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Rosacea is a chronic skin inflammatory disease with a global prevalence ranging from 1% to 20%. It is characterized by facial erythema, telangiectasia, papules, pustules, and ocular manifestations. Its pathogenesis involves a complex interplay of genetic, environmental, immune, microbial, and neurovascular factors. Recent studies have advanced our understanding of its molecular basis, focusing on toll-like receptor (TLR) 2 pathways, LL37 expression, mammalian target of rapamycin (mTOR) activation, interleukin (IL)-17 signaling, transient receptor potential vanilloid (TRPV) functions, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. LL37-associated signaling pathways, particularly involving TLR2 and mTORC1, are critical in the pathogenesis of rosacea. LL37 interacts with signaling molecules such as extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear factor kappa B (NF-κB), inflammasomes, C-X-C motif chemokine ligand 8 (CXCL8), mas-related G-protein-coupled receptor X2 (MRGPRX2)-TRPV4, and vascular endothelial growth factor (VEGF). This interaction activates macrophages, neutrophils, mast cells, and vascular endothelial cells, leading to cytokine release including tumor necrosis factor-alpha (TNF-α), IL-6, IL-1ß, C motif chemokine ligand (CCL) 5, CXCL9, and CXCL10. These processes contribute to immune response modulation, inflammation, and angiogenesis in rosacea pathophysiology. The IL-17 signaling pathway also plays a crucial role in rosacea, affecting angiogenesis and the production of inflammatory cytokines. In addition, recent insights into the JAK/STAT pathways have revealed their integral role in inflammatory and angiogenic mechanisms associated with rosacea. Rosacea treatment currently focuses on symptom management, with emerging insights into these molecular pathways providing more targeted and effective therapies. Biological agents targeting specific cytokines, IL-17 inhibitors, JAK inhibitors, and VEGF antagonists are promising for future rosacea therapy, aiming for enhanced efficacy and fewer side effects. This review provides a comprehensive overview of the current knowledge regarding signaling pathways in rosacea and potential targeted therapeutic strategies.
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Terapia de Alvo Molecular , Rosácea , Transdução de Sinais , Humanos , Rosácea/tratamento farmacológico , Rosácea/imunologia , Rosácea/metabolismo , Animais , CatelicidinasRESUMO
Rosacea is a chronic inflammatory skin disease that typically affects the central facial area. Its main clinical symptoms include paroxysmal flushing, telangiectasia, and non-temporary erythema. Cell-free adipose tissue extracts (ATEs) are liquid components extracted from human adipose tissue that contain large amounts of growth factors. Despite the scar-reducing, anti-aging, and wound-healing effects of ATEs, the efficacy of ATEs in rosacea remains unknown. Therefore, the anti-rosacea effects of ATEs were investigated in human cathelicidin peptide (LL-37) induced rosacea mice and capsaicin (CAP)-stimulated HaCaT keratinocytes. In vitro, ATEs significantly reduced TRPV1 expression, intracellular calcium ions influx and the release of inflammatory factors (such as KLK5, IL-6, IL-8 and TNF-α) after intervening in CAP-stimulated cells. The in vivo results revealed that ATEs alleviated rosacea symptoms, such as erythema score, erythema area, transepidermal water loss, abnormal epidermal thickness, mast cell infiltration and telangiectasia upon downregulating TRPV1 and CD31 expression. Moreover, the up-regulated TRPV1 protein expression was also recovered by ATEs administration in vivo and in vitro. Meanwhile, ATEs demonstrated good biocompatibility. In summary, ATEs could be a potential therapeutic agent for rosacea by regulating inflammation and alleviating telangiectasia.
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Tecido Adiposo , Rosácea , Canais de Cátion TRPV , Canais de Cátion TRPV/metabolismo , Rosácea/tratamento farmacológico , Rosácea/metabolismo , Rosácea/patologia , Animais , Humanos , Camundongos , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Capsaicina/farmacologia , Células HaCaT , Catelicidinas , Masculino , Modelos Animais de Doenças , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/metabolismoRESUMO
Patients with neurogenic rosacea (NR) frequently demonstrate pronounced neurological manifestations, often unresponsive to conventional therapeutic approaches. A molecular-level understanding and diagnosis of this patient cohort could significantly guide clinical interventions. In this study, we amalgamated our sequencing data (n = 46) with a publicly accessible database (n = 38) to perform an unsupervised cluster analysis of the integrated dataset. The eighty-four rosacea patients were partitioned into two distinct clusters. Neurovascular biomarkers were found to be elevated in cluster 1 compared to cluster 2. Pathways in cluster 1 were predominantly involved in neurotransmitter synthesis, transmission, and functionality, whereas cluster 2 pathways were centered on inflammation-related processes. Differential gene expression analysis and WGCNA were employed to delineate the characteristic gene sets of the two clusters. Subsequently, a diagnostic model was constructed from the identified gene sets using linear regression methodologies. The model's C index, comprising genes PNPLA3, CUX2, PLIN2, and HMGCR, achieved a remarkable value of 0.9683, with an area under the curve (AUC) for the training cohort's nomogram of 0.9376. Clinical characteristics from our dataset (n = 46) were assessed by three seasoned dermatologists, forming the NR validation cohort (NR, n = 18; non-neurogenic rosacea, n = 28). Upon application of our model to NR diagnosis, the model's AUC value reached 0.9023. Finally, potential therapeutic candidates for both patient groups were predicted via the Connectivity Map. In summation, this study unveiled two clusters with unique molecular phenotypes within rosacea, leading to the development of a precise diagnostic model instrumental in NR diagnosis.
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Aprendizado de Máquina , Rosácea , Transcriptoma , Humanos , Rosácea/genética , Rosácea/diagnóstico , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Técnicas de Diagnóstico Molecular , Análise por Conglomerados , BiomarcadoresRESUMO
(1) Background: Periocular or periorbital dermatitis is a common term for all inflammatory skin diseases affecting the area of skin around the eyes. The clear etiopathogenesis of periocular dermatitis is still not fully understood. Advances in molecular techniques for studying microorganisms living in and on our bodies have highlighted the microbiome as a possible contributor to disease, as well as a promising diagnostic marker and target for innovative treatments. The aim of this study was to compare the composition and diversity of the skin microbiota in the periocular region between healthy individuals and individuals affected by the specific entity of periocular dermatitis. (2) Methods: A total of 35 patients with periocular dermatitis and 39 healthy controls were enrolled in the study. After a skin swab from the periocular region was taken from all participants, DNA extraction and 16S rRNA gene amplicon sequencing using Illumina NovaSeq technology were performed. (3) Results: Staphylococcus and Corynebacterium were the most abundant bacterial genera in the microbiota of healthy skin. Analysis of alpha diversity revealed a statistically significant change (p < 0.05) in biodiversity based on the Faith's PD index between patients and healthy individuals. We did not observe changes in beta diversity. The linear discriminant analysis effect size (LEfSe) revealed that Rothia, Corynebacterium, Bartonella, and Paracoccus were enriched in patients, and Anaerococcus, Bacteroides, Porphyromonas, and Enhydrobacter were enriched in healthy controls. (4) Conclusions: According to the results obtained, we assume that the observed changes in the bacterial microbiota on the skin, particularly Gram-positive anaerobic cocci and skin commensals of the genus Corynebacterium, could be one of the factors in the pathogenesis of the investigated inflammatory diseases. The identified differences in the microbiota between healthy individuals and patients with periocular dermatitis should be further investigated.
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BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a common, yet underdiagnosed, gut condition caused by gut dysbiosis. A previous study has shown the potential of herbal therapy, providing equivalent results to rifaximin. OBJECTIVES: The objective of this study was to assess how the use of an oral botanical regimen may modulate the gut microbiome, facial erythema, and intestinal permeability in those with SIBO. METHODS: This was an open-label prospective study of adults that had lactulose breath test-confirmed SIBO. Participants received a 10-week oral supplementation of a Biocidin liquid tincture and GI Detox+. If participants were found to be non-responsive to treatment after 10 weeks with a persistently positive lactulose breath test, a third oral supplement, Olivirex, was administered for an additional 4 weeks. Lactulose breath tests were administered at baseline, weeks 6, 10, and 14 to assess for SIBO status. A high-resolution photographic analysis system was utilized to analyze changes in facial erythema. Stool sample collections and venipuncture were performed to analyze the gut microbiome and intestinal permeability. RESULTS: A total of 33 subjects were screened with breath testing, and 19 subjects were found to have SIBO. Three of the subjects withdrew during the screening period prior to baseline, and sixteen subjects enrolled. Four subjects dropped out after baseline. Hydrogen-dominant SIBO was the most common subtype of SIBO, followed by methane and hydrogen sulfide. The botanical regimen was most effective for hydrogen- and hydrogen sulfide-dominant SIBO, leading to negative breath test results at week 10 in 42.8% and 66.7% of participants, respectively. Compared to baseline, supplementation with the botanical regimen led to positive shifts in short-chain fatty acid-producing bacteria such as A. muciniphila, F. prausnitzii, C. eutectus, and R. faecis by 31.4%, 35.4%, 24.8%, and 48.7% percent at week 10, respectively. The mean abundance of Firmicutes decreased by 20.2%, Bacteroides increased by 30%, and the F/B ratio decreased by 25.4% at week 10 compared to baseline. At week 10, there was a trending 116% increase in plasma LPS/IgG (p = 0.08). There were no significant changes in plasma zonulin, DAO, histamine, DAO/histamine, LPS/IgG, LPS/IgA, or LPS/IgM. Facial erythema was not statistically different at week 6, but at week 10, there was a 20% decrease (p = 0.001) in redness intensity. Among the patients that extended to week 14, there was no statistical change in erythema. CONCLUSIONS: Supplementation with an antimicrobial botanical supplemental regimen may have therapeutic potential in hydrogen and hydrogen-sulfide subtypes of SIBO. Furthermore, the botanical supplemental regimen may reduce facial erythema, increase SCFA-producing bacteria, decrease the F/B ratio, and modulate markers of intestinal permeability.
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Testes Respiratórios , Suplementos Nutricionais , Microbioma Gastrointestinal , Intestino Delgado , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Microbioma Gastrointestinal/efeitos dos fármacos , Estudos Prospectivos , Intestino Delgado/microbiologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Eritema/tratamento farmacológico , Eritema/microbiologia , Síndrome da Alça Cega/tratamento farmacológico , Face , Lactulose , Disbiose/microbiologia , Disbiose/tratamento farmacológico , Permeabilidade , Administração Oral , IdosoRESUMO
BACKGROUND: Facial erythema from acne, vascular rosacea, or photoaging is a common difficult-to-treat dermatologic challenge. OBJECTIVE: The objective of this study was to examine the role of lapachol in alleviating facial erythema associated with a variety of common dermatologic conditions. METHODS: Twenty-five healthy female and male subjects 35-65 years of age of Fitzpatrick skin types I-II with mild-to-moderate stable facial erythema from acne, rosacea or photoaging were enrolled in a single-site monadic study. Subjects received the study cream for twice daily application and were assessed at baseline, Week 4, and Week 8. The dermatologist investigator and subjects assessed efficacy and tolerability and facial photographic images were taken of all subjects at each visit. Noninvasive erythema assessments of the face were conducted using a colorimeter at baseline, Week 4, and Week 8 to document improvement in facial erythema. RESULTS: Twenty-five out of 25 subjects successfully completed the study without tolerability issues including 12 subjects with rosacea, 6 subjects with photoaging and 7 subjects with acne. After 8 weeks of use, the investigator rated a 44% decrease in facial erythema while the subjects rated a 40% decrease. Facial erythema was also noninvasively assessed with a colorimeter and dermaspectrophotometer (DSP). There was a 26% decrease in skin redness at Week 4 and a 31% decrease in skin redness at Week 8 on the colorimeter L*a*b* scale. This finding was collaborated by the DSP which registered a 29% decrease on the erythema scale at Week 8. CONCLUSION: Lapachol in a moisturizer formulation was found to be effective in reducing facial erythema from acne, rosacea, and photoaging.
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Rosacea is a common dermatosis with multiple pathogeneses, among which, rosacea fulminans may serve as a rare but severe subtype. This inflammatory disease usually presents as abrupt multiple erythema, pustules, and nodules localized on the face. Pregnancy and related changes of hormone levels may play a key role in the development and progression of the disease, although the exact mechanisms are unknown. In particular, treatment options, which includes systemic glucocorticosteroids, isotretinoin, and partial oral antibiotics, may be limited in pregnancy. Owing to the limited number of reported cases, standard diagnosis, treatment, and management guidelines remain unclear. Here, we report a case of rosacea fulminans happening in pregnancy treated successfully with oral erythromycin and short-term glucocorticosteroids, and share our review of the characteristics of RF cases during pregnancy.
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Background: Rosacea has a high incidence, significantly impacts quality of life, and lacks sufficient diagnostic techniques. This study aimed to investigate the feasibility of laser speckle contrast imaging (LSCI) for measuring facial blood perfusion in patients with rosacea and to identify differences in blood flow among various facial regions associated with different rosacea subtypes. Methods: From June to December 2023, 45 patients were recruited, with 9 excluded, leaving 36 subjects: 12 with erythematotelangiectatic rosacea (ETR), 12 with papulopustular rosacea (PPR), and 12 healthy controls. The Think View multispectral imaging analyzer assessed inflammation via gray reading values across the full face and five facial areas: forehead, nose, cheeks, and chin. LSCI measured and analyzed blood perfusion in the same areas. Plasma biomarkers interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) were tested in different groups. Results: Both ETR and PPR groups showed increased average blood perfusion and facial inflammation intensity by gray values compared to controls, with statistically significant differences. Average blood perfusion of ETR and PPR groups showed increased values in the forehead, cheeks, and nose, compared to controls, and the values in the cheeks were statistically different between ETR and PPR. The facial inflammation intensity of the ETR group showed increased values in the forehead and cheeks, and the PPR group showed increased gray values in the forehead, cheeks, nose, and chin compared to controls, and the values for the cheeks, nose, and chin were statistically significantly different between ETR and PPR. Plasma biomarkers IL-6, IL-1ß, and TNF-α were significantly elevated in both ETR and PPR groups compared to controls. Conclusion: LSCI is a valuable, non-invasive tool for assessing blood flow dynamics in rosacea, providing a data foundation for clinical research. Different rosacea subtypes exhibit distinct lesion distribution and blood flow patterns, and both ETR and PPR could affect all facial areas, particularly the cheeks in ETR and the forehead, nose, and chin in PPR.
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Face , Imagem de Contraste de Manchas a Laser , Rosácea , Humanos , Rosácea/diagnóstico , Rosácea/sangue , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Face/irrigação sanguínea , Fluxo Sanguíneo Regional , Biomarcadores/sangueRESUMO
OBJECTIVE: The primary aim of this systematic review and meta-analysis was to synthesize and compare the clinical efficacy of intense pulsed light (IPL) and pulsed-dye laser (PDL) therapies for the management of rosacea. METHODS: The literatures were searched in the Web of Science, PubMed, Embase, and Cochrane Library databases to identify relevant studies investigating the use of IPL and PDL for the treatment of rosacea. Screening of the retrieved articles and data extraction were performed as per the pre-established inclusion and exclusion criteria. The primary outcome measures evaluated in this meta-analysis included clearance rates, erythema scores, and pain scores. RESULTS: The meta-analysis incorporated data from four studies involving a total of 141 participants. The meta-analysis did not reveal a statistically significant difference between IPL and PDL in the rate of achieving greater than 50% clearance (RR = -0.07, 95% CI: -0.19, 0.05). However, the IPL group demonstrated a significantly higher rate of clearance exceeding 75% compared to the PDL group (RR = -0.13, 95% CI: -0.23, -0.04). The change in erythema index, a key measure of rosacea severity, was similar between the two treatment modalities (SMD = -0.15, 95% CI: -0.55, 0.26). Interestingly, the PDL group reported a notably lower VAS pain score than the IPL group (SMD = 1.54, 95% CI: 0.08, 3.00). CONCLUSION: Either PDL or IPL appears to be effective modalities for the management of rosacea. IPL exhibits a slight advantage in achieving a higher rate of substantial (>75%) clearance, while PDL may be preferable for patients with lower tolerance for post-treatment discomfort. However, the existing literature directly comparing these two laser/light-based therapies is limited, warranting further well-designed, large-scale studies to establish the optimal treatment algorithm for this chronic inflammatory skin condition.
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BACKGROUND: Rosacea, a chronic inflammatory skin condition, is marked by enduring redness, visible blood vessels, and inflammatory eruptions in facial areas. Managing rosacea remains a persistent challenge for dermatologists, especially in cases unresponsive to conventional treatments. Injectable poly-d,l-lactic acid (PDLLA) has shown promise in treating erythema and telangiectasia associated with rosacea in addition to age-related concerns. Employing Mirajet, a laser-induced microjet system, for administering PDLLA is a novel and promising treatment for rosacea. AIMS: We aimed to evaluate the efficacy and safety of injectable PDLLA delivered via a needle-free microjet system for managing rosacea. METHODS: Four Korean women with persistent and refractory rosacea received five monthly sessions of PDLLA needle-free injections. Clinical assessments were conducted using the Clinician's Erythema Assessment and Patient's Self-Assessment (PSA) at baseline, 4 weeks post-treatment, and 22 weeks post-final treatment. Adverse events were monitored throughout the study period. RESULTS: At 4 weeks post-treatment, both Clinician's Erythema Assessment and PSA scores indicated significant improvements in erythema that were sustained up to the 22-week follow-up. Patients reported high satisfaction with resolution of redness and improved skin texture. Mild swelling, redness, and petechiae were observed post-treatment but resolved spontaneously. No product-related adverse events were noted during the study period. CONCLUSION: Injectable PDLLA delivered via laser-induced microjet injection demonstrated promising efficacy in improving rosacea symptoms and skin quality for up to 22 weeks without significant adverse effects. Larger randomized controlled trials are needed to confirm these findings and evaluate long-term safety and sustainability of outcomes.
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Background: Rosacea, a recurring dermatological disorder, demands effective therapeutic approaches. Traditional Chinese medicine, particularly Liangxue Siwu Decoction (LXSWD), has shown promise in managing inflammatory skin diseases, such as rosacea. This study focuses on uncovering LXSWD's specific effects on the inflammatory symptoms of rosacea. Objective: Our research investigates LXSWD's therapeutic effectiveness in rosacea treatment and delves into its underlying mechanisms. Methods: Network pharmacology was utilized to identify LXSWD's key components and their targets in rosacea management, which were then validated by molecular docking. An in vivo rosacea-like model in LL-37-induced mice was developed, subdividing them into control, model, and LXSWD groups. The LXSWD group received oral administration (25.0 g/kg/day) for six days before model induction. Post-treatment evaluations included skin tissue analyses to verify our network pharmacology predictions. Results: Key active ingredients in LXSWD, such as quercetin, kaempferol, and luteolin, were identified alongside central target proteins like TNF and MMPs. Our molecular docking study confirmed the interactions between these ingredients and targets. Analyses through GO and KEGG pathways indicated LXSWD's role in mitigating inflammation, particularly influencing the TNF and IL-17 pathways. LXSWD treatment in vivo markedly alleviated LL-37-induced symptoms in mice, showing a marked reduction in inflammatory cytokines (p < 0.05) and modulation of crucial genes (p < 0.05). These results, supported by immunofluorescence analysis and Western blot, underline the modulatory effects of LXSWD on MMPs, offering significant protection against rosacea's inflammation alterations (p < 0.05). Conclusion: Integrating network pharmacology, molecular docking, and in vivo experiments, this study elucidates LXSWD's potential mechanisms in rosacea treatment. It offers a novel theoretical framework for its clinical use in managing rosacea.
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BACKGROUND: Atopic dermatitis (AD), psoriasis (PSO), rosacea, and other related immune skin diseases are affected by multiple complex factors such as genetic and microbial components. This research investigates the causal relationships between specific skin microbiota and these diseases by using Mendelian randomization (MR), and Bayesian weighted Mendelian randomization (BWMR). METHODS: We utilized genome-wide association study (GWAS) data to analyze the associations between various skin bacteria and three dermatological diseases. Single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) in MR methods, including inverse variance weighted (IVW), and MR Egger. BWMR was employed to validate results and address pleiotropy. RESULTS: The IVW analysis identified significant associations between specific skin microbiota and dermatological diseases. ASV006_Dry, ASV076_Dry, and Haemophilus_Dry were significantly positively associated with AD, whereas Kocuria_Dry was negatively associated. In PSO, ASV005_Dry was negatively associated, whereas ASV004_Dry, Rothia_Dry, and Streptococcus_Moist showed positive associations. For rosacea, ASV023_Dry was significantly positively associated, while ASV016_Moist, Finegoldia_Dry, and Rhodobacteraceae_Moist were significantly negatively associated. These results were corroborated by BWMR analysis. CONCLUSION: Bacterial species such as Finegoldia, Rothia, and Streptococcus play crucial roles in the pathogenesis of AD, PSO, and rosacea. Understanding these microbial interactions can aid in developing targeted treatments and preventive strategies, enhancing patient outcomes and quality of life.
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Teorema de Bayes , Dermatite Atópica , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Microbiota , Polimorfismo de Nucleotídeo Único , Humanos , Microbiota/genética , Dermatite Atópica/microbiologia , Dermatite Atópica/genética , Pele/microbiologia , Rosácea/microbiologia , Rosácea/genética , Dermatopatias/microbiologia , Dermatopatias/genética , Psoríase/microbiologia , Psoríase/genéticaRESUMO
Rosacea is a chronic inflammatory disorder primarily affecting the facial skin, prominently involving the cheeks, nose, chin, forehead, and periorbital area. Cutaneous manifestations encompass persistent facial erythema, phymas, papules, pustules, telangiectasia, and flushing. The pathogenesis of rosacea is associated with various exacerbating or triggering factors, including microbial infestation, temperature fluctuations, sunlight exposure, physical exertion, emotional stress, consumption of hot beverages and spicy foods, and exposure to airborne pollen. These environmental factors interact with genetic predispositions in the development of rosacea. The roles of the lipophilic microbiome, ultraviolet radiation, nociceptive responses, and vascular alterations have been proposed as significant factors in the pathogenesis. These insights contribute to understanding the anatomical specificity of facial involvement and the progressive nature of rosacea. East Asian skin, predominantly classified as Fitzpatrick skin phototypes III to IV, is characterized by relatively diminished skin barrier function and increased sensitivity to irritants. Airborne pollen exposure may particularly act as a trigger in East Asian individuals, possibly mediated through toll-like receptors. The lack of specificity in objective clinical and histopathological findings leads to diagnostic challenges for individuals with colored skin, including East Asians, particularly when erythema is the sole objective manifestation. An alternative diagnostic scheme may thus be necessary. A diagnostic approach emphasizing vascular manifestations and nociceptive symptoms potentially holds promise for individuals with darker skin tones. More research focusing on potential variations in skin physiology across different racial groups is essential to establish more effective diagnostic schemes applicable to both dark and light skin colors.
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Rosácea , Humanos , População do Leste Asiático , Predisposição Genética para Doença , Pólen/efeitos adversos , Pólen/imunologia , Rosácea/diagnóstico , Rosácea/etiologia , Rosácea/fisiopatologia , Pele/patologia , Pigmentação da PeleRESUMO
Objective: We sought to evaluate changes in microbiome biodiversity and physical properties of the skin after eight weeks of once-daily topical microencapsulated benzoyl peroxide (E-BPO) compared to vehicle cream in participants with rosacea. Methods: This was a randomized, double-blind, crossover, single-center, vehicle-controlled evaluation of E-BPO on the skin microbiome in rosacea. Participants had facial rosacea with global severity of 3 or 4 on the Investigator Global Assessment (IGA) scale. In the Treatment 1-2 group, participants received E-BPO for eight weeks then switched to vehicle cream for four weeks. In the Treatment 2-1 group, participants received vehicle cream for eight weeks, then E-BPO for four weeks. Results: Thirty-one participants were enrolled and randomly assigned to either group. Demographic characteristics were comparable between the treatment groups. After eight weeks of E-BPO treatment, there was a marked reduction in the relative abundance of Staphylococcus accompanied by an increase in Cutibacterium. At the species level, there was an increase in the relative abundance of C. acnes and a decrease in abundance of S. epidermidis. No noticeable difference was detected at the genus or species level at Week 8 in the 2-1 group. Sebum level, IGA, lesion counts, facial erythema, and inflammatory scores were improved with E-BPO versus vehicle cream. Adverse events were mild or moderate in severity. Limitations: The study included a small number of subjects and only surface-swabs were used for microbiome sampling. Conclusion: E-BPO shifted the skin microbiome in rosacea and demonstrated improvements in clinical symptoms and skin physical properties and a well-tolerated safety profile. US National Library of Medicine; Trial ID: NCT05675501]; URL: clinicaltrials.gov.
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Numerous recent evidence highlights epidemiological connections between rosacea and metabolic disorders. However, the precise path through which metabolic factors impact rosacea risk is still unclear. Therefore, this study aims to investigate the role of adiponectin, a crucial adipokine that regulates metabolic homeostasis, in the pathogenesis of rosacea. We elucidated a detrimental feedback loop between rosacea-like skin inflammation and decreased levels of skin adiponectin. To elaborate, rosacea lesional skin exhibits diminished adiponectin expression compared with nonlesional areas in the same patients. Induction of rosacea-like inflammation reduced adiponectin levels in the skin by generating inflammatory cytokines that suppress adiponectin production from subcutaneous adipocytes. Conversely, complete depletion of adiponectin exacerbated rosacea-like features in the mouse model. Mechanistically, adiponectin deficiency led to heightened S6 phosphorylation, a marker of the mTORC1 signaling pathway, in the epidermis. Adiponectin significantly inhibited S6 phosphorylation in cultured keratinocytes. Notably, replenishing adiponectin whole protein or topically applying an agonist for adiponectin receptor 1 successfully improved rosacea-like features in mice. This study contributes to understanding the role of adiponectin in skin inflammation associated with rosacea pathophysiology, suggesting that restoring adiponectin function in the skin could be a potential therapeutic strategy.
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BACKGROUND/ OBJECTIVES: Rosacea is a common chronic inflammatory skin disorder. Endocrinedisrupting chemicals (EDC) are toxic substances, that may gain entry through the skin and subsequently interfere with hormonal and immune functions. Bisphenol A (BPA) and pentachlorophenol sodium (PCS) are two of these EDCs, incriminated in the pathogenesis of certain inflammatory skin disorders. We aimed to test the hypothesis that exposure to BPA and PCS might be involved in the pathogenesis of rosacea. METHODS: This prospective cross-sectional study involved 34 patients with rosacea (18F/16 M; mean age 48.5 ± 11 years) and 34 age and sex-matched healthy controls (20 F/14 M; mean age 48.2 ± 10.2 years). Main anthropometric measures, fasting plasma glucose (FPG), insulin, HOMA-IR, lipids, C-reactive protein (CRP), BPA, and PCS levels were quantified and recorded. RESULTS: Serum CRP (9.6 ± 3.4 vs. 3.7 ± 1.6 mg/L, respectively, p0.05 for all). Serum BPA levels were 55.8 ± 14.4 and 51.9 ± 19.2 ng/mL, and PCS levels were 63.3 ± 45.9 ng/mL and 68.6 ± 40.8 ng/mL for patients and healthy controls, respectively. There was no significant difference in BPA and PCS levels between the two groups (p > 0.05 for both). No significant association was found among HOMAIR, CRP, BPA, and PCS levels (p > 0.05 for all). CONCLUSIONS: Although the present study fails to provide presumptive evidence for the role of BPA and PCS in rosacea, the question as to other EDCs might be involved in its etiopathogenesis remains. This hypothesis requires confirmation in large-scale future prospective trials.
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Compostos Benzidrílicos , Pentaclorofenol , Fenóis , Rosácea , Humanos , Compostos Benzidrílicos/sangue , Compostos Benzidrílicos/efeitos adversos , Pessoa de Meia-Idade , Masculino , Feminino , Rosácea/induzido quimicamente , Rosácea/sangue , Pentaclorofenol/sangue , Adulto , Estudos Transversais , Estudos Prospectivos , Disruptores Endócrinos/sangue , Disruptores Endócrinos/efeitos adversos , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , GlicemiaRESUMO
Background Rosacea is a chronic inflammatory disease of the skin characterised by facial erythema, oedema, telangiectasias, papules, pustules and nodules. There is a paucity of effective therapeutic modalities for the management of rosacea. Intense Pulsed Light (IPL), a modality in which flash lamps installed in an optical treatment device (head or tip) with mirrors to reflect light, has in recent times gained popularity in the management of this condition. Aim This systematic review aims to evaluate the efficacy, safety and adverse effects of IPL treatment for rosacea. Methods This systematic review was conducted in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-Analysis. The electronic databases searched were Medline, PubMed and Scopus databases. The Risk of bias in non-randomised studies of interventions (ROBINS-I) and risk-of-bias tools for randomised trials (RoB-2) was employed to assess the risk of bias. Results Of a total of 233 articles retrieved from Medline, Scopus and PubMed databases, 14 studies qualified for final analysis. The studies included patients with Fitzpatrick skin types I to IV, with ages ranging from 15 to 78 years. Although the included studies showed heterogeneity between the parameters used, most studies demonstrated positive effects of IPL treatment on telangiectasia and erythema in rosacea and that the adverse effects presented were transitory. Limitation The methodological quality of the included studies was poor. Conclusion Although most studies showed the efficacy of IPL in the treatment of rosacea, the poor quality of the studies was of concern.
Assuntos
Terapia de Luz Pulsada Intensa , Rosácea , Humanos , Terapia de Luz Pulsada Intensa/efeitos adversos , Terapia de Luz Pulsada Intensa/métodos , Rosácea/terapia , Resultado do TratamentoRESUMO
Rosacea is a chronic dermatological condition that currently lacks a clear treatment approach due to an uncomprehensive knowledge of its pathogenesis. The main obstacle lies in understanding its etiology and the mode of action of the different drugs used. This study aims to clarify these aspects by employing drug repositioning. Using an in silico approach, we performed a transcriptomic analysis comparing samples from individuals with diverse types of rosacea to those from healthy controls to identify genes deregulated in this disease. Subsequently, we realized molecular docking and molecular dynamics studies to assess the binding affinity of drugs currently used to treat rosacea and drugs that target proteins interacting with, and thus affecting, proteins deregulated in rosacea. Our findings revealed that the downregulation of SKAP2 and upregulation of S100A7A in rosacea, could be involved in the pathogenesis of the disease. Furthermore, considering the drugs currently used for rosacea management, we demonstrated stable interactions between isotretinoin and BFH772 with SKAP2, and permethrin and PAC-14028 with S100A7A. Similarly, considering drugs targeting SKAP2 and S100A7A interactome proteins, we found that pitavastatin and dasatinib exert stable interactions with SKAP2, and lovastatin and tirbanibulin with S100A7A. In addition, we determine that the types of bonds involved in the interactions were different in SKAP2 from S100A7A. The drug-SKAP2 interactions are hydrogen bonds, whereas the drug-S100A7A interactions are of the hydrophobic type. In conclusion, our study provides evidence for the possible contribution of SKAP2 and S100A7A to rosacea pathology. Furthermore, it provides significant information on the molecular interactions between drugs and these proteins, highlighting the importance of considering structural features and binding interactions in the design of targeted therapies for skin disorders such as rosacea.