Inflammatory Skin Lesions Research Articles

An S100A8/A9 neutralizing antibody potently ameliorates contact hypersensitivity and atopic dermatitis symptoms.

Contact hypersensitivity (CHS) and atopic dermatitis (AD) are pervasive inflammatory skin diseases with similar symptoms, and the global prevalence of both conditions is steadily rising. Many compounds and biotics have been developed to target molecules critical to the etiology or pathogenesis of CHS and AD. However, such molecules are sometimes ineffective or lose potency over the therapeutic course. Therefore, innovative medicines are still needed for the treatment of intractable cases. We have been focused on S100A8/A9, a heterodimer complex of S100A8 and S100A9 abundant in the extracellular milieu of the inflammatory skin lesion. Although S100A8/A9 is recognized primarily as a diagnostic marker protein, we previously showed that it also plays a crucial role in CHS and AD progression. This insight inspired us to develop its inhibitory antibody, leading to the groundbreaking Ab45. In the present study, we demonstrated that Ab45 effectively prevented disease symptoms in various models, and that its disease-ameliorating activity likely involves the downregulation of several disease-relevant molecules, including Il-23a, Il-36g, S100a8, and S100a9. We also created a humanized version of Ab45, HuAb45, which exhibited similar effectiveness. These antibodies show great promise for the treatment of CHS and AD, and possibly for other inflammatory skin diseases as well.

Investigating the antioxidant and anti-inflammatory potential of Nypa fruticans: a multifaceted approach to skin protection and aging

Reactive oxygen species (ROS) produced in the mitochondria of skin cells play a significant role in the degradation of the extracellular matrix and induction of inflammatory responses, both of which are major contributors to skin aging. Antioxidants that reduce ROS production and inhibit inflammatory skin lesions are considered beneficial for the treatment of inflammatory skin diseases and prevention of skin aging. In this study, we evaluated the potential of Nypa fruticans (NF), which is known for its antioxidant properties, to mitigate tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-induced damage in normal human epidermal keratinocytes. The major active constituents identified in NF include protocatechuic acid, hydroxybenzoic acid, procyanidin B, catechin, and epicatechin. NF significantly suppressed the production of ROS, nitric oxide (NO), and prostaglandin E2 (PGE2), while also reducing the levels of inflammatory cytokines interleukin-6 (IL-6) and interleukin-1 beta (IL-1β), which were elevated by TNF-α/IFN-γ stimulation. Furthermore, NF restored the expression of key skin barrier-related proteins such as serine peptidase inhibitor kazal type 5 (SPINK5), collagen type I alpha 1 chain (COLIA1), loricrin (LOR), aquaporin-3 (AQP3), and filaggrin (FLG). Additionally, NF significantly upregulated the expression of hyaluronan synthase (HAS) -1 and − 2 and human β-defensin (HBD) -2 and − 3, which are important for skin hydration and innate immune defense. These findings underscore the potential therapeutic applications of Nypa fruticans (NF) in mitigating oxidative stress, inflammation, skin barrier dysfunction, dehydration, and microbial imbalances. By targeting multiple pathways implicated in skin aging, NF represents a promising comprehensive approach for preserving skin health and addressing age-related dermatological conditions. Moreover, NF holds significant potential not only to alleviate the manifestations of skin aging but also to provide a basis for the development of innovative dermatological therapies. Future investigations should aim to further elucidate the clinical applications of NF in dermatology to maximize its therapeutic benefits.

Pharmacological Modulation of the Unfolded Protein Response as a Therapeutic Approach in Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a rare T-cell malignancy characterized by inflamed and painful rash-like skin lesions that may affect large portions of the body's surface. Patients experience recurrent infections due to a compromised skin barrier and generalized immunodeficiency resulting from a dominant Th2 immune phenotype of CTCL cells. Given the role of the unfolded protein response (UPR) in normal and malignant T-cell development, we investigated the impact of UPR-inducing drugs on the viability, transcriptional networks, and Th2 phenotype of CTCL. We found that CTCL cells were >5-fold more sensitive to the proteasome inhibitor bortezomib (Btz) and exhibited a distinct signaling and transcriptional response compared to normal CD4+ cells. The CTCL response was dominated by the induction of the HSP70 family member HSPA6 (HSP70B') and, to a lesser extent, HSPA5 (BiP/GRP78). To understand the significance of these two factors, we used a novel isoform selective small-molecule inhibitor of HSPA5/6 (JG-023). JG-023 induced pro-apoptotic UPR signaling and enhanced the cytotoxic effects of proteasome inhibitors and other UPR-inducing drugs in CTCL but not normal T cells. Interestingly, JG-023 also selectively suppressed the production of Th2 cytokines in CTCL and normal CD4+ T cells. Conditioned media (CM) from CTCL were immunosuppressive to normal T cells through an IL-10-dependent mechanism. This immunosuppression could be reversed by JG-023, other HSP70 inhibitors, Btz, and combinations of these UPR-targeted drugs. Our study points to the importance of the UPR in the pathology of CTCL and demonstrates the potential of proteasome and targeted HSPA5/6 inhibitors for therapy.

Pulsed dye laser in jellyfish-induced keloids

ABSTRACT Jellyfish stings can cause acute inflammatory skin lesions that may hesitate in keloids. Pulsed dye laser (PDL) represents one of the most effective treatments for newly developed keloids. Aim of this study was to evaluate the efficacy of PDL on newly developed keloids specifically induced by jellyfish stings in pediatric patients.We conducted a retrospective observational study on pediatric patients with newly developed keloids from jellyfish stings, treated in the last two years with 595 nm wavelength PDL with a duration of 0.45–1.5 msec, spot-size 7 mm and fluence 8.5–9.5 J/cm2. PDL therapy was administered for a mean of 7.4 treatment sessions, every 1–3 months. Two expert dermatologists evaluated the vascularity, pigmentation, height, and pliability of keloids, according to the Vancouver Scar Scale (VSS), pre-and-post treatment. A total of 17 patients (7 males, 10 females) were included in the study, mean age of 11 years. Overall, mean pre-treatment global VSS was 11.0 ± 1.50. After treatment, global VSS was 3.88 ± 1.87. At paired t-test, the difference between pre-treatment and post-treatment was highly statistically significant (p < .0001). Commonly, manipulation and therapeutic intervention on jellyfish scars and keloids is feared. The present study supports the use of PDL in keloids secondary to jellyfish stings, though conducted on a limited number of patients.

Distinct Cutibacterium acnes subspecies defendens strains classified by multi-omics dissection alleviate inflammatory skin lesions of a rosacea-like mouse model

IntroductionCutibacterium acnes (C. acnes) resides in various organs such as the skin, prostate, eye, nose, stomach, and intestine, indicating the possibility of extensive crosstalk between this bacterium and the human body. C. acnes strains are classified into three subspecies based on phylogenetics and distinguishable phenotypes. Among them, C. acnes subsp. defendens strains are characterized by anti-inflammatory features, raising expectations for their potential as future microbiome therapeutics. However, the heterogeneity of C. acnes subsp. defendens and its corresponding immunological functions have not been clearly addressed.MethodsThe genetic diversity of the strains was assessed using single- and multi-locus sequence typing. Their immune-modulatory functions were evaluated in vitro using 2D and 3D assays with immune and epithelial cells. The anti-inflammatory effects were further confirmed in vivo using a rosacea-like mouse model. Comparative genomic and transcriptomic analyses were conducted to uncover mechanisms underlying the immunosuppressive activity of the strains.ResultsWe demonstrated that the newly isolated C. acnes subsp. defendens strains, exhibiting phenotypic heterogeneity, are distinctly clustered using single- and multi-locus sequence typing methods. These strains showed strong immune-regulatory functions in immune and epithelial cell-based 2D and 3D in vitro assays. Furthermore, their anti-inflammatory role was functionally confirmed in vivo using a rosacea-like mouse model, where they alleviated skin lesions characterized by hyperplasia and dermal inflammation. Comparative transcriptomics revealed that these strains may exert their immunosuppressive effects through the enhanced expression of acnecins and transcriptional variation in envelope stress regulators (specifically the two-component systems, CesSR homologs). Additionally, we propose that these C. acnes type II strains produce anti-inflammatory metabolites or peptides smaller than 3 kDa, which are associated with elevated pyrimidine and reduced L-arginine biosynthesis.DiscussionThe newly isolated C. acnes subsp. defendens strains demonstrate significant anti-inflammatory properties both in vitro and in vivo, suggesting their potential as microbiome-based therapeutics. Their unique genomic and transcriptomic profiles, including the production of small bioactive compounds and specific transcriptomic patterns, underpin their immunosuppressive capabilities. These findings provide a foundation for developing novel treatments for inflammatory skin conditions, such as rosacea.

Annular Hailey–Hailey disease

AbstractHailey–Hailey disease (HHD) is a genodermatosis that typically presents with crusted erosions located in skin folds and the perineum. We report two cases of a highly atypical form of HHD, characterised by inflammatory annular skin lesions on the trunk, isolated and sparing the folds in one patient. Diagnosis was confirmed by histology or genetic analysis. Clinicians should consider this exceptional subset of HHD when encountering annular lesions resistant to antifungals even when a relevant familial background is lacking.

The Prevalence of Dermoscopy Use Among Dermatology Residents in Riyadh, Saudi Arabia: Cross-Sectional Study.

Dermoscopy is a noninvasive technology used to examine the skin's invisible microstructures in dermatological practice and is gaining prominence as a crucial tool. Dermoscopy is an evidence-based practice used to enhance the early detection of skin malignancies and to help distinguish between various skin conditions, including pigmented and nonpigmented skin malignancies. Currently, the vast majority of global guidelines for skin cancer recommend dermoscopy as a critical component. Dermoscopy use is increasing worldwide, but to date, no study has documented the attitudes toward and use of dermoscopy among future dermatologists in Saudi Arabia. We aimed to determine the proportion of dermatology residents in Riyadh who use dermoscopy in their clinical practice; identify factors influencing the use of dermoscopy, such as availability of equipment, training, and the perceived importance of dermoscopy in clinical practice; explore barriers to dermoscopy use, including the lack of access to necessary resources (eg, dermoscopes) and insufficient training; and provide insights into the adoption and integration of dermoscopy into dermatology training and clinical practice in Saudi Arabia. In January 2024, a validated and published questionnaire was modified to meet research requirements and was sent to all registered dermatology residents in the The Saudi Board of Dermatology and Venereology Program. In total, 63 dermatology residents in Riyadh, Saudi Arabia, completed the web-based questionnaire (response rate=87.5%). The sample was predominantly female (n=34, 54.0%), with the majority (n=53, 84.1%) aged between 26 and 30 years. A notable proportion of participants (n=22, 34.9%) were in their final year of residency. Over half of the participants (n=34, 54.0%) owned a dermoscope, and a substantial number of them (n=23, 36.5%) reported conducting 21-30 clinic consultations per month on average. More than half of the participants (n=36, 57.1%) had received dermoscopy training, and 16 (36.4%) had used dermoscopy for 2 years. Additionally, most participants (n=20, 45.5%) had used nonpolarized immersion-contact dermoscopy, while 19 (43.2%) had used polarized light dermoscopy. Furthermore, the majority (n=22, 50.0%) used dermoscopy in fewer than 10% of cases involving patients with inflammatory skin lesions. Statistical analysis revealed significant associations between the participants' ages (P=.003), residency levels (P=.001), and practice centers and the use of dermoscopy (P=.004). Dermoscopy has been widely adopted by dermatology residents in their daily clinical practice due to its benefits in early detection and diagnosis of skin diseases. However, the overall extent of dermoscopy use within the dermatology community remains unclear, highlighting the need for further education. In Saudi Arabia, the key factors influencing dermoscopy use include residents' ages, residency levels, and practice centers. Younger dermatologists have expressed strong interest in improving their dermoscopy knowledge and skills. Expanding access to dermoscopy equipment and providing training during residency could further promote its use across the country.

Evaluation of OVOL1 and Filaggrin immunohistochemical expression and clinical relevance in psoriasis

BackgroundPsoriasis is a disease of overactive immune system. OVOL1 and Filaggrin have been associated with many inflammatory skin lesions. To the best of our knowledge, the correlation between OVOL1 and Filaggrin in psoriasis was not previously investigated. This work aims to search the immunohistochemical expression and correlation between OVOL1 and Filaggrin in psoriasis.Materials and methodsSlides cut from paraffin blocks of 30 psoriasis cases and 30 control subjects were stained with OVOL1 and Filaggrin. Clinicopathological data were correlated with the results of staining.ResultsOVOL1 and Filaggrin expression in epidermis showed a significant gradual reduction from normal skin to peri-lesional and psoriasis biopsies (P < 0.001). In contrast, psoriasis dermis showed a significant overexpression of OVOL1 in inflammatory cells in relation to peri-lesional biopsies (P < 0.002). OVOL1 demonstrated a significant direct correlation with Filaggrin expression in psoriasis (r = 0.568, P < 0.004). OVOL1 and Filaggrin expression in psoriasis skin epidermis demonstrated a statistically significant negative correlation with PASI score.ConclusionOVOL1 and Filaggrin might be involved in psoriasis-associated inflammation and skin hyperproliferation. OVOL1 might have a protective barrier function in the skin and could be used to stratify progressive disease. Filaggrin may play a role in progression of psoriasis. OVOL1 inhibition could be considered in suppression of Filaggrin function. OVOL1 agonists may be beneficial in psoriasis treatment.

How Do Omega-3 and Omega-6 Fatty Acids Influence the Development of Common Acne?

Introduction: Acne is one of the most common skin problems affecting people worldwide, especially young individuals. Despite many years of research into the etiology of acne, its exact causes remain a subject of debate. In recent years, increasing scientific interest has focused on the role of diet in shaping skin health, including the influence of omega-3 and omega-6 fatty acids on the severity of acne symptoms. Objective: The aim of this study is to review the scientific literature regarding the relationship between a diet rich in omega-3 and omega-6 fatty acids and the reduction of acne. We will analyze available scientific evidence and attempt to determine whether dietary changes to increase the intake of these fatty acids may have a beneficial impact on skin condition and reducing the severity of acne symptoms. Results: Several studies suggest that a diet rich in omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and relatively low in omega-6 fatty acids may be associated with a reduction in acne severity. Some clinical studies have shown that supplementation with omega-3 fatty acids can lead to a reduction in the number of comedones and inflammatory skin lesions in acne patients. Conclusions: Our literature review suggests that a diet rich in omega-3 fatty acids and lower in omega-6 fatty acids may be beneficial for individuals struggling with acne. However, further clinical research is needed to confirm these observations and better understand the mechanisms of action of fatty acids on skin health. In the meantime, a balanced diet rich in omega-3-containing foods such as fatty fish, nuts, and seeds is recommended as a potential adjunct to acne treatment.

IgA Vasculitis Secondary to Enterococcus Faecalis Cardiac Device Infective Endocarditis; A Case Report, Discussion of the Literature and Protocol for Assessment of Inflammatory Skin Lesions in Emergency Medicine

A 68-year-old Caucasian male presented to the emergency department for administration of IV ceftriaxone post discharge for Enterococcus faecalis Cardiac Device Infective Endocarditis (CDIE). The patient reported a rash on his legs which had been present for many weeks. On examination the rash a revealed non-blanching purpuric rash resembling leukocytoclastic vasculitis. Biopsy and serology performed in our rural emergency department confirmed IgA vasculitis (IgAV). The patient had no systemic features to suggest IgA nephritis, or other systemic disease and the rash resolved with no additional treatment. A discussion of the differential diagnoses in this case highlights the importance of opportunistic biopsy and vasculitis serology in the rural emergency department setting and recommends screening for underlying cancer given the close association of IgAV with malignancy. The importance of emergency department protocols for assessment of skin lesions suggestive of an underlying systemic disease is also discussed.

The interferon-rich skin environment regulates Langerhans cell ADAM17 to promote photosensitivity in lupus.

The autoimmune disease lupus erythematosus (lupus) is characterized by photosensitivity, where even ambient ultraviolet radiation (UVR) exposure can lead to development of inflammatory skin lesions. We have previously shown that Langerhans cells (LCs) limit keratinocyte apoptosis and photosensitivity via a disintegrin and metalloprotease 17 (ADAM17)-mediated release of epidermal growth factor receptor (EGFR) ligands and that LC ADAM17 sheddase activity is reduced in lupus. Here, we sought to understand how the lupus skin environment contributes to LC ADAM17 dysfunction and, in the process, differentiate between effects on LC ADAM17 sheddase function, LC ADAM17 expression, and LC numbers. We show through transcriptomic analysis a shared IFN-rich environment in non-lesional skin across human lupus and three murine models: MRL/lpr, B6.Sle1yaa, and imiquimod (IMQ) mice. IFN-I inhibits LC ADAM17 sheddase activity in murine and human LCs, and IFNAR blockade in lupus model mice restores LC ADAM17 sheddase activity, all without consistent effects on LC ADAM17 protein expression or LC numbers. Anti-IFNAR-mediated LC ADAM17 sheddase function restoration is associated with reduced photosensitive responses that are dependent on EGFR signaling and LC ADAM17. Reactive oxygen species (ROS) is a known mediator of ADAM17 activity; we show that UVR-induced LC ROS production is reduced in lupus model mice, restored by anti-IFNAR, and is cytoplasmic in origin. Our findings suggest that IFN-I promotes photosensitivity at least in part by inhibiting UVR-induced LC ADAM17 sheddase function and raise the possibility that anifrolumab ameliorates lupus skin disease in part by restoring this function. This work provides insight into IFN-I-mediated disease mechanisms, LC regulation, and a potential mechanism of action for anifrolumab in lupus.

Fatty Acid Profile of Erythrocyte Membranes in Patients with Psoriasis.

Psoriasis is a chronic systemic disease with a multifaceted pathomechanism and immunological basis, with the presence of inflammatory skin lesions and joint ailments. Diseases accompanying psoriasis include metabolic and cardiovascular disorders. It has been suggested that inflammation is involved in the development of each of these conditions. The main objective of this study was to analyse the fatty acid profile, including polyunsaturated fatty acids, in the erythrocyte membranes of patients suffering from psoriasis. A total of 58 adult patients of the Department of Skin and Venereal Diseases of the Pomeranian Medical University in Szczecin, suffering from psoriasis, were qualified for this study. The patients had undergone an interview and physical examination, during which the severity of psoriasis was assessed. All patients had their weight and height measured to assess their body mass index (BMI). After 3 months of treatment, biochemical parameters (ALT, AST, total cholesterol) and inflammatory markers (CRP) in the blood were assessed. In addition, the isolation of fatty acids (PUFAs, SFAs, MUFAs) from erythrocyte membranes and the qualitative and quantitative analysis of their profile using a gas chromatograph were carried out. In patients with severe psoriasis requiring systemic treatment, an altered profile of fatty acids in erythrocyte membranes was found, including a significantly lower concentration of polyunsaturated fatty acids (omega-3), which have an anti-inflammatory effect; a significantly higher concentration of saturated fatty acids; and a decreased concentration of oleic acid (omega-9), compared to the results obtained in patients with less severe psoriasis receiving topical treatment. In patients with psoriasis and BMI ≥ 25, significantly higher concentrations of AST and ALT in the blood and significantly higher concentrations of pro-inflammatory arachidonic acid in erythrocyte membranes were found. Elevated concentrations of saturated (R = 0.31) and monounsaturated fatty acids (R = 0.29) may correlate with a greater severity of psoriasis.

New Molecules of Importance in the Prevention and Treatment of Acne: A Systematic Patent Review (2016-2020).

Acne is a highly prevalent disease that mainly affects the pilosebaceous units associated with sebaceous glands, causing inflammatory skin lesions and affecting the self-esteem, mental health, and quality of life of those who suffer from this disease. Different treatments exist today to prevent, reduce, and improve symptoms; however, over the years, there have been problems with bacterial resistance and slight effectiveness with prolonged use. The purpose of this article is based on the review of patents of new products of principal topical administration for the treatment of acne in recent years 2016-2020, to evaluate and analyze novel synthetic molecules and semi-synthetics with potential therapeutic and preventive in the acne treatment. A systematic review of patents was conducted through the official database of the European Patent Office - Espacenet, where the search focused on the keywords: "acne and bacteria" in the title or abstract. Only patents granted between the years 2016-2020 were included, with products having molecules with a synthetic and semi-synthetic origin, without considering natural, biological products or those used as diagnostic means. A total of 19 patents were selected, most with principally antimicrobial and antiinflammatory action, where the reduction in the appearance of resistance by C. acnes is verified, and its action is complemented by inhibiting the different pathophysiological mechanisms that lead to the worsening of the disease. Novel approaches in the treatment and prevention of acne, mainly topically, are focused on the reduction of bacterial resistance and irritation compared to current treatments. The use of combined formulations provides better results with additional benefits, improving treatment times and patient adherence.

An Open-label Study to Investigate the Efficacy and Tolerability of Dapsone Gel, 7.5% in the Treatment of Acne Vulgaris in Men and Women With Skin of Color

Acne vulgaris is a common skin disease prevalent in skin of color patients. Studies have demonstrated that dapsone gel, 7.5% (Aczone) used once daily is effective, safe, and well-tolerated for the treatment of acne in both men and women. However, minimal data are available in skin of color populations. This single-center, open-label clinical study investigated the efficacy and safety of dapsone gel, 7.5% in the treatment of moderate to severe acne vulgaris in patients with Fitzpatrick skin types IV-VI. Twenty (20) adult subjects with moderate to severe acne and Fitzpatrick skin types IV-VI were enrolled in this study and treated with dapsone gel, 7.5% once daily for 24 weeks. Dapsone gel, 7.5% applied daily for 24 weeks reduced acne severity, post-inflammatory hyperpigmentation, and decreased new inflammatory and noninflammatory acne lesions in skin of color patients with moderate to severe acne vulgaris. Treatment resulted in improved acne health-related quality of life and patient symptoms related to acne, including patient-reported post-inflammatory hyperpigmentation, especially with a treatment duration of 18 weeks or longer.&nbsp; Limitations: The sample size was small and underpowered to detect statistically significant changes in some endpoints. Dapsone gel 7.5% was safe, well-tolerated, and efficacious in treating acne vulgaris and post-inflammatory hyperpigmentation in skin-of-color patients. Larger studies involving skin-of-color populations with acne vulgaris are warranted. J Drugs Dermatol. 2024;23(6):410-417. doi:10.36849/JDD.7897.

A-FABP and E-FABP as cutaneous biomarkers of Metabolic Syndrome

Introduction: In Metabolic syndrome (MetS), tissues such as adipose, liver, and skin with very active lipid metabolism are dysfunctional, making it diffcult to store the excess fat. Fatty acid binding proteins (FABPs) are cytosolic proteins that can reversibly bind to lipids and transport them to different cell organelles. In this work, we focus on adipocyte (A-FABP) and epidermal (E-FABP) FABPs, which have been proposed as potential biomarkers of MetS due to their different tissue expression patterns. When MetS impacts the skin, the integrity of the barrier is affected, such as changes in the structure and function of collagen fibers, changes in microcirculation and macrocirculation, damage to lymphatic vessels, diffculty in wound healing, increased production of sebum and sweat. All those changes seem to depend on the abnormal function of lipids and FABPs. In MetS, E-FABP and A-FABP increase significantly in serum and probably in the skin in order to facilitate lipid transport. For this reason, they can be considered a molecular sensors of the inflammation induced in the skin by MetS. Objective: Analyze the concentrations of A-FABP and E-FABP in the skin of a MetS model to determine their value as biomarkers. Methods: We used a Wistar rat model (N=32) of MetS with a 41% extra fat diet during 8, 18, 28, and 52 weeks. The protocol was approved by the "Internal Committee for the Care and Use of Laboratory Animals of the Faculty of Medicine of the Autonomous University of San Luis Potosí" (assigned code: BGFMUASLP -07-19). At the end of every period of time (8, 18, etc) a biopsy of the skin (1 cm2) was took and cleaned from connective and subcutaneous adipose tissue. For Western Blot (WB) experiments the protein extraction was performed using cell lysis and homogenization, and 50 μg of protein of each sample was used. The WB was performed following the supplier's specifications and the standardized protocol in our laboratory. The primary antibodies used for incubation were rat A-FABP antibody (R&amp;D Systems, AF1443) and rat E-FABP antibody (R&amp;D Systems, AF1476). The secondary antibody was Goat IgG HRP-conjugated Antibody (R&amp;D Systems, HAF017). As a control gene, GAPDH reconstituted as indicated by the supplier. Bands were visualized using chemiluminescent detection, and their density in each group was analyzed using ImageJ software. Results: animals developed MetS after being 28 weeks in high fat diet showing excess of abdominal fat, hypertension, high triglycerides, and low cholesterol-HDL. At 52 weeks, we observed an increase in total cholesterol and in the severity of the blood lipids mentioned. Also, 40% of the animals showed visible skin lesions characterized by redness, eruptions, scratching marks, and wounds that do not heal, mainly in the cervical region, suggesting an inflammatory process. A-FABP expression was increased in MetS rats at 8 and 18 weeks and remained high at 28 and 52 weeks, although the increase was not significant. On the other hand E-FABP expression increased in MetS rats from week 18 and 28 but decreasing at 52. It suggests a greater presence of the protein and a probable participation of it in the inflammatory processes and skin lesions observed. Conclusions: E-FABP and A-FABP, increase significantly in the skin of MetS rats, mainly in the in the initial stages of MetS. E-FABP can considered a molecular sensor of skin inflammation induced by obesity. We also observed the presence of A-FABP in the skin, probably from subcutaneous adipose tissue. We propose the feasibility of both FABPs as early markers of MetS. This work has been supported by the National Council of Science and Technology (CONAHCYT) Project No. 320024. GE Donjuán-Loredo thanks CONAHCYT CVU 775467. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Topical application of vitamin D cream in particiants with inflammatory acne due to vitamin D deficiency

Acne vulgaris (AV) represents a chronic inflammatory condition affecting pilosebaceous units, characterized by a multifactorial etiology. AV can manifest as both inflammatory and non-inflammatory skin lesions. Non-inflammatory acne is termed a comedone, which can be either closed (whiteheads) or open (blackheads). Inflammatory acne encompasses papules, pustules, nodules, and pseudocysts. The most common regions for acne occurrence are the facial region (90%), thoracic area (14%), and dorsal region (60%). In the study involving transdermal application of vitamin D cream (applied twice daily; morning and evening) in subjects with inflammatory acne due to vitamin D deficiency, 33 participants took part, comprising 8 males and 25 females. The age group most affected was 18-25 years (adolescent age), followed by a lesser impact in the 26-30 age group, and the lowest incidence observed in the late 36-45 age group. Among males, facial and thoracic regions were most affected by inflammatory acne (37.5%), while among females, the facial region showed a higher percentage of 54%, and the thoracic area was at 40%, with a minimal impact on the dorsal region (M=25%; F=8%). Reductions in inflammatory acne ranged from 100% to 10%, with substantial improvements noted in the male population, achieving 100% and 80% reduction (100% reduction: facial region 25%, thoracic area 12.5%, 80% reduction: dorsal region 25%). Similarly, the female group, with a larger sample size (25 participants), demonstrated significant reductions (100% reduction: facial region 36%, thoracic area 24%, 80% reduction: dorsal area 4%). Overall, improvements were evident in all participants, with none falling below a 30% reduction, indicating remarkable outcomes after one month of vitamin D cream use. Numerous factors contribute to the onset of inflammatory acne, with this study specifically highlighting vitamin D deficiency in the blood. Other indications include the occurrence of polycystic ovaries and reduced thyroid function in women, heightened stress, and prostate issues in men. Reduced or deficient vitamin D levels may be associated with further immune system suppression, activating the aforementioned factors. This research marks a significant stride in uncovering the manifold health benefits of vitamin D. Keywords: acne, vitamin D, participants

Dermoscopy to differentiate clinically similar inflammatory and neoplastic skin lesions.

Over the few last decades, dermoscopy has become an invaluable and popular imaging technique that complements the diagnostic armamentarium of dermatologists, being employed for both tumors and inflammatory diseases. Whereas distinction between neoplastic and inflammatory lesions is often straightforward based on clinical data, there are some scenarios that may be troublesome, e.g., solitary inflammatory lesions or tumors superimposed to a widespread inflammatory condition that may share macroscopic morphological findings. We reviewed the literature to identify dermoscopic clues to support the differential diagnosis of clinically similar inflammatory and neoplastic skin lesions, also providing the histological background of such dermoscopic points of differentiation. Dermoscopic differentiating features were identified for 12 relatively common challenging scenarios, including Bowen's disease and basal cell carcinoma vs. psoriasis and dermatitis, erythroplasia of Queyrat vs. inflammatory balanitis, mammary and extramammary Paget's disease vs. inflammatory mimickers, actinic keratoses vs. discoid lupus erythematosus, squamous cell carcinoma vs. hypertrophic lichen planus and lichen simplex chronicus, actinic cheilitis vs. inflammatory cheilitis, keratoacanthomas vs. prurigo nodularis, nodular lymphomas vs. pseudolymphomas and inflammatory mimickers, mycosis fungoides vs. parapsoriasis and inflammatory mimickers, angiosarcoma vs granuloma faciale, and Kaposi sarcoma vs pseudo-Kaposi. Dermoscopy may be of aid in differentiating clinically similar inflammatory and neoplastic skin lesions.

Vitamin D in Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphoma (CTCL) is characterized by the proliferation of malignant T cells in inflamed skin lesions. Mycosis fungoides (MF)-the most common variant of CTCL-often presents with skin lesions around the abdomen and buttocks ("bathing suit" distribution), i.e., in skin areas devoid of sun-induced vitamin D. For decades, sunlight and vitamin D have been connected to CTCL. Thus, vitamin D induces apoptosis and inhibits the expression of cytokines in malignant T cells. Furthermore, CTCL patients often display vitamin D deficiency, whereas phototherapy induces vitamin D and has beneficial effects in CTCL, suggesting that light and vitamin D have beneficial/protective effects in CTCL. Inversely, vitamin D promotes T helper 2 (Th2) cell specific cytokine production, regulatory T cells, tolerogenic dendritic cells, as well as the expression of immune checkpoint molecules, all of which may have disease-promoting effects by stimulating malignant T-cell proliferation and inhibiting anticancer immunity. Studies on vitamin D treatment in CTCL patients showed conflicting results. Some studies found positive effects, others negative effects, while the largest study showed no apparent clinical effect. Taken together, vitamin D may have both pro- and anticancer effects in CTCL. The balance between the opposing effects of vitamin D in CTCL is likely influenced by treatment and may change during the disease course. Therefore, it remains to be discovered whether and how the effect of vitamin D can be tilted toward an anticancer response in CTCL.

Adenosine A2B receptor agonist improves epidermal barrier integrity in a murine model of epidermal hyperplasia

Adenosine regulates multiple physiological processes through the activation of four receptor subtypes, of which the A2B adenosine receptor (A2BAR) has the lowest affinity for adenosine. Being the adenosine receptor subtype most prominently expressed in epidermis, we recently described the antiproliferative and anti-inflammatory effect of the selective A2BAR agonist BAY60–6583 (BAY) in human keratinocytes stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), so we sought to establish the effect of topical application of BAY in a model of murine epidermal hyperplasia.Topical application of BAY (1 or 10 μg/site) prevented the inflammatory reaction and skin lesions induced by TPA, minimizing hyperproliferation and acanthosis, as well as the expression of specific markers of proliferative keratinocytes. On the other hand, pre-treatment with the selective A2BAR antagonist, PSB-1115 (PSB, 5 or 50 μg/site) reversed these beneficial effects. Additionally, BAY application normalized the expression of epidermal barrier proteins, whose integrity is altered in inflammatory skin diseases, while treatment with the antagonist alone worsened it.Our results, besides confirming the anti-inflammatory and antiproliferative effects of the A2BAR agonist, further demonstrate a role of A2BAR activation to preserve the epidermal barrier. Therefore, the activation of A2BAR may constitute a possible new pharmacological target for the treatment of skin inflammatory diseases such as psoriasis.

P230 Clinical characteristics, risk factors and management of patients with inflammatory bowel disease and hidradenitis suppurativa: a nationwide multicenter study of the GETECCU ENEIDA registry

Abstract Background Hidradenitis suppurativa (HS) is a relapsing skin disease. Evidence supports an association between HS and inflammatory bowel disease(IBD). Aim, to explore the characteristics of patients with IBD and HS(IBD-HS) and to compare with IBD patients without HS(controls). Methods Retrospective, observational, multi-centre, case-control study of the Spanish nationwide ENEIDA registry. We selected all IBD patients with HS confirmed by a dermatologist. Patients were matched 2:1 by hospital and year of diagnosis with controls. A form regarding HS was completed by researchers. Efficacy of HS therapy was defined as≥50% reduction in the number of inflammatory skin lesions. Results A total of 273 patients(mean age 43±12 years) with IBD-HS and 546 matched controls(mean age 53±15) were included. Diagnosis of IBD preceded HS diagnosis in 208 IBD-HS patients(77%). Female sex(62 vs 44%, p=0.0001), smoking habit(45 vs 15%, p=0.0001), Crohn disease(CD) (82 vs 54%, p=0.0001), ileocolonic CD location(46 vs 36%, p=0.0001), perianal disease(55 vs 20%, p=0.0001), extensive ulcerative colitis (59 vs 45% p &amp;lt; 0.05) and extraintestinal manifestations(EIM)(joint and cutaneous)(38 vs 17, p=0.0001) were more frequent in IBD-HS than among controls. Body mass index(BMI) was higher in IBD-HS vs controls(28 ±7 vs 26±4, p=0.05). Hypotiroidism (4,4 vs 1,1%, p &amp;lt; 0.05) and psychiatric disorders(18% vs 2%, p&amp;lt; 0.05) were more prevalent in IBD-HS cohort. More IBD-HS patients underwent abdominal(29 vs 23, p=0,04) and perianal (35 vs 8%, p=0.000) IBD-related surgeries. The use of biologics was more frequent in IBD-HS patients(73 vs 54%, p=0.0001). HS characteristics are shown in Table 1. HS affected mainly axillary(57%) and inguinal regions (57%) followed by genital(42%), perianal(31%), buttocks(27%) and breast(17%). Paradoxical HS was observed in 19(7%) IBD-HS patients, associated to infliximab(IFX)(4, 21%), adalimumab(ADA)(11, 58%) and ustekinumab (UST)(3,16%), leading to stop them in 7(41%) patients. Regarding HS therapy, the efficacy to treatments was: IFX(30/49, 59%), ADA(49/86, 57%), UST(31/49, 69%), and other biologic(5/14, 36%). Conclusion In the largest cohort of IBD-HS patients ever reported, female sex, BMI, CD, smoking, and perianal disease are risk factors for HS among IBD patients. Skin and joint EMI, abdominal and perianal IBD surgeries and need of biologic therapy are more frequent among IBD-HS patients than in controls. Notably, more than half of these patients responded to anti-TNF while 2 thirds of those treated with UST exhibited a favorable response regarding HS lesions.