxon signed-rank tests and PERMANOVA. Results showed that Ascomycota was the dominant fungal phylum in both treatment groups, with Saccharomyces, Penicillium, Candida, and Debaryomyces as prevalent genera. No significant changes occurred at the phylum level after switching to brodalumab, though minor genome-level variations were observed. Beta diversity analysis highlighted inter-patient variability, with no significant correlation between fungal composition and clinical outcomes. Despite improved clinical scores, the fungal gut microbiota remained largely stable, suggesting that brodalumab does not significantly alter fungal communities in psoriasis patients. Further research is needed for a comprehensive understanding.

Vitamin D plays a role in inflammatory skin disease, but the exact mechanisms and the clinical significance remain unclear. According to the free hormone hypothesis, it is the free concentration of 25-hydroxy vitamin D (25(OH)D) that is biologically active. Vitamin D-binding protein (DBP) acts as the major transporter of vitamin D in the circulation, and DBP concentration defines the free 25(OH)D levels. DBP levels are elevated in various inflammatory conditions, including psoriasis. Narrowband-ultraviolet B (NB-UVB) is the most widely used phototherapy and is an established first-line treatment for psoriasis and atopic dermatitis (AD), often used before proceeding to systemic treatment. The aim of this study was to investigate the influence of NB-UVB phototherapy on DBP and high-sensitivity C-reactive protein (hsCRP) levels, as markers of systemic inflammation, in inflammatory skin disease. Thirty adults (psoriasis (n = 20) and AD (n = 10)) were treated with NB-UVB. Serum DBP, hsCRP, total and free 25(OH)D, and 1,25-dihydroxy vitamin D (1,25(OH)₂D) were measured before and after NB-UVB. Disease severity was assessed with Psoriasis Area and Severity Index (PASI), SCORing Atopic Dermatitis (SCORAD), and Visual Analogue Scale (VAS). DBP decreased in psoriasis patients and varied with no clear trend in AD patients. HsCRP decreased in both groups, but this did not reach statistical significance. PASI, SCORAD, and VAS improved, and vitamin D levels increased after NB-UVB. Sub-analysis indicated a better response to NB-UVB for patients with vitamin D deficiency and insufficiency compared to vitamin D-sufficient patients. The decrease in DBP after NB-UVB in psoriasis patients suggests a potential systemic anti-inflammatory effect of phototherapy. Measurement of vitamin D levels may potentially serve as a tool to identify patients who would derive the greatest benefit from NB-UVB phototherapy.

Biological agents used to treat severe psoriasis may alter the gut microbiota, though current knowledge is limited. This study examines whether switching from TNFα inhibitors, from which patients had reduced or lost effect, to brodalumab, an IL-17 inhibitor, affects the gut microbiota in patients with psoriasis and how these changes correlate with the clinical variables of psoriasis severity and depressive symptoms. Fecal samples from patients were collected before the treatment switch and 12 weeks after the switch and were analyzed for the microbiota composition using next-generation sequencing targeting the V3–V5 region of the 16S rRNA gene, followed by bioinformatics analysis. No significant changes in overall gut microbiota composition were observed after the treatment switch, although individual variations in the Firmicutes/Bacteroidetes ratio were noted, and no significant correlations with clinical variables were found. These findings suggest that short-term changes in gut microbiota in patients with psoriasis are limited and that dysbiosis may be influenced by the interplay of various microbial populations rather than specific taxa. This study provides a foundation for further research into the effects of biological treatments on the gut microbiota in patients with psoriasis.

Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an urgent need for additional descriptive research to enhance our understanding and treatment of SS. The aim of this retrospective register-based study was to outline patients’ demographic characteristics; investigate the clinical, histopathological, and molecular findings; and assess treatment effectiveness with a focus on time to next treatment (TTNT) and disease progression. Data on 17 patients with SS were obtained from the primary cutaneous lymphoma register in West Sweden between 2012 and 2024. The results revealed that not all patients exhibited the classical triad of symptoms at diagnosis, emphasizing the need for personalized diagnostic approaches. The median survival was only 2.1 years, which reflects the aggressive nature of SS. The longest median TTNT was observed in triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP). There was no significant difference in TTNT between various lines of treatment. Early initiation of ECP treatment did not result in improved outcomes. This study highlights the importance of combination therapy for improved outcomes and underscores the need for future studies to identify optimal treatment approaches.

Vitamin D plays an important role in skin inflammation in psoriasis. The beneficial effects of ultraviolet light B (UVB) phototherapy in psoriasis are partly attributed to UVB-induced increase of vitamin D levels. In clinical practice, total 25-hydroxy vitamin D (25(OH)D) levels are measured to assess sufficiency, but it might be more accurate to measure free 25(OH)D levels. The aim of this study was to measure free serum 25(OH)D levels in psoriasis patients before and after phototherapy and to investigate if free 25(OH)D correlates stronger to disease severity than total 25(OH)D. Twenty adults (>18 years) with psoriasis were included for treatment with narrow-band UVB (NB-UVB) phototherapy for 10–12 weeks. Psoriasis Area and Severity Index (PASI) and Visual Analogue Scale (VAS) were used to assess disease severity. Serum levels of total 25(OH)D, free 25(OH)D, and 1,25(OH)₂D were measured before and after NB-UVB. Total 25(OH)D, free 25(OH)D, 1,25(OH)₂D and the percentage of free 25(OH)D increased after NB-UVB, and PASI and VAS improved. The increase in total and free 25(OH)D remained significant when stratifying for vitamin D confounders. No correlations between disease severity and vitamin D levels were found. Total and free 25(OH)D levels were positively correlated before and after NB-UVB. NB-UVB is an effective treatment for mild to severe plaque psoriasis and increases not only total but also free 25(OH)D levels, as well as the percentage of free 25(OH)D, suggesting an increased bioavailability of skin-produced vitamin D.

There is a lack of research on women with infertility in the northern latitudes, where vitamin D insufficiency is high. Therefore, this study aimed to assess the prevalence and determinants of vitamin D insufficiency (serum 25(OH)D concentration < 50 nmol/L) among women undergoing in vitro fertilization (IVF) treatment. Thus, 265 women scheduled for IVF/intracytoplasmic sperm injection (ICSI) between September 2020 and August 2021 at Sahlgrenska University Hospital in Gothenburg, Sweden, were included. Data on serum 25(OH)D concentration, vitamin D intake, and sun exposure were collected via questionnaires and blood samples. Approximately 27% of the women had 25(OH)D insufficiency, which was associated with longer infertility duration. The likelihood of insufficiency was higher among women from non-Nordic European countries (OR 2.92, 95% CI 1.03–8.26, adjusted p = 0.043), the Middle East (OR 9.90, 95% CI 3.32–29.41, adjusted p < 0.001), and Asia (OR 5.49, 95% CI 1.30–23.25, adjusted p = 0.020) than among women from Nordic countries. Women who did not use vitamin D supplements were more likely to have insufficiency compared with supplement users (OR 3.32, 95% CI 1.55–7.10, adjusted p = 0.002), and those who avoided sun exposure had higher odds of insufficiency compared to those who stayed “in the sun all the time” (OR 3.24, 95% CI 1.22–8.62, adjusted p = 0.018). Women with infertility in northern latitudes and those from non-Nordic countries who avoid sun exposure and do not take vitamin supplements have a higher prevalence of 25(OH)D insufficiency and longer infertility duration.