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Background: Empirical decisions to select therapies for psoriasis (PSO) and atopic dermatitis (AD) can lead to delays in disease control and increased health care costs. However, routine molecular testing for AD and PSO are lacking. Objective: To examine (1) how clinicians choose systemic therapies for patients with PSO and AD without molecular testing and (2) to determine how often the current approach leads to patients switching medications. Methods: A 20-question survey designed to assess clinician strategies for systemic treatment of AD and PSO was made available to attendees of a national dermatology conference in 2022. Results: Clinicians participating in the survey (265/414, 64% response rate) ranked “reported efficacy” as the most important factor governing treatment choice (P

Protease-activated receptor-2 (PAR2) is a class-A G protein-coupled receptor (GPCR) activated by serine proteases and is expressed by multiple tissues, including the skin. PAR2 is involved in the skin inflammatory response, promoting Th2 inflammation, delaying skin barrier repair, and affecting the differentiation of keratinocytes. It also participates in the transmission of itch and pain sensations in the skin. Increasing evidence indicates that PAR2 plays an important role in the pathogenesis of inflammatory skin diseases such as acne vulgaris, rosacea, psoriasis, and atopic dermatitis. Additional focus will be placed on potential targeted therapies based on PAR2. The Goal of this review is to outline the emerging effects of PAR2 activation in inflammatory skin disease and highlight the promise of PAR2 modulators. [ABSTRACT FROM AUTHOR]

Clindamycin is a lincosamide antibiotic that has been used as a topical, oral, or injectable formulation for over five decades. It exhibits a narrow spectrum of microbiologic activity, primarily against gram-positive and anaerobic bacteria. In dermatology, clindamycin has been used primarily as a topical agent, usually for the treatment of acne vulgaris. Despite questions surrounding antibiotic resistance and/or its relative contribution to antibiotic treatment efficacy, a large body of data support the therapeutic value of topical clindamycin for acne vulgaris. As a systemic agent, clindamycin is used orally to treat a variety of cutaneous bacterial infections, and sometimes for acne vulgaris, with oral treatment for the latter less common in more recent years. The modes of action of clindamycin are supported by data showing both its anti-inflammatory and antibiotic mechanisms, which are discussed here along with pharmacokinetic profiles and structure-activity relationships. The diverse applications of clindamycin for multiple disease states, its efficacy, and safety considerations are also reviewed here, including for both topical and systemic formulations. Emphasis is placed on uses in dermatology, but other information on clindamycin relevant to clinicians is also discussed. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin barrier permeability, regulating cell proliferation/differentiation, and modulating antioxidant and inflammatory responses upon ligand binding. Therefore, PPARγ activation has important implications for skin homeostasis. Over the past 20 years, with increasing interest in the role of PPARs in skin physiopathology, considerable effort has been devoted to the development of PPARγ ligands as a therapeutic option for skin inflammatory disorders. In addition, PPARγ also regulates sebocyte differentiation and lipid production, making it a potential target for inflammatory sebaceous disorders such as acne. A large number of studies suggest that PPARγ also acts as a skin tumor suppressor in both melanoma and non-melanoma skin cancers, but its role in tumorigenesis remains controversial. In this review, we have summarized the current state of research into the role of PPARγ in skin health and disease and how this may provide a starting point for the development of more potent and selective PPARγ ligands with a low toxicity profile, thereby reducing unwanted side effects. [ABSTRACT FROM AUTHOR]

The cutaneous microbiome represents a topic of high interest nowadays. Multiple studies have suggested the importance of the skin microbiome in different dermatological pathologies, highlighting the possible implications of cutaneous microorganisms in either the pathogenesis or prognosis of skin maladies. Psoriasis represents a common inflammatory skin disease, with a high prevalence in the worldwide population. The role of the cutaneous microbiome in psoriasis could explain a number of pathogenic theories and treatment objectives of this incurable skin disease. Our interest in the characteristics of the cutaneous microbiome, especially in psoriatic patients who attended a tertiary dermatological centre in Galati, Romania, is reflected in our current study, of which the preliminary results are discussed in this article. Using three types of skin sampling techniques (swabs, adhesive tape, and punch biopsies), we tried to characterise the microorganisms harboured in the skin of psoriatic patients and healthy individuals. This study was performed using culture-based probes, which were analysed using MALDI-TOF mass spectrometer equipment. Our preliminary results suggested that the greatest diversity was observed in the perilesional areas of psoriatic patients. The lowest cutaneous diversity was obtained from sampling psoriatic plaques. These results are similar to other studies of the cutaneous microbiome in psoriasis. The most frequent microorganisms found in all groups studied were of the Staphylococcus species: Staphylococcus epidermidis, Staphylococcus hominis, and Staphylococcus aureus. Analysing the living environment of each individual from this study, our preliminary results suggested different results from other studies, as higher diversity and heterogenicity was observed in urban environments than in rural living areas. Regarding the differences between sexes, our preliminary results showed higher quantitative and qualitative changes in the skin microbiome of male participants than female participants, opposite to the results found in other studies of the cutaneous microbiome in psoriasis. Given these preliminary results, we can conclude that we have found important differences by studying the cutaneous microbiome of psoriatic patients and healthy control individuals from a population that, to our knowledge, has not been yet studied from this point of view. Our results showed important characteristics of the skin microbiome in an Eastern European population, where cultural and environmental living habits could influence the cutaneous microbiome. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In-person dermatology clinical research studies often face recruitment and participation challenges due to travel-, time-, and cost-associated barriers. Studies incorporating virtual/asynchronous formats can potentially enhance research subject participation and satisfaction, but few mobile health tools are available to enable remote study conduct. We developed SkinTracker, a patient-facing mobile app and researcher-facing web platform, that enables longitudinal collection of skin photos, patient reported outcomes, and biometric health and environmental data. METHODS: Eight design thinking sessions including dermatologists, clinical research staff, software engineers, and graphic designers were held to create the components of SkinTracker. Following iterative prototyping, SkinTracker was piloted across six adult and four pediatric subjects with atopic dermatitis (AD) of varying severity levels to test and provide feedback on SkinTracker for six months. RESULTS: The SkinTracker app enables collection of informed consent for study participation, baseline medical history, standardized skin photographs, patient-reported outcomes (e.g., Patient Oriented Eczema Measure (POEM), Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI)), medication use, adverse events, voice diary to document qualitative experiences, chat function for communication with research team, environmental and biometric data such as exercise and sleep metrics through integration with an Apple Watch. The researcher web portal allows for management and visualization of subject enrollment, skin photographs for examination and severity scoring, survey completion, and other patient modules. The pilot study requested that subjects complete surveys and photographs on a weekly to monthly basis via the SkinTracker app. Afterwards, participants rated their experience in a 7-item user experience survey covering app function, design, and desire for participation in future studies using SkinTracker. Almost all subjects agreed or strongly agreed that SkinTracker enabled more convenient participation in skin research studies compared to an in-person format. DISCUSSION: To our knowledge, SkinTracker is one of the first integrated app- and web-based platforms allowing collection and management of data commonly obtained in clinical research studies. SkinTracker enables detailed, frequent capture of data that may better reflect the fluctuating course of conditions such as AD, and can be modularly customized for different skin conditions to improve dermatologic research participation and patient access.

Engagement of microribonucleic acids (miRNA) in the regulation of cutaneous cellular health and diseases is a rapidly advancing niche in dermatology basic research. miRNAs have been identified to play a key role in the pathogenesis of various cutaneous inflammatory, autoimmune and neoplastic conditions, among others. In addition, their purported role as therapeutic targets and biomarkers in diseased conditions harbours exciting news for the approaching years in clinical research. The current review outlines the possible translational role of miRNA in skin health and diseases (encompassing pathogenesis, diagnosis, biomarkers and therapy) from bench to bedside.

Clindamycin is a highly effective antibiotic of the lincosamide class. It has been widely used for decades to treat a range of skin and soft tissue infections in dermatology and medicine. Clindamycin is commonly prescribed for acne vulgaris, with current practice standards utilizing fixed-combination topicals containing clindamycin that prevent Cutibacterium acnes growth and reduce inflammation associated with acne lesion formation. Certain clinical presentations of folliculitis, rosacea, staphylococcal infections, and hidradenitis suppurativa are also responsive to clindamycin, demonstrating its suitability and versatility as a treatment option. This review describes the use of clindamycin in dermatological practice, the mechanism of protein synthesis inhibition by clindamycin at the level of the bacterial ribosome, and clindamycin's anti-inflammatory properties with a focus on its ability to ameliorate inflammation in acne. A comparison of the dermatologic indications for similarly utilized antibiotics, like the tetracycline class antibiotics, is also presented. Finally, this review addresses both the trends and mechanisms for clindamycin and antibiotic resistance, as well as the current clinical evidence in support of the continued, targeted use of clindamycin in dermatology. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory dermatological condition characterized by painful and recurrent nodules and purulent abscesses. HS can have a devastating impact on the quality of life of patients. This condition is commonly localized to the axilla, groin, perineal, and inframammary regions, and can develop fistulas and sinus tracts over time. Its pathogenesis remains elusive and is best characterized at the moment as multi-factorial. Additionally, questions remain about the role of cutaneous dysbiosis as a primary HS trigger or as a secondary perturbation due to HS inflammation. This article features works in relation to HS and its interplay with bacterial microflora. We address current treatment approaches and their impact on HS-related bacteria, as well as areas of therapeutic innovation. In the future, disease-modifying or remittive therapy will likely combine an advanced/targeted anti-inflammatory approach with one that effectively modulates cutaneous and deep tissue dysbiosis. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS), recognized as a chronic and debilitating skin disease, presents significant challenges in both diagnosis and treatment. This review explores the clinical manifestations, genetic landscape, and molecular mechanisms underlying HS. The disease's association with a predisposing genetic background, obesity, smoking, and skin occlusion underscores the complexity of its etiology. Genetic heterogeneity manifests in sporadic, familial, and syndromic forms, with a focus on mutations in the γ-secretase complex genes, particularly NCSTN. The dysregulation of immune mediators, including TNF-α, IL-17, IL-1β, and IL-12/23, plays a crucial role in the chronic inflammatory nature of HS. Recent advancements in genetic research have identified potential therapeutic targets, leading to the development of anti-TNF-α, anti-IL-17, anti-IL-1α, and anti-IL-12/23 therapies and JAK inhibitors. These interventions offer promise in alleviating symptoms and improving the quality of life for HS patients. [ABSTRACT FROM AUTHOR]

Jason E Hawkes,1,* Dale V Reisner,2 Tina Bhutani3,* 1Department of Dermatology, University of California at Davis, Sacramento, CA, USA; 2Patient Author, Yankton, SD, USA; 3Psoriasis and Skin Treatment Center, Department of Dermatology, University of California at San Francisco, San Francisco, CA, USA*These authors contributed equally to this workCorrespondence: Tina Bhutani, Email tina.bhutani@ucsf.eduAbstract: Generalized pustular psoriasis (GPP) is a rare, chronic, and debilitating disease characterized by flares of widespread erythema, desquamation, and pustule formation. GPP flares can be accompanied by systemic symptoms including fever, fatigue, malaise, and skin pain; severe cases may be fatal if untreated. Although GPP may occur concurrently with plaque psoriasis, they represent two distinct inflammatory conditions. Patients with GPP experience a substantial burden of disease, and the impact of GPP on an individual’s mental health and quality-of-life (QoL) goes far beyond skin pain and discomfort. The rarity of GPP may result in a misdiagnosis, as the sudden onset of skin pustules may be mistaken for a primary infection. Misdiagnosis with a subsequent delay in treatment has tremendous negative consequences for the affected patient. In September 2022, spesolimab became the first FDA-approved medication in the US for the treatment of GPP flares in adults. Spesolimab has since been approved by regulatory agencies in numerous countries, including Japan, Mainland China, and the EU. Prior to spesolimab, the clinical management of GPP relied on the off-label use of systemic or biologic therapies approved for plaque psoriasis or other inflammatory conditions. There is a need for increased education among healthcare providers regarding the clinical diagnosis, risk stratification, and therapeutic management of this rare disease, including the other novel GPP-specific therapies in development. In this podcast, two dermatologists and a patient who has plaque psoriasis and GPP discuss the clinical presentation, symptoms, disease burden, QoL impacts, diagnostic challenges, and therapeutic strategies for the management of GPP.Keywords: generalized pustular psoriasis, GPP, pustules, quality-of-life, IL-36, spesolimab, plaque psoriasis, inflammatory skin disease

Nutrition is a complex topic encompassing diet and a variety of supplements including vitamins, fish oil, herbal products, and probiotics. Patients with psoriasis display high interest in understanding the potential impact of nutritional modifications on their psoriasis. In this review, we examine the evidence for nutritional interventions in psoriasis and summarize important concepts. We found that certain diets, such as low-calorie diets for obese patients, gluten-free diets for patients with comorbid celiac disease, and the Mediterranean diet, may have benefits for psoriasis patients. Supplements in general do not show strong evidence of benefit, though more studies are required given the heterogeneity of these trials. Finally, the gut microbiome has drawn considerable interest in recent years, with specific probiotics showing promising results for psoriasis patients and warranting further exploration.

Psoriasis is a chronic autoimmune inflammatory disease characterized by erroneous metabolism of keratinocytes. The development of psoriasis is closely related to abnormal activation and disorders of the immune system. Dysregulated skin protective mechanisms can activate inflammatory pathways within the epithelial immune microenvironment (EIME), leading to the development of autoimmune-related and inflammatory skin diseases. In this review, we initially emphasized the pathogenesis of psoriasis, paying particular attention to the interactions between the abnormal activation of immune cells and the production of cytokines in psoriasis. Subsequently, we delved into the significance of the interactions between EIME and immune cells in the emergence of psoriasis. A thorough understanding of these immune processes is crucial to the development of targeted therapies for psoriasis. Finally, we discussed the potential novel targeted therapies aimed at modulating the EIME in psoriasis. This comprehensive examination sheds light on the intricate underlying immune mechanisms and provides insights into potential therapeutic avenues of immune-mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

Inflammatory skin diseases are a group of diseases caused by the disruption of skin tissue due to immune system disorders. Histone modification plays a pivotal role in the pathogenesis and treatment of chronic inflammatory skin diseases, encompassing a wide range of conditions, including psoriasis, atopic dermatitis, lupus, systemic sclerosis, contact dermatitis, lichen planus, and alopecia areata. Analyzing histone modification as a significant epigenetic regulatory approach holds great promise for advancing our understanding and managing these complex disorders. Additionally, therapeutic interventions targeting histone modifications have emerged as promising strategies for effectively managing inflammatory skin disorders. This comprehensive review provides an overview of the diverse types of histone modification. We discuss the intricate association between histone modification and prevalent chronic inflammatory skin diseases. We also review current and potential therapeutic approaches that revolve around modulating histone modifications. Finally, we investigated the prospects of research on histone modifications in the context of chronic inflammatory skin diseases, paving the way for innovative therapeutic interventions and improved patient outcomes. [ABSTRACT FROM AUTHOR]

Inflammatory skin diseases, such as psoriasis, atopic dermatitis, and alopecia areata, occur when the regulatory tolerance of the innate immune system is disrupted, resulting in the activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inflammatory signaling pathway by interleukin 6 (IL-6) and other key inflammatory cytokines. JAK inhibitors, such as tofacitinib, bind to these enzymes which are coupled to receptors on cell surfaces and block the transcription of inflammatory cytokine-induced genes. The first topical applications are being marketed, yet insufficient effects regarding indications, such as alopecia areata, suggest that improved delivery technologies could help increase the efficacy. In this study, we used sulfated dendritic polyglycerol with caprolactone segments integrated in its backbone (dPGS-PCL), with a molecular weight of 54 kDa, as a degradable carrier to load and solubilize the hydrophobic drug tofacitinib (TFB). TFB loaded in dPGS-PCL (dPGS-PCL@TFB), at a 11 w/w% loading capacity in aqueous solution, showed in an ex-vivo human skin model better penetration than free TFB in a 30:70 (v/v) ethanol/water mixture. We also investigated the anti-inflammatory efficacy of dPGS-PCL@TFB (0.5 w/w%), dPGS-PCL, and free TFB in the water/ethanol mixture by measuring their effects on IL-6 and IL-8 release, and STAT3 and STAT5 activation in ex vivo skin models of simulated inflamed human skin. Our results suggest that dPGS-PCL@TFB reduces the activation of STAT3 and STAT5 by increasing the penetration of the tofacitinib. However, no statistically significant differences with respect to the inhibition of IL-6 and IL-8 were observed in this short incubation time. [ABSTRACT FROM AUTHOR]

In recent years, attention has increasingly focused on various infectious diseases. Although some fatalities are directly attributed to the causative virus, many result from complications and reactive inflammation. Patients with comorbidities are at a higher risk of mortality. Refractory skin conditions such as atopic dermatitis, psoriasis, and epidermolysis bullosa, known for an elevated risk of sepsis, partly owe this to compromised surface barrier function. However, the detailed mechanisms underlying this phenomenon remain elusive. Conversely, although the detrimental effects of a high-fat diet on health, including the onset of metabolic syndrome, are widely recognized, the association between diet and susceptibility to sepsis has not been extensively explored. In this study, we examined the potential causes and pathogenesis of increased sepsis susceptibility in inflammatory skin diseases using a mouse dermatitis model: keratin 14-driven caspase-1 is overexpressed (KCASP1Tg) in mice on a high-fat diet. Our findings reveal that heightened mortality in the dermatitis mouse model is caused by the inflamed immune system due to the chronic inflammatory state of the local skin, and administration of LPS causes a rapid increase in inflammatory cytokine levels in the spleen. Intake of a high-fat diet exacerbates these cytokine levels. Interestingly, we also observed a reduced expression of Toll-like receptor 4 (TLR4) in monocytes from KCASP1Tg mice, potentially predisposing these animals to heightened infection risks and associated complications. Histological analysis showed a clear decrease in T and B cells in the spleen of KCASP1Tg mice fed a high-fat diet. Thickening of the alveolar wall, inflammatory cell infiltration, and alveolar hemorrhage were more prominent in the lungs of KCASP1Tg and KCASP1Tg with fat mice. We postulate that the chronic, non-infectious inflammation induces a negative feedback loop within the inflammatory cascade, and the suppressed expression of TLR4 renders the mice more susceptible to infections. Therefore, it is imperative for individuals with chronic skin inflammation to closely monitor disease progression upon infection and seek timely and appropriate treatment. Additionally, chronic inflammation of adipose tissue, induced by high-fat food intake, combined with dermatitis inflammation, may exacerbate infections, necessitating a review of dietary habits. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The simultaneous occurrence of pyoderma gangrenosum and systemic lupus erythematosus is exceedingly rare and poses diagnostic challenges due to the similarity of skin manifestations in both conditions. The exact relationship between the two conditions remains unclear; however, it is hypothesized that immune dysregulation and neutrophilic infiltration may play a role in the development of pyoderma gangrenosum in SLE patients. Clinicians should be vigilant in recognizing such uncommon associations to ensure prompt and appropriate management. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin barrier permeability, regulating cell proliferation/differentiation, and modulating antioxidant and inflammatory responses upon ligand binding. Therefore, PPARγ activation has important implications for skin homeostasis. Over the past 20 years, with increasing interest in the role of PPARs in skin physiopathology, considerable effort has been devoted to the development of PPARγ ligands as a therapeutic option for skin inflammatory disorders. In addition, PPARγ also regulates sebocyte differentiation and lipid production, making it a potential target for inflammatory sebaceous disorders such as acne. A large number of studies suggest that PPARγ also acts as a skin tumor suppressor in both melanoma and non-melanoma skin cancers, but its role in tumorigenesis remains controversial. In this review, we have summarized the current state of research into the role of PPARγ in skin health and disease and how this may provide a starting point for the development of more potent and selective PPARγ ligands with a low toxicity profile, thereby reducing unwanted side effects.

The cutaneous microbiome represents a topic of high interest nowadays. Multiple studies have suggested the importance of the skin microbiome in different dermatological pathologies, highlighting the possible implications of cutaneous microorganisms in either the pathogenesis or prognosis of skin maladies. Psoriasis represents a common inflammatory skin disease, with a high prevalence in the worldwide population. The role of the cutaneous microbiome in psoriasis could explain a number of pathogenic theories and treatment objectives of this incurable skin disease. Our interest in the characteristics of the cutaneous microbiome, especially in psoriatic patients who attended a tertiary dermatological centre in Galati, Romania, is reflected in our current study, of which the preliminary results are discussed in this article. Using three types of skin sampling techniques (swabs, adhesive tape, and punch biopsies), we tried to characterise the microorganisms harboured in the skin of psoriatic patients and healthy individuals. This study was performed using culture-based probes, which were analysed using MALDI-TOF mass spectrometer equipment. Our preliminary results suggested that the greatest diversity was observed in the perilesional areas of psoriatic patients. The lowest cutaneous diversity was obtained from sampling psoriatic plaques. These results are similar to other studies of the cutaneous microbiome in psoriasis. The most frequent microorganisms found in all groups studied were of the Staphylococcus species: Staphylococcus epidermidis, Staphylococcus hominis, and Staphylococcus aureus. Analysing the living environment of each individual from this study, our preliminary results suggested different results from other studies, as higher diversity and heterogenicity was observed in urban environments than in rural living areas. Regarding the differences between sexes, our preliminary results showed higher quantitative and qualitative changes in the skin microbiome of male participants than female participants, opposite to the results found in other studies of the cutaneous microbiome in psoriasis. Given these preliminary results, we can conclude that we have found important differences by studying the cutaneous microbiome of psoriatic patients and healthy control individuals from a population that, to our knowledge, has not been yet studied from this point of view. Our results showed important characteristics of the skin microbiome in an Eastern European population, where cultural and environmental living habits could influence the cutaneous microbiome.

Key Clinical Message The simultaneous occurrence of pyoderma gangrenosum and systemic lupus erythematosus is exceedingly rare and poses diagnostic challenges due to the similarity of skin manifestations in both conditions. The exact relationship between the two conditions remains unclear; however, it is hypothesized that immune dysregulation and neutrophilic infiltration may play a role in the development of pyoderma gangrenosum in SLE patients. Clinicians should be vigilant in recognizing such uncommon associations to ensure prompt and appropriate management.

cDC2s occur abundantly in peripheral tissues and arise from circulating blood cDC2s. However, the factors governing cDC2 differentiation in tissues, especially under inflammatory conditions, remained poorly defined. We here found that psoriatic cDC2s express the efferocytosis receptor Axl and exhibit a bone morphogenetic protein (BMP) and p38MAPK signaling signature. BMP7, strongly expressed within the lesional psoriatic epidermis, cooperates with canonical TGF-β1 signaling for inducing Axl+cDC2s from blood cDC2s in vitro. Moreover, downstream induced p38MAPK promotes Axl+cDC2s at the expense of Axl+CD207+ Langerhans cell differentiation from blood cDC2s. BMP7 supplementation allowed to model cDC2 generation and their further differentiation into LCs from CD34+ hematopoietic progenitor cells in defined serum-free medium. Additionally, p38MAPK promoted the generation of another cDC2 subset lacking Axl but expressing the non-classical NFkB transcription factor RelB in vitro. Such RelB+cDC2s occurred predominantly at dermal sites in the inflamed skin. Finally, we found that cDC2s can be induced to acquire high levels of the monocyte lineage identity factor kruppel-like-factor-4 (KLF4) along with monocyte-derived DC and macrophage phenotypic characteristics in vitro. In conclusion, inflammatory and psoriatic epidermal signals instruct blood cDC2s to acquire phenotypic characteristics of several tissue-resident cell subsets. [ABSTRACT FROM AUTHOR]

The microbiome and gut-skin axis are popular areas of interest in recent years concerning inflammatory skin diseases. While many bacterial species have been associated with commensalism of both the skin and gastrointestinal tract in certain disease states, less is known about specific bacterial metabolites that regulate host pathways and contribute to inflammation. Some of these metabolites include short chain fatty acids, amine, and tryptophan derivatives, and more that when dysregulated, have deleterious effects on cutaneous disease burden. This review aims to summarize the knowledge of wealth surrounding bacterial metabolites of the skin and gut and their role in immune homeostasis in inflammatory skin diseases such as atopic dermatitis, psoriasis, and hidradenitis suppurativa. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. Patients with this condition often experience a significant negative impact on their quality of life, self-esteem, and overall well-being. Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. In this comprehensive review, we investigate the pathogenesis of rosacea in depth, with a focus on emerging and novel mechanisms, and provide an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms of rosacea. Lastly, we discuss potential future research directions aimed at enhancing our understanding of the condition and developing effective treatments. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic, debilitating disease that manifests as painful nodules, abscesses, sinus tracts, and scars with a predilection for intertriginous sites. HS disproportionately affects women of childbearing age and often leads to impairments in patients' health-related quality of life. Women with HS face unique challenges related to menstruation, pregnancy, and lactation that require additional strategies for optimization of management. Practical interventions include lifestyle modifications, treatment of premenstrual HS flares, enhancing HS management during pregnancy, and creating optimal delivery plans in collaboration with obstetricians. This discussion is based on expert recommendations and aims to highlight the special challenges for women with HS, as well as provide a practical discourse on optimizing care of female patients with HS.

Background: Indoleamine 2,3-dioxygenase (IDO), an enzyme in the first step of tryptophan catabolism, plays a role in the pathogenesis of various malignancies and inflammatory diseases. Although its pathogenesis is unclear, vascular dysregulation and chronic inflammation are the most common culprits for rosacea. Objectives: The aim of this study is to evaluate the relationship between IDO and rosacea and whether there is a correlation with disease severity. Methods: Fifty-two patients with rosacea and 29 healthy volunteers were recruited. The patients were grouped according to severity stage, period, and subtype of the disease. Serum IDO levels were measured with enzyme-linked immunosorbent assay. Results: Serum IDO levels were significantly higher in the patients with rosacea compared to the healthy controls (P < 0.001) and were significantly higher in the patients in remission period and with papulopustular type rosacea compared to the controls (P = 0.002 and P = 0.001, respectively). The serum IDO levels of the female rosacea patients were higher than those of the healthy female controls (P < 0.001). When the diagnostic value of the parameter was investigated, it was observed that the serum IDO level has high sensitivity (83.3%) and specificity (76.1%), with a cutoff value of 47.1 ng/mL for female rosacea patients. Conclusion: IDO was found to increase in rosacea patients. With the high specificity and sensitivity observed, especially in female patients, IDO may be a supporting parameter in the diagnosis of rosacea.

Kallapan Pakornphadungsit,1 Poonkiat Suchonwanit,1 Kunlawat Thadanipon,2 Yingluck Visessiri,3 Suthinee Rutnin1 1Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Suthinee Rutnin, Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, Thailand, 10400, Tel +66-2-2011141, Fax +66-2-201-1211 ext 4, Email suthinee.rutnin@gmail.comBackground: Dermoscopy is a non-invasive tool widely used to improve the diagnostic accuracy of general dermatological conditions.Objective: To determine the dermoscopic features and their diagnostic value in distinguishing common inflammatory and infectious dermatoses.Materials and Methods: A cross-sectional study was conducted on patients clinically diagnosed with common inflammatory or infectious skin diseases. Baseline characteristics and clinical and dermoscopic findings were recorded. Dermoscopic variables were analyzed using a correlation matrix. A skin biopsy was performed for each patient for a definitive diagnosis.Results: Of 102 patients, 43 with dermatitis, 30 with psoriasis, 14 with lichen planus (LP), 5 with pityriasis rosea (PR), and 10 with others were included. Dull red background, patchy vessels, and scales showed significant positive correlations with dermatitis (r = 0.401, 0.488, and 0.327, respectively; p < 0.01), whereas bright red background, glomerular vessels, regular vascular distribution, and diffuse scales revealed significant positive correlations with psoriasis (r = 0.412, 0.266, 0.798, and 0.401, respectively; p < 0.01). For LP, whitish reticulate structures, purplish background, and dotted vessels mixed with linear vessels in the peripheral distribution were significantly positively correlated (r = 0.831, 0.771, 0.224, and 0.558, respectively; p < 0.05). Yellowish background and peripheral scales were predictive of PR diagnosis (r = 0.254 and 0.583, respectively; p < 0.01).Conclusion: Dermoscopy can be used as an adjunctive tool to differentiate conditions among common inflammatory and infectious dermatoses in order to minimize unnecessary invasive diagnostic procedures.Keywords: dermoscopy, dermoscopic finding, inflammatory skin disease, infectious skin disease, papulosquamous disease

Psoriasis is a chronic inflammatory skin disease characterized by the appearance of clearly demarcated erythematous and scaly plaques. It can be divided into various types, including plaque, nail, guttate, inverse, and pustular psoriasis. Plaque psoriasis is the most commonly occurring type, though there is another rare but severe pustular autoinflammatory skin disease called generalized pustular psoriasis (GPP), which manifests with acute episodes of pustulation and systemic symptoms. Though the etiopathogenesis of psoriasis is not yet fully understood, a growing body of literature has demonstrated that both genetic and environmental factors play a role. The discovery of genetic mutations associated with GPP has shed light on our comprehension of the mechanisms of the disease, promoting the development of targeted therapies. This review will summarize genetic determinants as known and provide an update on the current and potential treatments for GPP. The pathogenesis and clinical presentation of the disease are also included for a comprehensive discussion. [ABSTRACT FROM AUTHOR]

IntroductionIn-person dermatology clinical research studies often face recruitment and participation challenges due to travel-, time-, and cost-associated barriers. Studies incorporating virtual/asynchronous formats can potentially enhance research subject participation and satisfaction, but few mobile health tools are available to enable remote study conduct. We developed SkinTracker, a patient-facing mobile app and researcher-facing web platform, that enables longitudinal collection of skin photos, patient reported outcomes, and biometric health and environmental data.MethodsEight design thinking sessions including dermatologists, clinical research staff, software engineers, and graphic designers were held to create the components of SkinTracker. Following iterative prototyping, SkinTracker was piloted across six adult and four pediatric subjects with atopic dermatitis (AD) of varying severity levels to test and provide feedback on SkinTracker for six months.ResultsThe SkinTracker app enables collection of informed consent for study participation, baseline medical history, standardized skin photographs, patient-reported outcomes (e.g., Patient Oriented Eczema Measure (POEM), Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI)), medication use, adverse events, voice diary to document qualitative experiences, chat function for communication with research team, environmental and biometric data such as exercise and sleep metrics through integration with an Apple Watch. The researcher web portal allows for management and visualization of subject enrollment, skin photographs for examination and severity scoring, survey completion, and other patient modules. The pilot study requested that subjects complete surveys and photographs on a weekly to monthly basis via the SkinTracker app. Afterwards, participants rated their experience in a 7-item user experience survey covering app function, design, and desire for participation in future studies using SkinTracker. Almost all subjects agreed or strongly agreed that SkinTracker enabled more convenient participation in skin research studies compared to an in-person format.DiscussionTo our knowledge, SkinTracker is one of the first integrated app- and web-based platforms allowing collection and management of data commonly obtained in clinical research studies. SkinTracker enables detailed, frequent capture of data that may better reflect the fluctuating course of conditions such as AD, and can be modularly customized for different skin conditions to improve dermatologic research participation and patient access.

Clindamycin is a highly effective antibiotic of the lincosamide class. It has been widely used for decades to treat a range of skin and soft tissue infections in dermatology and medicine. Clindamycin is commonly prescribed for acne vulgaris, with current practice standards utilizing fixed-combination topicals containing clindamycin that prevent Cutibacterium acnes growth and reduce inflammation associated with acne lesion formation. Certain clinical presentations of folliculitis, rosacea, staphylococcal infections, and hidradenitis suppurativa are also responsive to clindamycin, demonstrating its suitability and versatility as a treatment option. This review describes the use of clindamycin in dermatological practice, the mechanism of protein synthesis inhibition by clindamycin at the level of the bacterial ribosome, and clindamycin’s anti-inflammatory properties with a focus on its ability to ameliorate inflammation in acne. A comparison of the dermatologic indications for similarly utilized antibiotics, like the tetracycline class antibiotics, is also presented. Finally, this review addresses both the trends and mechanisms for clindamycin and antibiotic resistance, as well as the current clinical evidence in support of the continued, targeted use of clindamycin in dermatology.

Hidradenitis suppurativa (HS), recognized as a chronic and debilitating skin disease, presents significant challenges in both diagnosis and treatment. This review explores the clinical manifestations, genetic landscape, and molecular mechanisms underlying HS. The disease’s association with a predisposing genetic background, obesity, smoking, and skin occlusion underscores the complexity of its etiology. Genetic heterogeneity manifests in sporadic, familial, and syndromic forms, with a focus on mutations in the γ-secretase complex genes, particularly NCSTN. The dysregulation of immune mediators, including TNF-α, IL-17, IL-1β, and IL-12/23, plays a crucial role in the chronic inflammatory nature of HS. Recent advancements in genetic research have identified potential therapeutic targets, leading to the development of anti-TNF-α, anti-IL-17, anti-IL-1α, and anti-IL-12/23 therapies and JAK inhibitors. These interventions offer promise in alleviating symptoms and improving the quality of life for HS patients.

Abstract The skin serves as the interface between the human body and the environment and interacts with the microbial community. The skin microbiota consists of microorganisms, such as bacteria, fungi, mites, and viruses, and they fluctuate depending on the microenvironment defined by anatomical location and physiological function. The balance of interactions between the host and microbiota plays a pivotal role in the orchestration of skin homeostasis; however, the disturbance of the balance due to an alteration in the microbial communities, namely, dysbiosis, leads to various skin disorders. Recent developments in sequencing technology have provided new insights into the structure and function of skin microbial communities. Based on high-throughput sequencing analysis, a growing body of evidence indicates that a new treatment using live bacteria, termed bacteriotherapy, is a feasible therapeutic option for cutaneous diseases caused by dysbiosis. In particular, the administration of specific bacterial strains has been investigated as an exclusionary treatment strategy against pathogens associated with chronic skin disorders, whereas the safety, efficacy, and sustainability of this therapeutic approach using isolated live bacteria need to be further explored. In this review, we summarize our current understanding of the skin microbiota, as well as therapeutic strategies using characterized strains of live bacteria for skin inflammatory diseases. The ecosystem formed by interactions between the host and skin microbial consortium is still largely unexplored; however, advances in our understanding of the function of the skin microbiota at the strain level will lead to the development of new therapeutic methods.

cDC2s occur abundantly in peripheral tissues and arise from circulating blood cDC2s. However, the factors governing cDC2 differentiation in tissues, especially under inflammatory conditions, remained poorly defined. We here found that psoriatic cDC2s express the efferocytosis receptor Axl and exhibit a bone morphogenetic protein (BMP) and p38MAPK signaling signature. BMP7, strongly expressed within the lesional psoriatic epidermis, cooperates with canonical TGF-β1 signaling for inducing Axl+cDC2s from blood cDC2s in vitro. Moreover, downstream induced p38MAPK promotes Axl+cDC2s at the expense of Axl+CD207+ Langerhans cell differentiation from blood cDC2s. BMP7 supplementation allowed to model cDC2 generation and their further differentiation into LCs from CD34+ hematopoietic progenitor cells in defined serum-free medium. Additionally, p38MAPK promoted the generation of another cDC2 subset lacking Axl but expressing the non-classical NFkB transcription factor RelB in vitro. Such RelB+cDC2s occurred predominantly at dermal sites in the inflamed skin. Finally, we found that cDC2s can be induced to acquire high levels of the monocyte lineage identity factor kruppel-like-factor-4 (KLF4) along with monocyte-derived DC and macrophage phenotypic characteristics in vitro. In conclusion, inflammatory and psoriatic epidermal signals instruct blood cDC2s to acquire phenotypic characteristics of several tissue-resident cell subsets.

Short-chain fatty acids (SCFAs) are metabolites of gut microbes that can modulate the host inflammatory response, and contribute to health and homeostasis. Since the introduction of the gut-skin axis concept, the link between SCFAs and inflammatory skin diseases has attracted considerable attention. In this review, we have summarized the literature on the role of SCFAs in skin inflammation, and the correlation between SCFAs and inflammatory skin diseases, especially atopic dermatitis, urticaria, and psoriasis. Studies show that SCFAs are signaling factors in the gut-skin axis and can alleviate skin inflammation. The information presented in this review provides new insights into the molecular mechanisms driving gut-skin axis regulation, along with possible pathways that can be targeted for the treatment and prevention of inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

Mimi Chung, Erin Bartholomew, Samuel Yeroushalmi, Marwa Hakimi, Tina Bhutani, Wilson Liao The University of California, San Francisco, Department of Dermatology, San Francisco, CA, USACorrespondence: Mimi Chung, 515 Spruce Street, San Francisco, CA, 94118, USA, Tel +415-944-7618, Email mimi.chung244@gmail.comAbstract: Nutrition is a complex topic encompassing diet and a variety of supplements including vitamins, fish oil, herbal products, and probiotics. Patients with psoriasis display high interest in understanding the potential impact of nutritional modifications on their psoriasis. In this review, we examine the evidence for nutritional interventions in psoriasis and summarize important concepts. We found that certain diets, such as low-calorie diets for obese patients, gluten-free diets for patients with comorbid celiac disease, and the Mediterranean diet, may have benefits for psoriasis patients. Supplements in general do not show strong evidence of benefit, though more studies are required given the heterogeneity of these trials. Finally, the gut microbiome has drawn considerable interest in recent years, with specific probiotics showing promising results for psoriasis patients and warranting further exploration.Keywords: nutrition, supplements, probiotics, inflammatory skin disease

Engagement of microribonucleic acids (miRNA) in the regulation of cutaneous cellular health and diseases is a rapidly advancing niche in dermatology basic research. miRNAs have been identified to play a key role in the pathogenesis of various cutaneous inflammatory, autoimmune and neoplastic conditions, among others. In addition, their purported role as therapeutic targets and biomarkers in diseased conditions harbours exciting news for the approaching years in clinical research. The current review outlines the possible translational role of miRNA in skin health and diseases (encompassing pathogenesis, diagnosis, biomarkers and therapy) from bench to bedside. [ABSTRACT FROM AUTHOR]

Inflammatory skin diseases, such as psoriasis, atopic dermatitis, and alopecia areata, occur when the regulatory tolerance of the innate immune system is disrupted, resulting in the activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inflammatory signaling pathway by interleukin 6 (IL-6) and other key inflammatory cytokines. JAK inhibitors, such as tofacitinib, bind to these enzymes which are coupled to receptors on cell surfaces and block the transcription of inflammatory cytokine-induced genes. The first topical applications are being marketed, yet insufficient effects regarding indications, such as alopecia areata, suggest that improved delivery technologies could help increase the efficacy. In this study, we used sulfated dendritic polyglycerol with caprolactone segments integrated in its backbone (dPGS-PCL), with a molecular weight of 54 kDa, as a degradable carrier to load and solubilize the hydrophobic drug tofacitinib (TFB). TFB loaded in dPGS-PCL (dPGS-PCL@TFB), at a 11 w/w% loading capacity in aqueous solution, showed in an ex-vivo human skin model better penetration than free TFB in a 30:70 (v/v) ethanol/water mixture. We also investigated the anti-inflammatory efficacy of dPGS-PCL@TFB (0.5 w/w%), dPGS-PCL, and free TFB in the water/ethanol mixture by measuring their effects on IL-6 and IL-8 release, and STAT3 and STAT5 activation in ex vivo skin models of simulated inflamed human skin. Our results suggest that dPGS-PCL@TFB reduces the activation of STAT3 and STAT5 by increasing the penetration of the tofacitinib. However, no statistically significant differences with respect to the inhibition of IL-6 and IL-8 were observed in this short incubation time.

Inflammatory skin diseases are difficult to treat because of a lack of available treatment options for severe disease. However, recent advances have shown that vagus nerve stimulation can be used to decrease inflammation and reduce disease severity in rheumatoid arthritis and inflammatory bowel disease. Changes in cytokine profiles observed in these studies are similar to those seen with use of biologics in inflammatory skin disease, suggesting that they act along similar pathways to disrupt chronic inflammation and treat inflammatory disease. This commentary explores the existing evidence demonstrating the efficacy of neuromodulation in inflammatory disease, and outlines reasons why these findings could translate to the dermatology setting to treat inflammatory skin disease.

Background: Indoleamine 2,3-dioxygenase (IDO), an enzyme in the first step of tryptophan catabolism, plays a role in the pathogenesis of various malignancies and inflammatory diseases. Although its pathogenesis is unclear, vascular dysregulation and chronic inflammation are the most common culprits for rosacea. Objectives: The aim of this study is to evaluate the relationship between IDO and rosacea and whether there is a correlation with disease severity. Methods: Fifty-two patients with rosacea and 29 healthy volunteers were recruited. The patients were grouped according to severity stage, period, and subtype of the disease. Serum IDO levels were measured with enzyme-linked immunosorbent assay. Results: Serum IDO levels were significantly higher in the patients with rosacea compared to the healthy controls (P < 0.001) and were significantly higher in the patients in remission period and with papulopustular type rosacea compared to the controls (P = 0.002 and P = 0.001, respectively). The serum IDO levels of the female rosacea patients were higher than those of the healthy female controls (P < 0.001). When the diagnostic value of the parameter was investigated, it was observed that the serum IDO level has high sensitivity (83.3%) and specificity (76.1%), with a cutoff value of 47.1 ng/mL for female rosacea patients. Conclusion: IDO was found to increase in rosacea patients. With the high specificity and sensitivity observed, especially in female patients, IDO may be a supporting parameter in the diagnosis of rosacea. [ABSTRACT FROM AUTHOR]

The microbiome and gut-skin axis are popular areas of interest in recent years concerning inflammatory skin diseases. While many bacterial species have been associated with commensalism of both the skin and gastrointestinal tract in certain disease states, less is known about specific bacterial metabolites that regulate host pathways and contribute to inflammation. Some of these metabolites include short chain fatty acids, amine, and tryptophan derivatives, and more that when dysregulated, have deleterious effects on cutaneous disease burden. This review aims to summarize the knowledge of wealth surrounding bacterial metabolites of the skin and gut and their role in immune homeostasis in inflammatory skin diseases such as atopic dermatitis, psoriasis, and hidradenitis suppurativa.

Recently, green synthesis-based nanoformulations using plants or microorganisms have attracted great interest because of their several advantages. Nanotechnology-based biological macromolecules are emerging materials with potential applications in cosmetics and medications for ameliorating and treating inflammatory skin diseases (ISDs). Eupatorium japonicum (EJ), a native Korean medicinal plant belonging to the family Asteraceae, has been traditionally used to prepare prescriptions for the treatment of various inflammatory diseases. EJ-based gold nanoparticles (EJ-AuNPs) were biosynthesized under optimal conditions and characterized their physicochemical properties using various microscopic and spectrometric techniques. Additionally, the effects of EJ-AuNPs on ISDs as well as their underlying mechanisms were investigated in the tumor necrosis factor-α/interferon-γ (T+I)-induced skin HaCaT keratinocytes. The MTT and live/dead cell staining assays showed that EJ-AuNP treatment was considerably safer than EJ treatment alone in HaCaT cells. Moreover, EJ-AuNP treatment effectively suppressed the production of T+I-stimulated inflammatory cytokines (RANTES, TARC, CTACK, IL-6, and IL-8) and intracellular reactive oxygen species, and such EJ-driven anti-inflammatory effects were shown to be associated with the downregulation of intracellular mitogen-activated protein kinase and nuclear factor-κB signaling pathways. The present study provides preliminary results and a valuable strategy for developing novel anti-skin dermatitis drug candidates using plant extract-based gold nanoparticles. [ABSTRACT FROM AUTHOR]

Prurigo nodularis (PN), or chronic prurigo, is a distinct disease characterized by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. While there are few epidemiologic studies describing the prevalence of PN, it is thought to be relatively rare, but is likely underdiagnosed and underrecognized. Management of PN is challenging, and there are no approved drugs that can relieve the distress as well as signs and symptoms caused by PN and its pruritus. Improved understanding of the neuroimmune pathways involved in management of PN have led to discovery and trial of emerging treatments for PN. This publication provides an overview of PN and discusses several of the most promising treatments that are undergoing evaluation. [ABSTRACT FROM AUTHOR]

Women with cardiovascular disease are underdiagnos-ed, undertreated and under-represented in research. Even though the increased risk of cardiovascular disease among patients with psoriasis is well establi-shed, only a few studies have examined women with psoriasis. This study examined the prevalence of cardio-vascular risk factors and cardiovascular disease among women with psoriasis. Using the Copenhagen City Heart Study and the Copenhagen General Population Study, 66,420 women were included in a cross-sectional design. Of these, 374 (0.56%) women had hospital-diagnosed psoriasis. Women with vs with-out hospital-diagnosed psoriasis had higher odds ratios of having traditional cardiovascular risk factors, including hypertriglyceridaemia, smoking, obesity, type 2 diabetes, and low physical activity, and of having non-traditional cardiovascular risk factors, including low level of education, high level of psycho-social stress, and low-grade inflammation. Compared with women from the general population, the multi-variable adjusted odds ratio of heart failure and ischaemic cerebrovascular disease in women with hospital-diagnosed psoriasis was 2.51 (95% confidence interval 1.33–4.73) and 2.06 (1.27–3.35). In conclusion, women with hospital-diagnosed psoriasis have a higher prevalence of traditional and non- traditional cardiovascular risk factors, and increased risk of heart failure and ischaemic cerebrovascular disease, even after adjusting for these cardiovascular risk factors.

Background: Prurigo pigmentosa (PP) is a rare inflammatory dermatosis characterized by pruritic erythematous papules that coalesce to form a reticulate pattern. PP is often misdiagnosed, and patients are treated with ineffective therapies. Although the majority of reports about PP are from East Asia, patients of all backgrounds can be affected. Objectives: To perform a systematic review of reported PP cases with the purpose of summarizing the clinical presentation and treatment of PP. Methods: MEDLINE and Embase were searched for original articles describing PP. We identified 115 studies from 24 countries representing 369 patients to include in the analysis. Results: Of the 369 patients included in the analysis, the mean age was 25.6 years (range: 13-72 years) with 72.1% (266 of 369) female. Risk factors or aggravating factors were described in 52.3% (193 of 369) of patients and included dietary changes (25.5%, 94 of 369), friction (8.4%, 31 of 369), sweat (7.6%, 28 of 369), and ketonuria (5.1%, 19 of 369). Of those patients who experienced PP following dietary changes, 40.4% (38 of 94) started a ketogenic diet. Minocycline monotherapy was the most frequently prescribed treatment for PP (20.9%, 77 of 369), achieving complete resolution in 48.1% (37 of 77) of patients. Conclusions: PP is sometimes associated with ketogenic diets and can be effectively managed with oral tetracyclines.

Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. Patients with this condition often experience a significant negative impact on their quality of life, self-esteem, and overall well-being. Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. In this comprehensive review, we investigate the pathogenesis of rosacea in depth, with a focus on emerging and novel mechanisms, and provide an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms of rosacea. Lastly, we discuss potential future research directions aimed at enhancing our understanding of the condition and developing effective treatments.

The targeted inhibition of effector cytokines such as interleukin 17 (IL-17) in psoriasis and IL-13 in atopic dermatitis offers impressive efficacy with a favorable side effect profile. In contrast, the downregulation of interferon gamma (IFN-g) in T helper (Th) 1-dominant skin disorders may lead to more adverse events, given the crucial role of IFN-g in antiviral and antitumoral immunity. Modulating Th17 and Th2 cell differentiation is performed by blocking IL-23 and IL-4, respectively, whereas anti-IL-12 antibodies are only moderately effective in downregulating Th1 lymphocyte differentiation. Therefore, a targeted approach of IFN-g-driven disorders remains challenging. Recent literature suggests that certain pathogenic Th17 cell subsets with Th1 characteristics, such as CD4+CD161+CCR6+CXCR3+IL-17+IFN-y+ (Th17.1) and CD4+CD161+CCR6+CXCR3+IL-17-IFN-y+ (exTh17), are important contributors in Th1-mediated autoimmunity. Differentiation to a Th17.1 or exTh17 profile results in the upregulation of IFN-y. Remarkably, these pathogenic Th17 cell subsets are resistant to glucocorticoid therapy and the dampening effect of regulatory T cells (Treg). The identification of Th17.1/exTh17 cells in auto-immune disorders may explain the frequent treatment failure of conventional immunosuppressants. In this review, we summarize the current evidence regarding the cellular plasticity of Th17 cells in inflammatory skin disorders. A deeper understanding of this phenomenon may lead to better insights into the pathogenesis of various skin diseases and the discovery of a potential new treatment target. [ABSTRACT FROM AUTHOR]