Materiały źródłowe

• #1 Rosacea: Epidemiology, pathogenesis, and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5821167/

  Rosacea’s exact pathogenesis is still unclear. […] Various environmental stimuli and endogenous factors have been shown to stimulate an augmented innate immune response and aberrant neurovascular signaling. […] Accumulating evidence points to activation of cellular pattern recognition receptors like the toll like receptor (TLR) 2 and transient receptor potential (TRP) ion channels, and release of inflammatory mediators within the skin as key steps that lead to the clinical manifestation of rosacea. […] The exact molecular mechanisms involved in rosacea’s pathophysiology are unknown, and a multifactorial etiology with a genetic preposition is likely. […] There is accumulating evidence that triggers such as microbes, ultraviolet (UV) radiation, nutrition, extremes of temperatures, (skin) barrier disruption, psychosocial stress, and hormones may stimulate an augmented innate immune response and/or neurovascular dysregulation.

• #2 Rosacea: Epidemiology, pathogenesis, and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5821167/

  In addition to these innate immune receptors and molecules, neuronal dysregulation, including vascular dysfunction, and release of proinflammatory neuropeptides have been shown to contribute to rosacea’s pathophysiology. […] Activation of TRP results in release of vasoactive neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating polypeptide (PACAP), which were elevated in rosacea. […] Rosacea is an inflammatory skin disease characterized by immune dysfunction and neurovascular dysregulation.

• #3 Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

  https://www.mdpi.com/2227-9059/11/8/2153

  Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. […] Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. […] 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. […] Recent studies have also highlighted the role of microbial dysbiosis, neuroimmune interactions, metabolic dysfunction, and sebaceous gland dysregulation in the development of rosacea.

• #4 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  Rosacea is a chronic inflammatory condition of which there is no cure. The pathogenesis of rosacea is likely multifactorial, involving genetic and environmental contributions. Current understanding suggests that pro-inflammatory pathways involving cathelicidins and inflammasome complexes are central to rosacea pathogenesis. […] The pathogenesis of rosacea likely involves a complex interplay between several factors and pathways, including neurovascular dysregulation and innate immune system dysregulation involving cathelicidins and inflammasomes. […] Rosacea pathogenesis is likely to be multifaceted with neurovascular dysregulation being a major component. […] Key to the dysregulation of neurovascular processes are the transient receptor potential channels (TRPs), which are nonselective Ca2+ channels with sensory and signalling roles.

• #5

  https://scholars.duke.edu/publication/1620275

  Rosacea is a chronic inflammatory skin disorder that is not fully understood but involves the complex interplay of genetic factors, immune dysregulation, neurovascular dysregulation, presence of microorganisms, and environmental factors. Increased activation of the immune system occurs through multiple stimuli, including increased levels of cathelicidin and kallikrein 5, Toll-like receptor 2, matrix metalloproteinases, and mast cells within the skin. Their effects are enhanced by the presence of microorganisms and external triggers, such as UV radiation.

• #6 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Rosacea has several triggers, and its pathogenesis involves multiple factors, which means there are several treatment options, and these options can be combined. […] The pathogenesis of rosacea is complex and involves a variety of factors that can trigger both inflammatory and vascular responses. […] Rosacea skin has higher levels of TLR-2, KLK-5, cathelicidin, and matrix metalloproteinases (MMPs) than healthy skin. […] In rosacea patients, keratinocytes produce pro-inflammatory cytokines and chemokines when TLR-2 is activated by triggering factors, leading to the increased expression of pro-inflammatory cytokine genes such as IL (interleukin)-8, IL-1b, and TNF (tumor necrosis factor)-α. […] TLR-2 was found to positively mediate a pro-inflammatory response following UV-B irradiation in an in vivo study.

• #7 Rosacea: Symptoms, Causes, and Management – DermNet

  https://dermnetnz.org/topics/rosacea

  Rosacea is a chronic inflammatory skin condition predominantly affecting the central face and most often starts between the age of 30-60 years. […] The pathogenesis of rosacea is thought to be multifactorial and includes: Genetic susceptibility, Altered microbiome of the skin and gut, Neurocutaneous mechanisms, Impaired skin barrier. […] Dysregulation of the immune response may lead to excessive inflammation, vasodilation, lymphatic dilatation, and angiogenesis. […] In the skin of patients with rosacea, there is increased expression and activity of toll-like receptor 2, cathelicidins, kallikrein 5, and mast cells. […] The result is an exaggerated innate immune reaction to the initial trigger. […] Dominant T-helper (Th)1/Th17 gene expression in all features of rosacea. […] Increased Th17 expression can increase levels of cathelicidin LL-37 in keratinocytes and drive further inflammation. […] The most significant environmental trigger is UV radiation; affected skin is more sensitive to exposure. UV radiation can damage the dermis and increase skin inflammation.

• #8 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Rosacea has several triggers, and its pathogenesis involves multiple factors, which means there are several treatment options, and these options can be combined. […] The pathogenesis of rosacea is complex and involves a variety of factors that can trigger both inflammatory and vascular responses. […] Rosacea skin has higher levels of TLR-2, KLK-5, cathelicidin, and matrix metalloproteinases (MMPs) than healthy skin. […] In rosacea patients, keratinocytes produce pro-inflammatory cytokines and chemokines when TLR-2 is activated by triggering factors, leading to the increased expression of pro-inflammatory cytokine genes such as IL (interleukin)-8, IL-1b, and TNF (tumor necrosis factor)-α. […] TLR-2 was found to positively mediate a pro-inflammatory response following UV-B irradiation in an in vivo study.

• #9 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  IL-8 induces neutrophil chemotaxis in the skin, resulting in the release of proteases such as cathepsin G, elastase, and protease-3. […] In addition, IL-b and TNF-α also act as the angiogenic factor and vascular endothelial growth factor (VEGF) and may cause the vascular changes seen in rosacea. […] Cathelicidin, an antimicrobial protein, is found in the lamellar body of keratinocytes and the granules of neutrophils. […] The LL-37 peptide in rosacea skin differs from healthy skin by having shorter fragment forms. […] These fragments have been implicated in symptoms characteristic of rosacea, including erythema, vasodilatation, flushing, and telangiectasia. […] MMPs indirectly influence the pathogenesis of rosacea by activating the preproenzyme form of KLK5 after cleavage with MMP-9.

• #10 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  Cathelicidins is a family of antimicrobial peptides expressed in the skin in many vertebrates and have been implicated in rosacea pathogenesis. […] Activation of TLR2 leads to the production of cathelicidin (LL-37) and cytokines in the pro-inflammatory cathelicidins pathway are described in more detail in this article. […] Human cathelicidin antimicrobial peptide (CAMP) is intimately involved in the pathogenesis of rosacea, with both immunomodulatory and angiogenic properties. […] The increased abundance of CAMP and KLK5 activity has been shown to increase the levels of bioactive cathelicidin fragments in rosacea patients. […] Inflammasomes are multiprotein complexes of the innate immune system that trigger inflammatory responses through the activation of caspase-1. […] NLRP3, caspase-1, and IL-1 are known to be elevated in rosacea patients, implicating the inflammasome in rosacea pathogenesis.

• #11 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  Cathelicidins is a family of antimicrobial peptides expressed in the skin in many vertebrates and have been implicated in rosacea pathogenesis. […] Activation of TLR2 leads to the production of cathelicidin (LL-37) and cytokines in the pro-inflammatory cathelicidins pathway are described in more detail in this article. […] Human cathelicidin antimicrobial peptide (CAMP) is intimately involved in the pathogenesis of rosacea, with both immunomodulatory and angiogenic properties. […] The increased abundance of CAMP and KLK5 activity has been shown to increase the levels of bioactive cathelicidin fragments in rosacea patients. […] Inflammasomes are multiprotein complexes of the innate immune system that trigger inflammatory responses through the activation of caspase-1. […] NLRP3, caspase-1, and IL-1 are known to be elevated in rosacea patients, implicating the inflammasome in rosacea pathogenesis.

• #12 A Cosmetic Regimen Formulated to Address the Multi-Modal Pathogenesis of Rosacea Demonstrates Efficacy for Treating Facial Redness and Skin’s Appearance – JDDonline – Journal of Drugs in Dermatology

  https://jddonline.com/articles/cosmetic-regimen-formulated-address-multi-modal-pathogenesis-of-rosacea-demonstrates-efficacy-treating-facial-redness-skins-appearance-S1545961624P8460X/

  Rosacea is a multifactorial condition that involves a complex interaction between genetics, immune system dysregulation, microorganisms, UV light, neurovascular dysregulation, and impaired barrier function. […] Dysregulation of the innate immune system plays a key role in the pathogenesis of rosacea. It occurs due to the activation of toll-like receptor 2 (TLR2) triggering the production of antimicrobial peptides (AMPs) including cathelicidins. […] The stimulus for TLR2 activation remains elusive although chitin from Demodex mites and Demodex-associated Bacillus oleronius have been implicated. […] Cathelicidins are cleaved by the serine protease kallikrein 5 (KLK5) which is overexpressed in the facial skin of rosacea patients. KLK5 cleaves the precursor protein to its active peptide form LL-37 and various other proteolytic fragments. […] These proteolytic fragments influence processes including cytokine release, angiogenesis, leukocyte chemotaxis, and extracellular matrix components.

• #13 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  IL-8 induces neutrophil chemotaxis in the skin, resulting in the release of proteases such as cathepsin G, elastase, and protease-3. […] In addition, IL-b and TNF-α also act as the angiogenic factor and vascular endothelial growth factor (VEGF) and may cause the vascular changes seen in rosacea. […] Cathelicidin, an antimicrobial protein, is found in the lamellar body of keratinocytes and the granules of neutrophils. […] The LL-37 peptide in rosacea skin differs from healthy skin by having shorter fragment forms. […] These fragments have been implicated in symptoms characteristic of rosacea, including erythema, vasodilatation, flushing, and telangiectasia. […] MMPs indirectly influence the pathogenesis of rosacea by activating the preproenzyme form of KLK5 after cleavage with MMP-9.

• #14 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  IL-8 induces neutrophil chemotaxis in the skin, resulting in the release of proteases such as cathepsin G, elastase, and protease-3. […] In addition, IL-b and TNF-α also act as the angiogenic factor and vascular endothelial growth factor (VEGF) and may cause the vascular changes seen in rosacea. […] Cathelicidin, an antimicrobial protein, is found in the lamellar body of keratinocytes and the granules of neutrophils. […] The LL-37 peptide in rosacea skin differs from healthy skin by having shorter fragment forms. […] These fragments have been implicated in symptoms characteristic of rosacea, including erythema, vasodilatation, flushing, and telangiectasia. […] MMPs indirectly influence the pathogenesis of rosacea by activating the preproenzyme form of KLK5 after cleavage with MMP-9.

• #15 Pathogenesis of Rosacea | Encyclopedia MDPI

  https://encyclopedia.pub/entry/51272

  In addition, IL-b and TNF-α also act as the angiogenic factor and vascular endothelial growth factor (VEGF) and may cause the vascular changes seen in rosacea. […] Cathelicidin, an antimicrobial protein, is found in the lamellar body of keratinocytes and the granules of neutrophils. […] The LL-37 peptide in rosacea skin differs from healthy skin by having shorter fragment forms. […] These fragments have been implicated in symptoms characteristic of rosacea, including erythema, vasodilatation, flushing, and telangiectasia. […] MMPs indirectly influence the pathogenesis of rosacea by activating the preproenzyme form of KLK5 after cleavage with MMP-9. […] A study also suggested that mast cell degranulation in individuals with rosacea results in increased levels of MMP-9 and LL-37. […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses.

• #16 Pathogenesis of Rosacea | Encyclopedia MDPI

  https://encyclopedia.pub/entry/51272

  In addition, IL-b and TNF-α also act as the angiogenic factor and vascular endothelial growth factor (VEGF) and may cause the vascular changes seen in rosacea. […] Cathelicidin, an antimicrobial protein, is found in the lamellar body of keratinocytes and the granules of neutrophils. […] The LL-37 peptide in rosacea skin differs from healthy skin by having shorter fragment forms. […] These fragments have been implicated in symptoms characteristic of rosacea, including erythema, vasodilatation, flushing, and telangiectasia. […] MMPs indirectly influence the pathogenesis of rosacea by activating the preproenzyme form of KLK5 after cleavage with MMP-9. […] A study also suggested that mast cell degranulation in individuals with rosacea results in increased levels of MMP-9 and LL-37. […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses.

• #17 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  Cathelicidins is a family of antimicrobial peptides expressed in the skin in many vertebrates and have been implicated in rosacea pathogenesis. […] Activation of TLR2 leads to the production of cathelicidin (LL-37) and cytokines in the pro-inflammatory cathelicidins pathway are described in more detail in this article. […] Human cathelicidin antimicrobial peptide (CAMP) is intimately involved in the pathogenesis of rosacea, with both immunomodulatory and angiogenic properties. […] The increased abundance of CAMP and KLK5 activity has been shown to increase the levels of bioactive cathelicidin fragments in rosacea patients. […] Inflammasomes are multiprotein complexes of the innate immune system that trigger inflammatory responses through the activation of caspase-1. […] NLRP3, caspase-1, and IL-1 are known to be elevated in rosacea patients, implicating the inflammasome in rosacea pathogenesis.

• #18 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  Cathelicidins is a family of antimicrobial peptides expressed in the skin in many vertebrates and have been implicated in rosacea pathogenesis. […] Activation of TLR2 leads to the production of cathelicidin (LL-37) and cytokines in the pro-inflammatory cathelicidins pathway are described in more detail in this article. […] Human cathelicidin antimicrobial peptide (CAMP) is intimately involved in the pathogenesis of rosacea, with both immunomodulatory and angiogenic properties. […] The increased abundance of CAMP and KLK5 activity has been shown to increase the levels of bioactive cathelicidin fragments in rosacea patients. […] Inflammasomes are multiprotein complexes of the innate immune system that trigger inflammatory responses through the activation of caspase-1. […] NLRP3, caspase-1, and IL-1 are known to be elevated in rosacea patients, implicating the inflammasome in rosacea pathogenesis.

• #19 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  The enhanced activity of IL-1 results in upregulation of other pro-inflammatory cytokines including IL-8 and tumor necrosis factor (TNF)-, angiogenesis, and chemotaxis of neutrophils. […] While the bulk of rosacea pathogenesis centres around vascular hyperactivity and dysregulation of the innate immune system, evidence of adaptive immune involvement is emerging. […] Rosacea is a chronic inflammatory condition that likely involves vascular hyperactivity, cathelicidins, and inflammasome complex activation. […] Differences in genetics and environmental factors may alter the pathogenesis process and contribute to the differences observed in clinical presentation and severity.

• #20 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  The enhanced activity of IL-1 results in upregulation of other pro-inflammatory cytokines including IL-8 and tumor necrosis factor (TNF)-, angiogenesis, and chemotaxis of neutrophils. […] While the bulk of rosacea pathogenesis centres around vascular hyperactivity and dysregulation of the innate immune system, evidence of adaptive immune involvement is emerging. […] Rosacea is a chronic inflammatory condition that likely involves vascular hyperactivity, cathelicidins, and inflammasome complex activation. […] Differences in genetics and environmental factors may alter the pathogenesis process and contribute to the differences observed in clinical presentation and severity.

• #21 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Dysregulation of the Adaptive Immune System in Rosacea […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses. […] Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] The connection between cytokines and chemokines with the Th1/Th17 pathways and rosacea supports the notion of their association. […] The relationship between TLRs and B cells involves mechanisms where TLR activation is necessary for certain antigen-specific antibody responses in B cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin.

• #22 Rosacea: Symptoms, Causes, and Management – DermNet

  https://dermnetnz.org/topics/rosacea

  Rosacea is a chronic inflammatory skin condition predominantly affecting the central face and most often starts between the age of 30-60 years. […] The pathogenesis of rosacea is thought to be multifactorial and includes: Genetic susceptibility, Altered microbiome of the skin and gut, Neurocutaneous mechanisms, Impaired skin barrier. […] Dysregulation of the immune response may lead to excessive inflammation, vasodilation, lymphatic dilatation, and angiogenesis. […] In the skin of patients with rosacea, there is increased expression and activity of toll-like receptor 2, cathelicidins, kallikrein 5, and mast cells. […] The result is an exaggerated innate immune reaction to the initial trigger. […] Dominant T-helper (Th)1/Th17 gene expression in all features of rosacea. […] Increased Th17 expression can increase levels of cathelicidin LL-37 in keratinocytes and drive further inflammation. […] The most significant environmental trigger is UV radiation; affected skin is more sensitive to exposure. UV radiation can damage the dermis and increase skin inflammation.

• #23 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Dysregulation of the Adaptive Immune System in Rosacea […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses. […] Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] The connection between cytokines and chemokines with the Th1/Th17 pathways and rosacea supports the notion of their association. […] The relationship between TLRs and B cells involves mechanisms where TLR activation is necessary for certain antigen-specific antibody responses in B cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin.

• #24 Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

  https://www.mdpi.com/2227-9059/11/8/2153

  The current understanding of adaptive immunity in rosacea is limited, with studies indicating a high prevalence of CD4+ T cell infiltration around hair follicles and blood vessels in affected skin lesions, while there is no significant increase in CD8+ T cells. […] Overall, while the involvement of innate immune cells in the pathogenesis of rosacea has been extensively investigated, the roles of adaptive immunity and specialized cells in this condition are still largely unknown. […] Rosacea is a multifaceted skin disorder characterized by facial erythema and flushing, which can be attributed to various physiological changes, including increased skin blood flow, vasodilation, angiogenesis, elevated permeability, and upregulated levels of vascular endothelial growth factor (VEGF), a critical mediator of angiogenesis and vasopermeability.

• #25 Pathogenesis of Rosacea | Encyclopedia MDPI

  https://encyclopedia.pub/entry/51272

  Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] IL-17 induces angiogenesis through the VEGF pathway and has an effect on the expression of LL-37. […] A neutrophil chemotactic factor, CXCL8, was found to be increased in rosacea via the upregulation of its mRNA gene modification. […] These chemokines in rosacea have angiogenic properties that also attract neutrophils and TH17 cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin. […] The exacerbation of rosacea by sunlight has been linked to the inflammatory effects of UV radiation on keratinocytes.

• #26 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Dysregulation of the Adaptive Immune System in Rosacea […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses. […] Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] The connection between cytokines and chemokines with the Th1/Th17 pathways and rosacea supports the notion of their association. […] The relationship between TLRs and B cells involves mechanisms where TLR activation is necessary for certain antigen-specific antibody responses in B cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin.

• #27 Rosacea: Epidemiology, pathogenesis, and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5821167/

  In addition to these innate immune receptors and molecules, neuronal dysregulation, including vascular dysfunction, and release of proinflammatory neuropeptides have been shown to contribute to rosacea’s pathophysiology. […] Activation of TRP results in release of vasoactive neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating polypeptide (PACAP), which were elevated in rosacea. […] Rosacea is an inflammatory skin disease characterized by immune dysfunction and neurovascular dysregulation.

• #28 Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

  https://www.mdpi.com/2227-9059/11/8/2153

  The current understanding of adaptive immunity in rosacea is limited, with studies indicating a high prevalence of CD4+ T cell infiltration around hair follicles and blood vessels in affected skin lesions, while there is no significant increase in CD8+ T cells. […] Overall, while the involvement of innate immune cells in the pathogenesis of rosacea has been extensively investigated, the roles of adaptive immunity and specialized cells in this condition are still largely unknown. […] Rosacea is a multifaceted skin disorder characterized by facial erythema and flushing, which can be attributed to various physiological changes, including increased skin blood flow, vasodilation, angiogenesis, elevated permeability, and upregulated levels of vascular endothelial growth factor (VEGF), a critical mediator of angiogenesis and vasopermeability.

• #29 Rosacea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1071429-overview

  Central facial flushing, often accompanied by burning or stinging, is the predominant sign in erythematotelangiectatic rosacea (ETR). […] The etiology of rosacea is unknown. It is likely, however, that several factors play a role in its development, including vasculature, climatic exposures, dermal matrix degeneration, chemicals and ingested agents, pilosebaceous unit abnormalities, microbial organisms, ferritin expression, reactive oxygen species (ROS), increased neoangiogenesis, and dysfunction of antimicrobial peptides (AMPs). […] Increased blood flow to the blood vessels of the face and an increased number of blood vessels closer to the surface of the face are thought to be responsible for the redness and flushing associated with rosacea. […] Rosacea involves associated damage to the endothelium and degeneration of the dermal matrix. However, it is not known whether (A) the initial damage is in the dermal matrix, leading to poor tissue support of cutaneous vessels and causing pooling of serum, inflammatory mediators, and metabolic waste; or (B) the initial abnormality exists in the cutaneous vasculature, leading to leaky vessels and delayed clearance of serum proteins, inflammatory mediators, and metabolic waste, thus resulting in matrix degeneration.

• #30 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  Rosacea is a chronic inflammatory condition of which there is no cure. The pathogenesis of rosacea is likely multifactorial, involving genetic and environmental contributions. Current understanding suggests that pro-inflammatory pathways involving cathelicidins and inflammasome complexes are central to rosacea pathogenesis. […] The pathogenesis of rosacea likely involves a complex interplay between several factors and pathways, including neurovascular dysregulation and innate immune system dysregulation involving cathelicidins and inflammasomes. […] Rosacea pathogenesis is likely to be multifaceted with neurovascular dysregulation being a major component. […] Key to the dysregulation of neurovascular processes are the transient receptor potential channels (TRPs), which are nonselective Ca2+ channels with sensory and signalling roles.

• #31 Rosacea: Epidemiology, pathogenesis, and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5821167/

  In addition to these innate immune receptors and molecules, neuronal dysregulation, including vascular dysfunction, and release of proinflammatory neuropeptides have been shown to contribute to rosacea’s pathophysiology. […] Activation of TRP results in release of vasoactive neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating polypeptide (PACAP), which were elevated in rosacea. […] Rosacea is an inflammatory skin disease characterized by immune dysfunction and neurovascular dysregulation.

• #32 Rosacea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1071429-overview

  Demodex species (mites that normally inhabit human hair follicles) may play a role in the pathogenesis of rosacea. […] Iron catalyzes the conversion of hydrogen peroxide to free radicals, which leads to tissue injury by damaging cellular membranes, proteins, and DNA. […] Early in the inflammatory process, ROS are released by neutrophils, which are postulated to play a central role in the inflammation associated with rosacea. […] Studies performed using video capillaroscopy on ETR lesions showed increased neoangiogenesis and blood-vessel enlargement. […] AMPs are low-molecular-weight proteins that are a part of the innate immune response and have demonstrated broad-spectrum antimicrobial activity against bacteria, viruses, and fungi.

• #33 Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

  https://www.mdpi.com/2227-9059/11/8/2153

  The current understanding of adaptive immunity in rosacea is limited, with studies indicating a high prevalence of CD4+ T cell infiltration around hair follicles and blood vessels in affected skin lesions, while there is no significant increase in CD8+ T cells. […] Overall, while the involvement of innate immune cells in the pathogenesis of rosacea has been extensively investigated, the roles of adaptive immunity and specialized cells in this condition are still largely unknown. […] Rosacea is a multifaceted skin disorder characterized by facial erythema and flushing, which can be attributed to various physiological changes, including increased skin blood flow, vasodilation, angiogenesis, elevated permeability, and upregulated levels of vascular endothelial growth factor (VEGF), a critical mediator of angiogenesis and vasopermeability.

• #34 Rosacea: Epidemiology, pathogenesis, and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5821167/

  Rosacea’s exact pathogenesis is still unclear. […] Various environmental stimuli and endogenous factors have been shown to stimulate an augmented innate immune response and aberrant neurovascular signaling. […] Accumulating evidence points to activation of cellular pattern recognition receptors like the toll like receptor (TLR) 2 and transient receptor potential (TRP) ion channels, and release of inflammatory mediators within the skin as key steps that lead to the clinical manifestation of rosacea. […] The exact molecular mechanisms involved in rosacea’s pathophysiology are unknown, and a multifactorial etiology with a genetic preposition is likely. […] There is accumulating evidence that triggers such as microbes, ultraviolet (UV) radiation, nutrition, extremes of temperatures, (skin) barrier disruption, psychosocial stress, and hormones may stimulate an augmented innate immune response and/or neurovascular dysregulation.

• #35 Rosacea

  https://www.racgp.org.au/afp/2017/may/rosacea

  Rosacea is thought to have a genetic component, with a higher incidence found in fair-skinned individuals of Celtic or northern European descent. Genetic vascular reactivity results in increased blood vessel density near the skin surface. Increased blood flow to the facial vasculature then leads to flushing or transient erythema. This is controlled by vasodilatory mechanisms. There are a number of factors that may trigger flushing in rosacea, including harsh climate, extreme temperature, solar radiation, emotion, spicy food, alcohol and hot beverages. An association between Demodex follicularum and rosacea has been reported. D. follicularum is a mite that lives in sebaceous follicles. In vitro investigations have found that D. follicularum has antigens that react with sera from patients with rosacea, and are capable of stimulating mononuclear cells to proliferate. Patients with rosacea have more mites in the follicles around the nose and cheek, compared with other patients, and these often have a surrounding inflammatory response. Studies have shown that treatment of Demodex mites with topical ivermectin improves inflammatory rosacea. Patients with rosacea have elevated epidermal serine protease activity, which causes the deposition of cathelicidin-derived peptides in the skin. These are pro-inflammatory peptides. Abnormal skin barriers often show elevation of serine proteases. The level of serine proteases normalises when the skin barrier is restored. […] Rosacea is managed mainly with general measures and treatments targeted at the specific presenting symptoms. The goals of pharmacotherapy for rosacea are to reduce morbidity and symptoms, and achieve disease control, as rosacea is not curable.

• #36 Factors in rosacea pathogenesis clearer

  https://www.dermatologytimes.com/view/factors-rosacea-pathogenesis-clearer

  Triggers such as heat, stress and spices stimulate the transient receptor potential vanilloid (TRPV 1 through 4) and transient receptor potential ankyrin (TRPA) channels. […] The impact of other potential pathogens remains unsettled. […] „If you ask me, or many American dermatologists, it’s less decided.” […] Although D. folliculorum levels are elevated in rosacea, he explained, people can have heavy D. folliculorum colonization, but no rosacea, and vice versa. […] „The issue is confounded by the fact that the anti-mite drug Soolantra (topical ivermectin, Galderma) works well in rosacea.” […] „It sounds like something’s going on there. Also, the immune response to B. oleronius was found to be especially elevated in ocular rosacea.” […] „Much remains to be worked out.” […] „We must give Richard Gallo, M.D., Ph.D., a lot of credit. He’s done much of the research in rosacea.”

• #37 Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

  https://www.mdpi.com/2227-9059/11/8/2153

  Recent research suggests the involvement of the nervous system and intricate neuroimmune interactions. […] The complex pathophysiology of vascular dysregulation involves the activation of multiple pro-angiogenic mediators. […] Patients with rosacea present with sensitivity to various triggering factors, such as cold, heat, ultraviolet (UV) radiation, capsaicin, alcohol, and stress, which are defining characteristics of sensitive skin. […] The integrity of the skin barrier is of utmost importance in shielding the body against external agents and preserving its internal balance. […] Skin barrier dysfunction can contribute to the development and progression of inflammatory skin disorders. […] The cutaneous microbiota, consisting of a diverse array of microorganisms, such as bacteria, viruses, fungi, and mites that colonize both on and within the skin, constitutes a crucial constituent of the skin’s barrier function.

• #38 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Dysregulation of the Adaptive Immune System in Rosacea […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses. […] Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] The connection between cytokines and chemokines with the Th1/Th17 pathways and rosacea supports the notion of their association. […] The relationship between TLRs and B cells involves mechanisms where TLR activation is necessary for certain antigen-specific antibody responses in B cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin.

• #39 Rosacea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1071429-overview

  Demodex species (mites that normally inhabit human hair follicles) may play a role in the pathogenesis of rosacea. […] Iron catalyzes the conversion of hydrogen peroxide to free radicals, which leads to tissue injury by damaging cellular membranes, proteins, and DNA. […] Early in the inflammatory process, ROS are released by neutrophils, which are postulated to play a central role in the inflammation associated with rosacea. […] Studies performed using video capillaroscopy on ETR lesions showed increased neoangiogenesis and blood-vessel enlargement. […] AMPs are low-molecular-weight proteins that are a part of the innate immune response and have demonstrated broad-spectrum antimicrobial activity against bacteria, viruses, and fungi.

• #40 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Dysregulation of the Adaptive Immune System in Rosacea […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses. […] Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] The connection between cytokines and chemokines with the Th1/Th17 pathways and rosacea supports the notion of their association. […] The relationship between TLRs and B cells involves mechanisms where TLR activation is necessary for certain antigen-specific antibody responses in B cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin.

• #41 Novel Rosacea Compound, Ivermectin Cream, Offers Unique Mechanism of Action

  https://www.ahdbonline.com/payer-perspectives-in-dermatology/novel-rosacea-compound-ivermectin-cream-offers-unique-mechanism-of-action

  The pathogenesis of rosacea, a chronic inflammatory disorder that is characterized by facial papules, pustules, and persistent erythema, is multifactorial. Many factors are believed to activate neurovascular and immune responses, leading to inflammation that results in flares. […] The exact role of Demodex in causing rosacea is not well understood, but it is believed that the mites or the Bacillus oleronius bacteria that they harbor trigger inflammatory or immune reactions that result in the symptoms of rosacea. […] Developing Demodex mites may be causative agents of rosacea through various mechanisms: they may mechanically block hair follicles, secrete digestive enzymes, destroy the epithelial barrier or trigger reactions of the immune system. […] Ivermectin 1% cream has a unique mechanism of action among current treatments for rosacea; unlike available treatments, this unique mechanism addresses the inflammatory process involved in rosacea and the key organism, Demodex.

• #42 Novel Rosacea Compound, Ivermectin Cream, Offers Unique Mechanism of Action

  https://www.ahdbonline.com/payer-perspectives-in-dermatology/novel-rosacea-compound-ivermectin-cream-offers-unique-mechanism-of-action

  The pathogenesis of rosacea, a chronic inflammatory disorder that is characterized by facial papules, pustules, and persistent erythema, is multifactorial. Many factors are believed to activate neurovascular and immune responses, leading to inflammation that results in flares. […] The exact role of Demodex in causing rosacea is not well understood, but it is believed that the mites or the Bacillus oleronius bacteria that they harbor trigger inflammatory or immune reactions that result in the symptoms of rosacea. […] Developing Demodex mites may be causative agents of rosacea through various mechanisms: they may mechanically block hair follicles, secrete digestive enzymes, destroy the epithelial barrier or trigger reactions of the immune system. […] Ivermectin 1% cream has a unique mechanism of action among current treatments for rosacea; unlike available treatments, this unique mechanism addresses the inflammatory process involved in rosacea and the key organism, Demodex.

• #43 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Helicobacter pylori may have an effect on increasing ROS, leading to inflammation in the gut. […] The intestinal microbial population may have an immunomodulatory effect upon non-gastrointestinal systems including the skin. […] Genetic factors are implicated in the manifestation of rosacea based on familial studies. […] The TAC1, MMP9, TNFA, and CXCL12 genes have been identified as significant, as they encode substances such as P, MMPs, TNF-α, and chemoattractants for mast cells. […] The etiopathogenesis of rosacea has revealed its association with neurovascular components. […] Psychological factors play roles in rosacea, where emotions of embarrassment or laughter can initiate flushing. […] Psychological stress in rosacea patients may modulate TLR signaling, induce ROS, and increase antimicrobial peptide and neuropeptide production.

• #44 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Helicobacter pylori may have an effect on increasing ROS, leading to inflammation in the gut. […] The intestinal microbial population may have an immunomodulatory effect upon non-gastrointestinal systems including the skin. […] Genetic factors are implicated in the manifestation of rosacea based on familial studies. […] The TAC1, MMP9, TNFA, and CXCL12 genes have been identified as significant, as they encode substances such as P, MMPs, TNF-α, and chemoattractants for mast cells. […] The etiopathogenesis of rosacea has revealed its association with neurovascular components. […] Psychological factors play roles in rosacea, where emotions of embarrassment or laughter can initiate flushing. […] Psychological stress in rosacea patients may modulate TLR signaling, induce ROS, and increase antimicrobial peptide and neuropeptide production.

• #45 Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

  https://www.mdpi.com/2227-9059/11/8/2153

  Recent research suggests the involvement of the nervous system and intricate neuroimmune interactions. […] The complex pathophysiology of vascular dysregulation involves the activation of multiple pro-angiogenic mediators. […] Patients with rosacea present with sensitivity to various triggering factors, such as cold, heat, ultraviolet (UV) radiation, capsaicin, alcohol, and stress, which are defining characteristics of sensitive skin. […] The integrity of the skin barrier is of utmost importance in shielding the body against external agents and preserving its internal balance. […] Skin barrier dysfunction can contribute to the development and progression of inflammatory skin disorders. […] The cutaneous microbiota, consisting of a diverse array of microorganisms, such as bacteria, viruses, fungi, and mites that colonize both on and within the skin, constitutes a crucial constituent of the skin’s barrier function.

• #46 Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

  https://www.mdpi.com/2227-9059/11/8/2153

  Recent research suggests the involvement of the nervous system and intricate neuroimmune interactions. […] The complex pathophysiology of vascular dysregulation involves the activation of multiple pro-angiogenic mediators. […] Patients with rosacea present with sensitivity to various triggering factors, such as cold, heat, ultraviolet (UV) radiation, capsaicin, alcohol, and stress, which are defining characteristics of sensitive skin. […] The integrity of the skin barrier is of utmost importance in shielding the body against external agents and preserving its internal balance. […] Skin barrier dysfunction can contribute to the development and progression of inflammatory skin disorders. […] The cutaneous microbiota, consisting of a diverse array of microorganisms, such as bacteria, viruses, fungi, and mites that colonize both on and within the skin, constitutes a crucial constituent of the skin’s barrier function.

• #47 Reddit – The heart of the internet

  https://www.reddit.com/r/SkincareAddiction/comments/8omjau/research_rosacea_the_curse_of_the_celts/

  Disruption of the skin barrier (the stratum corneum permeability barrier) plays a large part in rosacea, and all rosacean patients experience increased trans-epidermal water-loss (TEWL), particularly in the areas of the face most effected, such as the cheeks and along the sides of the nose. This disruption plays a large part in why rosacean skin is so hyper-reactive. […] Researchers have discovered two genetic variants that may be associated with the disorder, and fairly recent research suggests that the facial redness is likely the start of an „inflammatory continuum initiated by a combination of neurovascular dysregulation and the innate immune system.” Beyond this, mites have also been considered a contributing factor to the condition (particularly the demodex folliculorum mite). While this mite is present on all people’s skin, it was found to be even more abundant in the facial skin of rosaceans. […] Rosacea is also a highly inflammatory disease, and some patients may see mild to moderate improvement by adopting a healthier lifestyle that reduces inflammation in the body, such as eating probiotic rich foods (particularly ferments) and turmeric and ginger.

• #48 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Helicobacter pylori may have an effect on increasing ROS, leading to inflammation in the gut. […] The intestinal microbial population may have an immunomodulatory effect upon non-gastrointestinal systems including the skin. […] Genetic factors are implicated in the manifestation of rosacea based on familial studies. […] The TAC1, MMP9, TNFA, and CXCL12 genes have been identified as significant, as they encode substances such as P, MMPs, TNF-α, and chemoattractants for mast cells. […] The etiopathogenesis of rosacea has revealed its association with neurovascular components. […] Psychological factors play roles in rosacea, where emotions of embarrassment or laughter can initiate flushing. […] Psychological stress in rosacea patients may modulate TLR signaling, induce ROS, and increase antimicrobial peptide and neuropeptide production.

• #49 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Helicobacter pylori may have an effect on increasing ROS, leading to inflammation in the gut. […] The intestinal microbial population may have an immunomodulatory effect upon non-gastrointestinal systems including the skin. […] Genetic factors are implicated in the manifestation of rosacea based on familial studies. […] The TAC1, MMP9, TNFA, and CXCL12 genes have been identified as significant, as they encode substances such as P, MMPs, TNF-α, and chemoattractants for mast cells. […] The etiopathogenesis of rosacea has revealed its association with neurovascular components. […] Psychological factors play roles in rosacea, where emotions of embarrassment or laughter can initiate flushing. […] Psychological stress in rosacea patients may modulate TLR signaling, induce ROS, and increase antimicrobial peptide and neuropeptide production.

• #50 Rosacea: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2015/0801/p187.html

  Rosacea is a chronic facial skin condition of unknown cause. It is characterized by marked involvement of the central face with transient or persistent erythema, telangiectasia, inflammatory papules and pustules, or hyperplasia of the connective tissue. […] The etiology of rosacea is unknown but is likely multifactorial. Factors involved in the pathophysiology include the dense presence of sebaceous glands on the face, the physiology of the nerve innervation, and the vascular composition of the skin. […] A predilection for fair-skinned individuals of Celtic or northern European descent suggests a genetic component to rosacea. However, no specific gene has been identified. Patients with the genetic predisposition have a receptor that mediates neovascular regulation. When exposed to triggers, neuropeptide release (flushing, edema) occurs, resulting in recruitment of proinflammatory cells to the skin.

• #51 Rosacea: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2015/0801/p187.html

  Rosacea is a chronic facial skin condition of unknown cause. It is characterized by marked involvement of the central face with transient or persistent erythema, telangiectasia, inflammatory papules and pustules, or hyperplasia of the connective tissue. […] The etiology of rosacea is unknown but is likely multifactorial. Factors involved in the pathophysiology include the dense presence of sebaceous glands on the face, the physiology of the nerve innervation, and the vascular composition of the skin. […] A predilection for fair-skinned individuals of Celtic or northern European descent suggests a genetic component to rosacea. However, no specific gene has been identified. Patients with the genetic predisposition have a receptor that mediates neovascular regulation. When exposed to triggers, neuropeptide release (flushing, edema) occurs, resulting in recruitment of proinflammatory cells to the skin.

• #52 Rosacea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1071429-overview

  Demodex species (mites that normally inhabit human hair follicles) may play a role in the pathogenesis of rosacea. […] Iron catalyzes the conversion of hydrogen peroxide to free radicals, which leads to tissue injury by damaging cellular membranes, proteins, and DNA. […] Early in the inflammatory process, ROS are released by neutrophils, which are postulated to play a central role in the inflammation associated with rosacea. […] Studies performed using video capillaroscopy on ETR lesions showed increased neoangiogenesis and blood-vessel enlargement. […] AMPs are low-molecular-weight proteins that are a part of the innate immune response and have demonstrated broad-spectrum antimicrobial activity against bacteria, viruses, and fungi.

• #53 Rosacea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1071429-overview

  Demodex species (mites that normally inhabit human hair follicles) may play a role in the pathogenesis of rosacea. […] Iron catalyzes the conversion of hydrogen peroxide to free radicals, which leads to tissue injury by damaging cellular membranes, proteins, and DNA. […] Early in the inflammatory process, ROS are released by neutrophils, which are postulated to play a central role in the inflammation associated with rosacea. […] Studies performed using video capillaroscopy on ETR lesions showed increased neoangiogenesis and blood-vessel enlargement. […] AMPs are low-molecular-weight proteins that are a part of the innate immune response and have demonstrated broad-spectrum antimicrobial activity against bacteria, viruses, and fungi.

• #54 Pathogenesis of Rosacea | Encyclopedia MDPI

  https://encyclopedia.pub/entry/51272

  Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] IL-17 induces angiogenesis through the VEGF pathway and has an effect on the expression of LL-37. […] A neutrophil chemotactic factor, CXCL8, was found to be increased in rosacea via the upregulation of its mRNA gene modification. […] These chemokines in rosacea have angiogenic properties that also attract neutrophils and TH17 cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin. […] The exacerbation of rosacea by sunlight has been linked to the inflammatory effects of UV radiation on keratinocytes.

• #55 Pathogenesis of Rosacea | Encyclopedia MDPI

  https://encyclopedia.pub/entry/51272

  Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] IL-17 induces angiogenesis through the VEGF pathway and has an effect on the expression of LL-37. […] A neutrophil chemotactic factor, CXCL8, was found to be increased in rosacea via the upregulation of its mRNA gene modification. […] These chemokines in rosacea have angiogenic properties that also attract neutrophils and TH17 cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin. […] The exacerbation of rosacea by sunlight has been linked to the inflammatory effects of UV radiation on keratinocytes.

• #56 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Helicobacter pylori may have an effect on increasing ROS, leading to inflammation in the gut. […] The intestinal microbial population may have an immunomodulatory effect upon non-gastrointestinal systems including the skin. […] Genetic factors are implicated in the manifestation of rosacea based on familial studies. […] The TAC1, MMP9, TNFA, and CXCL12 genes have been identified as significant, as they encode substances such as P, MMPs, TNF-α, and chemoattractants for mast cells. […] The etiopathogenesis of rosacea has revealed its association with neurovascular components. […] Psychological factors play roles in rosacea, where emotions of embarrassment or laughter can initiate flushing. […] Psychological stress in rosacea patients may modulate TLR signaling, induce ROS, and increase antimicrobial peptide and neuropeptide production.

• #57 Pathogenesis of Rosacea | Encyclopedia MDPI

  https://encyclopedia.pub/entry/51272

  UV radiation stimulates ROS production in keratinocytes and activates cellular signaling pathways. […] Psychological factors play roles in rosacea, where emotions of embarrassment or laughter can initiate flushing. […] The impact on appearance can cause a lack of self-confidence, anxiety, and depression, which can lead to psychological stress and affect sleep quality. […] Rosacea is a chronic and multifactorial disease with various factors contributing to its pathogenesis.

• #58 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Helicobacter pylori may have an effect on increasing ROS, leading to inflammation in the gut. […] The intestinal microbial population may have an immunomodulatory effect upon non-gastrointestinal systems including the skin. […] Genetic factors are implicated in the manifestation of rosacea based on familial studies. […] The TAC1, MMP9, TNFA, and CXCL12 genes have been identified as significant, as they encode substances such as P, MMPs, TNF-α, and chemoattractants for mast cells. […] The etiopathogenesis of rosacea has revealed its association with neurovascular components. […] Psychological factors play roles in rosacea, where emotions of embarrassment or laughter can initiate flushing. […] Psychological stress in rosacea patients may modulate TLR signaling, induce ROS, and increase antimicrobial peptide and neuropeptide production.

• #59 Pathogenesis of Rosacea | Encyclopedia MDPI

  https://encyclopedia.pub/entry/51272

  UV radiation stimulates ROS production in keratinocytes and activates cellular signaling pathways. […] Psychological factors play roles in rosacea, where emotions of embarrassment or laughter can initiate flushing. […] The impact on appearance can cause a lack of self-confidence, anxiety, and depression, which can lead to psychological stress and affect sleep quality. […] Rosacea is a chronic and multifactorial disease with various factors contributing to its pathogenesis.

• #60 Reddit – The heart of the internet

  https://www.reddit.com/r/SkincareAddiction/comments/8omjau/research_rosacea_the_curse_of_the_celts/

  Rosacea is a frustrating skin condition. This seems to be the universal problem with rosacea. It is confounding, chronic, and difficult to treat. There is no universal treatment, and for some, the recommended cures can turn into the cause. Compounding that is the fact that rosacea frequently looks like other skin conditions, such as acne, and the prescriptions for acne can also aggravate the rosacea, undoing any benefits. To make matters worse, rosacea is frequently misdiagnosed and under-treated, leaving sufferers with worsening symptoms that are difficult to reverse. […] According to the National Rosacea Society, nearly 90% of rosacea patients say the condition lowers their self-confidence and self-esteem, and 41% report it causing them to avoid public contact or social engagements. […] The common link between all types of rosacea is the constant blush or flush — called erythema — that remains present in the central portions of the face.

• #61 Rosacea Pathogenesis | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-319-49274-2_13

  Multiple factors are involved in rosacea pathogenesis such as disturbed epidermal barrier function, cathelicidin antimicrobial peptide (CAMP)-mediated inflammation with inflammasome activation, aberrations of vascular reactivity, enhanced innate immunity, neurogenic inflammation, angiogenesis, fibrosis, and Demodex mite hypercolonization. […] The lack of appropriate animal models of rosacea underlines the importance of translational research approaching rosacea pathogenesis. […] Endoplasmic reticulum stress: key promoter of rosacea pathogenesis. […] Rosacea as a disease of cathelicidins and skin innate immunity. […] Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea.

• #62 Rosacea: The Blessing of the Celts – An Approach to Pathogenesis Through Translational Research | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2220

  Increased expression of cathelicidin antimicrobial peptide (CAMP) is related to the pathogenesis of rosacea. […] At the molecular level, all clinical trigger factors for rosacea can be regarded as ER stressors. A mutation-based upregulation of ER stress responsiveness in rosacea may thus explain patients reduced threshold for ER stressors. […] The aim of this review is to present a new unifying concept of rosacea pathogenesis focusing on increased endoplasmic reticulum (ER) stress responsiveness, which is mediated via enhanced sphingosine-1-phosphate (S1P) signalling in rosacea skin. […] Thus, all trigger factors for clinical rosacea increase the skins ER stress response, also known as the unfolded protein response (UPR). Upregulated ER stress results in enhanced activation of C/EBP, increasing CAMP expression.

• #63 Ocular Rosacea – EyeWiki

  https://eyewiki.org/Ocular_Rosacea

  Rosacea is thought to be an inflammatory condition with altered immune system responses and vascular dysregulation. […] These factors contribute to activation of the inflammatory response and immune system, which expresses an enhanced level of Toll-like receptor 2 (TLR2) in the epidermis. Upregulated TLR2 in keratinocytes leads to an increase in activity of an enzyme serine protease, KLK5, which has a role in cathelicidin production. Cathelicidin in turn causes an increase in the vascular endothelial growth factor (VEGF) level in epidermal keratinocytes leading to vascular endothelial changes and angiogenesis. […] Additional sources of inflammation include elevated levels of interleukin-1a and b, gelatinase B (metalloproteinase-9) and collagenase-2 (MMP-8) in the tear fluids of patients with ocular rosacea. Elevated serum level of Tumor necrosis factor (TNF-alfa) and overexpression of ICAM-1 (intercellular adhesion molecule 1) and HLA-DR in conjunctival epithelial cells of these patients is also observed.

• #64 Rosacea: Symptoms, Causes, and Management – DermNet

  https://dermnetnz.org/topics/rosacea

  Rosacea is a chronic inflammatory skin condition predominantly affecting the central face and most often starts between the age of 30-60 years. […] The pathogenesis of rosacea is thought to be multifactorial and includes: Genetic susceptibility, Altered microbiome of the skin and gut, Neurocutaneous mechanisms, Impaired skin barrier. […] Dysregulation of the immune response may lead to excessive inflammation, vasodilation, lymphatic dilatation, and angiogenesis. […] In the skin of patients with rosacea, there is increased expression and activity of toll-like receptor 2, cathelicidins, kallikrein 5, and mast cells. […] The result is an exaggerated innate immune reaction to the initial trigger. […] Dominant T-helper (Th)1/Th17 gene expression in all features of rosacea. […] Increased Th17 expression can increase levels of cathelicidin LL-37 in keratinocytes and drive further inflammation. […] The most significant environmental trigger is UV radiation; affected skin is more sensitive to exposure. UV radiation can damage the dermis and increase skin inflammation.

• #65 Rosacea: A Misunderstood, Serious Medical Condition

  https://www.ahdbonline.com/payer-perspectives-in-dermatology/1469-article-1469

  With this hyperreactive immune system as background, environmental triggers can incite an exaggerated immune response. This triggering of the innate immune response system induces a signaling cascade of inflammatory factors that lead to chronic inflammation and an altered vascular state. […] Part of this inflammatory response most likely involves the toll-like receptor 2 (TLR2), which is a pattern recognition receptor that is expressed in the skin of patients with rosacea, but not in other people; abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli. […] In explaining the facial erythema (or redness) of rosacea, Del Rosso and colleagues pulled all these factors together to construct a picture of inflammation and vascular reactivity that includes an augmented innate immune response (ie, an increase in TLR2, cathelicidin precursors and peptides, and kallikrein-5); changes in the vasculature (ie, increased vascular endothelial growth factor, increased mast cells, and downstream effects of LL-37); neurovascular dysregulation (ie, vascular response, vasodilation, and neurosensory symptoms); dermal matrix degradation (ie, an increase in reactive oxygen species and matrix metalloproteinases, and a decrease in antioxidant reserve); vasodilation (ie, neurovascular dysfunction and increased nitric oxide leading to dilation and increased blood flow); and rosacea dermatitis (ie, stratum corneum barrier dysfunction and an increase in cytokines).

• #66 A Cosmetic Regimen Formulated to Address the Multi-Modal Pathogenesis of Rosacea Demonstrates Efficacy for Treating Facial Redness and Skin’s Appearance – JDDonline – Journal of Drugs in Dermatology

  https://jddonline.com/articles/cosmetic-regimen-formulated-address-multi-modal-pathogenesis-of-rosacea-demonstrates-efficacy-treating-facial-redness-skins-appearance-S1545961624P8460X/

  Rosacea is a multifactorial condition that involves a complex interaction between genetics, immune system dysregulation, microorganisms, UV light, neurovascular dysregulation, and impaired barrier function. […] Dysregulation of the innate immune system plays a key role in the pathogenesis of rosacea. It occurs due to the activation of toll-like receptor 2 (TLR2) triggering the production of antimicrobial peptides (AMPs) including cathelicidins. […] The stimulus for TLR2 activation remains elusive although chitin from Demodex mites and Demodex-associated Bacillus oleronius have been implicated. […] Cathelicidins are cleaved by the serine protease kallikrein 5 (KLK5) which is overexpressed in the facial skin of rosacea patients. KLK5 cleaves the precursor protein to its active peptide form LL-37 and various other proteolytic fragments. […] These proteolytic fragments influence processes including cytokine release, angiogenesis, leukocyte chemotaxis, and extracellular matrix components.

• #67 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  IL-8 induces neutrophil chemotaxis in the skin, resulting in the release of proteases such as cathepsin G, elastase, and protease-3. […] In addition, IL-b and TNF-α also act as the angiogenic factor and vascular endothelial growth factor (VEGF) and may cause the vascular changes seen in rosacea. […] Cathelicidin, an antimicrobial protein, is found in the lamellar body of keratinocytes and the granules of neutrophils. […] The LL-37 peptide in rosacea skin differs from healthy skin by having shorter fragment forms. […] These fragments have been implicated in symptoms characteristic of rosacea, including erythema, vasodilatation, flushing, and telangiectasia. […] MMPs indirectly influence the pathogenesis of rosacea by activating the preproenzyme form of KLK5 after cleavage with MMP-9.

• #68 Ocular Rosacea: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1197341-overview

  Moreover, toll-like receptor 2 activity in the innate immune system is increased in patients with rosacea. […] A variety of rosacea triggers have been described including skin colonization with Demodex mites (along with bacteria in their gut) and Staphylococcus epidermidis. […] Eradication of Helicobacter pylori has been shown to improve rosacea in some patients, and the organism may play a role in the pathogenesis of inflammation in rosacea. […] Four distinct rosacea subtypes have been described: erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea.

• #69 Rosacea: A Misunderstood, Serious Medical Condition

  https://www.ahdbonline.com/payer-perspectives-in-dermatology/1469-article-1469

  With this hyperreactive immune system as background, environmental triggers can incite an exaggerated immune response. This triggering of the innate immune response system induces a signaling cascade of inflammatory factors that lead to chronic inflammation and an altered vascular state. […] Part of this inflammatory response most likely involves the toll-like receptor 2 (TLR2), which is a pattern recognition receptor that is expressed in the skin of patients with rosacea, but not in other people; abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli. […] In explaining the facial erythema (or redness) of rosacea, Del Rosso and colleagues pulled all these factors together to construct a picture of inflammation and vascular reactivity that includes an augmented innate immune response (ie, an increase in TLR2, cathelicidin precursors and peptides, and kallikrein-5); changes in the vasculature (ie, increased vascular endothelial growth factor, increased mast cells, and downstream effects of LL-37); neurovascular dysregulation (ie, vascular response, vasodilation, and neurosensory symptoms); dermal matrix degradation (ie, an increase in reactive oxygen species and matrix metalloproteinases, and a decrease in antioxidant reserve); vasodilation (ie, neurovascular dysfunction and increased nitric oxide leading to dilation and increased blood flow); and rosacea dermatitis (ie, stratum corneum barrier dysfunction and an increase in cytokines).

• #70 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  Cathelicidins is a family of antimicrobial peptides expressed in the skin in many vertebrates and have been implicated in rosacea pathogenesis. […] Activation of TLR2 leads to the production of cathelicidin (LL-37) and cytokines in the pro-inflammatory cathelicidins pathway are described in more detail in this article. […] Human cathelicidin antimicrobial peptide (CAMP) is intimately involved in the pathogenesis of rosacea, with both immunomodulatory and angiogenic properties. […] The increased abundance of CAMP and KLK5 activity has been shown to increase the levels of bioactive cathelicidin fragments in rosacea patients. […] Inflammasomes are multiprotein complexes of the innate immune system that trigger inflammatory responses through the activation of caspase-1. […] NLRP3, caspase-1, and IL-1 are known to be elevated in rosacea patients, implicating the inflammasome in rosacea pathogenesis.

• #71 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Rosacea has several triggers, and its pathogenesis involves multiple factors, which means there are several treatment options, and these options can be combined. […] The pathogenesis of rosacea is complex and involves a variety of factors that can trigger both inflammatory and vascular responses. […] Rosacea skin has higher levels of TLR-2, KLK-5, cathelicidin, and matrix metalloproteinases (MMPs) than healthy skin. […] In rosacea patients, keratinocytes produce pro-inflammatory cytokines and chemokines when TLR-2 is activated by triggering factors, leading to the increased expression of pro-inflammatory cytokine genes such as IL (interleukin)-8, IL-1b, and TNF (tumor necrosis factor)-α. […] TLR-2 was found to positively mediate a pro-inflammatory response following UV-B irradiation in an in vivo study.

• #72 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Rosacea has several triggers, and its pathogenesis involves multiple factors, which means there are several treatment options, and these options can be combined. […] The pathogenesis of rosacea is complex and involves a variety of factors that can trigger both inflammatory and vascular responses. […] Rosacea skin has higher levels of TLR-2, KLK-5, cathelicidin, and matrix metalloproteinases (MMPs) than healthy skin. […] In rosacea patients, keratinocytes produce pro-inflammatory cytokines and chemokines when TLR-2 is activated by triggering factors, leading to the increased expression of pro-inflammatory cytokine genes such as IL (interleukin)-8, IL-1b, and TNF (tumor necrosis factor)-α. […] TLR-2 was found to positively mediate a pro-inflammatory response following UV-B irradiation in an in vivo study.

• #73 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  Cathelicidins is a family of antimicrobial peptides expressed in the skin in many vertebrates and have been implicated in rosacea pathogenesis. […] Activation of TLR2 leads to the production of cathelicidin (LL-37) and cytokines in the pro-inflammatory cathelicidins pathway are described in more detail in this article. […] Human cathelicidin antimicrobial peptide (CAMP) is intimately involved in the pathogenesis of rosacea, with both immunomodulatory and angiogenic properties. […] The increased abundance of CAMP and KLK5 activity has been shown to increase the levels of bioactive cathelicidin fragments in rosacea patients. […] Inflammasomes are multiprotein complexes of the innate immune system that trigger inflammatory responses through the activation of caspase-1. […] NLRP3, caspase-1, and IL-1 are known to be elevated in rosacea patients, implicating the inflammasome in rosacea pathogenesis.

• #74 Facial Erythema of Rosacea – Aetiology, Different Pathophysiologies and Treatment Options | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2335

  The inflammatory infiltrate, which is present in all 4 subtypes, is still poorly characterised. […] The mechanism by which LL-37 enhances the release of inflammatory mediators and promotes angiogenesis is through NLRP3 inflammasome activation. […] The vicious circle of vascular and inflammatory changes causes a persistent dilation of blood and lymphatic vessels, neoangiogenesis, telangiectasia formation and dermal matrix degradation.

• #75 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  Cathelicidins is a family of antimicrobial peptides expressed in the skin in many vertebrates and have been implicated in rosacea pathogenesis. […] Activation of TLR2 leads to the production of cathelicidin (LL-37) and cytokines in the pro-inflammatory cathelicidins pathway are described in more detail in this article. […] Human cathelicidin antimicrobial peptide (CAMP) is intimately involved in the pathogenesis of rosacea, with both immunomodulatory and angiogenic properties. […] The increased abundance of CAMP and KLK5 activity has been shown to increase the levels of bioactive cathelicidin fragments in rosacea patients. […] Inflammasomes are multiprotein complexes of the innate immune system that trigger inflammatory responses through the activation of caspase-1. […] NLRP3, caspase-1, and IL-1 are known to be elevated in rosacea patients, implicating the inflammasome in rosacea pathogenesis.

• #76 Rosacea: Pathogenesis and Therapeutic Correlates

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11015710/

  The enhanced activity of IL-1 results in upregulation of other pro-inflammatory cytokines including IL-8 and tumor necrosis factor (TNF)-, angiogenesis, and chemotaxis of neutrophils. […] While the bulk of rosacea pathogenesis centres around vascular hyperactivity and dysregulation of the innate immune system, evidence of adaptive immune involvement is emerging. […] Rosacea is a chronic inflammatory condition that likely involves vascular hyperactivity, cathelicidins, and inflammasome complex activation. […] Differences in genetics and environmental factors may alter the pathogenesis process and contribute to the differences observed in clinical presentation and severity.

• #77 Rosacea: The Blessing of the Celts – An Approach to Pathogenesis Through Translational Research | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2220

  Increased expression of cathelicidin antimicrobial peptide (CAMP) is related to the pathogenesis of rosacea. […] At the molecular level, all clinical trigger factors for rosacea can be regarded as ER stressors. A mutation-based upregulation of ER stress responsiveness in rosacea may thus explain patients reduced threshold for ER stressors. […] The aim of this review is to present a new unifying concept of rosacea pathogenesis focusing on increased endoplasmic reticulum (ER) stress responsiveness, which is mediated via enhanced sphingosine-1-phosphate (S1P) signalling in rosacea skin. […] Thus, all trigger factors for clinical rosacea increase the skins ER stress response, also known as the unfolded protein response (UPR). Upregulated ER stress results in enhanced activation of C/EBP, increasing CAMP expression.

• #78 Rosacea: The Blessing of the Celts – An Approach to Pathogenesis Through Translational Research | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2220

  Increased expression of cathelicidin antimicrobial peptide (CAMP) is related to the pathogenesis of rosacea. […] At the molecular level, all clinical trigger factors for rosacea can be regarded as ER stressors. A mutation-based upregulation of ER stress responsiveness in rosacea may thus explain patients reduced threshold for ER stressors. […] The aim of this review is to present a new unifying concept of rosacea pathogenesis focusing on increased endoplasmic reticulum (ER) stress responsiveness, which is mediated via enhanced sphingosine-1-phosphate (S1P) signalling in rosacea skin. […] Thus, all trigger factors for clinical rosacea increase the skins ER stress response, also known as the unfolded protein response (UPR). Upregulated ER stress results in enhanced activation of C/EBP, increasing CAMP expression.

• #79 Rosacea: The Blessing of the Celts – An Approach to Pathogenesis Through Translational Research | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2220

  Increased expression of cathelicidin antimicrobial peptide (CAMP) is related to the pathogenesis of rosacea. […] At the molecular level, all clinical trigger factors for rosacea can be regarded as ER stressors. A mutation-based upregulation of ER stress responsiveness in rosacea may thus explain patients reduced threshold for ER stressors. […] The aim of this review is to present a new unifying concept of rosacea pathogenesis focusing on increased endoplasmic reticulum (ER) stress responsiveness, which is mediated via enhanced sphingosine-1-phosphate (S1P) signalling in rosacea skin. […] Thus, all trigger factors for clinical rosacea increase the skins ER stress response, also known as the unfolded protein response (UPR). Upregulated ER stress results in enhanced activation of C/EBP, increasing CAMP expression.

• #80 Rosacea: The Blessing of the Celts – An Approach to Pathogenesis Through Translational Research | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2220

  Increased expression of cathelicidin antimicrobial peptide (CAMP) is related to the pathogenesis of rosacea. […] At the molecular level, all clinical trigger factors for rosacea can be regarded as ER stressors. A mutation-based upregulation of ER stress responsiveness in rosacea may thus explain patients reduced threshold for ER stressors. […] The aim of this review is to present a new unifying concept of rosacea pathogenesis focusing on increased endoplasmic reticulum (ER) stress responsiveness, which is mediated via enhanced sphingosine-1-phosphate (S1P) signalling in rosacea skin. […] Thus, all trigger factors for clinical rosacea increase the skins ER stress response, also known as the unfolded protein response (UPR). Upregulated ER stress results in enhanced activation of C/EBP, increasing CAMP expression.

• #81 Rosacea: The Blessing of the Celts – An Approach to Pathogenesis Through Translational Research | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2220

  Notably, enhanced ER stress signalling is associated with upregulation of activating transcription factor 4 (ATF4). […] Taken together, upregulated ER stress with increased ATF4/TLR2/S1P/C/EBP-driven activation of CAMP explains LL-37-mediated NLRP3 inflammasome activation and inflammatory Th17 cell activation with subsequent inflammatory cell infiltration in rosacea skin. […] The concept presented here opens possible new avenues for rosacea treatment. S1P receptor antagonism may be a very promising future approach in balancing ER stress-mediated S1P signalling in rosacea.

• #82 Rosacea: The Blessing of the Celts – An Approach to Pathogenesis Through Translational Research | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2220

  Notably, enhanced ER stress signalling is associated with upregulation of activating transcription factor 4 (ATF4). […] Taken together, upregulated ER stress with increased ATF4/TLR2/S1P/C/EBP-driven activation of CAMP explains LL-37-mediated NLRP3 inflammasome activation and inflammatory Th17 cell activation with subsequent inflammatory cell infiltration in rosacea skin. […] The concept presented here opens possible new avenues for rosacea treatment. S1P receptor antagonism may be a very promising future approach in balancing ER stress-mediated S1P signalling in rosacea.

• #83 Rosacea Biomarkers May Provide Insight Into Pathogenesis and Management

  https://www.dermatologyadvisor.com/news/rosacea-biomarkers-may-provide-insight-into-pathogenesis-and-management/

  In patients with rosacea, Th1 and Th17 cytokine levels were found to be elevated. […] Rosacea pathogenesis and treatment efficacy can be assessed effectively using biomarkers, the validation of which supports the innate cathelicidin and inflammasome Th1 and Th17 pathways, according to study findings published in the Journal of the European Academy of Dermatology Venerology. […] The most prominent mechanism of rosacea pathogenesis is characterized by innate immune system dysregulation driven by cathelicidin (LL-37, an antimicrobial peptide), the activation and production of which involves toll-like receptors (TLR2; reported by 2 studies, with both indicating increased levels in rosacea), serine proteases (such as KLK5; reported by 1 study noting increased levels in rosacea), and MMP-9 (with increased levels in rosacea reported in 5 studies).

• #84 Rosacea Biomarkers May Provide Insight Into Pathogenesis and Management

  https://www.dermatologyadvisor.com/news/rosacea-biomarkers-may-provide-insight-into-pathogenesis-and-management/

  Results of the review support involvement of Th1 and Th17 responses in rosacea pathogenesis, with levels of several Th1 and Th17 cytokines elevated in patients with rosacea. […] Current findings add support for other mechanisms of rosacea pathogenesis, including increased oxidative stress and increased levels of Demodex folliculorum mites. […] Although several Th2 related cytokines were elevated in patients with rosacea, Th2 responses have not been implicated in rosacea pathogenesis.

• #85 Rosacea: Symptoms, Causes, and Management – DermNet

  https://dermnetnz.org/topics/rosacea

  Rosacea is a chronic inflammatory skin condition predominantly affecting the central face and most often starts between the age of 30-60 years. […] The pathogenesis of rosacea is thought to be multifactorial and includes: Genetic susceptibility, Altered microbiome of the skin and gut, Neurocutaneous mechanisms, Impaired skin barrier. […] Dysregulation of the immune response may lead to excessive inflammation, vasodilation, lymphatic dilatation, and angiogenesis. […] In the skin of patients with rosacea, there is increased expression and activity of toll-like receptor 2, cathelicidins, kallikrein 5, and mast cells. […] The result is an exaggerated innate immune reaction to the initial trigger. […] Dominant T-helper (Th)1/Th17 gene expression in all features of rosacea. […] Increased Th17 expression can increase levels of cathelicidin LL-37 in keratinocytes and drive further inflammation. […] The most significant environmental trigger is UV radiation; affected skin is more sensitive to exposure. UV radiation can damage the dermis and increase skin inflammation.

• #86 Rosacea: Symptoms, Causes, and Management – DermNet

  https://dermnetnz.org/topics/rosacea

  Rosacea is a chronic inflammatory skin condition predominantly affecting the central face and most often starts between the age of 30-60 years. […] The pathogenesis of rosacea is thought to be multifactorial and includes: Genetic susceptibility, Altered microbiome of the skin and gut, Neurocutaneous mechanisms, Impaired skin barrier. […] Dysregulation of the immune response may lead to excessive inflammation, vasodilation, lymphatic dilatation, and angiogenesis. […] In the skin of patients with rosacea, there is increased expression and activity of toll-like receptor 2, cathelicidins, kallikrein 5, and mast cells. […] The result is an exaggerated innate immune reaction to the initial trigger. […] Dominant T-helper (Th)1/Th17 gene expression in all features of rosacea. […] Increased Th17 expression can increase levels of cathelicidin LL-37 in keratinocytes and drive further inflammation. […] The most significant environmental trigger is UV radiation; affected skin is more sensitive to exposure. UV radiation can damage the dermis and increase skin inflammation.

• #87 Exploring the association between rosacea and acne by integrated bioinformatics analysis | Scientific Reports

  https://www.nature.com/articles/s41598-024-53453-x

  A total of 151 up-regulated and 18 down-regulated co-DEGs were identified. KEGG pathway analysis of up-regulated co-DEGs demonstrated that they were mainly involved in IL-17 signaling pathway, NF-B signaling pathway, Toll-like receptor signaling pathway, and TNF signaling pathway. This is consistent with previous findings that these pathways are involved in the development of both rosacea and acne. […] The expression of CXCL10, MMP9, IL1B, CXCL8, and CXCR4 were co-regulated by IRF1, STAT1, STAT3, IKBKB, HDAC1, ETS1, and CEBPB, which were highly expressed in rosacea and acne lesions. […] The infiltration of gamma delta T cells was significantly increased and positively correlated with almost all hub genes in both rosacea and acne, suggesting that gamma delta T cells may play a crucial role in the pathogenesis of these two diseases.

• #88 Rosacea – Dermatologic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/dermatologic-disorders/acne-and-related-disorders/rosacea

  Rosacea is a chronic inflammatory disorder characterized by facial flushing, telangiectasias, erythema, papules, pustules, and, in severe cases, phymatous changes such as rhinophyma. […] The etiology of rosacea is unknown, but some proposed associations include abnormal vasomotor control, impaired facial venous drainage, increased follicle mites (Demodex folliculorum), increased angiogenesis, ferritin expression, and reactive oxygen species, and dysfunction of antimicrobial peptides (eg, cathelicidin). […] Diet plays no consistent role, but some agents (eg, amiodarone, topical and nasal corticosteroids, high doses of B6 and B12) may worsen rosacea. […] In the vascular phase, patients develop facial erythema and edema with multiple telangiectases, possibly as a result of persistent vasomotor instability.

• #89 Rosacea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1071429-overview

  Central facial flushing, often accompanied by burning or stinging, is the predominant sign in erythematotelangiectatic rosacea (ETR). […] The etiology of rosacea is unknown. It is likely, however, that several factors play a role in its development, including vasculature, climatic exposures, dermal matrix degeneration, chemicals and ingested agents, pilosebaceous unit abnormalities, microbial organisms, ferritin expression, reactive oxygen species (ROS), increased neoangiogenesis, and dysfunction of antimicrobial peptides (AMPs). […] Increased blood flow to the blood vessels of the face and an increased number of blood vessels closer to the surface of the face are thought to be responsible for the redness and flushing associated with rosacea. […] Rosacea involves associated damage to the endothelium and degeneration of the dermal matrix. However, it is not known whether (A) the initial damage is in the dermal matrix, leading to poor tissue support of cutaneous vessels and causing pooling of serum, inflammatory mediators, and metabolic waste; or (B) the initial abnormality exists in the cutaneous vasculature, leading to leaky vessels and delayed clearance of serum proteins, inflammatory mediators, and metabolic waste, thus resulting in matrix degeneration.

• #90 Rosacea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1071429-overview

  Central facial flushing, often accompanied by burning or stinging, is the predominant sign in erythematotelangiectatic rosacea (ETR). […] The etiology of rosacea is unknown. It is likely, however, that several factors play a role in its development, including vasculature, climatic exposures, dermal matrix degeneration, chemicals and ingested agents, pilosebaceous unit abnormalities, microbial organisms, ferritin expression, reactive oxygen species (ROS), increased neoangiogenesis, and dysfunction of antimicrobial peptides (AMPs). […] Increased blood flow to the blood vessels of the face and an increased number of blood vessels closer to the surface of the face are thought to be responsible for the redness and flushing associated with rosacea. […] Rosacea involves associated damage to the endothelium and degeneration of the dermal matrix. However, it is not known whether (A) the initial damage is in the dermal matrix, leading to poor tissue support of cutaneous vessels and causing pooling of serum, inflammatory mediators, and metabolic waste; or (B) the initial abnormality exists in the cutaneous vasculature, leading to leaky vessels and delayed clearance of serum proteins, inflammatory mediators, and metabolic waste, thus resulting in matrix degeneration.

• #91 Rosacea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1071429-overview

  Demodex species (mites that normally inhabit human hair follicles) may play a role in the pathogenesis of rosacea. […] Iron catalyzes the conversion of hydrogen peroxide to free radicals, which leads to tissue injury by damaging cellular membranes, proteins, and DNA. […] Early in the inflammatory process, ROS are released by neutrophils, which are postulated to play a central role in the inflammation associated with rosacea. […] Studies performed using video capillaroscopy on ETR lesions showed increased neoangiogenesis and blood-vessel enlargement. […] AMPs are low-molecular-weight proteins that are a part of the innate immune response and have demonstrated broad-spectrum antimicrobial activity against bacteria, viruses, and fungi.

• #92 Rosacea – Dermatologic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/dermatologic-disorders/acne-and-related-disorders/rosacea

  An inflammatory phase often follows, in which sterile papules and pustules (leading to the designation of rosacea as adult acne) develop. […] The late phase (developing in some patients), is characterized by coarse tissue hyperplasia of the cheeks and nose (phymatous changes, including rhinophyma causing a large, erythematous, bulbous nose) caused by tissue inflammation, collagen deposition, and sebaceous gland hyperplasia. […] Diagnosis of rosacea is based on the characteristic appearance; there are no specific diagnostic tests. […] The objective of treatment is control of symptoms, not cure. […] Metronidazole cream (1%), lotion (0.75%), or gel (0.75%) and azelaic acid 20% cream or 15% gel, applied 2 times a day, are equally effective; 2.5% benzoyl peroxide in any form (eg, gel, lotion, cream), applied once a day or 2 times a day, can be added for improved control.

• #93 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Dysregulation of the Adaptive Immune System in Rosacea […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses. […] Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] The connection between cytokines and chemokines with the Th1/Th17 pathways and rosacea supports the notion of their association. […] The relationship between TLRs and B cells involves mechanisms where TLR activation is necessary for certain antigen-specific antibody responses in B cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin.

• #94 Pathogenesis of Rosacea | Encyclopedia MDPI

  https://encyclopedia.pub/entry/51272

  In addition, IL-b and TNF-α also act as the angiogenic factor and vascular endothelial growth factor (VEGF) and may cause the vascular changes seen in rosacea. […] Cathelicidin, an antimicrobial protein, is found in the lamellar body of keratinocytes and the granules of neutrophils. […] The LL-37 peptide in rosacea skin differs from healthy skin by having shorter fragment forms. […] These fragments have been implicated in symptoms characteristic of rosacea, including erythema, vasodilatation, flushing, and telangiectasia. […] MMPs indirectly influence the pathogenesis of rosacea by activating the preproenzyme form of KLK5 after cleavage with MMP-9. […] A study also suggested that mast cell degranulation in individuals with rosacea results in increased levels of MMP-9 and LL-37. […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses.

• #95 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Dysregulation of the Adaptive Immune System in Rosacea […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses. […] Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] The connection between cytokines and chemokines with the Th1/Th17 pathways and rosacea supports the notion of their association. […] The relationship between TLRs and B cells involves mechanisms where TLR activation is necessary for certain antigen-specific antibody responses in B cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin.

• #96 Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

  https://www.mdpi.com/2227-9059/11/8/2153

  The current understanding of adaptive immunity in rosacea is limited, with studies indicating a high prevalence of CD4+ T cell infiltration around hair follicles and blood vessels in affected skin lesions, while there is no significant increase in CD8+ T cells. […] Overall, while the involvement of innate immune cells in the pathogenesis of rosacea has been extensively investigated, the roles of adaptive immunity and specialized cells in this condition are still largely unknown. […] Rosacea is a multifaceted skin disorder characterized by facial erythema and flushing, which can be attributed to various physiological changes, including increased skin blood flow, vasodilation, angiogenesis, elevated permeability, and upregulated levels of vascular endothelial growth factor (VEGF), a critical mediator of angiogenesis and vasopermeability.

• #97 Pathogenesis of Rosacea | Encyclopedia MDPI

  https://encyclopedia.pub/entry/51272

  Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] IL-17 induces angiogenesis through the VEGF pathway and has an effect on the expression of LL-37. […] A neutrophil chemotactic factor, CXCL8, was found to be increased in rosacea via the upregulation of its mRNA gene modification. […] These chemokines in rosacea have angiogenic properties that also attract neutrophils and TH17 cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin. […] The exacerbation of rosacea by sunlight has been linked to the inflammatory effects of UV radiation on keratinocytes.

• #98 Rosacea – Dermatologic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/dermatologic-disorders/acne-and-related-disorders/rosacea

  An inflammatory phase often follows, in which sterile papules and pustules (leading to the designation of rosacea as adult acne) develop. […] The late phase (developing in some patients), is characterized by coarse tissue hyperplasia of the cheeks and nose (phymatous changes, including rhinophyma causing a large, erythematous, bulbous nose) caused by tissue inflammation, collagen deposition, and sebaceous gland hyperplasia. […] Diagnosis of rosacea is based on the characteristic appearance; there are no specific diagnostic tests. […] The objective of treatment is control of symptoms, not cure. […] Metronidazole cream (1%), lotion (0.75%), or gel (0.75%) and azelaic acid 20% cream or 15% gel, applied 2 times a day, are equally effective; 2.5% benzoyl peroxide in any form (eg, gel, lotion, cream), applied once a day or 2 times a day, can be added for improved control.

• #99 Rosacea – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/rosacea/symptoms-causes/syc-20353815

  The cause of rosacea is not known. It could be due to genetics, an overactive immune system or things in your daily life. Rosacea is not caused by poor hygiene, and you can’t catch it from other people. […] Over time, rosacea can thicken the skin on the nose, causing it to look bigger. This condition is called rhinophyma. It occurs more often in men than in women. […] Flare-ups might be brought on by: Sun or wind. Hot drinks. Spicy foods. Alcohol. Very hot and cold temperatures. Emotional stress. Exercise. Drugs that dilate blood vessels, including some blood pressure medicines. Some cosmetic, skin and hair care products.

• #100 Facial Erythema of Rosacea – Aetiology, Different Pathophysiologies and Treatment Options | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2335

  The inflammatory infiltrate, which is present in all 4 subtypes, is still poorly characterised. […] The mechanism by which LL-37 enhances the release of inflammatory mediators and promotes angiogenesis is through NLRP3 inflammasome activation. […] The vicious circle of vascular and inflammatory changes causes a persistent dilation of blood and lymphatic vessels, neoangiogenesis, telangiectasia formation and dermal matrix degradation.

• #101 Rosacea: A Misunderstood, Serious Medical Condition

  https://www.ahdbonline.com/payer-perspectives-in-dermatology/1469-article-1469

  Rosacea is a medical condition with biological underpinnings; it is not a cosmetic problem. Its underlying features are inflammation and vascular reactivity, which lead to erythema and papulopustules. […] The pathophysiology of rosacea has become an active area of research in the past decade, especially with the increasing understanding of the role of inflammation in many diseases. Rosacea is now understood to be an inflammatory disorder, based on the finding of an abnormal innate immune response system in persons with rosacea-prone skin. […] Del Rosso and colleagues recently elaborated on what they call the 2 inherent characteristics of rosacea-prone skin: neurovascular dysregulation and inflammation that produce physiochemical and structural changes in the skin. […] Current evidence supports neurovascular dysregulation and altered immune response as integral components of vasodilatory reactivity and neurogenic symptoms such as stinging and burning.

• #102 Rosacea: A Misunderstood, Serious Medical Condition

  https://www.ahdbonline.com/payer-perspectives-in-dermatology/1469-article-1469

  Rosacea is a medical condition with biological underpinnings; it is not a cosmetic problem. Its underlying features are inflammation and vascular reactivity, which lead to erythema and papulopustules. […] The pathophysiology of rosacea has become an active area of research in the past decade, especially with the increasing understanding of the role of inflammation in many diseases. Rosacea is now understood to be an inflammatory disorder, based on the finding of an abnormal innate immune response system in persons with rosacea-prone skin. […] Del Rosso and colleagues recently elaborated on what they call the 2 inherent characteristics of rosacea-prone skin: neurovascular dysregulation and inflammation that produce physiochemical and structural changes in the skin. […] Current evidence supports neurovascular dysregulation and altered immune response as integral components of vasodilatory reactivity and neurogenic symptoms such as stinging and burning.

• #103 Rosacea: A Misunderstood, Serious Medical Condition

  https://www.ahdbonline.com/payer-perspectives-in-dermatology/1469-article-1469

  With this hyperreactive immune system as background, environmental triggers can incite an exaggerated immune response. This triggering of the innate immune response system induces a signaling cascade of inflammatory factors that lead to chronic inflammation and an altered vascular state. […] Part of this inflammatory response most likely involves the toll-like receptor 2 (TLR2), which is a pattern recognition receptor that is expressed in the skin of patients with rosacea, but not in other people; abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli. […] In explaining the facial erythema (or redness) of rosacea, Del Rosso and colleagues pulled all these factors together to construct a picture of inflammation and vascular reactivity that includes an augmented innate immune response (ie, an increase in TLR2, cathelicidin precursors and peptides, and kallikrein-5); changes in the vasculature (ie, increased vascular endothelial growth factor, increased mast cells, and downstream effects of LL-37); neurovascular dysregulation (ie, vascular response, vasodilation, and neurosensory symptoms); dermal matrix degradation (ie, an increase in reactive oxygen species and matrix metalloproteinases, and a decrease in antioxidant reserve); vasodilation (ie, neurovascular dysfunction and increased nitric oxide leading to dilation and increased blood flow); and rosacea dermatitis (ie, stratum corneum barrier dysfunction and an increase in cytokines).

• #104 Rosacea: Epidemiology, pathogenesis, and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5821167/

  Rosacea’s exact pathogenesis is still unclear. […] Various environmental stimuli and endogenous factors have been shown to stimulate an augmented innate immune response and aberrant neurovascular signaling. […] Accumulating evidence points to activation of cellular pattern recognition receptors like the toll like receptor (TLR) 2 and transient receptor potential (TRP) ion channels, and release of inflammatory mediators within the skin as key steps that lead to the clinical manifestation of rosacea. […] The exact molecular mechanisms involved in rosacea’s pathophysiology are unknown, and a multifactorial etiology with a genetic preposition is likely. […] There is accumulating evidence that triggers such as microbes, ultraviolet (UV) radiation, nutrition, extremes of temperatures, (skin) barrier disruption, psychosocial stress, and hormones may stimulate an augmented innate immune response and/or neurovascular dysregulation.

• #105 Rosacea: Symptoms, Causes, and Management – DermNet

  https://dermnetnz.org/topics/rosacea

  Rosacea is a chronic inflammatory skin condition predominantly affecting the central face and most often starts between the age of 30-60 years. […] The pathogenesis of rosacea is thought to be multifactorial and includes: Genetic susceptibility, Altered microbiome of the skin and gut, Neurocutaneous mechanisms, Impaired skin barrier. […] Dysregulation of the immune response may lead to excessive inflammation, vasodilation, lymphatic dilatation, and angiogenesis. […] In the skin of patients with rosacea, there is increased expression and activity of toll-like receptor 2, cathelicidins, kallikrein 5, and mast cells. […] The result is an exaggerated innate immune reaction to the initial trigger. […] Dominant T-helper (Th)1/Th17 gene expression in all features of rosacea. […] Increased Th17 expression can increase levels of cathelicidin LL-37 in keratinocytes and drive further inflammation. […] The most significant environmental trigger is UV radiation; affected skin is more sensitive to exposure. UV radiation can damage the dermis and increase skin inflammation.

• #106 Rosacea: Symptoms, Causes, and Management – DermNet

  https://dermnetnz.org/topics/rosacea

  Rosacea is a chronic inflammatory skin condition predominantly affecting the central face and most often starts between the age of 30-60 years. […] The pathogenesis of rosacea is thought to be multifactorial and includes: Genetic susceptibility, Altered microbiome of the skin and gut, Neurocutaneous mechanisms, Impaired skin barrier. […] Dysregulation of the immune response may lead to excessive inflammation, vasodilation, lymphatic dilatation, and angiogenesis. […] In the skin of patients with rosacea, there is increased expression and activity of toll-like receptor 2, cathelicidins, kallikrein 5, and mast cells. […] The result is an exaggerated innate immune reaction to the initial trigger. […] Dominant T-helper (Th)1/Th17 gene expression in all features of rosacea. […] Increased Th17 expression can increase levels of cathelicidin LL-37 in keratinocytes and drive further inflammation. […] The most significant environmental trigger is UV radiation; affected skin is more sensitive to exposure. UV radiation can damage the dermis and increase skin inflammation.

• #107 Rosacea – Dermatologic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/dermatologic-disorders/acne-and-related-disorders/rosacea

  Topical ivermectin 1% cream also has efficacy in the treatment of inflammatory lesions of rosacea. […] Oral antibiotics are indicated for patients with multiple papules or pustules and for those with ocular rosacea. […] Persistent erythema or flushing may be treated with the topical alpha-2-selective adrenergic agonist brimonidine 0.33% gel applied once a day or with the primarily alpha-1a agonist oxymetazoline hydrochloride 1% cream applied once a day. […] Recalcitrant cases may respond to oral isotretinoin. […] Techniques for treatment of rhinophyma include dermabrasion, laser ablation, and tissue excision; cosmetic results are good. […] Consider rosacea if patients have facial flushing and blushing, with or without stinging, often triggered by sun exposure, emotional stress, cold or hot weather, alcohol, spicy foods, exercise, wind, cosmetics, or hot baths or hot drinks. […] Treat rosacea with avoidance of triggers; treat inflammation, depending on severity, with topical antibiotics and/or azelaic acid, oral antibiotics, isotretinoin, or topical ivermectin.

• #108 Rosacea – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/rosacea/symptoms-causes/syc-20353815

  The cause of rosacea is not known. It could be due to genetics, an overactive immune system or things in your daily life. Rosacea is not caused by poor hygiene, and you can’t catch it from other people. […] Over time, rosacea can thicken the skin on the nose, causing it to look bigger. This condition is called rhinophyma. It occurs more often in men than in women. […] Flare-ups might be brought on by: Sun or wind. Hot drinks. Spicy foods. Alcohol. Very hot and cold temperatures. Emotional stress. Exercise. Drugs that dilate blood vessels, including some blood pressure medicines. Some cosmetic, skin and hair care products.

• #109 Rosacea – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/rosacea/symptoms-causes/syc-20353815

  The cause of rosacea is not known. It could be due to genetics, an overactive immune system or things in your daily life. Rosacea is not caused by poor hygiene, and you can’t catch it from other people. […] Over time, rosacea can thicken the skin on the nose, causing it to look bigger. This condition is called rhinophyma. It occurs more often in men than in women. […] Flare-ups might be brought on by: Sun or wind. Hot drinks. Spicy foods. Alcohol. Very hot and cold temperatures. Emotional stress. Exercise. Drugs that dilate blood vessels, including some blood pressure medicines. Some cosmetic, skin and hair care products.

• #110 Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

  https://www.mdpi.com/2227-9059/11/8/2153

  Recent research suggests the involvement of the nervous system and intricate neuroimmune interactions. […] The complex pathophysiology of vascular dysregulation involves the activation of multiple pro-angiogenic mediators. […] Patients with rosacea present with sensitivity to various triggering factors, such as cold, heat, ultraviolet (UV) radiation, capsaicin, alcohol, and stress, which are defining characteristics of sensitive skin. […] The integrity of the skin barrier is of utmost importance in shielding the body against external agents and preserving its internal balance. […] Skin barrier dysfunction can contribute to the development and progression of inflammatory skin disorders. […] The cutaneous microbiota, consisting of a diverse array of microorganisms, such as bacteria, viruses, fungi, and mites that colonize both on and within the skin, constitutes a crucial constituent of the skin’s barrier function.

• #111 Rosacea: An Overview of Its Etiological Factors, Pathogenesis, Classification and Therapy Options

  https://www.mdpi.com/2673-6179/3/4/19

  Dysregulation of the Adaptive Immune System in Rosacea […] In the pathogenesis of rosacea, pro-inflammatory cytokines and chemokines play dominant roles in the infiltration of inflammatory cells and trigger immune responses. […] Among the total T cells in rosacea skin, an increase in CD4+ over CD8+ T cells has been demonstrated. […] The connection between cytokines and chemokines with the Th1/Th17 pathways and rosacea supports the notion of their association. […] The relationship between TLRs and B cells involves mechanisms where TLR activation is necessary for certain antigen-specific antibody responses in B cells. […] Demodex folliculorum is the predominant microbial agent within the skin that is commonly associated with the development of rosacea. […] High densities of D. folliculorum lead to the release of pro-inflammatory mediators such as TNF-α, IL-1b, IL-8, and LL-37 into the skin.

• #112 Ocular Rosacea: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1197341-overview

  Moreover, toll-like receptor 2 activity in the innate immune system is increased in patients with rosacea. […] A variety of rosacea triggers have been described including skin colonization with Demodex mites (along with bacteria in their gut) and Staphylococcus epidermidis. […] Eradication of Helicobacter pylori has been shown to improve rosacea in some patients, and the organism may play a role in the pathogenesis of inflammation in rosacea. […] Four distinct rosacea subtypes have been described: erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea.

• #113 Factors in rosacea pathogenesis clearer

  https://www.dermatologytimes.com/view/factors-rosacea-pathogenesis-clearer

  Triggers such as heat, stress and spices stimulate the transient receptor potential vanilloid (TRPV 1 through 4) and transient receptor potential ankyrin (TRPA) channels. […] The impact of other potential pathogens remains unsettled. […] „If you ask me, or many American dermatologists, it’s less decided.” […] Although D. folliculorum levels are elevated in rosacea, he explained, people can have heavy D. folliculorum colonization, but no rosacea, and vice versa. […] „The issue is confounded by the fact that the anti-mite drug Soolantra (topical ivermectin, Galderma) works well in rosacea.” […] „It sounds like something’s going on there. Also, the immune response to B. oleronius was found to be especially elevated in ocular rosacea.” […] „Much remains to be worked out.” […] „We must give Richard Gallo, M.D., Ph.D., a lot of credit. He’s done much of the research in rosacea.”

• #114 Factors in rosacea pathogenesis clearer

  https://www.dermatologytimes.com/view/factors-rosacea-pathogenesis-clearer

  Triggers such as heat, stress and spices stimulate the transient receptor potential vanilloid (TRPV 1 through 4) and transient receptor potential ankyrin (TRPA) channels. […] The impact of other potential pathogens remains unsettled. […] „If you ask me, or many American dermatologists, it’s less decided.” […] Although D. folliculorum levels are elevated in rosacea, he explained, people can have heavy D. folliculorum colonization, but no rosacea, and vice versa. […] „The issue is confounded by the fact that the anti-mite drug Soolantra (topical ivermectin, Galderma) works well in rosacea.” […] „It sounds like something’s going on there. Also, the immune response to B. oleronius was found to be especially elevated in ocular rosacea.” […] „Much remains to be worked out.” […] „We must give Richard Gallo, M.D., Ph.D., a lot of credit. He’s done much of the research in rosacea.”

• #115 Additional evidence that rosacea pathogenesis may involve demodex: new information from the topical efficacy of ivermectin and praziquantel

  https://escholarship.org/uc/item/13v249f5

  Additional evidence that Demodex folliculorum may contribute to the pathogenesis of papulopustular rosacea are new studies of two topical antiparasitic agents. Ivermectin and praziquantel have recently been shown to be effective in decreasing the severity of papulopustular rosacea. […] Higher numbers of Demodex mites are found in the skin of patients with rosacea than in people with normal skin. If Demodex play a role in pathogenesis, then hypersensitivity to the mites, their flora, or their products could explain the observed efficacy of antidemodectic therapy.

• #116 Novel Rosacea Compound, Ivermectin Cream, Offers Unique Mechanism of Action

  https://www.ahdbonline.com/payer-perspectives-in-dermatology/novel-rosacea-compound-ivermectin-cream-offers-unique-mechanism-of-action

  The pathogenesis of rosacea, a chronic inflammatory disorder that is characterized by facial papules, pustules, and persistent erythema, is multifactorial. Many factors are believed to activate neurovascular and immune responses, leading to inflammation that results in flares. […] The exact role of Demodex in causing rosacea is not well understood, but it is believed that the mites or the Bacillus oleronius bacteria that they harbor trigger inflammatory or immune reactions that result in the symptoms of rosacea. […] Developing Demodex mites may be causative agents of rosacea through various mechanisms: they may mechanically block hair follicles, secrete digestive enzymes, destroy the epithelial barrier or trigger reactions of the immune system. […] Ivermectin 1% cream has a unique mechanism of action among current treatments for rosacea; unlike available treatments, this unique mechanism addresses the inflammatory process involved in rosacea and the key organism, Demodex.

• #117 Novel Rosacea Compound, Ivermectin Cream, Offers Unique Mechanism of Action

  https://www.ahdbonline.com/payer-perspectives-in-dermatology/novel-rosacea-compound-ivermectin-cream-offers-unique-mechanism-of-action

  The pathogenesis of rosacea, a chronic inflammatory disorder that is characterized by facial papules, pustules, and persistent erythema, is multifactorial. Many factors are believed to activate neurovascular and immune responses, leading to inflammation that results in flares. […] The exact role of Demodex in causing rosacea is not well understood, but it is believed that the mites or the Bacillus oleronius bacteria that they harbor trigger inflammatory or immune reactions that result in the symptoms of rosacea. […] Developing Demodex mites may be causative agents of rosacea through various mechanisms: they may mechanically block hair follicles, secrete digestive enzymes, destroy the epithelial barrier or trigger reactions of the immune system. […] Ivermectin 1% cream has a unique mechanism of action among current treatments for rosacea; unlike available treatments, this unique mechanism addresses the inflammatory process involved in rosacea and the key organism, Demodex.

• #118 Factors in rosacea pathogenesis clearer

  https://www.dermatologytimes.com/view/factors-rosacea-pathogenesis-clearer

  Triggers such as heat, stress and spices stimulate the transient receptor potential vanilloid (TRPV 1 through 4) and transient receptor potential ankyrin (TRPA) channels. […] The impact of other potential pathogens remains unsettled. […] „If you ask me, or many American dermatologists, it’s less decided.” […] Although D. folliculorum levels are elevated in rosacea, he explained, people can have heavy D. folliculorum colonization, but no rosacea, and vice versa. […] „The issue is confounded by the fact that the anti-mite drug Soolantra (topical ivermectin, Galderma) works well in rosacea.” […] „It sounds like something’s going on there. Also, the immune response to B. oleronius was found to be especially elevated in ocular rosacea.” […] „Much remains to be worked out.” […] „We must give Richard Gallo, M.D., Ph.D., a lot of credit. He’s done much of the research in rosacea.”

• #119 Rosacea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1071429-overview

  Central facial flushing, often accompanied by burning or stinging, is the predominant sign in erythematotelangiectatic rosacea (ETR). […] The etiology of rosacea is unknown. It is likely, however, that several factors play a role in its development, including vasculature, climatic exposures, dermal matrix degeneration, chemicals and ingested agents, pilosebaceous unit abnormalities, microbial organisms, ferritin expression, reactive oxygen species (ROS), increased neoangiogenesis, and dysfunction of antimicrobial peptides (AMPs). […] Increased blood flow to the blood vessels of the face and an increased number of blood vessels closer to the surface of the face are thought to be responsible for the redness and flushing associated with rosacea. […] Rosacea involves associated damage to the endothelium and degeneration of the dermal matrix. However, it is not known whether (A) the initial damage is in the dermal matrix, leading to poor tissue support of cutaneous vessels and causing pooling of serum, inflammatory mediators, and metabolic waste; or (B) the initial abnormality exists in the cutaneous vasculature, leading to leaky vessels and delayed clearance of serum proteins, inflammatory mediators, and metabolic waste, thus resulting in matrix degeneration.

• #120 Rosacea: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1071429-overview

  Central facial flushing, often accompanied by burning or stinging, is the predominant sign in erythematotelangiectatic rosacea (ETR). […] The etiology of rosacea is unknown. It is likely, however, that several factors play a role in its development, including vasculature, climatic exposures, dermal matrix degeneration, chemicals and ingested agents, pilosebaceous unit abnormalities, microbial organisms, ferritin expression, reactive oxygen species (ROS), increased neoangiogenesis, and dysfunction of antimicrobial peptides (AMPs). […] Increased blood flow to the blood vessels of the face and an increased number of blood vessels closer to the surface of the face are thought to be responsible for the redness and flushing associated with rosacea. […] Rosacea involves associated damage to the endothelium and degeneration of the dermal matrix. However, it is not known whether (A) the initial damage is in the dermal matrix, leading to poor tissue support of cutaneous vessels and causing pooling of serum, inflammatory mediators, and metabolic waste; or (B) the initial abnormality exists in the cutaneous vasculature, leading to leaky vessels and delayed clearance of serum proteins, inflammatory mediators, and metabolic waste, thus resulting in matrix degeneration.

• #121 Facial Erythema of Rosacea – Aetiology, Different Pathophysiologies and Treatment Options | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2335

  The key pathophysiological elements that are often present are augmented immune activation and response, and neurovascular dysregulation. […] However, a critical problem is that early ETR (commonly-termed pre-rosacea or early-onset rosacea), which manifests as transient flushing without any other rosacea signs or symptoms and is dependent on rosacea trigger factors, has not been thoroughly investigated. […] Various microbes including bacteria or mites have been implicated in the pathophysiology of rosacea. […] Demodex folliculorum or bacteria digested within Demodex mites have been implicated in the pathophysiology of rosacea and are thought to trigger the innate immune responses rather than be a mandatory component. […] In patients with ETR, there is a marked upregulation of proinflammatory and vasoregulatory genes.

• #122 Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

  https://www.mdpi.com/2227-9059/11/8/2153

  The current understanding of adaptive immunity in rosacea is limited, with studies indicating a high prevalence of CD4+ T cell infiltration around hair follicles and blood vessels in affected skin lesions, while there is no significant increase in CD8+ T cells. […] Overall, while the involvement of innate immune cells in the pathogenesis of rosacea has been extensively investigated, the roles of adaptive immunity and specialized cells in this condition are still largely unknown. […] Rosacea is a multifaceted skin disorder characterized by facial erythema and flushing, which can be attributed to various physiological changes, including increased skin blood flow, vasodilation, angiogenesis, elevated permeability, and upregulated levels of vascular endothelial growth factor (VEGF), a critical mediator of angiogenesis and vasopermeability.

• #123 Mast cells may play key role in rosacea pathogenesis

  https://www.dermatologytimes.com/view/mast-cells-may-play-key-role-rosacea-pathogenesis

  Mast cells appear to play an intricate role in the pathophysiology of rosacea and could serve as potential targets for future therapies, according to recent study findings. […] Rosacea is a complex disorder caused by immune dysfunction and neurovascular dysregulation involving many types of inflammatory cells, writes Lin Wang, M.D., and fellow colleagues, department of dermatology, West China Hospital, Sichuan University, Chengdu, China, in the paper that recently appeared in Frontiers in Medicine. […] Mast cells participate in the pathogenesis of rosacea through innate immune responses, neurogenetic inflammation, angiogenesis, and fibrosis. Mast cells can be important immune cells that connect innate immunity, nerves, and blood vessels in the development of rosacea, no matter what the subtypes, the authors write. […] According to the study authors, the important role of mast cells makes them a potential target for drug therapy however, more studies are needed to evaluate the efficacy for its inhibition in the treatment of rosacea.

• #124 Mast cells may play key role in rosacea pathogenesis

  https://www.dermatologytimes.com/view/mast-cells-may-play-key-role-rosacea-pathogenesis

  Mast cells appear to play an intricate role in the pathophysiology of rosacea and could serve as potential targets for future therapies, according to recent study findings. […] Rosacea is a complex disorder caused by immune dysfunction and neurovascular dysregulation involving many types of inflammatory cells, writes Lin Wang, M.D., and fellow colleagues, department of dermatology, West China Hospital, Sichuan University, Chengdu, China, in the paper that recently appeared in Frontiers in Medicine. […] Mast cells participate in the pathogenesis of rosacea through innate immune responses, neurogenetic inflammation, angiogenesis, and fibrosis. Mast cells can be important immune cells that connect innate immunity, nerves, and blood vessels in the development of rosacea, no matter what the subtypes, the authors write. […] According to the study authors, the important role of mast cells makes them a potential target for drug therapy however, more studies are needed to evaluate the efficacy for its inhibition in the treatment of rosacea.

• #125 Mast cells may play key role in rosacea pathogenesis

  https://www.dermatologytimes.com/view/mast-cells-may-play-key-role-rosacea-pathogenesis

  Mast cells appear to play an intricate role in the pathophysiology of rosacea and could serve as potential targets for future therapies, according to recent study findings. […] Rosacea is a complex disorder caused by immune dysfunction and neurovascular dysregulation involving many types of inflammatory cells, writes Lin Wang, M.D., and fellow colleagues, department of dermatology, West China Hospital, Sichuan University, Chengdu, China, in the paper that recently appeared in Frontiers in Medicine. […] Mast cells participate in the pathogenesis of rosacea through innate immune responses, neurogenetic inflammation, angiogenesis, and fibrosis. Mast cells can be important immune cells that connect innate immunity, nerves, and blood vessels in the development of rosacea, no matter what the subtypes, the authors write. […] According to the study authors, the important role of mast cells makes them a potential target for drug therapy however, more studies are needed to evaluate the efficacy for its inhibition in the treatment of rosacea.

• #126 Mast cells may play key role in rosacea pathogenesis

  https://www.dermatologytimes.com/view/mast-cells-may-play-key-role-rosacea-pathogenesis

  Mast cells appear to play an intricate role in the pathophysiology of rosacea and could serve as potential targets for future therapies, according to recent study findings. […] Rosacea is a complex disorder caused by immune dysfunction and neurovascular dysregulation involving many types of inflammatory cells, writes Lin Wang, M.D., and fellow colleagues, department of dermatology, West China Hospital, Sichuan University, Chengdu, China, in the paper that recently appeared in Frontiers in Medicine. […] Mast cells participate in the pathogenesis of rosacea through innate immune responses, neurogenetic inflammation, angiogenesis, and fibrosis. Mast cells can be important immune cells that connect innate immunity, nerves, and blood vessels in the development of rosacea, no matter what the subtypes, the authors write. […] According to the study authors, the important role of mast cells makes them a potential target for drug therapy however, more studies are needed to evaluate the efficacy for its inhibition in the treatment of rosacea.

• #127 Factors in rosacea pathogenesis clearer

  https://www.dermatologytimes.com/view/factors-rosacea-pathogenesis-clearer

  „We believe that some of the normal innate immune pathways are working overtime in people with rosacea. There’s too much toll-like receptor (TLR)-2 activity, cathelicidin activity and kallikrein 5, which turns the inactive form of cathelicidin into LL37, the antimicrobial peptide at work in rosacea.” […] Within the innate immune system, mast cells may represent a promising target. […] „Mast cells communicate with nerves. And one of the things we know for sure about rosacea is that the nerves trigger blood vessel functions including vasodilation and constriction. The mast cell may well be at the heart of rosacea if one can calm it down, rosacea also may calm down, in theory.” […] „One might say that there is one prime driver I’d conjecture that it may be a neurological stimulus and all the other factors are epiphenomena.”

• #128 Factors in rosacea pathogenesis clearer

  https://www.dermatologytimes.com/view/factors-rosacea-pathogenesis-clearer

  „We believe that some of the normal innate immune pathways are working overtime in people with rosacea. There’s too much toll-like receptor (TLR)-2 activity, cathelicidin activity and kallikrein 5, which turns the inactive form of cathelicidin into LL37, the antimicrobial peptide at work in rosacea.” […] Within the innate immune system, mast cells may represent a promising target. […] „Mast cells communicate with nerves. And one of the things we know for sure about rosacea is that the nerves trigger blood vessel functions including vasodilation and constriction. The mast cell may well be at the heart of rosacea if one can calm it down, rosacea also may calm down, in theory.” […] „One might say that there is one prime driver I’d conjecture that it may be a neurological stimulus and all the other factors are epiphenomena.”

• #129 Eyelid Protein Reveals Rosacea Pathogenesis

  https://www.reviewofoptometry.com/article/eyelid-protein-reveals-rosacea-pathogenesis

  Rosacea is a common condition among the US population, affecting as much as 10% of the population. […] New research from the Lions Eye Institute in New York used eyelid specimens from patients with rosacea to discovered increased amounts of the protein nuclear factor kappa-B (NFKB), which may have implications for treatment one day. […] The activated form of NFKB is enriched in rosacea, indicating a role for this pathway in the pathogenesis of this disease. Interference with NFKB signaling may represent a novel therapy for rosacea as clinical agents become available, the study concludes.

• #130 Eyelid Protein Reveals Rosacea Pathogenesis

  https://www.reviewofoptometry.com/article/eyelid-protein-reveals-rosacea-pathogenesis

  Rosacea is a common condition among the US population, affecting as much as 10% of the population. […] New research from the Lions Eye Institute in New York used eyelid specimens from patients with rosacea to discovered increased amounts of the protein nuclear factor kappa-B (NFKB), which may have implications for treatment one day. […] The activated form of NFKB is enriched in rosacea, indicating a role for this pathway in the pathogenesis of this disease. Interference with NFKB signaling may represent a novel therapy for rosacea as clinical agents become available, the study concludes.

• #131 Eyelid Protein Reveals Rosacea Pathogenesis

  https://www.reviewofoptometry.com/article/eyelid-protein-reveals-rosacea-pathogenesis

  Rosacea is a common condition among the US population, affecting as much as 10% of the population. […] New research from the Lions Eye Institute in New York used eyelid specimens from patients with rosacea to discovered increased amounts of the protein nuclear factor kappa-B (NFKB), which may have implications for treatment one day. […] The activated form of NFKB is enriched in rosacea, indicating a role for this pathway in the pathogenesis of this disease. Interference with NFKB signaling may represent a novel therapy for rosacea as clinical agents become available, the study concludes.

• #132 Exploring the association between rosacea and acne by integrated bioinformatics analysis | Scientific Reports

  https://www.nature.com/articles/s41598-024-53453-x

  A total of 151 up-regulated and 18 down-regulated co-DEGs were identified. KEGG pathway analysis of up-regulated co-DEGs demonstrated that they were mainly involved in IL-17 signaling pathway, NF-B signaling pathway, Toll-like receptor signaling pathway, and TNF signaling pathway. This is consistent with previous findings that these pathways are involved in the development of both rosacea and acne. […] The expression of CXCL10, MMP9, IL1B, CXCL8, and CXCR4 were co-regulated by IRF1, STAT1, STAT3, IKBKB, HDAC1, ETS1, and CEBPB, which were highly expressed in rosacea and acne lesions. […] The infiltration of gamma delta T cells was significantly increased and positively correlated with almost all hub genes in both rosacea and acne, suggesting that gamma delta T cells may play a crucial role in the pathogenesis of these two diseases.

• #133 ACSL5 mediates macrophage infiltration and lipid metabolism in erythrotelangiectasia rosacea via potential pathogenic mechanisms and therapeutic targets | Scientific Reports

  https://www.nature.com/articles/s41598-025-96756-3

  Rosacea, an inflammatory skin disorder with complex pathogenesis, remains poorly understood. […] These findings provide new insights into ETR pathogenesis and highlight ACSL5 as a promising therapeutic target for inflammatory skin disorders. […] It is believed that neurovascular dysregulation and abnormalities in both the adaptive and innate immune systems predispose individuals to this condition, leading to aberrant and persistent vasodilation of the facial skin. […] Th1 and Th17 cell-mediated immune responses may impact adaptive immunity among individuals afflicted with an abnormal increase in ROS levels. […] Our findings revealed differential expression of lipid metabolism-related genes and increased M1 macrophage infiltration in ETR lesions, with ACSL5 potentially serving as a critical bridging gene connecting these two aspects.

• #134 ACSL5 mediates macrophage infiltration and lipid metabolism in erythrotelangiectasia rosacea via potential pathogenic mechanisms and therapeutic targets | Scientific Reports

  https://www.nature.com/articles/s41598-025-96756-3

  The enhanced ACSL5 expression and its co-localization with M1 macrophage markers suggest a potential association between lipid metabolism dysregulation and increased M1 macrophage polarization in the pathogenesis of rosacea. […] These findings provide new insights into the disease mechanism and highlight ACSL5 as a potential therapeutic target. […] Given its role in both lipid metabolism and macrophage polarization, ACSL5 may serve as a therapeutic target in rosacea.

• #135 ACSL5 mediates macrophage infiltration and lipid metabolism in erythrotelangiectasia rosacea via potential pathogenic mechanisms and therapeutic targets | Scientific Reports

  https://www.nature.com/articles/s41598-025-96756-3

  The enhanced ACSL5 expression and its co-localization with M1 macrophage markers suggest a potential association between lipid metabolism dysregulation and increased M1 macrophage polarization in the pathogenesis of rosacea. […] These findings provide new insights into the disease mechanism and highlight ACSL5 as a potential therapeutic target. […] Given its role in both lipid metabolism and macrophage polarization, ACSL5 may serve as a therapeutic target in rosacea.

• #136 Potential Role of Tranexamic Acid in Rosacea Treatment | CCID

  https://www.dovepress.com/potential-role-of-tranexamic-acid-in-rosacea-treatment-conquering-flus-peer-reviewed-fulltext-article-CCID

  Rosacea is a chronic inflammatory skin disease that affects a patients appearance and quality of life. […] The precise pathogenesis of rosacea remains unclear, with hypotheses that it could be associated with genetic background, abnormal innate and adaptive immunity, dysregulated neurovascular system, impaired skin barrier function, and an altered microbiome. […] In rosacea, several molecules related to innate immunity, including toll-like receptor 2, serine proteinase kallikrein 5 (KLK5), and cathelicidin, are overexpressed. […] Considering the aforementioned pathogenesis, a series of topical and systemic medications are available for different targets. […] The underlying mechanisms of TA in rosacea treatment are unknown. […] Two experimental studies focused on the effect of TA on the function of the skin permeability barrier, immune reactions, and angiogenesis.

• #137 Potential Role of Tranexamic Acid in Rosacea Treatment | CCID

  https://www.dovepress.com/potential-role-of-tranexamic-acid-in-rosacea-treatment-conquering-flus-peer-reviewed-fulltext-article-CCID

  Rosacea is a chronic inflammatory skin disease that affects a patients appearance and quality of life. […] The precise pathogenesis of rosacea remains unclear, with hypotheses that it could be associated with genetic background, abnormal innate and adaptive immunity, dysregulated neurovascular system, impaired skin barrier function, and an altered microbiome. […] In rosacea, several molecules related to innate immunity, including toll-like receptor 2, serine proteinase kallikrein 5 (KLK5), and cathelicidin, are overexpressed. […] Considering the aforementioned pathogenesis, a series of topical and systemic medications are available for different targets. […] The underlying mechanisms of TA in rosacea treatment are unknown. […] Two experimental studies focused on the effect of TA on the function of the skin permeability barrier, immune reactions, and angiogenesis.

• #138 Potential Role of Tranexamic Acid in Rosacea Treatment | CCID

  https://www.dovepress.com/potential-role-of-tranexamic-acid-in-rosacea-treatment-conquering-flus-peer-reviewed-fulltext-article-CCID

  TA may alleviate the clinical manifestations of rosacea via at least two pathways: regulating the immune response and reducing angiogenesis. […] The mechanisms that have been clarified thus far are depicted in Figure 1. […] However, it is not yet clear which one plays a major role, and whether a synergistic mechanism exists among these drugs.

• #139 Potential Role of Tranexamic Acid in Rosacea Treatment | CCID

  https://www.dovepress.com/potential-role-of-tranexamic-acid-in-rosacea-treatment-conquering-flus-peer-reviewed-fulltext-article-CCID

  TA may alleviate the clinical manifestations of rosacea via at least two pathways: regulating the immune response and reducing angiogenesis. […] The mechanisms that have been clarified thus far are depicted in Figure 1. […] However, it is not yet clear which one plays a major role, and whether a synergistic mechanism exists among these drugs.

• #140

  https://scholars.duke.edu/individual/pub1243207

  TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. […] These findings render TRPV4 a translational-medical target in rosacea. […] However, signaling mechanisms causing increased expression of TRPV4 await elucidation. […] Moreover, we ask whether TRPV4-mediated Ca++-influx evokes mast cell degranulation.

• #141

  https://scholars.duke.edu/individual/pub1243207

  TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. […] These findings render TRPV4 a translational-medical target in rosacea. […] However, signaling mechanisms causing increased expression of TRPV4 await elucidation. […] Moreover, we ask whether TRPV4-mediated Ca++-influx evokes mast cell degranulation.

• #142

  https://scholars.duke.edu/individual/pub1243207

  TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. […] These findings render TRPV4 a translational-medical target in rosacea. […] However, signaling mechanisms causing increased expression of TRPV4 await elucidation. […] Moreover, we ask whether TRPV4-mediated Ca++-influx evokes mast cell degranulation.

• #143

  https://scholars.duke.edu/individual/pub1243207

  TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. […] These findings render TRPV4 a translational-medical target in rosacea. […] However, signaling mechanisms causing increased expression of TRPV4 await elucidation. […] Moreover, we ask whether TRPV4-mediated Ca++-influx evokes mast cell degranulation.

• #144 Surgical & Cosmetic Dermatology | Prospective study for the treatment of rosacea flushing with botulinum toxin type A

  http://www.surgicalcosmetic.org.br/details/634/en-US/prospective-study-for-the-treatment-of-rosacea-flushing-with-botulinum-toxin-type-a

  It has been proposed that acetylcholine, an important neuromediator linked to the mechanism of neurogenic inflammation through peripheral nerves, plays a role in cutaneous vasodilation and consequently in rosacea-reactive erythema. The precise mechanism of action in the improvement of erythema has not yet been fully elucidated, however the action in the blocking of acetylcholine is one of the main evidences.

• #145 Surgical & Cosmetic Dermatology | Prospective study for the treatment of rosacea flushing with botulinum toxin type A

  http://www.surgicalcosmetic.org.br/details/634/en-US/prospective-study-for-the-treatment-of-rosacea-flushing-with-botulinum-toxin-type-a

  It has been proposed that acetylcholine, an important neuromediator linked to the mechanism of neurogenic inflammation through peripheral nerves, plays a role in cutaneous vasodilation and consequently in rosacea-reactive erythema. The precise mechanism of action in the improvement of erythema has not yet been fully elucidated, however the action in the blocking of acetylcholine is one of the main evidences.

• #146 Surgical & Cosmetic Dermatology | Prospective study for the treatment of rosacea flushing with botulinum toxin type A

  http://www.surgicalcosmetic.org.br/details/634/en-US/prospective-study-for-the-treatment-of-rosacea-flushing-with-botulinum-toxin-type-a

  Rosacea is a chronic facial condition characterized by erythema, edema, telangiectasias, papules and possibly pustules and nodules. Its pathogenesis is multifactorial, and the treatments, diverse. […] The exact pathogenesis of rosacea is still unknown, however some factors are deemed relevant for its occurrence, such as: dysfunction in the innate immune system; exposure to ultraviolet radiation, which causes increased angiogenesis and the production of reactive oxygen species; vascular changes, increasing the expression of vascular endothelial growth factor and lymphatic endothelial markers; epidermal barrier dysfunction; neurogenic inflammation (sensory nerves release neuromediators at the site of inflammation resulting in vasodilation); recruitment of inflammatory cells; extravasation of plasma proteins; and microbial action – Demodex foliculorum and Demodex brevis, and intense perifollicular inflammatory infiltrate. Such factors lead to a persistent inflammatory state that becomes chronic.

• #147 New insights into the mutual promotion of rosacea | CCID

  https://www.dovepress.com/new-insights-into-the-mutual-promotion-of-rosacea-anxiety-and-depressi-peer-reviewed-fulltext-article-CCID

  Extensive literature has confirmed that TRP channels, especially transient receptor potential ankyrin 1(TRPA1), as cation channels activated by active compounds, are the gatekeepers of cytokine signals that mediate skin inflammation and activate sensory nerves. […] The hypothalamus-pituitary-adrenal axis(HPA) plays a vital role in the course of rosacea. […] Like many other inflammatory skin diseases, rosacea begins with the perception of external physical, chemical, and biological stimuli by the skins nervous and immune systems, such as ultraviolet radiation, which is the primary initial stressor triggering the skins inflammatory response. […] A large body of previous evidence suggests that dysfunction of the HPA axis is closely associated with the development of anxiety and depression disorders.

• #148 New insights into the mutual promotion of rosacea | CCID

  https://www.dovepress.com/new-insights-into-the-mutual-promotion-of-rosacea-anxiety-and-depressi-peer-reviewed-fulltext-article-CCID

  Extensive literature has confirmed that TRP channels, especially transient receptor potential ankyrin 1(TRPA1), as cation channels activated by active compounds, are the gatekeepers of cytokine signals that mediate skin inflammation and activate sensory nerves. […] The hypothalamus-pituitary-adrenal axis(HPA) plays a vital role in the course of rosacea. […] Like many other inflammatory skin diseases, rosacea begins with the perception of external physical, chemical, and biological stimuli by the skins nervous and immune systems, such as ultraviolet radiation, which is the primary initial stressor triggering the skins inflammatory response. […] A large body of previous evidence suggests that dysfunction of the HPA axis is closely associated with the development of anxiety and depression disorders.

• #149 New insights into the mutual promotion of rosacea | CCID

  https://www.dovepress.com/new-insights-into-the-mutual-promotion-of-rosacea-anxiety-and-depressi-peer-reviewed-fulltext-article-CCID

  Extensive literature has confirmed that TRP channels, especially transient receptor potential ankyrin 1(TRPA1), as cation channels activated by active compounds, are the gatekeepers of cytokine signals that mediate skin inflammation and activate sensory nerves. […] The hypothalamus-pituitary-adrenal axis(HPA) plays a vital role in the course of rosacea. […] Like many other inflammatory skin diseases, rosacea begins with the perception of external physical, chemical, and biological stimuli by the skins nervous and immune systems, such as ultraviolet radiation, which is the primary initial stressor triggering the skins inflammatory response. […] A large body of previous evidence suggests that dysfunction of the HPA axis is closely associated with the development of anxiety and depression disorders.

• #150 Exploring the association between rosacea and acne by integrated bioinformatics analysis | Scientific Reports

  https://www.nature.com/articles/s41598-024-53453-x

  A total of 151 up-regulated and 18 down-regulated co-DEGs were identified. KEGG pathway analysis of up-regulated co-DEGs demonstrated that they were mainly involved in IL-17 signaling pathway, NF-B signaling pathway, Toll-like receptor signaling pathway, and TNF signaling pathway. This is consistent with previous findings that these pathways are involved in the development of both rosacea and acne. […] The expression of CXCL10, MMP9, IL1B, CXCL8, and CXCR4 were co-regulated by IRF1, STAT1, STAT3, IKBKB, HDAC1, ETS1, and CEBPB, which were highly expressed in rosacea and acne lesions. […] The infiltration of gamma delta T cells was significantly increased and positively correlated with almost all hub genes in both rosacea and acne, suggesting that gamma delta T cells may play a crucial role in the pathogenesis of these two diseases.

• #151 New insights into the mutual promotion of rosacea | CCID

  https://www.dovepress.com/new-insights-into-the-mutual-promotion-of-rosacea-anxiety-and-depressi-peer-reviewed-fulltext-article-CCID

  Previous literature suggests that Th17 cells are recruited into the CNS beginning in the initial stages of chronic stress, propagating from the peripheral immune response to the CNS and progressively exacerbating depression-like symptoms. […] The overlap of inflammatory immune disorders in psychiatric disorders and rosacea also suggests a complex of co-morbidities and homeostatic imbalance in the organism.

• #152 New insights into the mutual promotion of rosacea | CCID

  https://www.dovepress.com/new-insights-into-the-mutual-promotion-of-rosacea-anxiety-and-depressi-peer-reviewed-fulltext-article-CCID

  Previous literature suggests that Th17 cells are recruited into the CNS beginning in the initial stages of chronic stress, propagating from the peripheral immune response to the CNS and progressively exacerbating depression-like symptoms. […] The overlap of inflammatory immune disorders in psychiatric disorders and rosacea also suggests a complex of co-morbidities and homeostatic imbalance in the organism.

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