Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Rosacea. Core disease mechanisms, molecular and cellular pathways, involve...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 17
• Snippets retrieved: 20

Relevant Papers

[1] Cutaneous lesions of the nose

• Authors: M. Sand, D. Sand, Christina Thrandorf, V. Paech, P. Altmeyer et al.
• Year: 2010
• Venue: Head & Face Medicine
• URL: https://www.semanticscholar.org/paper/225d599a8fe838041291aab676cb50ef2394f711
• DOI: 10.1186/1746-160X-6-7
• PMID: 20525327
• PMCID: 2903548
• Citations: 30
• Influential citations: 2
• Summary: This article is the second part of a review series dealing with cutaneous lesions on the head and face, which are frequently seen in daily practice by a dermatologic surgeon.
• Evidence snippets:
• Snippet 1 (score: 0.497) > Rosacea is a multiphasic inflammatory condition that typically affects the skin of the face and nose. Clinically, rosacea has been classified in four different stages. Stage I, also called rosacea erythematosa telangiectasia (prerosacea), shows facial flushing and telangiectasia. Stage II, rosacea papulopustulosa (vascular rosacea), is characterized by persistent facial erythema, telangiectasia, thickened skin, papules and pustules (Fig 9). Stage III, glandular-hypertrophic or inflammatory rosacea, shows erythematous papules and pustules, telangiectasias, edema, connective tissue and sebaceous gland hyperplasia. Stage IV, or rhinophyma, shows dermal and sebaceous gland hyperplasia, and dilated and cystic sebaceous glands. Most individuals affected by rosacea are of northern European origin, and up to one-third have a family history of the disorder [91]. Clinical signs include facial flushing, erythema, telangiectasia and papulopustular efflorescence similar to acne as described previously. Women are three times more likely to be affected than men, with the reported prevalence between 0.5 and 10% [92,93]. The pathophysiology has been poorly understood, and there have been only limited descriptions of factors that exacerbate or improve this disease [94]. Recent molecular studies suggest that an altered innate immune response is involved in the pathogenesis of vascular and inflammatory disease and is responsible for the observed clinical findings in patients with rosacea [95]. > A variety of topical, systemic and physical treatment options are available that have been adjusted to the stage and severity of the disease [96]. Standard topical therapy includes metronidazole 0.75% or 1% gel. Alternatively, azelaic acid 15% gel or 20% cream has also been successfully used in five randomized and controlled studies with good results [97].

[2] Elucidating the potential pharmaceutical mechanism of Gyejibokryeong-hwan on rosacea using network analysis

• Authors: Jundong Kim, Kyuseok Kim
• Year: 2023
• Venue: Medicine
• URL: https://www.semanticscholar.org/paper/11e9f13d08ccf6bfa9dd044db6b1e054bc8d88c1
• DOI: 10.1097/MD.0000000000033023
• PMID: 36862896
• PMCID: 9981404
• Citations: 3
• Summary: Gyejibokryeong-hwan has the potential to act on IL-17 signaling pathway, neuroinflammatory response and vascular wound healing pathway, and further studies are needed to determine the potential mechanism of GBH in rosacea.
• Evidence snippets:
• Snippet 1 (score: 0.496) > Rosacea is a chronic erythematous disease with telangiectasia that affects the central area of the face. However, because of the ambiguity in the pathophysiology of rosacea, its treatment has not been clearly elucidated; therefore, new therapeutic options need to be developed. Gyejibokryeong-hwan (GBH) is widely used in clinical practice for various blood circulation disorders, including hot flushes. Therefore, we explored the potential pharmaceutical mechanism of GBH on rosacea and investigated the therapeutic points exclusive to GBH through comparative analysis with chemical drugs recommended in 4 guidelines for rosacea based on network analysis. The active compounds in GBH were identified, and the proteins targeted by these compounds and the genes related to rosacea were searched. Additionally, the proteins targeted by the guideline drugs were also searched to compare their effects. And the pathway/term analysis of common genes was conducted. Ten active compounds were obtained for rosacea. There were 14 rosacea-related genes targeted by GBH, with VEGFA, TNF, and IL-4, which were suggested as core genes. The pathway/term analysis of the 14 common genes revealed that GBH could potentially act on rosacea via 2 pathways: the “interleukin 17 signaling pathway” and the “neuroinflammatory response.” Comparison and analysis of the protein targets between GBH and guideline drugs revealed that only GBH separately acts on the “vascular wound healing pathway.” GBH has the potential to act on IL-17 signaling pathway, neuroinflammatory response and vascular wound healing pathway. Further studies are needed to determine the potential mechanism of GBH in rosacea.

[3] Unveiling the Molecular Mechanisms of Rosacea: Insights From Transcriptomics and In Vitro Experiments

• Authors: Luxi Chen, Juan Wang
• Year: 2025
• Venue: Journal of Cosmetic Dermatology
• URL: https://www.semanticscholar.org/paper/29caec1e8ca2ad4852ea656bfc9ea8c22c8ae2e1
• DOI: 10.1111/jocd.16753
• PMID: 39823143
• PMCID: 11739675
• Summary: Rosacea is a prevalent inflammatory skin condition, but its molecular mechanisms and treatment responses remain poorly understood.
• Evidence snippets:
• Snippet 1 (score: 0.484) > Rosacea is a common chronic skin disease characterized by facial skin erythema, papules, and pustules, severely impacting the patient's appearance and quality of life [1][2][3]. However, the pathogenesis of rosacea remains poorly understood at present [4][5][6]. Although some studies have identified potential influences of inflammatory reactions and genetic factors, there is still a lack of in-depth understanding regarding its molecular mechanisms and individualized treatment strategies [7][8][9]. > Transcriptomics, a high-throughput technology for studying gene expression, has been widely applied to investigate the pathogenesis and treatment response of various diseases [10][11][12]. Therefore, in this study, we conducted a systematic analysis of gene expression patterns in rosacea patients using high-throughput RNA sequencing technology. Through this approach, we can identify key genes and signaling pathways related to rosacea development and treatment response, providing important insights for a deeper understanding of the pathogenesis of this disease [13][14][15]. > To investigate the molecular mechanisms and drug response of rosacea further, a series of in vitro experiments were performed. First, techniques such as RT-qPCR, Western blot, and ELISA were used to assess the expression levels of rosacea-related cytokines and key genes [16]. Additionally, scratch assays and Transwell experiments were employed to study cell migration and proliferation [17]. These experimental results provide important clues for a comprehensive understanding of the roles of inflammatory reactions and cellular functions in rosacea development. > The aim of this study is to reveal the pathogenesis and individualized treatment possibilities of rosacea by investigating its molecular mechanisms and drug response in depth. By utilizing a comprehensive research approach combining transcriptomics technology and in vitro experiments, we hope to gain a more comprehensive understanding of the development process of rosacea and explore new treatment strategies. The research findings may provide scientific evidence for individualized treatment and clinical practice, offering important information and directions to improve the quality of life of patients.
• Snippet 2 (score: 0.482) > In summary, this study employed transcriptomics and in vitro experiments to investigate the molecular pathological features of rosacea and identified potential therapeutic approaches. It was found that rosacea is closely associated with a chronic inflammatory state, particularly with significantly elevated expression of genes such as IL6, OSM, and TNF-α. Rosacea also displayed a close relationship with genes involved in cell proliferation and migration, as evidenced by increased expression of TLR2 and S100A9 (Figure 6). These findings not only enhance our understanding of the pathophysiology of rosacea but also provide a scientific basis for developing treatment strategies targeting specific types of rosacea. > The scientific significance of this study lies in its comprehensive exploration of the molecular mechanisms and drug responses in rosacea through transcriptomics analysis and in vitro experiments. Analysis of the gene expression patterns in rosacea patients revealed elevated levels of genes related to inflammatory reactions, leading to new insights into the pathogenesis of rosacea. In in vitro experiments, the study found that TLR2 and S100A9 protein levels increased in HaCaT cells under conditions simulating rosacea, and the cytokines IL6, OSM, and TNF-α were significantly elevated, implying their potential promoting roles in the progression of rosacea. Therefore, this study provides important scientific evidence for a deeper understanding and treatment of rosacea. > However, there are still some limitations to this study. First, the study only involved a cell line model, which limits the generalizability of the results, and it is possible that the results may differ from other animal models. In addition, more clinical data and human studies are needed to validate the reliability and applicability of these results. > Future research can further explore the molecular mechanisms and drug responses in rosacea. More key molecules can be studied at the genomic and proteomic levels to reveal the pathological mechanisms of rosacea. Additionally, in vivo experiments and clinical research can further validate the reliability of the research results and further optimize and improve existing treatment strategies. Personalized therapy can also be a future research direction, with the development of treatment strategies targeting specific molecular targets based on a deeper understanding of the pathogenesis of rosacea, providing more precise, safe, and effective treatment options.
• Snippet 3 (score: 0.441) > Rosacea is a common chronic skin disease with unclear pathogenic mechanisms [8,31,32]. The objective of this study is to explore the molecular mechanisms of rosacea and the effects of drug response through the application of transcriptomics and in vitro experiments. We analyzed the gene expression patterns of rosacea patients using high-throughput RNA sequencing and further validated them in vitro experiments [33]. Through these experiments, we aim to better understand the pathogenic mechanisms of rosacea and provide important information for the development of therapeutic strategies. > Compared to previous studies, our findings suggest a significant increase in the expression levels of genes associated with inflammatory reactions in rosacea patients [7][8][9]. Specifically, the expression of FLT1 and TLR2 genes is significantly elevated in rosacea patients [34]. These results are consistent with previous research and further support the crucial role of inflammatory reactions in the pathogenesis of rosacea [35]. The sustained activation of inflammatory reactions may contribute to the development of skin lesions and further exacerbate the expression of genes related to inflammatory reactions [36,37]. > Our study demonstrates that HaCaT cells exhibit enhanced proliferation and migration abilities under conditions simulating a rosacea environment. This finding is consistent with previous observations of behavioral changes in HaCaT cells in previous studies. The increased proliferation and migration of HaCaT cells may be associated with the upregulation of genes related to inflammatory reactions [38,39]. These results further support the crucial role of inflammatory reactions in the pathological progression of rosacea [40]. > Our findings also reveal a significant upregulation of TLR2 and S100A9 expression in rosacea patients, which is consistent with previous research on TLR2 and S100A9 [41][42][43]. The upregulation of TLR2 and S100A9 may promote the pathogenesis of rosacea and inflammatory reaction [44,45]. TLR2 is involved in the regulation of inflammatory reactions through the activation of the inflammatory pathway, while S100A9 serves as an inflammatory mediator involved in the spread and maintenance of inflammation [45]. > In summary, this study employed transcriptomics and in vitro experiments to investigate the molecular pathological features of rosacea and identified potential therapeutic approaches.

[4] Acne and Rosacea

• Authors: M. Picardo, L. Eichenfield, Jerry Tan
• Year: 2017
• Venue: Dermatology and Therapy
• URL: https://www.semanticscholar.org/paper/eafcdab44124661cdeba5997d4e2ca3cf5a7627e
• DOI: 10.1007/s13555-016-0168-8
• PMID: 28150107
• PMCID: 5289119
• Citations: 149
• Influential citations: 4
• Summary: An overview of current perspectives on the pathogenesis and treatment of acne and rosacea is provided, including a summary of findings from recent landmark pathophysiology studies considered to have important implications for future clinical practice.
• Evidence snippets:
• Snippet 1 (score: 0.470) > Rosacea has a multifactorial pathology involving vasoactive and neurocutaneous mechanisms, as well as innate and adaptive immunity. Each of these factors contributes to the disease to a different extent in each individual (Fig. 3). Over the past decade, the management of rosacea has evolved from empiricism to rational selection based on disease pathogenesis. While standard measures, including avoidance of triggers, gentle cleansers, and moisturizers in combination with sun protection, may mitigate flares, control signs and symptoms in some patients, others will require more specific therapy. > In the past, treatments for rosacea have primarily been confined to therapies indicated for other conditions (e.g., beta-blockers for flushing, antibiotics for acne vulgaris). However, more recently, treatments have been specifically developed based on our evolving understanding of the pathogenesis of rosacea (Fig. 4). Currently available treatment options based on positive outcomes from randomized controlled trials include topical brimonidine or intense pulsed light (IPL) for background persistent erythema; topical metronidazole, azelaic acid, ivermectin, or oral doxycycline and isotretinoin for papulopustules of rosacea; and cyclosporine eye drops for ocular rosacea [47]. Consensus on the optimal treatment for phymatous rosacea has yet to be reached because of a lack of robust clinical trial data. A useful summary of findings for all evidence-based interventions for treating different manifestations of rosacea is provided in a recently published Cochrane review [48]. > Although the past decade has witnessed important advances in our understanding and management of rosacea, it is anticipated that the findings from recent landmark pathophysiology studies will have important implications for future clinical practice. For example, gene array analyses indicate that each rosacea subtype can be differentiated by a selective gene profile, suggesting that the pathomechanisms of the different subtypes may vary with respect to the molecular pathways involved [49]. Other promising avenues of research include the role of cathelicidin antimicrobial peptides in aberrant innate immune responses [44,50], the role of mast cells as key mediators of cathelicidin-initiated inflammation in

[5] Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

• Authors: Cheng Chen, Peiru Wang, Linglin Zhang, Xiaojing Liu, Haiyan Zhang et al.
• Year: 2023
• Venue: Biomedicines
• URL: https://www.semanticscholar.org/paper/79a2e71639c81efae823ea0b5f4b691d9fbd7e38
• DOI: 10.3390/biomedicines11082153
• PMID: 37626650
• PMCID: 10452301
• Citations: 57
• Influential citations: 2
• Summary: This comprehensive review investigates the pathogenesis of rosacea in depth, with a focus on emerging and novel mechanisms, and provides an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms.
• Evidence snippets:
• Snippet 1 (score: 0.453) > Given the multifaceted pathogenic mechanisms involved in rosacea, investigating these emerging areas may offer novel therapeutic avenues for the condition. Our future goal is to pinpoint the key molecules or mechanisms that drive inflammation in rosacea, akin to the role of IL-17 in psoriasis, and to develop therapeutic agents based on these findings. > Recent advances in our understanding of the pathogenesis of rosacea have led to the emergence of various new therapies. In this paper, we have dedicated comprehensive chapters to elaborate on the current understanding and recent advancements in therapeutic strategies that specifically address (1) immune dysregulation, (2) neurovascular dysregulation, (3) neurological and psychological factors, and (4) microbial dysbiosis. Additionally, we have meticulously explored the latest developments in (5) physical treatment methods, encompassing photodynamic therapy and other innovative approaches. Moreover, we have delved into (6) miscellaneous therapeutic avenues, including the promising utilization of traditional herbal medicines, small-molecule inhibitors, and RNA medicines. These promising therapies have enriched the range of available treatment options, providing new avenues for managing the complex pathophysiology of rosacea. Nonetheless, the efficacy of many of these novel therapies necessitates further validation through rigorous clinical trials. Some physical therapies have also emerged as potential avenues for future development. These therapies target specific symptoms with minimal systemic adverse effects, making them suitable for combination with other therapeutic modalities or post-pharmacological intervention. Tailored combinations of physical therapies present advantages in optimizing treatment regimens for rosacea patients and may contribute to improved aesthetic outcomes. Given that rosacea may extend beyond the skin, personalized therapies that target the comorbidities associated with rosacea, such as β-adrenergic receptor antagonists for patients with anxiety and rifaximin for those with SIBO, could be another promising direction for the future of rosacea treatment. By addressing the individual needs of patients with specific comorbidities, these therapies have the potential to provide more effective and tailored treatment options. With the emergence of monoclonal antibodies, small-molecule drugs, and RNA medicines, we now have more precise drugs that target the disease development process.
• Snippet 2 (score: 0.415) > Rosacea is a common chronic inflammatory cutaneous disorder that affects about 5.46% of the global adult population [1]. It primarily affects the central facial skin and presents with symptoms such as recurrent episodes of flushing, persistent erythema, telangiectasia, papules, pustules, edema, phymatous changes, or a combination of these symptoms. Rosacea can be classified into four subtypes based on these symptoms: erythematotelangiectatic rosacea (ETR), papulopustular rosacea (PPR), phymatous rosacea (PhR), and ocular rosacea (OR) [2,3]. Although the pathophysiological mechanisms of rosacea remain unclear, the prevailing consensus is that the condition primarily stems from immune dysregulation and/or neurovascular dysfunction, as well as an impaired skin barrier. Triggers such as ultraviolet radiation, temperature changes, diet, and stress can exacerbate the underlying innate immune response and/or neurovascular dysfunction [4]. Recent studies have also highlighted the role of microbial dysbiosis, neuroimmune interactions, metabolic dysfunction, and sebaceous gland dysregulation in the development of rosacea. Other factors such as genetic predisposition and oxidative stress are also thought to play a role (Figure 1). > Regarding treatment, various guidelines and expert consensus offer a range of therapeutic options tailored to different phenotypes [2,[5][6][7]. In terms of addressing the pathogenesis of rosacea, the most traditional and commonly employed approach is through the use of anti-inflammatory treatments. Novel drugs targeting neurological and psychological factors have recently gained attention. Several other therapeutic options have emerged targeting other specific pathways, including vascular dysregulation, and microbial dysbiosis. New formulations or routes of administration for some drugs are also being explored. Physical therapies, such as laser and photodynamic therapy, have also shown promising outcomes in the treatment of rosacea. > In this article, we provide a detailed and comprehensive investigation o pathogenesis of rosacea, with a particular focus on the emerging and novel mechan that may contribute to its development.

[6] Advances in the pathogenesis of rosacea

• Authors: Hui Wang, Chen-Han Zhou
• Year: 2026
• Venue: Frontiers in Immunology
• URL: https://www.semanticscholar.org/paper/624cb421fe66bdc40aba068d85f82deb30776da2
• DOI: 10.3389/fimmu.2025.1705588
• PMID: 41646975
• PMCID: 12868226
• Citations: 1
• Summary: The latest significant advances in the pathogenesis of rosacea in recent years are summarized and the dysbiosis of skin and gut microbiota, together with the impairment of skin barrier function, is also closely associated with the onset and progression of this disease.
• Evidence snippets:
• Snippet 1 (score: 0.444) > Rosacea is a complex chronic inflammatory skin disease driven by the interaction of genetics, neurovascular function, immunity, skin barrier and microorganisms, with each factor amplifying the others to maintain the disease. In recent years, with the advancement of basic scientific research and the application of emerging technologies, the pathological mechanism of rosacea has gradually been revealed. Advances in genomics, immunology, and microbiology have helped to uncover more information about the susceptibility and inducing factors of the disease. However, the specific pathophysiological mechanism of rosacea has not been fully elucidated. Future research should further explore its molecular and cellular mechanisms, which will provide a theoretical basis for the establishment of personalized treatment strategies and the development of new treatment methods, thereby improving the clinical prognosis of patients.

[7] ACSL5 mediates macrophage infiltration and lipid metabolism in erythrotelangiectasia rosacea via potential pathogenic mechanisms and therapeutic targets

• Authors: Xiaoxia Ding, Youxia Xi, Y. Sheng, Yibin Fan, Yong Yu
• Year: 2025
• Venue: Scientific Reports
• URL: https://www.semanticscholar.org/paper/a303581a3610c61b54ad91d0bbb427dab34ee9bd
• DOI: 10.1038/s41598-025-96756-3
• PMID: 40195491
• PMCID: 11976930
• Summary: New insights into ETR pathogenesis are provided and the co-localization of ACSL5 with M1 macrophage markers suggests a mechanistic link between lipid metabolism and inflammatory responses.
• Evidence snippets:
• Snippet 1 (score: 0.440) > Rosacea is a chronic inflammatory skin disease characterized by centro-facial erythema, telangiectasia, papules, and pustules. Oral medication or light-based therapies for persistent erythema and flushing in rosacea may be ineffective in some cases. However, the efficacy of erythema rosacea is still not satisfactory, so more in-depth mechanism research and therapeutic target mining are still necessary. > In this study, a total of 304 differentially expressed genes associated with erythematotelangiectatic rosacea (ETR) were identified through differential gene analysis and weighted gene co-expression network analysis (WGCNA). Enrichment analysis revealed that these genes were primarily involved in metabolic pathways, PPAR signaling pathway, fatty acid metabolism, and lipid metabolic processes. While comprehensive lipidomic studies on rosacea skin lesions remain limited, one previous small-scale analysis reported no significant differences in major lipid components, including cholesterol, triglycerides, and squalene, between patients with rosacea and healthy controls 13 . This discrepancy may reflect limitations in the resolution and sensitivity of conventional lipidomic analyses. In contrast, our transcriptomic data revealed marked alterations in genes associated with lipid metabolism, particularly those involved in fatty acid pathways such as ACSL5 and ACADVL. These transcriptional changes indicate potential metabolic dysregulation that may not be reflected at the bulk lipid level. Such molecular alterations could influence enzyme function, lipid signaling, or metabolic fluxes, which may escape detection by untargeted lipid profiling. To address this gap, advanced approaches-such as targeted or spatial lipidomics-could complement transcriptomic findings and offer deeper insight into lipid pathway disturbances in rosacea. This integrative strategy may help uncover subtle metabolic shifts relevant to disease pathogenesis and expand the current understanding of rosacea at the molecular level. Previous research has indicated that inflammatory processes, triggered by oxidative stress and lipid oxidation, contribute to the development and progression of rosacea 14 .

[8] Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel

• Authors: Jerry Tan, L. Almeida, A. Bewley, B. Cribier, N. Dlova et al.
• Year: 2017
• Venue: British Journal of Dermatology
• URL: https://www.semanticscholar.org/paper/cc6ada668802c4547f0cb2246bdb471109c85dae
• DOI: 10.1111/bjd.15122
• PMID: 27718519
• Citations: 259
• Influential citations: 12
• Summary: Rosacea is currently diagnosed by consensus‐defined primary and secondary features and managed by subtype, however, individual features can span multiple subtypes, which has implications for clinical practice and research.
• Evidence snippets:
• Snippet 1 (score: 0.436) > • This study re-evaluates the primary and secondary features of rosacea in order to rationalize diagnosis and classification based on a phenotype approach. > • This study provides a global perspective on rosacea diagnosis and classification with representation from Africa, Asia, Europe, North America and South America. > Rosacea is a chronic inflammatory disease of the skin predominantly affecting the centrofacial region. Although several potential pathways are under investigation, its pathophysiology has yet to be fully determined. So far, dysregulation of the innate (keratinocytes, endothelial cells, macrophages, mast cells, dendritic cells) and adaptive [T helper (Th)1 cells, Th17 cells, plasma cells] immune system has been found. In this dysregulated network, increased levels of antimicrobial peptides, neuropeptides, nitric oxide radical species, proteases, cytokines, chemokines, vascular growth factor (VEGF) along with receptors for cytokines, chemokines, neurotransmitters, VEGF or transient receptor potential ion channels have been detected. [1][2][3][4][5][6][7][8][9][10][11] Trigger factors including Demodex and ultraviolet radiation exposure may activate some of these pathways, although the molecular mechanisms are poorly understood thus far. For this reason, no diagnostic laboratory test is available. Therefore, rosacea diagnosis and classification are based on the patient's presenting features. > Current diagnostic practice largely follows the recommendations of the National Rosacea Society (NRS) expert panel, which is composed of North American and European dermatologists. According to the NRS system, any one of the following is a primary diagnostic criterion for rosacea: transient erythema, persistent erythema, inflammatory papules/pustules and telangiectasia. 12 Secondary features, which may be present with primary features or appear independently, include phymatous changes, burning or stinging sensations, erythematous plaques, facial dryness and scaling, oedema, peripheral location and ocular manifestations. 12 As multiple features tend to present simultaneously, a subtype classification system was also proposed, grouping the most

[9] Multi-Transcriptomic Analysis and Experimental Validation Implicate a Central Role of STAT3 in Skin Barrier Dysfunction Induced Aggravation of Rosacea

• Authors: Yaling Wang, Ben Wang, Yingxue Huang, Yangfan Li, Sha Yan et al.
• Year: 2022
• Venue: Journal of Inflammation Research
• URL: https://www.semanticscholar.org/paper/87618144363399c0147ca2fad7eea0772561cac1
• DOI: 10.2147/JIR.S356551
• PMID: 35392024
• PMCID: 8980297
• Citations: 28
• Influential citations: 2
• Summary: The results showed that the destruction of the skin barrier aggravates the inflammation levels and immune infiltration of rosacea partly by activating STAT3-mediated cytokine signal pathways in keratinocytes.
• Evidence snippets:
• Snippet 1 (score: 0.423) > Rosacea is a chronic inflammatory skin disease characterized by flushing, persistent erythema, papules and pustules, telangiectasia and phyma, especially on the cheek, nose, chin, forehead and eyes. 1 The incidence of rosacea varies in different areas of the world and a cross-sectional study showed that about 3.48% of individuals are affected in China. 2 According to the National Rosacea Society Expert Committee in 2017, the updated classification of rosacea is based on phonotypes linked to clinical manifestations and provides criterion of diagnosis and severity assessment of the disease. 3 Although the pathophysiology of rosacea remains unclear, genetic factors, dysregulation of the innate and adaptive immune system, vascular and neuronal dysfunction, and microorganisms such as Demodex folliculorum appear to be involved. 4 Above these, Zuo et al found overcleaning were positively associated with rosacea, 5 indicating that rosacea is also associated with impairment of the skin barrier. > Skin barrier plays a critical role in skin homeostasis. Various skin barrier-related genes (SBRGs) have been reported to be involved in the progression of skin disease via regulating the skin barrier. The tight junction protein and Filaggrin (FLG) are important SBRGs, 6 playing a central role for the physical integrity of the skin barrier. The biological and chemical stimulations from the external environment disrupted the skin barrier by reducing tight junctions, triggering epithelial alarmin, including barrier alarms (KRT6A, KRT16), AMPs (DEFB4B, CAMP, LCN2, S100A7, S100A8, S100A9) and KLK enzyme. 7 Previous investigations have shown that patients with rosacea have impaired facial skin barrier, characterized by increased PH, abnormal fatty acid composition and increased trans epidermal water Loss (TEWL). 8,9 Previous research demonstrated the dysregulated SBRGs in rosacea patients 10,11 and barrier repair could be of therapeutic benefit in rosacea, revealing the potential role of skin barrier dysfunction (SBD) in the pathogenesis of rosacea. However, the underlying mechanism is still unknown. > STAT3 is a crucial signal transducer factor in the pathogenesis

[10] Major Pathophysiological Correlations of Rosacea: A Complete Clinical Appraisal

• Authors: R. Vemuri, R. Gundamaraju, S. Sekaran, R. Manikam
• Year: 2015
• Venue: International Journal of Medical Sciences
• URL: https://www.semanticscholar.org/paper/51b4e4217168b6531c70567d1884ae3fbd379a3c
• DOI: 10.7150/ijms.10608
• PMID: 26005373
• PMCID: 4441063
• Citations: 32
• Influential citations: 3
• Summary: Vasculature, chronic inflammatory responses, environmental triggers, food and chemicals ingested and microorganisms either alone or in combination are responsible for rosacea.
• Evidence snippets:
• Snippet 1 (score: 0.415) > Background: Rosacea is a characteristic cutaneous disorder with a diverse clinical manifestations ranging from facial vascular hyper-reactivity to sebaceous gland hyperplasia. Many theories on pathophysiology of rosacea were proposed over the past decade, however the pathogenicity is poorly understood. Aim: To review the evidence on different pathophysiological correlations of rosacea. Methods: A literature search was conducted for studies published between 1990 to March 2014. The inclusion criteria was pathophysiology, randomized controlled trials, controlled trials on rosacea. Results: Out of 5141 articles, 14 high quality studies met all the selection criteria. Of 14 articles, 5 are randomized control trials (RCTs), 2 are controlled trial, 3 comparative trials, 2 observational trials, 1 prospective and 1 diagnostic trial. The studies were categorized into two groups: the trigger factors and sub-types & symptoms. Of 7 high quality studies, 4 provided strong evidence that immune responses causing disease triggered by external/internal factors such as sunlight, food and chemical agents, 3 trials provided significant evidence of microorganisms as causative agents. The remaining trials did not provide significant evidences on pathophysiology. Conclusion: Vasculature, chronic inflammatory responses, environmental triggers, food and chemicals ingested and microorganisms either alone or in combination are responsible for rosacea. Many promising drugs are under various phases of clinical trials and interestingly, probiotics could also possibly be used as one of the treatment option.

[11] Mechanisms and Recent Advances of Small-Molecule Therapeutics in Rosacea Treatment

• Authors: M. Ye, P. Hao, Nana Luo, Tianhao Li
• Year: 2025
• Venue: Clinical, Cosmetic and Investigational Dermatology
• URL: https://www.semanticscholar.org/paper/d26e50b88d294744bc3e3985fe208bd4e62b021e
• DOI: 10.2147/CCID.S525787
• PMID: 40529547
• PMCID: 12170860
• Summary: This review summarizes the latest advances in small molecules targeting key inflammatory pathways in rosacea, provides new ideas for the treatment of rosacea and new directions for the clinical management of rosacea.
• Evidence snippets:
• Snippet 1 (score: 0.409) > Therefore, there is a need for effective new therapies. > Currently, small molecule inhibitors are at the vanguard of medical research endeavors. 28 In recent times, with the ongoing and profound exploration of inflammatory mediators and signaling cascades implicated in the pathophysiology of rosacea, more and more targeted therapies have emerged, including biologics and small-molecule drugs. 29,30 ompared with biologics, small-molecule drugs with a molecular weight <1 kDa have unique properties: they can act by targeting intracellular targets that biologics cannot act on through cell membranes; Reduce the loss of response caused by immunogenicity of macromolecular proteins; The adjustment of its chemical structure and dosage is conducive to achieving the balance of clinical pharmacokinetics and pharmacodynamics. Convenient oral or topical administration and relatively low cost are more acceptable to patients. 31,32 For patients with rosacea who are tolerated or even unable to respond to conventional treatment regimens, small-molecule drugs are a new alternative to treatment. This paper provides an overview of the mechanisms of action and advancements in clinical research concerning small-molecule drugs utilized for rosacea treatment in recent years.

[12] Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models

• Authors: Daniela Rodrigues-Braz, Min Zhao, N. Yesilirmak, S. Aractingi, F. Behar-Cohen et al.
• Year: 2021
• Venue: Molecular Vision
• URL: https://www.semanticscholar.org/paper/f6a633d5daa6cb8227a8f05de54fe713a1b48ff0
• PMID: 34035646
• PMCID: 8131178
• Citations: 67
• Influential citations: 3
• Summary: The common and specific molecular mechanisms involved in the pathogenesis of cutaneous and ocular rosacea are reviewed and laboratory and clinical studies, as well as experimental models are discussed.
• Evidence snippets:
• Snippet 1 (score: 0.406) > Finally, the molecular steps involved in the pathogenesis of ocular rosacea are not fully known. Meibomian gland dysfunction has been recognized as a major component [13,26]. Like in the skin, activation of the innate and adaptive immune response and abnormal vascular regulations have been identified. In the tears and in the ocular surface tissues of ocular rosacea patients, high levels of TLR-4 and LL-37 were measured together with cell infiltration and the release of proinflammatory factors [13,27,28]. A link between Demodex infestation and ocular rosacea has also been advocated [29,30]. Overall, all these phenomena in the skin and eye act in synergy to maintain chronic inflammation at the cutaneous, epidermal, conjunctival, and perivascular interface, eventually leading to secondary fibrosis [31]. In this paper, we aim to review the common and specific pathogenic mechanisms of cutaneous and ocular rosacea and focus on the few models used to study this disease. > Deregulation of the immune system: Activation of immunemediated inflammatory pathways appears to be at the center of the pathogenesis of rosacea and involves the coordinated activity of several cell types, such as mast cells and macrophages, and the release of proinflammatory mediators, such as IL-6, IL-1β, IL-18, or TNF-α [32,33]. Inhibition of these inflammatory pathways is correlated with clinical improvement.

[13] Probiotics and Diet in Rosacea: Current Evidence and Future Perspectives

• Authors: M. Manfredini, Michele Barbieri, Margherita Milandri, C. Longo
• Year: 2025
• Venue: Biomolecules
• URL: https://www.semanticscholar.org/paper/c662166e77008a0248667360e90bce45205ade0a
• DOI: 10.3390/biom15030411
• PMID: 40149947
• PMCID: 11940470
• Citations: 10
• Influential citations: 1
• Summary: Improved understanding of the gut–skin axis in rosacea is improved, focusing on how probiotic supplementation and diet could improve the clinical management of patients affected by this common and debilitating disease.
• Evidence snippets:
• Snippet 1 (score: 0.403) > Studies and reports over the past several decades have analyzed the association between common dietary triggers and rosacea pathogenesis. The avoidance of common triggers can reduce rosacea flares and improve the management of the disease. Probiotics, such as certain strains of Lactobacillus, Bifidobacteria and Saccharomyces, can positively influence several immune mechanisms that are implicated in rosacea pathogenesis by increasing IL10 and reducing TNF-a, IL-17A. Prebiotics, which supports gut colonization by beneficial gut bacteria, could favorably influence the gut-skin axis mechanisms involved in rosacea pathogenesis. To the best of our knowledge, the paucity of clinical studies and the lack of randomized trials and standardization of the use of probiotics are major limitations to the current adoption of probiotics as part of standard rosacea care and management. Diet and nutritional counseling may enhance rosacea management through the direct effects of food metabolites and the modulation of the gut microbiota. Highfiber diets, particularly those rich in vitamin A, may exhibit potent anti-inflammatory and sebum-regulating properties that help to manage the factors contributing to the progression of rosacea. Therefore, modulating the skin and gut microbiota through diet, prebiotics, probiotics, and postbiotics could represent an effective and innovative strategy for the therapeutic control and management of rosacea. However, few studies are available, and more rigorous clinical trials are needed.

[14] Rosacea pathogenesis and therapeutics: current treatments and a look at future targets

• Authors: Garrett W Fisher, J. B. Travers, C. Rohan
• Year: 2023
• Venue: Frontiers in Medicine
• URL: https://www.semanticscholar.org/paper/0acb3a9da9d339fdd67f5ed8c60b39fb03fc7ef5
• DOI: 10.3389/fmed.2023.1292722
• PMID: 38193038
• PMCID: 10773789
• Citations: 29
• Influential citations: 2
• Summary: Current concepts of rosacea pathogenesis will be addressed which involve skin barrier and permeability dysfunction, the innate and adaptive immune systems, and the neurovascular system.
• Evidence snippets:
• Snippet 1 (score: 0.402) > Research into the pathogenesis of rosacea is trending upward owing to rapid discoveries in the field, which indicates pathophysiology has attracted attention for future research (86). Novel discoveries increase our understanding of intrinsic and extrinsic pathways contributing to rosacea and allow for new opportunities of therapeutics. Descriptions of future therapies are broken down into subsections of implicated pathogenesis such as skin barrier dysfunction, cathelicidin pathway, mast cell targets, and microvesicle particles. Each pathogenic target then discusses proposed medications, and hypothetical targets based upon pathogenic insight. For reference, Figure 2 depicts the future treatment targets in relation to pathophysiology and Table 2 provides a summary of each target, proposed mechanism of action, and example medications.

[15] Cutaneous rosacea: a thorough overview of pathogenesis, clinical presentations, and current recommendations on management

• Authors: J. Rosso, Дел Россо Джим
• Year: 2016
• Venue: Vestnik dermatologii i venerologii
• URL: https://www.semanticscholar.org/paper/bfc788c245291c6dc7ace98ddb6c58f51e6c977a
• DOI: 10.25208/0042-4609-2016-92-2-21-31
• Citations: 4
• Summary: В обзоре обобщены и систематизированы имеющиеся международные данные по патогенезу, клиническим проявлениям и текущим рекомендациям по тактике ведения пациентов с розацеа.
• Evidence snippets:
• Snippet 1 (score: 0.402) > Publications devoted primarily to pathophysiology of rosacea appear elsewhere in the medical literature; nev ertheless, explanations of rosaceaprone skin and the basic pathophysiologic mechanisms that seem to be op erative in rosacea are necessary in order to better un derstand the direct correlations with specific signs and symptoms of rosacea and allow for more rational selec tion of individual therapies in each case that address spe cific clinical manifestations of rosacea [5, 6, 13, 22, 26 32]. Rosaceaprone skin is characterized by three major

[16] Molecular Mechanisms in the Etiopathology of Rosacea—Systematic Review

• Authors: Anastazja Andrusiewicz, Sofiia Khimuk, Daniel Mijas, Bohdan Shmorhun, D. Nowicka
• Year: 2025
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/46211301b204c0f77bf013d73f281a9dc16b296e
• DOI: 10.3390/ijms262311292
• PMID: 41373451
• PMCID: 12692705
• Citations: 3
• Summary: Results highlight that rosacea involves both cutaneous and systemic molecular alterations, and the evidence identifies multiple biomarkers with diagnostic potential and provides mechanistic insights into immune, vascular, and metabolic dysregulation.
• Evidence snippets:
• Snippet 1 (score: 0.391) > In analyzing the molecular mechanisms of rosacea, we categorized them into four main groups: (1) oxidative stress, (2) cytokine-driven signaling pathways, (3) immune cell signaling and skin barrier dysfunction, and (4) metabolic molecular markers. The schematic overview of these molecular mechanisms and their contribution to rosacea pathogenesis is presented in Figure 2.

[17] Exploring the molecular mechanisms of huperzine a in the treatment of rosacea through network pharmacology, machine learning, and molecular dynamics simulations

• Authors: Xin Luo, S. Yang, Lian Zhong, Peng Zhang
• Year: 2025
• Venue: Frontiers in Pharmacology
• URL: https://www.semanticscholar.org/paper/9ee98971fad0d5953c1934ff6437920464526139
• DOI: 10.3389/fphar.2025.1586829
• PMID: 40474977
• PMCID: 12137240
• Citations: 3
• Summary: This study systematically elucidates the potential mechanisms of Hup A in the treatment of rosacea and provides a theoretical basis for its application in rosacea therapy.
• Evidence snippets:
• Snippet 1 (score: 0.384) > Rosacea is a recurrent inflammatory skin condition, with a worldwide prevalence exceeding 5% (Gether et al., 2018). Although there are many treatments including topical therapies, systemic treatments, as well as light-based therapy, rosacea cannot be completely cured (Sharma et al., 2022;Hua et al., 2025). Therefore, more effective, and safe therapeutic strategy for rosacea is urgently required. This study integrated network pharmacology, molecular docking, and computational modeling to systematically investigate the potential mechanisms and core targets of Hup A in treating rosacea. > The precise mechanisms underlying rosacea remain elusive, but it is well known that dysregulation of the immune and neurovascular systems has been recognized as playing crucial roles in its pathogenesis (Schwab et al., 2011). Patients with rosacea have an increased risk of depression and anxiety, which may exacerbate flushing and disease progression (Yang et al., 2024;Sinikumpu et al., 2024), underscoring the interplay between neuropsychiatric factors and cutaneous pathophysiology. Hup A was initially identified as an inhibitor of acetylcholinesterase (AChE) based on Chinese databases, and it has been utilized in the treatment of cognitive disorders related to memory deficits, including Alzheimer's disease and other types of dementia (Damar et al., 2016). By network pharmacology and pathway enrichment analysis, we identified 21 overlapping targets between Hup A and rosacea. KEGG pathway analysis revealed multiple signaling pathways including the MAPK, NF-κB, TNF-a, and PI3K-AKT pathways between Hup A and rosacea (Figure 2). In rosacea, activation of the MAPK signaling cascade drives inflammatory responses via regulation of IL-1β release (Harden et al., 2021). Notably, Isosilybin A has been shown to attenuate rosacea symptoms through MAPK pathway inhibition (Wu et al., 2024), suggesting conserved therapeutic utility of this axis. Similarly, the NF-κB pathway plays a central role in disease progression.

Notes

• This provider combines search_papers_by_relevance with snippet_search.
• No synthesis or second-stage model call is performed.