Figure 3 - uploaded by Hye One Kim
Content may be subject to copyright.
Symptoms and signs in neurogenic rosacea (NR) versus erythematotelangiectatic rosacea (ETR) (*P < 0.05).
Source publication
Rosacea with severe neurological symptoms such as burning and stinging is often not treated effectively by conventional therapies. The aim of this study was to investigate the clinical characteristics of Korean rosacea patients with prominent neurological symptoms. The demographic features, medical history, clinical manifestations and treatment mod...
Context in source publication
Citations
... Research has suggested the involvement of serotonin in the ushing process of spontaneous midgut carcinoid tumors [30]. Studies have reported improvements in rosacea patients with severe neurological symptoms, clinical manifestations, and cutaneous signs through the administration of anticonvulsants like gabapentin or pregabalin, as well as antidepressants such as tianeptine, diazepam, or selective serotonin reuptake inhibitors (SSRIs) like duloxetine [31][32][33]. Currently, research exploring the association between blood metabolite levels and rosacea is limited. ...
Background
Rosacea is a facial skin condition characterized by inflammation and redness. Metabolic dysfunction has emerged as a significant contributor to the pathogenesis and progression of rosacea. However, the precise causal impact of blood metabolites on the development of rosacea remains uncertain.
Methods
Utilizing a genome-wide association dataset, we conducted two-sample Mendelian randomization (MR) analyses to investigate the causal relationship between 486 blood metabolites and rosacea. Our study included two distinct rosacea datasets, each representing different phenotypic characteristics. One dataset comprised cases identified by International Classification of Diseases (ICD) 10 diagnosis codes for rosacea (ROSA), consisting of four subtypes: Perioral dermatitis, Rhinophyma, Other rosacea, and Unspecified rosacea. The other dataset included cases defined by ICD10 diagnosis codes for Other and Unspecified rosacea (OUR), encompassing two subtypes: Other rosacea and Unspecified rosacea. Causality assessment was primarily conducted using the random inverse variance weighted (IVW) method, complemented by MR-Egger and weighted median methods. Sensitivity analyses were performed employing the Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Reverse MR, linkage disequilibrium regression score (LDSC), and colocalization analyses were conducted to address potential issues of reverse causation, genetic correlation, and linkage disequilibrium (LD). Additionally, multivariable Mendelian randomization (MVMR) analysis was employed to evaluate the independent effects of metabolites on rosacea while accounting for potential confounders. Furthermore, metabolic pathway analysis was performed using the web-based platform MetaboAnalyst 5.0. Statistical analyses were conducted using R software, and the STROBE-MR checklist was utilized to guide the reporting of our MR study.
Results
Our findings identified seven metabolites with causal effects on ROSA and 14 metabolites with causal effects on OUR. Reverse MR analysis provided no evidence supporting causal effects of rosacea on these metabolites. Multivariable MR analysis established the independent causal effects of various metabolites on rosacea. Colocalization analysis unveiled a presence of shared genetic variants occurring concurrently in both metabolites and rosacea. Moreover, analysis of metabolic pathways indicated the potential involvement of the arginine and proline metabolism pathway, as well as the caffeine metabolism pathway, in the underlying mechanism of rosacea pathogenesis.
Conclusion
Our study provides a comprehensive atlas that elucidates the causal relationships between plasma metabolites and rosacea. Furthermore, we have identified two pivotal metabolic pathways implicated in the pathogenesis of rosacea. These findings offer insights into potential predictive biomarkers and therapeutic targets for the treatment of rosacea.
... 2 Other treatments are surgical intervention (sympathectomy), botulinum toxin, and local cold stimuli. 4 Few NR cases are described, and there still exist gaps in its management. Our patient had a successful response to neuromodulators and IPL without side effects. ...
... Two senior dermatologists classified the clinical types of rosacea as NR and non-NR according to the criteria provided by Kim et al 6 and further classified the non-NR cases as ETR, PPR, or PHR according to the guidelines for rosacea. 14 Erythema distribution was divided into the peripheral type, in which erythema only affected the cheeks ( Figure 1A-F), and the centrofacial type, in which erythema also affected the forehead, nose, and chin ( Figure 1G-L), as reported in the literature. ...
... 14 Erythema distribution was divided into the peripheral type, in which erythema only affected the cheeks ( Figure 1A-F), and the centrofacial type, in which erythema also affected the forehead, nose, and chin ( Figure 1G-L), as reported in the literature. 6 The severity of rosacea was evaluated according to subjective scoring systems, such as the standard grading system (SGS) for rosacea, 15 clinician's erythema assessment (CEA), 16 and investigator's global assessment (IGA), 17 the details of which are provided in Tables S1-S3. Dermoscopic Examination and Scoring of the Capillary-Related Characteristics Dermoscopic images were obtained at the bilateral earlobes and auricles using a handheld dermoscope (DermLite ® DL4, 3 Gen Inc., San Juan Capistrano, CA, USA) in contact mode with polarized light. ...
Background and Aim
Clinical manifestations of rosacea include transient or persistent facial erythema, telangiectasia, papules, and pustules. The existing assessment tools primarily evaluate the facial area to assess the severity of rosacea. However, in addition to the face, telangiectasia, erythema, and flushing can occur in the ear. Here, we investigated the correlation between the dermoscopic characteristics of capillaries in the earlobe and auricle and the types and severity of rosacea.
Materials and Methods
Experienced dermatologists evaluated the clinical type, medical history, severity, and distribution pattern of facial erythema. The clinical severity of rosacea was assessed using the standard grading system (SGS), clinician’s erythema assessment (CEA), and investigator’s global assessment (IGA). Relationships of the clinical types and severity with the dermoscopic characteristics of capillaries in the earlobe and auricle were further analyzed.
Results
In total, 145 patients with rosacea were enrolled in this study. We found that SGS, CEA, and IGA correlated well with the dermoscopic features of capillaries in the earlobe (R = 0.357, 0.357, and 0.314, respectively) (p < 0.001) and auricle (R = 0.423, 0.443, and 0.374, respectively) (p < 0.001). However, there was no significant correlation between the features and types of rosacea.
Conclusion
The dermoscopic characteristics of capillaries in the earlobe and auricle can be used as indicators of the clinical severity of rosacea, regardless of the clinical subtype.
... Neurogenic rosacea generally does not respond well to traditional therapy. However, drugs used to treat SFN, such as TCAs, pregabalin, gabapentin, and duloxetine, are effective in treating neurogenic rosacea (16). Furthermore, pulsed dye lasers and endoscopic thoracic sympathectomy have been used to control facial flushing (17). ...
... Strong and universally accepted evidence suggests a potential pathogenesis of neurogenic dysregulation. For example, triggers (stress, spicy food and heat [66]) could be aggravating factors for rosacea. Comorbidity research also suggests a close relationship between neurogenic dysregulation and rosacea, such as psychosis (e.g., anxiety, depression) and neurological disorders (e.g., Parkinson's disease, Alzheimer's disease). ...
Background
Rosacea is a common and complex chronic inflammatory skin disorder, the pathophysiology and etiology of which remain unclear. Recently, significant new insights into rosacea pathogenesis have enriched and reshaped our understanding of the disorder. A systematic analysis based on current studies will facilitate further research on rosacea pathogenesis.
Objective
To establish an international core outcome and knowledge system of rosacea pathogenesis and develop a challenge, trend and hot spot analysis set for research and clinical studies on rosacea using bibliometric analysis and data mining.
Methods
A search of the WoS, and PubMed, MEDLINE, Embase and Cochrane collaboration databases was conducted to perform visual bibliometric and data analysis.
Results
A total of 2,654 studies were used for the visualization and 302 of the 6,769 outcomes for data analysis. It reveals an increased trend line in the field of rosacea, in which its fast-growing pathogenesis attracted attention closely related to risk, comorbidity and therapeutic strategies. The rosacea pathogenesis has undergone the great development on immunology, microorganisms, genes, skin barriers and neurogenetics. The major of studies have focused on immune and microorganisms. And keyword visualization and data analyses demonstrated the cross-talk between cells or each aspect of pathogenesis, such as gene-gene or gene-environment interactions, and neurological mechanisms associated with the rosacea phenotype warrant further research.
Limitations
Inherent limitations of bibliometrics; and reliance on research and retrospective studies.
Conclusions
The understanding of rosacea's pathogenesis has been significantly enhanced with the improved technology and multidisciplinary integration, but high-quality, strong evidence in favor of genomic and neurogenic requires further research combined with a better understanding of risks and comorbidities to guide clinical practice.
... 2 Other treatments are surgical intervention (sympathectomy), botulinum toxin, and local cold stimuli. 4 Few NR cases are described, and there still exist gaps in its management. Our patient had a successful response to neuromodulators and IPL without side effects. ...
Background: Rosacea is a common facial dermatological disease characterized by central erythema and flushing. It is more common in females than males, with a prevalence of approximately 5.5% in the global population and 2.4% among all dermatological outpatients. In 2002, the National Rosacea Society Expert Committee suggested a subtype-based standardized classification system. The most common subtype of rosacea is erythematotelangiectatic rosacea (ETR), followed by papulopustular rosacea (PPR), phymatous rosacea, and ocular rosacea.Current Concepts: Rosacea is characterized by hyperactive innate and neurovascular immune reactions, which lead to altered adaptive immune reactions and hyperreactive inflammation. In 2017, the National Rosacea Society Expert Committee developed a phenotype-based classification system. The diagnostic features include persistent centrofacial erythema and phymatous changes. ETR is associated with sensitive skin and may have a debilitating psychological impact, often leading to psychological conditions such as depression and anxiety. Doxycycline and minocycline are considered the gold-standard oral treatments for rosacea. Topical ivermectin and metronidazole are commonly used to treat PPR. Low-dose isotretinoin is an alternative to avoid long-term chronic antibiotic use. Carvedilol and propranolol are off-label medications used to reduce persistent facial flushing and erythema in rosacea. Some alpha-adrenergic receptor agonists have also been approved for the treatment of persistent erythema in rosacea.Discussion and Conclusion: Rosacea exhibits multiple phenotypic manifestations. The treatment approach is individualized for each patient through the customization of multimodal treatments, including the avoidance of trigger factors and the assessment of comorbid diseases.
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.
Rosacea is a common chronic inflammatory skin condition. It mainly affects the cheeks, nose, chin, and forehead, causing flushing or transient erythema, persistent erythema, phymatous changes, papules, pustules, and telangiectasias, and the eyes may also be affected by rosacea. Rosacea is more common in women than in men and can start at any age. Rosacea affects both fair-skinned and darker-skinned people. Physical changes in the face due to rosacea can cause embarrassment, leading to reduced quality of life and self-esteem. Rosacea has several triggers, and its pathogenesis involves multiple factors, which means there are several treatment options, and these options can be combined. A patient’s clinical findings and symptoms will help a doctor to diagnose and classify the condition. Treatment options may include lifestyle changes, topical medications, systemic antibiotics and light-based therapy. The best approach is to tailor the treatment to the individual’s condition and preferences. The aim of treatment is to manage symptoms and prevent the progression of the disease.
