Dysbiosis has been identified in many dermatological conditions (e.g., psoriasis, atopic dermatitis, systemic lupus erythematosus). One of the ways by which the microbiota affect homeostasis is through microbiota-derived molecules (metabolites). There are three main groups of metabolites: short-chain fatty acids (SCFAs), tryptophan metabolites, and amine derivatives including trimethylamine N-oxide (TMAO). Each group has its own uptake and specific receptors through which these metabolites can exert their systemic function. This review provides up-to-date knowledge about the impact that these groups of gut microbiota metabolites may have in dermatological conditions. Special attention is paid to the effect of microbial metabolites on the immune system, including changes in the profile of the immune cells and cytokine disbalance, which are characteristic of several dermatological diseases, especially psoriasis and atopic dermatitis. Targeting the production of microbiota metabolites may serve as a novel therapeutic approach in several immune-mediated dermatological diseases.

Raynaud’s phenomenon is a painful vascular condition in which abnormal vasoconstriction of the digital arteries causes blanching of the skin. The treatment approach can vary depending on the underlying cause of disease. Raynaud’s phenomenon can present as a primary symptom, in which there is no evidence of underlying disease, or secondary to a range of medical conditions or therapies. Systemic sclerosis is one of the most frequent causes of secondary Raynaud’s phenomenon; its appearance may occur long before other signs and symptoms. Timely, accurate identification of secondary Raynaud’s phenomenon may accelerate a final diagnosis and positively alter prognosis. Capillaroscopy is fundamental in the diagnosis and differentiation of primary and secondary Raynaud’s phenomenon. It is helpful in the very early stages of systemic sclerosis, along with its role in disease monitoring. An extensive range of pharmacotherapies with various routes of administration are available for Raynaud’s phenomenon but a standardized therapeutic plan is still lacking. This review provides insight into recent advances in the understanding of Raynaud’s phenomenon pathophysiology, diagnostic methods, and treatment approaches.

Systemic sclerosis is an autoimmune connective tissue disease characterized by vasculopathy and fibrosis of the skin and internal organs. The pathogenesis of systemic sclerosis is very complex. Mediators produced by immune cells are involved in the inflammatory processes occurring in the tissues. The currently available therapeutic options are often insufficient to halt disease progress. This article presents an overview of potential therapeutic targets and the pipeline of possible future therapeutic options. It is based on research of clinical trials involving novel, unestablished methods of treatment. Increasing knowledge of the processes and mediators involved in systemic scleroderma has led to the initiation of drug trials with therapeutic targets of CD28-CD80/86, CD19, CCL24, CD20, CD30, tumor necrosis factor (TNF), transforming growth factor β (TGF-β), B-cell activating factor (BAFF), lysophosphatidic acid receptor 1 (LPA1 receptor), soluble guanylate cyclase (sGC), Janus kinases (JAK), interleukin 6 (IL-6), endothelin receptor, and autotaxin. Data from clinical trials on these drugs indicate a significant potential for several new therapeutic options for systemic sclerosis in the upcoming future.

Introduction Systemic sclerosis is an autoimmune disease characterized by tissue fibrosis and microangiopathy. Vascular changes such as a decrease in capillary density diminish blood flow and impair tissue oxygenation. Reliable ways to monitor disease activity and predict disease progression are desired in the process of patient selection for clinical trials and to optimize individual patient outcomes. Hypoxia-inducible factor-1 (HIF-1) is a dimeric protein complex that plays an integral role in the body’s response to hypoxia. Our study aimed to investigate the potential abnormalities of HIF-1α plasma concentration and its possible association with disease activity and vascular abnormalities in patients with systemic sclerosis. Methods Blood plasma levels of HIF-1α were measured in patients with systemic sclerosis ( n = 50) and in healthy individuals ( n = 30) using commercially available ELISA test kits. Results The results showed a marked increase in HIF-1α levels in patients with systemic sclerosis (3.042 ng/ml [2.295–7.749]) compared to the control group (1.969 ng/ml [1.531–2.903] p < 0.01). Patients with diffuse cutaneous SSc (2.803 ng/ml, IQR 2.221–8.799) and limited cutaneous SSc (3.231 ng/ml, IQR 2.566–5.502) exhibited elevated serum HIF-1α levels compared to the control group ( p < 0.01). We found a notable increase in HIF-1α plasma concentration in patients with an “active” pattern (6.625 ng/ml, IQR 2.488–11.480) compared to those with either an “early” pattern (2.739, IQR 2.165–3.282, p < 0.05) or a “late” pattern (2.983 ng/ml, IQR 2.229–3.386, p < 0.05). Patients with no history of digital ulcers had significantly higher levels of HIF-1α (4.367 ng/ml, IQR 2.488–9.462) compared to patients with either active digital ulcers (2.832 ng/ml, IQR 2.630–3.094, p < 0.05) or healed digital ulcers (2.668 ng/ml, IQR 2.074–2.983, p < 0.05). Conclusions Our results indicate that HIF-1α may serve as a biomarker in assessing microcirculatory changes in individuals with systemic sclerosis.

Background Numerous studies have indicated that alopecia areata is associated with a chronic systemic inflammation, which is considered as a risk factor for venous thromboembolism. The aim of the study was to evaluate the following markers of venous thromboembolism risk: soluble fibrin monomer complex (SFMC), thrombin–antithrombin complex (TATC), and prothrombin fragment 1 + 2 (F1 + 2) in patients with alopecia areata and compare them with healthy controls. Methods In total, 51 patients with alopecia areata [35 women and 16 men; mean age: 38 (19–54) years] and 26 controls [18 women and 8 men; mean age: 37 (29–51) years] were enrolled in the study. The serum concentrations of thromboembolism markers were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Results An increased level of SFMC was detected in patients with alopecia areata compared with the controls [25.66 (20–34.86) versus 21.46 (15.38–29.48) µg/ml; p < 0.05)]. In addition, a higher level of F1 + 2 was observed in patients with alopecia areata in comparison with the control group [70150 (43720–86070) versus 38620 (31550–58840) pg/ml; p < 0.001]. No significant correlation was detected among SFMC or F1 + 2 and the Severity of Alopecia Tool (SALT) score, disease duration, or the number of the hair loss episodes. Conclusion Alopecia areata may be associated with an increased risk of venous thromboembolism. Regular screening and preventive management of venous thromboembolism may be beneficial in patients with alopecia areata, especially before and during systemic Janus kinase (JAK) inhibitors or glucocorticoid therapy.

Systemic sclerosis (SSc) is an immune-mediated connective tissue disease. Recent studies reported differences in the composition of intestinal microbiota (dysbiosis) in patients with SSc compared to nonsclerodermic subjects. Dysbiosis may disrupt the intestinal barrier, which leads to immunological activation via microbial antigen and metabolite translocation. The study aimed to assess the differences in intestinal permeability between SSc patients and controls and to examine the correlation between intestinal permeability and complications of SSc. The study comprised 50 patients with SSc and 30 matched subjects. Serum intestinal permeability markers: intestinal fatty acid binding protein, claudin-3, and lipopolysaccharides (LPS) were determined using an enzyme-linked immunosorbent assay. SSc patients had a significantly increased concentration of LPS compared to control subjects (232.30 [149.00–347.70] versus 161.00 [83.92–252.20] pg/mL, p < 0.05). The patients with shorter SSc duration (≤6 years) had an increased concentration of LPS and claudin-3 compared to the subgroup with longer disease length: LPS (280.75 [167.30–403.40] versus 186.00 [98.12–275.90] pg/mL, p < 0.05), and claudin-3 (16.99 [12.41–39.59] versus 13.54 [10.29–15.47] ng/mL, p < 0.05). The patients with esophageal dysmotility had a decreased LPS level compared to those without this complication (188.05 [102.31–264.40] versus 283.95 [203.20–356.30] pg/mL, p < 0.05). Increased intestinal permeability in SSc may exacerbate the course of the disease and increase the risk of developing complications. Lower LPS levels in SSc might be a hallmark of esophageal dysmotility.

Background Systemic sclerosis is a connective tissue disease characterized by vasculopathy and progressive fibrosis, leading to multiorgan dysfunction. Given the complex and not fully elucidated pathogenesis, biomarkers of rapid disease progression and therapeutic response are lacking. Copeptin, which reflects vasopressin activity in serum, is used in diagnosing or prognosing different cardiometabolic conditions. Objective The aim of study was to investigate the concentration of copeptin in patients with systemic sclerosis and correlate it with specific clinical symptoms. Patients and Methods Serum copeptin was measured in patients with systemic sclerosis (34 women and 3 men; mean age 57.6 years) and in healthy individuals (n=30) using commercially available ELISA kits. According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). The median duration of the disease was 10 [4–14] years. Results We found significantly higher copeptin concentration in patients with systemic sclerosis (4.21 pmol/L [3.04–5.42]) in comparison to control group (3.40 pmol/L [2.38–3.76], p<0.01). Copeptin significantly correlated with Raynaud’s condition score (r=0.801, p<0.05). Patients with “late” capillaroscopic patterns had higher copeptin concentrations (5.37 pmol/L [4.29–8.06]) than patients with “early” (2.43 pmol/L [2.25–3.20], p<0.05) and “active” patterns (3.93 pmol/L [2.92–5.16], p<0.05]). Copeptin was found to be significantly higher in SSc patients with DUs (5.71 pmol/L [IQR 4.85–8.06]) when compared to SSc patients without DUs (3.31 pmol/L, [2.28–4.30], p<0.05). Additionally, copeptin concentration had good diagnostic accuracy in discriminating between patients with and without digital ulcers (AUC=0.863). Alprostadil decreased copeptin concentration from 4.96 [4.02–6.01] to 3.86 pmol/L [3.17–4.63] (p<0.01) after 4–6 cycles of administration. Conclusion Our findings suggest that copeptin may be a promising biomarker of microcirculation alterations in systemic sclerosis.

Frontal fibrosing alopecia is a variant of lichen planus, leading to permanent hair loss from the frontal hairline. It occurs mainly in postmenopausal women, however, the role of hormonal factors in the pathogenesis of this type of alopecia has not been determined. The coexistence of frontal fibrosing alopecia and autoimmune diseases is observed, e.g., hypothyroidism, rheumatoid arthritis, vitiligo, polymyositis, systemic lupus erythematosus and discoid lupus erythematosus. Considering the possible role of genetic factors, research is underway to identify human leukocyte antigen (HLA) polymorphisms. One of the most studied factors is sunscreen, widely used in cosmetic products. The data available so far in this regard are controversial. Factors raising significant doubts include: the retrospective nature of the research, basing the collected data on the self-assessment of respondents and the lack of specification of the ingredients of these products. In the light of current data, sunscreen components cannot be considered as a factor playing a role in the pathogenesis of frontal fibrosing alopecia. Overestimation of the role of sunscreens in hair loss could lead to unjustified avoidance of their use and contribute to increased incidence of skin cancer.