Burden of atopic dermatitis in Europe: A population-centred approach leveraging web search data in 21 European countries.

BACKGROUND: The complexity, high prevalence, and substantial personal and socioeconomic burden collectively render atopic dermatitis (AD) a major public health concern. Using crowdsourced Internet data has the potential to provide unique insights into this concern, as demonstrated by several previous studies. However, a comprehensive comparison across European countries remains lacking. OBJECTIVES: The study aimed to investigate AD-related web searches across Europe to assess spatiotemporal variations and associations between disease-related and external factors. METHODS: AD-related web search data were extracted for 21 European countries between February 2019 and January 2023. Descriptive analysis and autocorrelation functions were performed to examine spatiotemporal patterns. Correlations (r) were used to evaluate the associations between web searches and disease-related, socioeconomic and meteorological data. RESULTS: Over 241 million AD-related web searches were identified, with search volume varying substantially among European countries (p < 0.001) and correlating with AD prevalence and disease burden (both r = 0.51, p = 0.019). Search volume increased between 2019 and 2023 in all countries and seasonally peaked in January and March. Negative correlations with median population age (r = -0.46, p = 0.039), number of general practitioners (r = -0.29, p = 0.226) and specialists (r = -0.27, p = 0.270) were observed. Moderate to strong correlations were found between search volume and cold, humid and windy weather with fewer sunshine hours, while higher online interest typically occurred 1-3 months after such weather conditions. CONCLUSION: The study highlights the great potential of online crowdsourced data analysis, for example, to investigate the impact of climate change or to identify unmet needs at a population level. Furthermore, the growing online interest in AD and the corresponding seasonal peaks emphasize the necessity of adapting treatment plans, intensifying public health campaigns, and disseminating reliable online information by governments and healthcare providers, especially during these periods.

Impact of asthma in Europe: A comparison of web search data in 21 European countries.

Background: Asthma is a chronic inflammatory disorder of the airways and one of the most important non-communicable diseases worldwide. Analyzing crowdsourced data can help understand public interest and unmet needs as well as potential factors influencing search behavior. Objective: The study aimed to investigate asthma-related web search data in Europe to identify possible regional and seasonal variations and to assess public interest. Methods: Google Ads Keyword Planner was used to measure search volume for search terms related to asthma, allergic asthma, and bronchial asthma in 21 European countries between January 2018 and December 2021. The top 10 keywords of each country were categorized qualitatively. Search volume per 100 000 inhabitants was descriptively assessed in terms of regional and seasonal trends. Spearman correlations between search volume and pollen concentration as well as coronavirus disease (COVID-19) cases were investigated. Results: The median search volume per 100 000 inhabitants for asthma and allergic asthma was highest in Northern and Western Europe, while the highest search volume for bronchial asthma was observed in Western and Eastern regions. A seasonal trend was identified for all search terms and in all regions. Correlations were found between search frequency and pollen load and search behavior and COVID-19 cases. Overall, Europeans were most interested in the diseases in general, their treatment options, and symptoms. Conclusion: These results highlighted the need for reliable and region-specific information about the disease and for public campaigns to improve asthma control. The study also emphasizes the importance of using crowdsourced data for a more encompassing overview beyond conventional healthcare data.

Dermatoscopy of Cutaneous Lichen Planus - Attempt to Translate Metaphoric Terminology Into Descriptive Terminology.

INTRODUCTION: Dermatoscopy is gaining appreciation in assisting the diagnosis of inflammatory dermatoses (inflammoscopy). Lichen planus (LP) is a common inflammatory skin disease with characteristic dermatoscopic features. Over the last few years, numerous articles were published on the dermatoscopy of LP and a high number of terms have been used to describe the dermatoscopic features of this disease. OBJECTIVES: The objective of this study was to review the literature on the dermatoscopy of LP and to re-evaluate the published descriptions in the light of the 2019 expert consensus on the terminology of dermatoscopy for non-neoplastic skin diseases. METHODS: We searched the PubMed database using the keywords 'lichen planus and dermatoscopy', 'lichen planus and dermoscopy', 'lichen planus and epiluminescence microscopy', and 'lichen planus and inflammoscopy'. RESULTS: Of 408 articles retrieved, we selected 67 articles for full-text review, and finally included 58 articles, mostly case reports or small case series, comprising 572 patients with LP. We identified 118 different terms or short descriptions that were used to characterize the dermatoscopy of LP and redescribed them according to International Dermoscopy Society consensus paper. Frequently, authors applied various terms or descriptions to variants of the same feature. Although reported under different designations, Wickham striae were the most consistent dermatoscopic feature of LP. Other characteristics of LP, such as vascular patterns, pigmented structures and follicular findings were less consistent or depended on skin type, anatomic site, disease stage and applied treatment. CONCLUSIONS: While Wickham striae are the single most important clue for the diagnosis, other dermatoscopic characteristics of LP are less consistent. Based on the descriptions published in the literature we established a dictionary of useful terms for the description of LP that is consistent with the terminology suggested by the recent consensus conference.

Hypoxia-Inducible Factor-1α (HIF-1α) as a Biomarker for Changes in Microcirculation in Individuals with Systemic Sclerosis.

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.

The Gut Microbial Metabolite Trimethylamine N-Oxide is Linked to Specific Complications of Systemic Sclerosis.

Background: Systemic sclerosis (SSc) is a rare immune-mediated connective tissue disease characterized by fibrosis of the skin and internal organs, whose pathogenesis is not fully understood. Recent studies have revealed dysbiosis in patients with systemic sclerosis and have indicated the possible role of the microbiota and its metabolites in the pathogenesis of the disease. Trimethylamine N-oxide (TMAO) is a compound produced by dysbiotic microbiota observed at higher concentrations in several autoimmune diseases. Objective: To determine concentrations of the bacteria-derived metabolite TMAO in patients with systemic sclerosis and to assess possible correlation between TMAO and a specific manifestation of the disease. Patients and Methods: The study included 63 patients with SSc and 47 matched control subjects. The concentration of TMAO was measured with high-performance liquid chromatography. Results: Plasma TMAO level was significantly increased in patients with SSc (283.0 [188.5-367.5] ng/mL versus 205.5 [101.0-318.0] ng/mL; p < 0.01). An increased concentration of TMAO was observed in patients with concomitant interstitial lung disease (ILD) (302.0 ng/mL [212.0-385.5] ng/mL versus 204.0 [135.5-292.0] ng/mL; p < 0.01) and esophageal dysmotility (289.75 [213.75-387.5] ng/mL versus 209.5 ng/mL [141.5-315.0] ng/mL; p < 0.05) compared to patients without these complications. Furthermore, TMAO concentration exhibited significant correlation with markers of heart involvement (left ventricle ejection fraction, NT-proBNP), marker of ILD severity and Scleroderma Clinical Trials Consortium Damage Index. Conclusion: The concentration of TMAO, gut microbiota-associated metabolite, is increased in systemic sclerosis, particularly in patients with advanced organ involvement. This is the first study evaluating plasma TMAO in systemic sclerosis. Bacterial metabolites may be a link between dysbiosis and organ involvement in the course of the disease. Modulation of gut bacterial-derived metabolites may represent a new therapeutic approach in the management of systemic sclerosis.

Copeptin as a Biomarker of Microcirculation Alterations in Systemic Sclerosis.

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.

The Clinical Significance of Serum Biomarkers of the Intestinal Barrier in Systemic Sclerosis: A Cross-Sectional Study.

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.

The Clinical Significance of Salusins in Systemic Sclerosis-A Cross-Sectional Study.

Background: Systemic sclerosis (SSc) is a connective tissue disease manifesting with progressive fibrosis of the skin and internal organs. Its pathogenesis is strictly associated with vascular disfunction and damage. Salusin-α and salusin-ß, endogenous peptides regulating secretion of pro-inflammatory cytokines and vascular smooth muscle proliferation, may potentially play a role in SSc pathogenesis. Objectives: The aim of this study was to assess the concentration of salusins in sera of patients with SSc and healthy controls and to evaluate correlations between the salusins levels and selected clinical parameters within the study group. Materials and methods: 48 patients with SSc (44 women; mean age, 56.4, standard deviation, 11.4) and 25 adult healthy volunteers (25 women; mean age, 55.2, standard deviation, 11.2) were enrolled. All patients with SSc were treated with vasodilators and twenty-seven of them (56%) also received immunosuppressive therapy. Results: Circulating salusin-α was significantly elevated in patients with SSc in comparison to healthy controls (U = 350.5, p = 0.004). Patients with SSc receiving immunosuppression had higher serum salusin-α concentrations compared with those without immunosuppressive therapy (U = 176.0, p = 0.026). No correlation was observed between salusins concentrations and skin or internal organ involvement parameters. Conclusions: Salusin-α, a bioactive peptide mitigating the endothelial disfunction, was elevated in patients with systemic sclerosis receiving vasodilators and immunosuppressants. Increased salusin-α concertation may be associated with the initiation of atheroprotective processes in patients with SSc managed pharmacologically, which requires verification in future studies.

Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases.

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.

Saliva as Blood Alternative in Therapeutic Monitoring of Teriflunomide-Development and Validation of the Novel Analytical Method.

Therapeutic drug monitoring (TDM) is extremely helpful in individualizing dosage regimen of drugs with narrow therapeutic ranges. It may also be beneficial in the case of drugs characterized by serious side effects and marked interpatient pharmacokinetic variability observed with leflunomide and its biologically active metabolite, teriflunomide. One of the most popular matrices used for TDM is blood. A more readily accessible body fluid is saliva, which can be collected in a much safer way comparing to blood. This makes it especially advantageous alternative to blood during life-threatening SARS-CoV-2 pandemic. However, drug's saliva concentration is not always a good representation of its blood concentration. The aim of this study was to verify whether saliva can be used in TDM of teriflunomide. We also developed and validated the first reliable and robust LC-MS/MS method for quantification of teriflunomide in saliva. Additionally, the effect of salivary flow and swab absorptive material from the collector device on teriflunomide concentration in saliva was evaluated. Good linear correlation was obtained between the concentration of teriflunomide in plasma and resting saliva (p < 0.000016, r = 0.88), and even better between plasma and the stimulated saliva concentrations (p < 0.000001, r = 0.95) confirming the effectiveness of this non-invasive method of teriflunomide's TDM. The analyzed validation criteria were fulfilled. No significant influence of salivary flow (p = 0.198) or type of swab in the Salivette device on saliva's teriflunomide concentration was detected. However, to reduce variability the use of stimulated saliva and synthetic swabs is advised.

Raynaud's Phenomenon with Focus on Systemic Sclerosis.

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.

Microbiota medicine: towards clinical revolution.

The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge.

Future Treatment Options in Systemic Sclerosis-Potential Targets and Ongoing Clinical Trials.

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 ß (TGF-ß), 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.

A Six-Year Gynecological Follow-Up of Immunosuppressed Women with a High-Risk Human Papillomavirus Infection.

Immunocompromised women are at an increased risk of developing malignancies, especially those that are viral-induced, such as invasive cervical cancer caused by the human papillomavirus (HPV). The aim of the study was to describe gynecological follow-up of women undergoing chronic immunosuppressive therapy for various reasons (e.g., kidney/liver transplant, systemic lupus erythematosus), diagnosed with a high-risk HPV (hrHPV) infection based on a self-sampling test. Twenty-six hrHPV-positive women were invited to take part in a gynecological follow-up, including a visual assessment of the anogenital region, two-handed gynecological examination, and cervical cytology as well as a colposcopy and cervical biopsy when necessary. Four women declined taking part in the study. Over six years of observation, low-grade squamous intraepithelial lesions (LSIL) were detected at least once in 7/22 women (31.8%), and a cervical intraepithelial lesion 1 (CIN 1) histopathologic result was obtained five times in 3/22 women. No cases of high-grade squamous intraepithelial lesions, CIN 2/3, or invasive cervical cancers were observed. Loop electrosurgical excision procedure (LEEP) was performed in three patients. As immunocompromised women are prone to persistent hrHPV infections, they should be under strict gynecological supervision because only vigilant surveillance enables fast detection and treatment of early dysplasia and, therefore, provides a chance for the reduction of the cervical cancer burden.

Nonscarring Alopecia and Hypopigmented Lesions May Be Unusual Signs of Secondary Syphilis.

Noncicatricial patchy alopecia of the scalp and focal areas of skin hypopigmentation imply a diagnosis of alopecia areata and vitiligo. We present a case of a 22-year-old patient in whom these symptoms were associated with positive spirochete reactions, which allowed making a diagnosis of syphilitic alopecia coexisting with leukoderma syphiliticum. Skin lesions and hair loss resolved after the treatment with benzathine benzylpenicillin. Trichoscopy in syphilitic alopecia is nonspecific, but the absence of features typical for alopecia areata such as exclamation mark hairs may be important on an early stage of the clinical workup.

Trimethylamine N-Oxide, a Gut Microbiota-Derived Metabolite, Is Associated with Cardiovascular Risk in Psoriasis: A Cross-Sectional Pilot Study.

INTRODUCTION: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, is involved in the pathogenesis of atherosclerosis and cardiovascular diseases. Psoriasis is associated with increased cardiovascular risk that is not captured by traditional biomarkers. The aim of the present study was to assess TMAO concentration in psoriasis and evaluate the relationship between TMAO and cardiovascular risk in psoriatic patients. METHODS: In 72 patients with psoriasis and 40 age- and sex-matched non-psoriatic controls, we evaluated fasting plasma TMAO, measured by high-performance liquid chromatography, and cardiovascular risk assessed by various scoring systems such as Framingham, QRISK2, AHA/ACC, and Reynolds risk scores. RESULTS: In patients with psoriasis, TMAO concentration was significantly higher than in the control group (195.68 [133.54-332.58] ng/ml versus 126.06 [84.29-156.88] ng/ml, respectively; p < 0.001). Plasma TMAO concentration was significantly correlated with age, total cholesterol, triglycerides, systolic and diastolic blood pressure. Furthermore, the receiver-operating characteristic (ROC) and multiple regression analysis showed that TMAO is an independent predictor of cardiovascular risk. CONCLUSION: TMAO is a valuable candidate for biomarker and a translational link between dysbiosis and atherosclerosis in psoriasis.

Clinical Implications of Intestinal Barrier Damage in Psoriasis.

BACKGROUND: An increasing amount of evidence suggests an association between increased intestinal permeability and the pathogenesis of chronic inflammatory diseases. However, the clinical significance of gut barrier dysfunction in psoriasis remains to be established. OBJECTIVE: To evaluate whether there are differences in disease activity, the severity of gastrointestinal symptoms and the blood concentration of bacterial metabolites in psoriatic patients with a normal and altered intestinal barrier. PATIENTS AND METHODS: Gut barrier integrity was assessed with the serum concentrations of claudin-3, a modulator of intestinal tight junctions and an intestinal fatty acid-binding protein, a marker of enterocyte damage. Gastrointestinal symptoms were evaluated with a validated questionnaire. The concentration of trimethylamine N-oxide (TMAO), a gut microbiota-associated metabolite, was measured with high-performance liquid chromatography. RESULTS: One hundred and fourteen patients with psoriasis were finally enrolled in the study - 68 with an altered gut barrier and 46 with a properly functioning intestinal barrier. Patients with an altered gut barrier showed a significantly higher score in the Gastrointestinal Symptom Rating Scale (3.20 vs 1.46, p<0.001). Moreover, patients with psoriasis and a disrupted intestinal barrier demonstrated a higher disease activity (PASI: 19.7 vs 10.3, p<0.001) and systemic inflammatory parameters (neutrophil-to-lymphocyte ratio: 2.86 vs 1.71, p<0.001; C-reactive protein 3.76 vs 1.92; p<0.05). The marker of bacterial translocation was significantly higher in psoriatic patients with damaged gut integrity (TMAO: 375.7±51.9 vs 119.4±27.5 ng/mL; p<0.05). CONCLUSION: The altered gut barrier in psoriasis is associated with gastrointestinal symptoms, systemic inflammatory profile and the increased blood concentration of gut microbiota-derived metabolite - TMAO. Intestinal barrier modulation represents a new promising therapeutic approach.

Cutaneous T-cell lymphoma in erythrodermic cases may be suspected on the basis of scalp examination with dermoscopy.

Erythrodermic variants of cutaneous T-cell lymphoma (CTLC) are one of the case of erythroderma. The aim of the study was to assess the value of scalp dermoscopy in differentiation between erythrodermic CTCL, psoriasis, and atopic dermatitis. A total of 76 patients were included into the study (16 patients with erythrodermic CTCL, 20 patients with psoriatic erythroderma, 20 with erythrodermic atopic dermatitis, and 20 healthy volunteers). The most common trichoscopic features of erythrodermic CTCL were: numerous pili torti, numerous broken hairs, white thick interfollicular bands, and patchy hyperpigmentation of the background. They were observed in 81% (13/16), 75% (12/16), 56% (9/16), and 37.5% (6/16) of patients with CTCL, respectively (p < 0.001). Other specific features of erythrodermic CTCL were 8-shaped hairs (19%; 3/16) and visible anagen bulbs (12.5%; 2/16) (p < 0.05 and p = 0.052, respectively). The most common vascular pattern of erythrodermic CTCL was perifollicular arrangement of glomerular (50%; 8/16; p < 0.001) or linear vessels (31%; 5/16; p < 0.05). Follicular spicules-like scaling was pathognomonic for erythrodermic CTCL (12%, 2/16) although its presence did not reach statistical significance (p = 0.052). In conclusion, the characteristic trichoscopic findings of erythrodermic CTCL are numerous pili torti, eight-shaped hairs, thick white interfollicular bands, color heterogeneity of the background and perifollicular arrangement of vessels.

BIOMARKERS OF DISEASE ACTIVITY IN SYSTEMIC SCLEROSIS.

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and uncontrolled cutaneous and internal organs fibrosis. Diagnosis of SSc in an early phase can be difficult because of a lack of typical symptoms. The delay in diagnosis and treatment of SSc may lead to uncontrolled progression of the disease, thus identification of possible early indicators of skin and organ involvement to prevent their further damage is necessary. The aim of this study is to review the latest biomarkers of organ involvement in SSc. In patients with lung fibrosis lung-epithelial-derived surfactant protein (SP-D), the glycoprotein Krebs von den Lungen-6 (KL-6), and chemokine ligands 2, 4 and 18 (CCL2, CXCL4, CCL18) are elevated, while in patients with skin fibrosis serum levels of heat shock protein 27 (Hsp27), interleukin 16 (IL-16), and IgG-galactosylation ratio are increased. Adiponectin concentration is inversely correlated with the intensity of cutaneous fibrosis. Skin gene profiling also seems very promising. In patients with heart involvement increased serum levels of brain natriuretic peptide (BNP) are present, as well as raised Midkine and Follistatin-like 3 (FSTL3) proteins, ratios of Cu/Se and ceruloplasmin(CP) /Circulating selenoprotein P(SELENOP) and higher whole blood viscosity level. Elevated calprotectin levels are found in individuals with gastrointestinal involvement. Increased levels of chemerin and ARA autoantibodies are associated with renal involvement, whereas high levels of adhesion molecules are found in patients with scleroderma renal crisis (SRC). Currently there are no biomarkers in use that can specifically identify the early involvement of organs.