Rosacea

Complex MONDO:0006604 Pathograph 29 Dermatological Disease Inflammatory Skin Disease

Rosacea is a chronic relapsing inflammatory facial dermatosis centered on persistent or episodic centrofacial erythema, flushing, telangiectasia, and papulopustular lesions, with phymatous and ocular involvement in a subset of patients. Current mechanistic models emphasize dysregulated innate immunity, neurovascular hyperreactivity, skin barrier impairment, and trigger-dependent disease amplification.

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Subtypes

Erythematotelangiectatic Rosacea

Predominantly vascular rosacea phenotype characterized by persistent centrofacial erythema, flushing, and telangiectasia without dominant papulopustular or phymatous change.

Show evidence (2 references)

PMID:28150107 SUPPORT Human Clinical

"Rosacea can be divided into four subtypes (erythemato-telangiectatic, papulopustular, phymatous, and ocular), with erythemato-telangiectatic rosacea being the most common"

This review explicitly recognizes erythematotelangiectatic rosacea as one of the four canonical clinical subtypes.

PMID:27718519 SUPPORT Human Clinical

"The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes."

This phenotype-led consensus supports the core vascular features that anchor erythematotelangiectatic rosacea.

Papulopustular Rosacea

Inflammatory rosacea subtype with persistent facial erythema accompanied by papules and pustules in the central face.

Show evidence (2 references)

PMID:28150107 SUPPORT Human Clinical

"Rosacea can be divided into four subtypes (erythemato-telangiectatic, papulopustular, phymatous, and ocular), with erythemato-telangiectatic rosacea being the most common"

This review explicitly recognizes papulopustular rosacea as a major clinical subtype.

PMID:28150107 SUPPORT Human Clinical

"Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema), persistent central facial erythema, inflammatory papules/pustules, and telangiectasia."

This supports the inflammatory papule-pustule phenotype that defines papulopustular rosacea.

Phymatous Rosacea

Tissue-remodeling subtype marked by thickening and hypertrophy of facial skin and sebaceous structures, most commonly affecting the nose as rhinophyma.

Show evidence (2 references)

PMID:28150107 SUPPORT Human Clinical

"Rosacea can be divided into four subtypes (erythemato-telangiectatic, papulopustular, phymatous, and ocular), with erythemato-telangiectatic rosacea being the most common"

This review explicitly recognizes phymatous rosacea as one of the canonical clinical subtypes.

PMID:41918801 SUPPORT Human Clinical

"Phymatous rosacea (PhR), also known as "rhinophyma", refers to a benign condition characterized by the excessive proliferation of sebaceous glands and fibrosis in the facial skin due to rosacea"

This supports the hypertrophic and fibrotic tissue-remodeling pattern characteristic of phymatous rosacea.

Ocular Rosacea

Ocular subtype involving chronic inflammatory disease of the eyelids and ocular surface, often with blepharitis, meibomian dysfunction, dryness, and photophobia.

Show evidence (2 references)

PMID:28150107 SUPPORT Human Clinical

"Rosacea can be divided into four subtypes (erythemato-telangiectatic, papulopustular, phymatous, and ocular), with erythemato-telangiectatic rosacea being the most common"

This review explicitly recognizes ocular rosacea as a canonical rosacea subtype.

PMID:40522449 SUPPORT Human Clinical

"Ocular rosacea is a chronic inflammatory disease that affects the surface of the eye and the eyelids."

This supports ocular rosacea as a distinct subtype centered on eyelid and ocular surface inflammation.

⚙

Pathophysiology

Skin barrier dysfunction

Epidermal barrier disruption amplifies inflammatory signaling in rosacea and serves as an early permissive event for downstream innate immune activation.

keratinocyte CL:0000312

establishment of skin barrier GO:0061436

Downstream

Pro-cathelicidin transcription Barrier-disrupting triggers increase keratinocyte pro-cathelicidin transcription.

STAT3-mediated cytokine signaling Barrier injury activates a keratinocyte cytokine-signaling program centered on STAT3.

Show evidence (1 reference)

PMID:35392024 SUPPORT Human Clinical

"our results showed that the destruction of the skin barrier aggravates the inflammation levels and immune infiltration of rosacea partly by activating STAT3-mediated cytokine signal pathways in keratinocytes."

This study establishes barrier dysfunction as a disease-amplifying mechanism in rosacea.

Pro-cathelicidin transcription

Keratinocytes in rosacea upregulate pro-cathelicidin transcription, creating substrate for downstream proteolytic generation of inflammatory peptides.

keratinocyte CL:0000312

Downstream

LL-37 generation Increased pro-cathelicidin availability supports downstream formation of LL-37 after proteolytic processing.

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"The sequence of innate immune activation in rosacea starts with factors increasing keratinocyte transcription of pro-cathelicidin"

This review explicitly places pro-cathelicidin transcription near the start of rosacea innate immune activation.

TLR2 upregulation

Keratinocyte TLR2 expression is increased in rosacea and sensitizes skin to environmental and microbial stimuli.

keratinocyte CL:0000312

Downstream

KLK5/KLK7 activation Increased TLR2 signaling promotes activation of kallikrein-family serine proteases.

Show evidence (1 reference)

PMID:39823143 SUPPORT In Vitro

"Specifically, Toll-like receptor 2 (TLR2) and S100A9 proteins were upregulated, potentially promoting these processes."

This study supports increased TLR2 expression as part of rosacea inflammatory activation.

KLK5/KLK7 activation

Kallikrein-family serine proteases are activated downstream of TLR2 and participate in cathelicidin processing.

Downstream

LL-37 generation Activated KLK5/KLK7 cleave pro-cathelicidin to generate LL-37 and related peptides.

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"the serine proteases of the KLK family, KLK5 and KLK7 (activation mediated by TLR-2, which is upregulated by environmental and microbial stimuli)"

This review identifies KLK5/KLK7 as activated proteases in rosacea innate immune signaling.

LL-37 generation

Proteolytic cathelicidin processing yields LL-37 and related peptides with inflammatory and angiogenic activity.

inflammatory response GO:0006954 angiogenesis GO:0001525

Downstream

Mast cell-mediated amplification Cathelicidin signaling recruits mast-cell-dependent amplification of inflammation and vascular reactivity.

Angiogenic vascular remodeling LL-37 and related peptides promote angiogenic changes in cutaneous vasculature.

Th1/Th17 adaptive inflammation LL-37-exposed keratinocytes induce chemokine programs that recruit pathogenic T cells and strengthen adaptive inflammatory polarization.

Show evidence (3 references)

PMID:28150107 SUPPORT Human Clinical

"This leads to the formation of LL-37 and other peptides that are inflammatory and angiogenic"

This review identifies LL-37 generation as a key inflammatory and angiogenic step in rosacea.

PMID:40835085 SUPPORT In Vitro

"Abnormal overexpression of human antimicrobial peptide LL-37 is a hallmark of rosacea."

This study reinforces LL-37 overexpression as a central proximal mechanism in rosacea biology.

PMID:41087666 SUPPORT Model Organism

"Both STING antagonist H-151 and LAPTM5 knockdown alleviate LL-37-induced rosacea-like phenotypes."

This model-organism evidence supports LL-37 as a proximal inducer of rosacea-like inflammatory disease programs.

Mast cell-mediated amplification

Mast cells amplify cathelicidin-initiated inflammation and increase local vasodilation within rosacea lesions.

mast cell CL:0000097

Downstream

Neurovascular vasodilation Mast-cell activation promotes vasodilatory responses in affected skin.

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"Mast cells are pivotal mediators of cathelicidin-initiated skin inflammation—amplifying inflammation, vasodilation, and generation of LL-37"

This review places mast cells in an amplification loop that increases inflammatory and vascular disease activity.

STAT3-mediated cytokine signaling

Keratinocyte STAT3-centered cytokine signaling links barrier injury to inflammatory persistence and immune-cell recruitment.

keratinocyte CL:0000312

cytokine-mediated signaling pathway GO:0019221

Downstream

Immune cell infiltration STAT3 activation promotes immune-cell accumulation within rosacea lesions.

Show evidence (1 reference)

PMID:35392024 SUPPORT Human Clinical

This study identifies STAT3-mediated cytokine signaling as a key inflammatory amplifier in rosacea.

Immune cell infiltration

Rosacea lesions show increased immune-cell infiltration that reinforces inflammatory lesion formation.

Downstream

Papulopustular inflammation Increased lesional immune infiltration supports development of inflammatory papules and pustules.

Show evidence (1 reference)

PMID:35392024 SUPPORT Human Clinical

"The XCell immune cell assays showed that the increased immune infiltration with SBD."

This transcriptomic analysis supports increased immune-cell infiltration in rosacea with barrier dysfunction.

Th1/Th17 adaptive inflammation

Chemokine and cytokine networks in rosacea polarize adaptive immunity toward Th1/Th17 inflammatory programs.

inflammatory response GO:0006954

Downstream

Papulopustular inflammation Th1/Th17-skewed adaptive inflammation contributes to inflammatory papulopustular lesions.

Show evidence (2 references)

PMID:28150107 SUPPORT Human Clinical

"Chemokine and cytokine signals interact to generate a Th1/Th17-polarized adaptive immune response in rosacea"

This review supports a Th1/Th17-polarized adaptive inflammatory response in rosacea.

PMID:40835085 SUPPORT In Vitro

"T-cell recruiting chemokine CXCL10 turns out to be the most abundant inflammatory mediator overexpressed upon LL-37 exposure."

This supports a chemokine-driven adaptive immune arm linking keratinocyte activation to pathogenic T-cell recruitment.

TRP and neuropeptide signaling

TRP-channel activation and neuropeptide signaling form a neurocutaneous branch of rosacea pathophysiology that increases vascular reactivity.

neuropeptide signaling pathway GO:0007218

Downstream

Neurovascular vasodilation TRP and neuropeptide signaling promote exaggerated vasodilatory responses in rosacea skin.

Show evidence (1 reference)

PMID:34035646 SUPPORT Human Clinical

"Recognized mechanisms include the innate immune system, with the implication of Toll-like receptors (TLRs) and cathelicidins; neurovascular deregulation involving vascular endothelial growth factor (VEGF), transient receptor potential (TRP) ion channels, and neuropeptides"

This review identifies TRP and neuropeptides as part of the neurovascular arm of rosacea pathophysiology.

Neurovascular vasodilation

Exaggerated vasodilation is a proximal vascular event that drives flushing and contributes to persistent background erythema.

Downstream

Flushing Vasodilatory surges produce episodic flushing.

Persistent centrofacial erythema Recurrent vasodilatory instability contributes to chronic background centrofacial erythema.

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"while the multifactorial pathology of rosacea is thought to involve both vasoactive and neurocutaneous mechanisms."

This overview supports a vasoreactive proximal mechanism in rosacea.

Angiogenic vascular remodeling

Angiogenic signaling contributes to persistent vascular remodeling and visible superficial telangiectatic change.

angiogenesis GO:0001525

Downstream

Facial telangiectasia Persistent angiogenic remodeling contributes to telangiectatic centrofacial vessels.

Persistent centrofacial erythema Remodeling of superficial vasculature helps sustain background facial erythema.

Show evidence (2 references)

PMID:28150107 SUPPORT Human Clinical

"This leads to the formation of LL-37 and other peptides that are inflammatory and angiogenic"

This supports angiogenic signaling as a discrete downstream consequence of cathelicidin pathway activation.

PMID:40567003 SUPPORT Computational

"angiogenesis and neutrophil activation may contribute to persistent erythema and a large number of papules and pustules in the severe stage of rosacea."

This molecular subtyping study supports angiogenesis as a driver of persistent erythema and lesion-rich severe rosacea.

Papulopustular inflammation

Convergent innate, adaptive, and keratinocyte inflammatory programs produce inflammatory papules and pustules in papulopustular rosacea.

inflammatory response GO:0006954

Downstream

Papules Inflammatory lesion formation produces papular eruptions.

Pustules Ongoing inflammatory lesion formation produces pustules.

Show evidence (1 reference)

PMID:39823143 SUPPORT Human Clinical

"Transcriptomic analysis revealed significantly elevated expression of inflammatory-related genes in rosacea patients."

This study supports a lesion-forming inflammatory state in rosacea skin.

Sebaceous gland dysfunction

Dysfunction of cutaneous sebaceous glands is recognized as part of the multifactorial tissue biology of rosacea.

Downstream

Sebaceous gland and soft tissue hyperplasia/fibrosis In advanced disease, altered sebaceous-unit biology can progress to hyperplastic and fibrotic phymatous tissue remodeling.

Show evidence (1 reference)

PMID:34035646 SUPPORT Human Clinical

This review identifies sebaceous gland dysfunction as a discrete component of rosacea pathophysiology.

Meibomian gland dysfunction

Ocular rosacea includes meibomian gland dysfunction as part of its site-specific pathophysiology.

Downstream

Ocular surface and eyelid inflammation Meibomian-gland disease contributes to chronic inflammatory involvement of the eyelids and ocular surface.

Show evidence (1 reference)

PMID:34035646 SUPPORT Human Clinical

This review identifies meibomian gland dysfunction as part of ocular rosacea biology.

Ocular surface and eyelid inflammation

Ocular rosacea produces chronic inflammatory involvement of the eyelids and ocular surface, with posterior blepharitis as a characteristic clinical expression.

inflammatory response GO:0006954

Downstream

Blepharitis Chronic eyelid inflammation manifests clinically as posterior blepharitis.

Show evidence (1 reference)

PMID:40522449 SUPPORT Human Clinical

"Ocular rosacea is a chronic inflammatory disease that affects the surface of the eye and the eyelids."

This review supports ocular rosacea as an inflammatory disease of the eyelids and ocular surface.

Fibrotic dermal remodeling

Advanced rosacea can shift toward a fibrotic remodeling program in which vascular changes are coupled to connective-tissue fibrosis.

Downstream

Sebaceous gland and soft tissue hyperplasia/fibrosis Fibrotic remodeling progresses to phymatous tissue overgrowth involving sebaceous units and surrounding soft tissue.

Show evidence (2 references)

PMID:25151931 SUPPORT Human Clinical

"Finaly, rhinophyma is linked to both vascular changes and activation of fibrosis, involving TGF beta."

This review supports fibrosis as a specific mechanism underlying rhinophyma development.

PMID:41139274 SUPPORT In Vitro

"GZMK also promoted cell proliferation and inflammatory factors (including IL-1β, IL-6, and TNFα) production in fibroblasts through activating the NF-κB pathway in vitro."

This directly supports fibroblast proliferative and inflammatory programs that can feed fibrotic remodeling in advanced rosacea.

Sebaceous gland and soft tissue hyperplasia/fibrosis

Rhinophyma reflects progressive hypertrophic remodeling of sebaceous glands and adjacent soft tissue in the nose.

Downstream

Phymatous change of the nose Hyperplastic and fibrotic tissue overgrowth produces the bulbous, progressively deformed nasal phenotype of rhinophyma.

Show evidence (1 reference)

PMID:19428039 SUPPORT Human Clinical

"Rhinophyma is an irregular and progressive nasal hypertrophy, due to hyperplasia and fibrosis of the sebaceous glands and surrounding soft tissues."

This abstract defines rhinophyma in terms of sebaceous-gland and soft tissue hyperplasia/fibrosis.

✶

Histopathology

Dermal vascular endothelial Angiopoietin 2 and Tie2 overexpression

Lesional erythematotelangiectatic and papulopustular rosacea skin shows increased Angiopoietin 2 and Tie2 staining in endothelial cells of dermal vessels compared with non-lesional skin, supporting a vascular remodeling-associated histopathology pattern.

Show evidence (1 reference)

PMID:41562711 SUPPORT Human Clinical

"Significantly increased expression of Tie2 and Angiopoietin 2 in the endothelial cells of the dermal vessels in rosacea skin vs. non-lesional skin (100% and 33.3% for Tie2, and 100% and 50% for Angiopoietin 2) was observed."

This provides direct biopsy-level immunohistochemical evidence for altered dermal vascular endothelium in rosacea lesions.

Early dermal fibrotic remodeling

Fibrotic remodeling is detectable in rosacea skin biopsies even at inflammation-dominant stages, indicating that tissue-remodeling changes begin before fully developed phymatous disease.

Show evidence (1 reference)

PMID:41800255 SUPPORT Human Clinical

"single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and histological staining of skin biopsies demonstrated that fibrotic remodeling was already evident at inflammation-dominant stages"

This study directly supports fibrosis as an observable tissue-level change in rosacea biopsies, not only in late rhinophyma.

Sebaceous gland and surrounding soft tissue hyperplasia with fibrosis

Rhinophyma shows hypertrophic remodeling of sebaceous glands and adjacent soft tissue accompanied by fibrosis, forming the core microscopic pattern of phymatous rosacea.

Show evidence (1 reference)

PMID:19428039 SUPPORT Human Clinical

"Rhinophyma is an irregular and progressive nasal hypertrophy, due to hyperplasia and fibrosis of the sebaceous glands and surrounding soft tissues."

This abstract directly supports sebaceous gland hyperplasia with fibrosis as a defining microscopic tissue-remodeling feature of rhinophyma.

Leaky vascular architecture in rhinophyma tissue

Rhinophyma tissue shows an abnormal vascular architecture with leaky vessel profiles rather than the stromal-enveloped vascular pattern seen in hypertrophic scars.

Show evidence (1 reference)

PMID:41909715 SUPPORT Human Clinical

"Vascular structures in hypertrophic scar tissues are enveloped by a significant number of stromal cells, in contrast to the leaky vascular profiles observed in rhinophyma tissues."

This study supports a distinctive vascular tissue architecture in rhinophyma that fits the disease's vascular-remodeling phenotype.

Immune-cell-rich rhinophyma tissue

Rhinophyma tissue contains a relatively expanded immune-cell compartment, consistent with persistent inflammatory remodeling in phymatous disease.

Show evidence (1 reference)

PMID:41909715 SUPPORT Human Clinical

"the number of immune cells in rhinophyma is significantly higher than in hypertrophic scar tissues."

This supports immune-cell enrichment as a tissue-level feature of rhinophyma.

Eyelid tissue lymphoedema in ocular rosacea

In rare ocular rosacea with persistent peri-orbital swelling, eyelid debulking biopsy can show rosacea-associated inflammatory change with superimposed lymphoedematous tissue remodeling.

Show evidence (1 reference)

PMID:41058755 SUPPORT Human Clinical

"Histopathological analysis of the debulking biopsy confirmed the diagnosis of rosacea, with additional features indicative of lymphoedema."

This provides direct biopsy-level support for lymphoedematous tissue change in a rare ocular rosacea presentation.

⬡

Pathograph

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Phenotypes

Cardiovascular 2

Persistent centrofacial erythema VERY_FREQUENT Facial erythema HP:0001041

Persistent background erythema of the central face is a core diagnostic phenotype in modern phenotype-led rosacea classification.

Show evidence (1 reference)

PMID:27718519 SUPPORT Human Clinical

"The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes."

ROSCO identifies persistent centrofacial erythema as one of the two diagnostic phenotypes for rosacea.

Facial telangiectasia FREQUENT Facial telangiectasia HP:0007380

Show evidence (1 reference)

PMID:37626650 SUPPORT Human Clinical

"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."

This review includes telangiectasia among the central defining manifestations of rosacea.

Eye 1

Blepharitis OCCASIONAL Blepharitis HP:0000498

Ocular rosacea often presents with eyelid margin inflammation.

Show evidence (1 reference)

PMID:40522449 SUPPORT Human Clinical

"It is characterized by bilateral chronic posterior blepharitis and meibomitis, which can involve the entire surface of the eye, including the cornea, during the course of the disease."

This directly supports chronic posterior blepharitis as a hallmark ocular phenotype of ocular rosacea.

Head and Neck 3

Phymatous change of the nose OCCASIONAL Bulbous nose HP:0000414

Phymatous rosacea is most often expressed as progressive tissue thickening of the nose (rhinophyma).

Show evidence (1 reference)

PMID:27718519 SUPPORT Human Clinical

"The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes."

ROSCO identifies phymatous change as the second independently diagnostic phenotype of rosacea.

Facial edema VERY_RARE Facial edema HP:0000282

A rare rosacea-associated lymphedematous presentation, often termed Morbihan disease, causes chronic persistent facial swelling.

Show evidence (1 reference)

PMID:41426892 SUPPORT Human Clinical

"Morbihan disease, also known as rosacea-associated solid facial edema, is a rare and chronic condition that presents with persistent facial swelling and often proves difficult to treat."

This directly supports persistent facial edema as a rare rosacea- associated phenotype.

Upper eyelid edema VERY_RARE Upper eyelid edema HP:0012724

Ocular rosacea can rarely present with persistent peri-orbital swelling, sometimes accompanied by secondary ptosis.

Show evidence (1 reference)

PMID:41058755 SUPPORT Human Clinical

"A 64-year-old Caucasian man presented with a 9-month history of persistent painless swelling of the right upper eyelid and secondary ptosis."

This case report supports persistent upper-eyelid edema as a rare ocular manifestation of rosacea.

Immune 1

Pustules FREQUENT Pustule HP:0200039

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema), persistent central facial erythema, inflammatory papules/pustules, and telangiectasia."

This overview identifies papulopustular lesions as part of the core clinical spectrum of rosacea.

Integument 2

Flushing FREQUENT Flushing HP:0031284

Episodic flushing commonly accompanies the vascular phenotype.

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema), persistent central facial erythema, inflammatory papules/pustules, and telangiectasia."

This overview identifies flushing as a characteristic clinical manifestation of rosacea.

Papules FREQUENT Erythematous papule HP:0030350

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema), persistent central facial erythema, inflammatory papules/pustules, and telangiectasia."

This overview identifies inflammatory papules as a characteristic lesion type in rosacea.

🧬

Genetic Associations

IRF1 (MR-supported druggable gene)

Gene: IRF1 hgnc:6116

Show evidence (1 reference)

PMID:40635520 SUPPORT Computational

"MR and SMR analyses identified IRF1 and SLC22A5 as druggable genes for rosacea, with Bayesian colocalization strongly supporting shared causal variants."

This directly supports IRF1 as a genetically prioritized therapeutic target in rosacea.

SLC22A5 (MR-supported druggable gene)

Gene: SLC22A5 hgnc:10969

Show evidence (1 reference)

PMID:40635520 SUPPORT Computational

"MR and SMR analyses identified IRF1 and SLC22A5 as druggable genes for rosacea, with Bayesian colocalization strongly supporting shared causal variants."

This directly supports SLC22A5 as a genetically prioritized therapeutic target in rosacea.

GZMK (MR-supported drug target)

Gene: GZMK hgnc:4711

Show evidence (1 reference)

PMID:41139274 SUPPORT Computational

"MR and colocalization identified Granzyme K (GZMK) as a drug target, whose expression increased in the affected samples."

This supports GZMK as a genetically prioritized rosacea target with increased expression in disease-associated samples.

MSR1 (MR-supported risk-promoting biomarker)

Gene: MSR1 hgnc:7376

Show evidence (1 reference)

PMID:40890957 SUPPORT Computational

"Further refinement through SMR and differential expression analysis reduced this to five key proteins, including four (ABHD14B, CHMP6, DBNL and MCFD2) that inhibit rosacea onset and one (MSR1) that promotes it."

This directly supports MSR1 as the risk-promoting protein among the final MR-prioritized rosacea biomarkers.

ABHD14B (MR-supported protective biomarker)

Gene: ABHD14B hgnc:28235

Show evidence (1 reference)

PMID:40890957 SUPPORT Computational

This supports ABHD14B as one of the final MR-prioritized proteins associated with lower rosacea risk.

CHMP6 (MR-supported protective biomarker)

Gene: CHMP6 hgnc:25675

Show evidence (1 reference)

PMID:40890957 SUPPORT Computational

This supports CHMP6 as one of the final MR-prioritized proteins associated with lower rosacea risk.

DBNL (MR-supported protective biomarker)

Gene: DBNL hgnc:2696

Show evidence (1 reference)

PMID:40890957 SUPPORT Computational

This supports DBNL as one of the final MR-prioritized proteins associated with lower rosacea risk.

MCFD2 (MR-supported protective biomarker)

Gene: MCFD2 hgnc:18451

Show evidence (1 reference)

PMID:40890957 SUPPORT Computational

This supports MCFD2 as one of the final MR-prioritized proteins associated with lower rosacea risk.

💊

Medical Actions

Trigger avoidance and photoprotection

Baseline management includes avoidance of provoking exposures, gentle skin care, moisturization, and sun protection to reduce flares.

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"While standard measures, including avoidance of triggers, gentle cleansers, and moisturizers in combination with sun protection, may mitigate flares, control signs and symptoms in some patients"

This review supports trigger avoidance, gentle skin care, and photoprotection as foundational rosacea management.

Papulopustular-directed pharmacotherapy

Action: Pharmacotherapy NCIT:C15986

Agent: metronidazole CHEBI:6909 azelaic acid NCIT:C47407 ivermectin CHEBI:6078 doxycycline CHEBI:50845 isotretinoin NCIT:C603

Papulopustular rosacea is commonly treated with topical metronidazole, azelaic acid, or ivermectin, and in more inflammatory disease with oral doxycycline or isotretinoin.

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"topical metronidazole, azelaic acid, ivermectin, or oral doxycycline and isotretinoin for papulopustules of rosacea"

This review summarizes standard pharmacologic options used for papulopustular rosacea.

Topical brimonidine therapy

Action: topical pharmacotherapy MAXO:0001573

Agent: brimonidine CHEBI:3175

Persistent background erythema can be treated with topical brimonidine to reduce visible vasodilatory erythema.

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"topical brimonidine or intense pulsed light (IPL) for background persistent erythema"

This review identifies brimonidine as a targeted therapy for persistent background erythema.

Vascular light-based therapy

Persistent vascular erythema may also be treated with light-based therapy such as intense pulsed light.

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"topical brimonidine or intense pulsed light (IPL) for background persistent erythema"

This review identifies light-based vascular therapy as another targeted approach for persistent erythema.

Cyclosporine eye drops

Action: Pharmacotherapy NCIT:C15986

Agent: cyclosporine CHEBI:4031

Ocular rosacea may require targeted ophthalmic anti-inflammatory therapy such as cyclosporine eye drops.

Show evidence (1 reference)

PMID:28150107 SUPPORT Human Clinical

"cyclosporine eye drops for ocular rosacea"

This review identifies cyclosporine eye drops as a treatment option for ocular rosacea.

Morbihan disease-directed pharmacotherapy

Action: Pharmacotherapy NCIT:C15986

Agent: isotretinoin NCIT:C603 triamcinolone NCIT:C901 ketotifen CHEBI:92511

Rosacea-associated solid facial edema may require individualized combination pharmacotherapy centered on isotretinoin and intralesional corticosteroid treatment, with ketotifen used in selected refractory cases.

Target Phenotypes: facial edema HP:0000282

Show evidence (2 references)

PMID:41426892 SUPPORT Human Clinical

"The patient reported partial improvement, most notably with higher isotretinoin dosing and intralesional corticosteroid injections, though intermittent flares persisted."

This supports isotretinoin and intralesional corticosteroid treatment as active components of Morbihan disease management.

PMID:41222206 SUPPORT Human Clinical

"Successful treatment with a series of triamcinolone injections to the upper and lower eyelids was achieved after several unsuccessful therapies."

This independently supports intralesional triamcinolone as a useful treatment option for rosacea-associated solid facial edema.

Laser surgical debulking for rhinophyma

Action: laser surgical procedure MAXO:0001578

CO2 laser or blue-laser debulking can remove phymatous nasal tissue and improve function and cosmesis in selected rhinophyma.

Target Phenotypes: rhinophyma HP:0000414

Show evidence (2 references)

PMID:41918801 SUPPORT Human Clinical

"we emphasize the surgical value of local anesthesia with CO2 laser for rhinophyma, reducing blood loss, operation time, and the need for secondary surgery."

This case report supports CO2 laser debulking as an effective rhinophyma procedure with practical operative advantages.

PMID:40791837 SUPPORT Human Clinical

"The use of blue laser to treat rhinophyma has shown to be an effective and safe procedure with very promising results."

This provides additional support for laser-based debulking in rhinophyma.

Excisional reconstruction for advanced rhinophyma

Action: surgical procedure MAXO:0000004

Severe rhinophyma may require excision with reconstructive approaches such as graft-based resurfacing when tissue overgrowth is extensive.

Target Phenotypes: rhinophyma HP:0000414

Show evidence (1 reference)

PMID:40860281 SUPPORT Human Clinical

"Surgical excision is the primary treatment, and various techniques are available."

This supports excisional surgery as the primary treatment framework for advanced rhinophyma, including graft-based reconstruction.

🌍

Environmental Factors

Ultraviolet B radiation

Ultraviolet B exposure is a recognized favoring factor that can worsen rosacea activity and amplify inflammatory and vascular responses.

Show evidence (1 reference)

PMID:34035646 SUPPORT Human Clinical

"Microorganisms, genetic predisposition, corticosteroid treatment, and ultraviolet B (UVB) radiation are favoring factors."

This review explicitly identifies UVB radiation as an important rosacea-promoting exposure.

Corticosteroid treatment

Corticosteroid exposure can favor rosacea expression and is a recognized exacerbating factor in susceptible patients.

Show evidence (1 reference)

PMID:34035646 SUPPORT Human Clinical

"Microorganisms, genetic predisposition, corticosteroid treatment, and ultraviolet B (UVB) radiation are favoring factors."

This review explicitly identifies corticosteroid treatment as a favoring factor for rosacea.

🔀

Differential Diagnoses

Conditions with similar clinical presentations that must be differentiated from Rosacea:

Acne MONDO:0011438

Overlapping Features Acne can overlap clinically with papulopustular rosacea because both produce inflammatory papules and pustules on the face.

Distinguishing Features

Acne more often shows open or closed comedones and broader sebaceous facial or truncal involvement.
Rosacea more often centers on persistent centrofacial erythema, flushing, and telangiectasia without comedones.

Show evidence (1 reference)

PMID:11582639 SUPPORT Human Clinical

"It can be difficult to distinguish acne vulgaris, seborrheic eczema, perioral dermatitis and lupus erythematosus from rosacea."

This review explicitly lists acne vulgaris among the core differential diagnoses for rosacea.

Seborrheic dermatitis MONDO:0006608

Overlapping Features Facial seborrheic dermatitis can mimic rosacea when patients present with chronic erythema in sebaceous facial regions.

Distinguishing Features

Seborrheic dermatitis more often has greasy yellow-white scale involving the eyebrows, nasolabial folds, and scalp.
Rosacea more often has flushing, telangiectasia, and papulopustular lesions without prominent greasy scale.

Show evidence (1 reference)

PMID:11582639 SUPPORT Human Clinical

"It can be difficult to distinguish acne vulgaris, seborrheic eczema, perioral dermatitis and lupus erythematosus from rosacea."

This review explicitly identifies seborrheic eczema as a major rosacea mimic; the corresponding MONDO disease term used here is seborrheic dermatitis.

Lupus erythematosus Not Yet Curated MONDO:0004670

Overlapping Features Lupus erythematosus can resemble rosacea when facial erythema or a butterfly-pattern eruption predominates.

Distinguishing Features

Lupus erythematosus more often has photosensitivity, scale, dyspigmentation, scarring plaques, or systemic autoimmune features.
Rosacea more often has trigger-provoked flushing, telangiectasia, and papulopustular centrofacial inflammation.

Show evidence (2 references)

PMID:11582639 SUPPORT Human Clinical

"It can be difficult to distinguish acne vulgaris, seborrheic eczema, perioral dermatitis and lupus erythematosus from rosacea."

This review explicitly lists lupus erythematosus among disorders that can be difficult to distinguish from rosacea.

PMID:41695827 SUPPORT Human Clinical

"The coexistence of rosacea and lupus-like lesions delayed diagnosis, highlighting the need for clinicopathological correlation."

This case report reinforces lupus erythematosus as a real-world rosacea mimic and overlap diagnosis.

Systemic sclerosis MONDO:0005100

Overlapping Features Rosacea-associated solid facial edema can mimic systemic sclerosis when facial induration or swelling dominates the presentation.

Distinguishing Features

Systemic sclerosis more often has Raynaud phenomenon, acral involvement, and broader connective-tissue disease manifestations.
Morbihan-type rosacea edema may remain centered on the face with sparing of the hands and feet.

Show evidence (1 reference)

PMID:41694889 SUPPORT Human Clinical

"Scleredema diabeticorum and Morbihan disease (solid facial edema) can mimic scleroderma, creating diagnostic challenges for rheumatologists."

This directly supports systemic sclerosis-spectrum disease as a differential diagnosis for edematous rosacea presentations.

Coccidioidomycosis MONDO:0005706

Overlapping Features Cutaneous coccidioidomycosis can mimic rosacea-like dermatitis, particularly in immunocompromised patients living in endemic regions.

Distinguishing Features

Coccidioidomycosis is favored by endemic exposure, immunosuppression, and biopsy evidence of fungal infection.
Rosacea lacks an infectious tissue diagnosis and more typically follows a chronic trigger-responsive vascular-inflammatory course.

Show evidence (1 reference)

PMID:41017054 SUPPORT Human Clinical

"An immunocompromised patient in Arizona, USA, experienced cutaneous coccidioidomycosis mimicking rosacea-like dermatitis"

This directly documents cutaneous coccidioidomycosis as a rosacea mimic in the appropriate epidemiologic context.

Lymphomatoid papulosis Not Yet Curated MONDO:0020326

Overlapping Features Recurrent periocular nodules can be misclassified as papulopustular rosacea before biopsy reveals a CD30-positive lymphoproliferative lesion.

Distinguishing Features

Lymphomatoid papulosis shows recurrent papulonodules with diagnostic CD30-positive atypical lymphoid infiltrates on histopathology.
Rosacea more typically produces diffuse erythema, papules, pustules, and telangiectasia rather than isolated recurrent nodules.

Show evidence (1 reference)

PMID:40827152 SUPPORT Human Clinical

"he was subsequently diagnosed with papulopustular rosacea and impetigo. However, despite multiple treatment trials, he still experienced recurrent flares with nodules"

This case report documents an initial rosacea diagnosis later revised to lymphomatoid papulosis after biopsy.

📊

Related Datasets

Th1/Th17 Immune Response in Rosacea geo:GSE65914

Human facial biopsy transcriptomic dataset spanning rosacea subtypes and healthy controls, used to define adaptive immune and inflammatory cell programs across erythematotelangiectatic, papulopustular, and phymatous disease.

human MICROARRAY n=58

Conditions: erythematotelangiectatic rosacea papulopustular rosacea phymatous rosacea healthy control facial skin

Show evidence (1 reference)

GEO:GSE65914 SUPPORT Human Clinical

"The T cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFNγ or IL-17, for example."

This GEO series directly supports subtype-spanning adaptive immune polarization in human rosacea tissue.

Paired transcriptomic and proteomic analysis implicates IL-1β in the pathogenesis of papulopustular rosacea explants [RNA-seq] geo:GSE155141

Human RNA-seq dataset from paired non-lesional and lesional papulopustular rosacea explants, linked to paired proteomic profiling and inflammatory pathway analysis.

human BULK RNA SEQ n=15

Conditions: non-lesional papulopustular rosacea skin lesional papulopustular rosacea skin IL-1beta-treated non-lesional rosacea skin

Show evidence (1 reference)

GEO:GSE155141 SUPPORT Human Clinical

"Our study suggests that MAPK and TNF signaling pathways are the most significantly upregulated pathways in lesional papulopustular rosacea human skins, highlighting IL-1β as a potential central mediator."

This dataset captures lesion-associated inflammatory pathway activity in papulopustular rosacea.

Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway geo:GSE303282

Human keratinocyte microarray dataset modeling LL-37-driven rosacea-like inflammation in vitro to resolve chemokine and JAK-STAT signaling outputs downstream of cathelicidin exposure.

human MICROARRAY n=6

Conditions: LL-37-treated primary keratinocytes untreated primary keratinocytes

Show evidence (1 reference)

GEO:GSE303282 SUPPORT In Vitro

"Mechanistically, LL-37 induced CXCL10 production relied on JAK-1/STAT-1 signaling pathway."

This in vitro transcriptomic dataset is directly relevant to the cathelicidin and STAT-linked mechanism nodes in rosacea.

Effect of eyelid UVB irradiation on gene expression of rat meibomian gland geo:GSE277020

Rat bulk RNA-seq dataset from a UVB-induced ocular rosacea model focused on meibomian gland dysfunction, ocular surface injury, and downstream inflammatory and keratinization pathways.

Rattus norvegicus BULK RNA SEQ n=7

Conditions: UVB-irradiated rat eyelids and meibomian glands non-irradiated rat controls

Show evidence (1 reference)

GEO:GSE277020 SUPPORT Model Organism

"We have developed a rat model of UVB-induced ocular surface and eyelid damages mimicking ocular rosacea, a common chronic inflammatory and neurovascular ocular surface disease associated with meibomian gland dysfunction."

This dataset provides an ocular/meibomian model aligned to the ocular rosacea subgraph in this entry.

🔬

Clinical Trials

NCT01493947 PHASE_III COMPLETED

Phase III comparative topical trial of ivermectin 1% cream versus metronidazole 0.75% cream in papulopustular rosacea, with an extension period assessing relapse-related outcomes.

Target Phenotypes: erythematous papule HP:0030350 pustule HP:0200039

Show evidence (1 reference)

clinicaltrials:NCT01493947 SUPPORT Human Clinical

"To compare efficacy and safety of Ivermectin 1% cream versus metronidazole 0.75% cream in subjects with papulopustular rosacea after 16-week topical treatment."

This registry summary supports a pivotal interventional trial focused on papulopustular rosacea lesion control.

NCT00126399 PHASE_III COMPLETED

Phase III placebo-controlled trial of once-daily 40 mg doxycycline controlled-release capsules for rosacea.

Target Phenotypes: erythematous papule HP:0030350 pustule HP:0200039

Show evidence (1 reference)

clinicaltrials:NCT00126399 SUPPORT Human Clinical

"The objective of this study is to evaluate the safety and efficacy of 40 mg doxycycline controlled-release capsules administered once daily for the treatment of rosacea compared with a placebo."

This registry entry supports controlled clinical evaluation of subantimicrobial-dose doxycycline for rosacea.

NCT03380390 PHASE_IV COMPLETED

Phase IV open-label study of oxymetazoline 1.0% cream used adjunctively with energy-based therapy for persistent facial erythema in rosacea.

Target Phenotypes: persistent centrofacial erythema HP:0001041

Show evidence (1 reference)

clinicaltrials:NCT03380390 SUPPORT Human Clinical

"This study will evaluate the safety and tolerability of oxymetazoline HCl cream 1.0% when used as an adjunctive treatment to energy-based therapy for participants with moderate to severe persistent facial erythema associated with rosacea."

This trial directly targets the persistent erythema phenotype that anchors erythematotelangiectatic rosacea.

NCT05616923 PHASE_I COMPLETED

Early-phase vehicle-controlled trial evaluating topical MEK inhibition in erythematotelangiectatic rosacea.

Target Phenotypes: persistent centrofacial erythema HP:0001041 flushing HP:0031284

Show evidence (1 reference)

clinicaltrials:NCT05616923 SUPPORT Human Clinical

"This is a prospective, vehicle controlled, double blinded study to evaluate the safety and potential efficacy of a topical formulation of a MEK inhibitor in patients with erythematotelangiectatic rosacea"

This registry entry supports a mechanism-oriented interventional study in the vascular erythematotelangiectatic phenotype.

{ }

Source YAML

click to show

name: Rosacea
creation_date: "2026-04-05T12:00:00Z"
updated_date: "2026-04-22T20:13:21Z"
category: Complex
description: >-
  Rosacea is a chronic relapsing inflammatory facial dermatosis centered on
  persistent or episodic centrofacial erythema, flushing, telangiectasia, and
  papulopustular lesions, with phymatous and ocular involvement in a subset of
  patients. Current mechanistic models emphasize dysregulated innate immunity,
  neurovascular hyperreactivity, skin barrier impairment, and trigger-dependent
  disease amplification.
disease_term:
  preferred_term: rosacea
  term:
    id: MONDO:0006604
    label: rosacea
parents:
- Dermatological Disease
- Inflammatory Skin Disease
has_subtypes:
- name: Erythematotelangiectatic Rosacea
  description: >-
    Predominantly vascular rosacea phenotype characterized by persistent
    centrofacial erythema, flushing, and telangiectasia without dominant
    papulopustular or phymatous change.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rosacea can be divided into four subtypes (erythemato-telangiectatic, papulopustular, phymatous, and ocular), with erythemato-telangiectatic rosacea being the most common"
    explanation: >-
      This review explicitly recognizes erythematotelangiectatic rosacea as
      one of the four canonical clinical subtypes.
  - reference: PMID:27718519
    reference_title: "Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes."
    explanation: >-
      This phenotype-led consensus supports the core vascular features that
      anchor erythematotelangiectatic rosacea.
- name: Papulopustular Rosacea
  description: >-
    Inflammatory rosacea subtype with persistent facial erythema accompanied
    by papules and pustules in the central face.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rosacea can be divided into four subtypes (erythemato-telangiectatic, papulopustular, phymatous, and ocular), with erythemato-telangiectatic rosacea being the most common"
    explanation: >-
      This review explicitly recognizes papulopustular rosacea as a major
      clinical subtype.
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema), persistent central facial erythema, inflammatory papules/pustules, and telangiectasia."
    explanation: >-
      This supports the inflammatory papule-pustule phenotype that defines
      papulopustular rosacea.
- name: Phymatous Rosacea
  description: >-
    Tissue-remodeling subtype marked by thickening and hypertrophy of facial
    skin and sebaceous structures, most commonly affecting the nose as
    rhinophyma.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rosacea can be divided into four subtypes (erythemato-telangiectatic, papulopustular, phymatous, and ocular), with erythemato-telangiectatic rosacea being the most common"
    explanation: >-
      This review explicitly recognizes phymatous rosacea as one of the
      canonical clinical subtypes.
  - reference: PMID:41918801
    reference_title: "CO(2) Laser Resection of Giant Rhinophyma Under Local Anesthesia: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Phymatous rosacea (PhR), also known as \"rhinophyma\", refers to a benign condition characterized by the excessive proliferation of sebaceous glands and fibrosis in the facial skin due to rosacea"
    explanation: >-
      This supports the hypertrophic and fibrotic tissue-remodeling pattern
      characteristic of phymatous rosacea.
- name: Ocular Rosacea
  description: >-
    Ocular subtype involving chronic inflammatory disease of the eyelids and
    ocular surface, often with blepharitis, meibomian dysfunction, dryness,
    and photophobia.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rosacea can be divided into four subtypes (erythemato-telangiectatic, papulopustular, phymatous, and ocular), with erythemato-telangiectatic rosacea being the most common"
    explanation: >-
      This review explicitly recognizes ocular rosacea as a canonical
      rosacea subtype.
  - reference: PMID:40522449
    reference_title: "[Ocular rosacea : Clinical aspects, diagnostics, management and treatment]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ocular rosacea is a chronic inflammatory disease that affects the surface of the eye and the eyelids."
    explanation: >-
      This supports ocular rosacea as a distinct subtype centered on eyelid
      and ocular surface inflammation.
pathophysiology:
- name: Skin barrier dysfunction
  description: >-
    Epidermal barrier disruption amplifies inflammatory signaling in rosacea
    and serves as an early permissive event for downstream innate immune
    activation.
  biological_processes:
  - preferred_term: establishment of skin barrier
    term:
      id: GO:0061436
      label: establishment of skin barrier
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  downstream:
  - target: Pro-cathelicidin transcription
    description: >-
      Barrier-disrupting triggers increase keratinocyte pro-cathelicidin
      transcription.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The sequence of innate immune activation in rosacea starts with factors increasing keratinocyte transcription of pro-cathelicidin (including vitamin D activated by UV, UV itself, infection, injury, and other triggers to barrier disruption)"
      explanation: >-
        This directly links barrier-disrupting triggers to increased
        pro-cathelicidin transcription in rosacea keratinocytes.
  - target: STAT3-mediated cytokine signaling
    description: >-
      Barrier injury activates a keratinocyte cytokine-signaling program
      centered on STAT3.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:35392024
      reference_title: "Multi-Transcriptomic Analysis and Experimental Validation Implicate a Central Role of STAT3 in Skin Barrier Dysfunction Induced Aggravation of Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "our results showed that the destruction of the skin barrier aggravates the inflammation levels and immune infiltration of rosacea partly by activating STAT3-mediated cytokine signal pathways in keratinocytes."
      explanation: >-
        This directly supports barrier dysfunction as an upstream driver
        of STAT3-mediated cytokine signaling.
  evidence:
  - reference: PMID:35392024
    reference_title: "Multi-Transcriptomic Analysis and Experimental Validation Implicate a Central Role of STAT3 in Skin Barrier Dysfunction Induced Aggravation of Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "our results showed that the destruction of the skin barrier aggravates the inflammation levels and immune infiltration of rosacea partly by activating STAT3-mediated cytokine signal pathways in keratinocytes."
    explanation: >-
      This study establishes barrier dysfunction as a disease-amplifying
      mechanism in rosacea.
- name: Pro-cathelicidin transcription
  description: >-
    Keratinocytes in rosacea upregulate pro-cathelicidin transcription,
    creating substrate for downstream proteolytic generation of inflammatory
    peptides.
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  downstream:
  - target: LL-37 generation
    description: >-
      Increased pro-cathelicidin availability supports downstream formation
      of LL-37 after proteolytic processing.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - kallikrein-mediated cathelicidin cleavage
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "This leads to the formation of LL-37 and other peptides that are inflammatory and angiogenic"
      explanation: >-
        This supports cathelicidin-processing output to LL-37 downstream
        of increased pro-cathelicidin availability.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The sequence of innate immune activation in rosacea starts with factors increasing keratinocyte transcription of pro-cathelicidin"
    explanation: >-
      This review explicitly places pro-cathelicidin transcription near the
      start of rosacea innate immune activation.
- name: TLR2 upregulation
  description: >-
    Keratinocyte TLR2 expression is increased in rosacea and sensitizes skin
    to environmental and microbial stimuli.
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  downstream:
  - target: KLK5/KLK7 activation
    description: >-
      Increased TLR2 signaling promotes activation of kallikrein-family
      serine proteases.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "the serine proteases of the KLK family, KLK5 and KLK7 (activation mediated by TLR-2, which is upregulated by environmental and microbial stimuli)"
      explanation: >-
        This directly supports TLR2 as an upstream driver of KLK5/KLK7
        activation in rosacea.
  evidence:
  - reference: PMID:39823143
    reference_title: "Unveiling the Molecular Mechanisms of Rosacea: Insights From Transcriptomics and In Vitro Experiments."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Specifically, Toll-like receptor 2 (TLR2) and S100A9 proteins were upregulated, potentially promoting these processes."
    explanation: >-
      This study supports increased TLR2 expression as part of rosacea
      inflammatory activation.
- name: KLK5/KLK7 activation
  description: >-
    Kallikrein-family serine proteases are activated downstream of TLR2 and
    participate in cathelicidin processing.
  downstream:
  - target: LL-37 generation
    description: >-
      Activated KLK5/KLK7 cleave pro-cathelicidin to generate LL-37 and
      related peptides.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "This leads to the formation of LL-37 and other peptides that are inflammatory and angiogenic"
      explanation: >-
        This supports KLK-mediated proteolytic generation of LL-37.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the serine proteases of the KLK family, KLK5 and KLK7 (activation mediated by TLR-2, which is upregulated by environmental and microbial stimuli)"
    explanation: >-
      This review identifies KLK5/KLK7 as activated proteases in rosacea
      innate immune signaling.
- name: LL-37 generation
  description: >-
    Proteolytic cathelicidin processing yields LL-37 and related peptides
    with inflammatory and angiogenic activity.
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: angiogenesis
    term:
      id: GO:0001525
      label: angiogenesis
  downstream:
  - target: Mast cell-mediated amplification
    description: >-
      Cathelicidin signaling recruits mast-cell-dependent amplification of
      inflammation and vascular reactivity.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Mast cells are pivotal mediators of cathelicidin-initiated skin inflammation"
      explanation: >-
        This directly supports mast cells as downstream mediators of
        cathelicidin signaling.
  - target: Angiogenic vascular remodeling
    description: >-
      LL-37 and related peptides promote angiogenic changes in cutaneous
      vasculature.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "This leads to the formation of LL-37 and other peptides that are inflammatory and angiogenic"
      explanation: >-
        This directly supports an angiogenic vascular effect downstream of
        LL-37 generation.
  - target: Th1/Th17 adaptive inflammation
    description: >-
      LL-37-exposed keratinocytes induce chemokine programs that recruit
      pathogenic T cells and strengthen adaptive inflammatory polarization.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - CXCL10 induction
    - Jak1/STAT1 signaling
    evidence:
    - reference: PMID:40835085
      reference_title: "Cathelicidin LL-37-Induced Transcriptome of Human Keratinocyte Identifies Chemokine CXCL10 Link to T-Cell-Mediated Rosacea Pathogenesis through Jak1/STAT1 Pathway."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "Mechanistically, LL-37-induced CXCL10 production relied on the Jak1/signal transducer and activator of transcription 1 signaling pathway."
      explanation: >-
        This supports a mechanistic bridge from LL-37 exposure to
        chemokine-driven adaptive inflammatory recruitment.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This leads to the formation of LL-37 and other peptides that are inflammatory and angiogenic"
    explanation: >-
      This review identifies LL-37 generation as a key inflammatory and
      angiogenic step in rosacea.
  - reference: PMID:40835085
    reference_title: "Cathelicidin LL-37-Induced Transcriptome of Human Keratinocyte Identifies Chemokine CXCL10 Link to T-Cell-Mediated Rosacea Pathogenesis through Jak1/STAT1 Pathway."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Abnormal overexpression of human antimicrobial peptide LL-37 is a hallmark of rosacea."
    explanation: >-
      This study reinforces LL-37 overexpression as a central proximal
      mechanism in rosacea biology.
  - reference: PMID:41087666
    reference_title: "LAPTM5 exacerbates STING-mediated inflammation induced by LL-37 through stabilizing STING in rosacea."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Both STING antagonist H-151 and LAPTM5 knockdown alleviate LL-37-induced rosacea-like phenotypes."
    explanation: >-
      This model-organism evidence supports LL-37 as a proximal inducer of
      rosacea-like inflammatory disease programs.
- name: Mast cell-mediated amplification
  description: >-
    Mast cells amplify cathelicidin-initiated inflammation and increase local
    vasodilation within rosacea lesions.
  cell_types:
  - preferred_term: mast cell
    term:
      id: CL:0000097
      label: mast cell
  downstream:
  - target: Neurovascular vasodilation
    description: >-
      Mast-cell activation promotes vasodilatory responses in affected skin.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Mast cells are pivotal mediators of cathelicidin-initiated skin inflammation—amplifying inflammation, vasodilation, and generation of LL-37"
      explanation: >-
        This directly supports mast cells as mediators of vasodilation in
        rosacea lesions.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Mast cells are pivotal mediators of cathelicidin-initiated skin inflammation—amplifying inflammation, vasodilation, and generation of LL-37"
    explanation: >-
      This review places mast cells in an amplification loop that increases
      inflammatory and vascular disease activity.
- name: STAT3-mediated cytokine signaling
  description: >-
    Keratinocyte STAT3-centered cytokine signaling links barrier injury to
    inflammatory persistence and immune-cell recruitment.
  biological_processes:
  - preferred_term: cytokine-mediated signaling pathway
    term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  downstream:
  - target: Immune cell infiltration
    description: >-
      STAT3 activation promotes immune-cell accumulation within rosacea
      lesions.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:35392024
      reference_title: "Multi-Transcriptomic Analysis and Experimental Validation Implicate a Central Role of STAT3 in Skin Barrier Dysfunction Induced Aggravation of Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "STAT3 could contribute to the progression of rosacea partly by dysregulating immune infiltration via activating the cytokine/chemokines signal."
      explanation: >-
        This directly links STAT3-mediated cytokine signaling to increased
        immune infiltration in rosacea.
  evidence:
  - reference: PMID:35392024
    reference_title: "Multi-Transcriptomic Analysis and Experimental Validation Implicate a Central Role of STAT3 in Skin Barrier Dysfunction Induced Aggravation of Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "our results showed that the destruction of the skin barrier aggravates the inflammation levels and immune infiltration of rosacea partly by activating STAT3-mediated cytokine signal pathways in keratinocytes."
    explanation: >-
      This study identifies STAT3-mediated cytokine signaling as a key
      inflammatory amplifier in rosacea.
- name: Immune cell infiltration
  description: >-
    Rosacea lesions show increased immune-cell infiltration that reinforces
    inflammatory lesion formation.
  downstream:
  - target: Papulopustular inflammation
    description: >-
      Increased lesional immune infiltration supports development of
      inflammatory papules and pustules.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:35392024
      reference_title: "Multi-Transcriptomic Analysis and Experimental Validation Implicate a Central Role of STAT3 in Skin Barrier Dysfunction Induced Aggravation of Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "our results showed that the destruction of the skin barrier aggravates the inflammation levels and immune infiltration of rosacea"
      explanation: >-
        This supports immune infiltration as part of the inflammatory
        lesion-forming program in rosacea.
  evidence:
  - reference: PMID:35392024
    reference_title: "Multi-Transcriptomic Analysis and Experimental Validation Implicate a Central Role of STAT3 in Skin Barrier Dysfunction Induced Aggravation of Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The XCell immune cell assays showed that the increased immune infiltration with SBD."
    explanation: >-
      This transcriptomic analysis supports increased immune-cell
      infiltration in rosacea with barrier dysfunction.
- name: Th1/Th17 adaptive inflammation
  description: >-
    Chemokine and cytokine networks in rosacea polarize adaptive immunity
    toward Th1/Th17 inflammatory programs.
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  downstream:
  - target: Papulopustular inflammation
    description: >-
      Th1/Th17-skewed adaptive inflammation contributes to inflammatory
      papulopustular lesions.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Chemokine and cytokine signals interact to generate a Th1/Th17-polarized adaptive immune response in rosacea"
      explanation: >-
        This supports an adaptive inflammatory branch converging on
        papulopustular disease activity.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Chemokine and cytokine signals interact to generate a Th1/Th17-polarized adaptive immune response in rosacea"
    explanation: >-
      This review supports a Th1/Th17-polarized adaptive inflammatory
      response in rosacea.
  - reference: PMID:40835085
    reference_title: "Cathelicidin LL-37-Induced Transcriptome of Human Keratinocyte Identifies Chemokine CXCL10 Link to T-Cell-Mediated Rosacea Pathogenesis through Jak1/STAT1 Pathway."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "T-cell recruiting chemokine CXCL10 turns out to be the most abundant inflammatory mediator overexpressed upon LL-37 exposure."
    explanation: >-
      This supports a chemokine-driven adaptive immune arm linking
      keratinocyte activation to pathogenic T-cell recruitment.
- name: TRP and neuropeptide signaling
  description: >-
    TRP-channel activation and neuropeptide signaling form a neurocutaneous
    branch of rosacea pathophysiology that increases vascular reactivity.
  biological_processes:
  - preferred_term: neuropeptide signaling pathway
    term:
      id: GO:0007218
      label: neuropeptide signaling pathway
  downstream:
  - target: Neurovascular vasodilation
    description: >-
      TRP and neuropeptide signaling promote exaggerated vasodilatory
      responses in rosacea skin.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:34035646
      reference_title: "Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Recognized mechanisms include the innate immune system, with the implication of Toll-like receptors (TLRs) and cathelicidins; neurovascular deregulation involving vascular endothelial growth factor (VEGF), transient receptor potential (TRP) ion channels, and neuropeptides"
      explanation: >-
        This directly supports TRP and neuropeptides as upstream drivers
        of rosacea neurovascular dysregulation.
  evidence:
  - reference: PMID:34035646
    reference_title: "Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Recognized mechanisms include the innate immune system, with the implication of Toll-like receptors (TLRs) and cathelicidins; neurovascular deregulation involving vascular endothelial growth factor (VEGF), transient receptor potential (TRP) ion channels, and neuropeptides"
    explanation: >-
      This review identifies TRP and neuropeptides as part of the
      neurovascular arm of rosacea pathophysiology.
- name: Neurovascular vasodilation
  description: >-
    Exaggerated vasodilation is a proximal vascular event that drives flushing
    and contributes to persistent background erythema.
  downstream:
  - target: Flushing
    description: Vasodilatory surges produce episodic flushing.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema)"
      explanation: >-
        This supports flushing as a direct clinical output of vascular
        hyperreactivity in rosacea.
  - target: Persistent centrofacial erythema
    description: >-
      Recurrent vasodilatory instability contributes to chronic background
      centrofacial erythema.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - recurrent vascular hyperreactivity
    - persistent superficial vasodilation
    evidence:
    - reference: PMID:27718519
      reference_title: "Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "persistent, centrofacial erythema associated with periodic intensification"
      explanation: >-
        This supports persistent erythema as a chronic vascular phenotype
        that periodically intensifies.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "while the multifactorial pathology of rosacea is thought to involve both vasoactive and neurocutaneous mechanisms."
    explanation: >-
      This overview supports a vasoreactive proximal mechanism in rosacea.
- name: Angiogenic vascular remodeling
  description: >-
    Angiogenic signaling contributes to persistent vascular remodeling and
    visible superficial telangiectatic change.
  biological_processes:
  - preferred_term: angiogenesis
    term:
      id: GO:0001525
      label: angiogenesis
  downstream:
  - target: Facial telangiectasia
    description: >-
      Persistent angiogenic remodeling contributes to telangiectatic
      centrofacial vessels.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:37626650
      reference_title: "Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "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."
      explanation: >-
        This supports telangiectasia as a major downstream vascular
        manifestation of rosacea.
  - target: Persistent centrofacial erythema
    description: >-
      Remodeling of superficial vasculature helps sustain background facial
      erythema.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - superficial vascular enlargement
    - persistent cutaneous hyperemia
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "This leads to the formation of LL-37 and other peptides that are inflammatory and angiogenic"
      explanation: >-
        This supports an angiogenic component in the pathway that sustains
        persistent erythematous change.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This leads to the formation of LL-37 and other peptides that are inflammatory and angiogenic"
    explanation: >-
      This supports angiogenic signaling as a discrete downstream consequence
      of cathelicidin pathway activation.
  - reference: PMID:40567003
    reference_title: "Novel Molecular Subtyping Revealed Molecular Pathways That Contribute to the Pathogenesis of Rosacea."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "angiogenesis and neutrophil activation may contribute to persistent erythema and a large number of papules and pustules in the severe stage of rosacea."
    explanation: >-
      This molecular subtyping study supports angiogenesis as a driver of
      persistent erythema and lesion-rich severe rosacea.
- name: Papulopustular inflammation
  description: >-
    Convergent innate, adaptive, and keratinocyte inflammatory programs
    produce inflammatory papules and pustules in papulopustular rosacea.
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  downstream:
  - target: Papules
    description: Inflammatory lesion formation produces papular eruptions.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema), persistent central facial erythema, inflammatory papules/pustules, and telangiectasia."
      explanation: >-
        This directly supports papules as a downstream inflammatory lesion
        type in rosacea.
  - target: Pustules
    description: Ongoing inflammatory lesion formation produces pustules.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:28150107
      reference_title: "Acne and Rosacea."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema), persistent central facial erythema, inflammatory papules/pustules, and telangiectasia."
      explanation: >-
        This directly supports pustules as a downstream inflammatory lesion
        type in rosacea.
  evidence:
  - reference: PMID:39823143
    reference_title: "Unveiling the Molecular Mechanisms of Rosacea: Insights From Transcriptomics and In Vitro Experiments."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Transcriptomic analysis revealed significantly elevated expression of inflammatory-related genes in rosacea patients."
    explanation: >-
      This study supports a lesion-forming inflammatory state in rosacea
      skin.
- name: Sebaceous gland dysfunction
  description: >-
    Dysfunction of cutaneous sebaceous glands is recognized as part of the
    multifactorial tissue biology of rosacea.
  downstream:
  - target: Sebaceous gland and soft tissue hyperplasia/fibrosis
    description: >-
      In advanced disease, altered sebaceous-unit biology can progress to
      hyperplastic and fibrotic phymatous tissue remodeling.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - chronic inflammation
    - connective tissue remodeling
    evidence:
    - reference: PMID:19428039
      reference_title: "[Rhinophyma in a black African male patient]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Rhinophyma is an irregular and progressive nasal hypertrophy, due to hyperplasia and fibrosis of the sebaceous glands and surrounding soft tissues."
      explanation: >-
        This supports progression from abnormal sebaceous-unit biology to
        sebaceous and soft-tissue hyperplasia/fibrosis in phymatous
        rosacea.
  evidence:
  - reference: PMID:34035646
    reference_title: "Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Recognized mechanisms include the innate immune system, with the implication of Toll-like receptors (TLRs) and cathelicidins; neurovascular deregulation involving vascular endothelial growth factor (VEGF), transient receptor potential (TRP) ion channels, and neuropeptides; and dysfunction of skin sebaceous glands and ocular meibomian glands."
    explanation: >-
      This review identifies sebaceous gland dysfunction as a discrete
      component of rosacea pathophysiology.
- name: Meibomian gland dysfunction
  description: >-
    Ocular rosacea includes meibomian gland dysfunction as part of its
    site-specific pathophysiology.
  downstream:
  - target: Ocular surface and eyelid inflammation
    description: >-
      Meibomian-gland disease contributes to chronic inflammatory
      involvement of the eyelids and ocular surface.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:40522449
      reference_title: "[Ocular rosacea : Clinical aspects, diagnostics, management and treatment]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "It is characterized by bilateral chronic posterior blepharitis and meibomitis, which can involve the entire surface of the eye, including the cornea, during the course of the disease."
      explanation: >-
        This directly links meibomian disease to chronic inflammatory
        involvement of the eyelids and ocular surface in ocular rosacea.
  evidence:
  - reference: PMID:34035646
    reference_title: "Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Recognized mechanisms include the innate immune system, with the implication of Toll-like receptors (TLRs) and cathelicidins; neurovascular deregulation involving vascular endothelial growth factor (VEGF), transient receptor potential (TRP) ion channels, and neuropeptides; and dysfunction of skin sebaceous glands and ocular meibomian glands."
    explanation: >-
      This review identifies meibomian gland dysfunction as part of ocular
      rosacea biology.
- name: Ocular surface and eyelid inflammation
  description: >-
    Ocular rosacea produces chronic inflammatory involvement of the eyelids
    and ocular surface, with posterior blepharitis as a characteristic
    clinical expression.
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  downstream:
  - target: Blepharitis
    description: >-
      Chronic eyelid inflammation manifests clinically as posterior
      blepharitis.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:40522449
      reference_title: "[Ocular rosacea : Clinical aspects, diagnostics, management and treatment]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "It is characterized by bilateral chronic posterior blepharitis and meibomitis, which can involve the entire surface of the eye, including the cornea, during the course of the disease."
      explanation: >-
        This directly supports blepharitis as a downstream phenotype of
        ocular rosacea inflammatory eyelid disease.
  evidence:
  - reference: PMID:40522449
    reference_title: "[Ocular rosacea : Clinical aspects, diagnostics, management and treatment]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ocular rosacea is a chronic inflammatory disease that affects the surface of the eye and the eyelids."
    explanation: >-
      This review supports ocular rosacea as an inflammatory disease of the
      eyelids and ocular surface.
- name: Fibrotic dermal remodeling
  description: >-
    Advanced rosacea can shift toward a fibrotic remodeling program in which
    vascular changes are coupled to connective-tissue fibrosis.
  downstream:
  - target: Sebaceous gland and soft tissue hyperplasia/fibrosis
    description: >-
      Fibrotic remodeling progresses to phymatous tissue overgrowth
      involving sebaceous units and surrounding soft tissue.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:25151931
      reference_title: "[Physiopathology of rosacea]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Finaly, rhinophyma is linked to both vascular changes and activation of fibrosis, involving TGF beta."
      explanation: >-
        This supports a fibrotic remodeling step in advanced phymatous
        rosacea.
  evidence:
  - reference: PMID:25151931
    reference_title: "[Physiopathology of rosacea]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Finaly, rhinophyma is linked to both vascular changes and activation of fibrosis, involving TGF beta."
    explanation: >-
      This review supports fibrosis as a specific mechanism underlying
      rhinophyma development.
  - reference: PMID:41139274
    reference_title: "Integrated Multi-Omics and Experimental Validation Unveil the GZMK/NF-κB Axis Driving Inflammation and Fibroblast Proliferation in Rosacea: A Novel Drug Target Selection Strategy."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "GZMK also promoted cell proliferation and inflammatory factors (including IL-1β, IL-6, and TNFα) production in fibroblasts through activating the NF-κB pathway in vitro."
    explanation: >-
      This directly supports fibroblast proliferative and inflammatory
      programs that can feed fibrotic remodeling in advanced rosacea.
- name: Sebaceous gland and soft tissue hyperplasia/fibrosis
  description: >-
    Rhinophyma reflects progressive hypertrophic remodeling of sebaceous
    glands and adjacent soft tissue in the nose.
  downstream:
  - target: Phymatous change of the nose
    description: >-
      Hyperplastic and fibrotic tissue overgrowth produces the bulbous,
      progressively deformed nasal phenotype of rhinophyma.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:19428039
      reference_title: "[Rhinophyma in a black African male patient]."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Rhinophyma is an irregular and progressive nasal hypertrophy, due to hyperplasia and fibrosis of the sebaceous glands and surrounding soft tissues."
      explanation: >-
        This directly supports phymatous nasal change as the clinical
        result of sebaceous-gland and soft-tissue hyperplasia/fibrosis.
  evidence:
  - reference: PMID:19428039
    reference_title: "[Rhinophyma in a black African male patient]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rhinophyma is an irregular and progressive nasal hypertrophy, due to hyperplasia and fibrosis of the sebaceous glands and surrounding soft tissues."
    explanation: >-
      This abstract defines rhinophyma in terms of sebaceous-gland and soft
      tissue hyperplasia/fibrosis.
phenotypes:
- name: Persistent centrofacial erythema
  category: Dermatological
  frequency: VERY_FREQUENT
  diagnostic: true
  subtype: Erythematotelangiectatic Rosacea
  notes: >-
    Persistent background erythema of the central face is a core diagnostic
    phenotype in modern phenotype-led rosacea classification.
  phenotype_term:
    preferred_term: persistent centrofacial erythema
    term:
      id: HP:0001041
      label: Facial erythema
  evidence:
  - reference: PMID:27718519
    reference_title: "Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes."
    explanation: >-
      ROSCO identifies persistent centrofacial erythema as one of the two
      diagnostic phenotypes for rosacea.
- name: Flushing
  category: Dermatological
  frequency: FREQUENT
  subtype: Erythematotelangiectatic Rosacea
  notes: Episodic flushing commonly accompanies the vascular phenotype.
  phenotype_term:
    preferred_term: flushing
    term:
      id: HP:0031284
      label: Flushing
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema), persistent central facial erythema, inflammatory papules/pustules, and telangiectasia."
    explanation: >-
      This overview identifies flushing as a characteristic clinical
      manifestation of rosacea.
- name: Facial telangiectasia
  category: Dermatological
  frequency: FREQUENT
  subtype: Erythematotelangiectatic Rosacea
  phenotype_term:
    preferred_term: facial telangiectasia
    term:
      id: HP:0007380
      label: Facial telangiectasia
  evidence:
  - reference: PMID:37626650
    reference_title: "Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "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."
    explanation: >-
      This review includes telangiectasia among the central defining
      manifestations of rosacea.
- name: Papules
  category: Dermatological
  frequency: FREQUENT
  subtype: Papulopustular Rosacea
  phenotype_term:
    preferred_term: erythematous papule
    term:
      id: HP:0030350
      label: Erythematous papule
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema), persistent central facial erythema, inflammatory papules/pustules, and telangiectasia."
    explanation: >-
      This overview identifies inflammatory papules as a characteristic
      lesion type in rosacea.
- name: Pustules
  category: Dermatological
  frequency: FREQUENT
  subtype: Papulopustular Rosacea
  phenotype_term:
    preferred_term: pustule
    term:
      id: HP:0200039
      label: Pustule
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rosacea is a chronic facial inflammatory dermatosis characterized by flushing (or transient facial erythema), persistent central facial erythema, inflammatory papules/pustules, and telangiectasia."
    explanation: >-
      This overview identifies papulopustular lesions as part of the core
      clinical spectrum of rosacea.
- name: Phymatous change of the nose
  category: Dermatological
  frequency: OCCASIONAL
  diagnostic: true
  subtype: Phymatous Rosacea
  notes: >-
    Phymatous rosacea is most often expressed as progressive tissue
    thickening of the nose (rhinophyma).
  phenotype_term:
    preferred_term: rhinophyma
    term:
      id: HP:0000414
      label: Bulbous nose
  evidence:
  - reference: PMID:27718519
    reference_title: "Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes."
    explanation: >-
      ROSCO identifies phymatous change as the second independently
      diagnostic phenotype of rosacea.
- name: Blepharitis
  category: Ophthalmological
  frequency: OCCASIONAL
  subtype: Ocular Rosacea
  notes: Ocular rosacea often presents with eyelid margin inflammation.
  phenotype_term:
    preferred_term: blepharitis
    term:
      id: HP:0000498
      label: Blepharitis
  evidence:
  - reference: PMID:40522449
    reference_title: "[Ocular rosacea : Clinical aspects, diagnostics, management and treatment]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It is characterized by bilateral chronic posterior blepharitis and meibomitis, which can involve the entire surface of the eye, including the cornea, during the course of the disease."
    explanation: >-
      This directly supports chronic posterior blepharitis as a hallmark
      ocular phenotype of ocular rosacea.
- name: Facial edema
  category: Dermatological
  frequency: VERY_RARE
  notes: >-
    A rare rosacea-associated lymphedematous presentation, often termed
    Morbihan disease, causes chronic persistent facial swelling.
  phenotype_term:
    preferred_term: facial edema
    term:
      id: HP:0000282
      label: Facial edema
  evidence:
  - reference: PMID:41426892
    reference_title: "Multimodal Management of Morbihan Disease: Isotretinoin, Intralesional Triamcinolone, and Ketotifen in a Recalcitrant Case."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Morbihan disease, also known as rosacea-associated solid facial edema, is a rare and chronic condition that presents with persistent facial swelling and often proves difficult to treat."
    explanation: >-
      This directly supports persistent facial edema as a rare rosacea-
      associated phenotype.
- name: Upper eyelid edema
  category: Ophthalmological
  frequency: VERY_RARE
  subtype: Ocular Rosacea
  notes: >-
    Ocular rosacea can rarely present with persistent peri-orbital swelling,
    sometimes accompanied by secondary ptosis.
  phenotype_term:
    preferred_term: upper eyelid edema
    term:
      id: HP:0012724
      label: Upper eyelid edema
  evidence:
  - reference: PMID:41058755
    reference_title: "Unilateral Peri-Orbital Oedema and Mechanical Ptosis: An Unusual Case Presentation of Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A 64-year-old Caucasian man presented with a 9-month history of persistent painless swelling of the right upper eyelid and secondary ptosis."
    explanation: >-
      This case report supports persistent upper-eyelid edema as a rare
      ocular manifestation of rosacea.
histopathology:
- name: Dermal vascular endothelial Angiopoietin 2 and Tie2 overexpression
  description: >-
    Lesional erythematotelangiectatic and papulopustular rosacea skin shows
    increased Angiopoietin 2 and Tie2 staining in endothelial cells of dermal
    vessels compared with non-lesional skin, supporting a vascular
    remodeling-associated histopathology pattern.
  context: Erythematotelangiectatic and papulopustular rosacea skin biopsies
  evidence:
  - reference: PMID:41562711
    reference_title: "Increased Expression of Angiopoietin 2 and Tie2 in Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Significantly increased expression of Tie2 and Angiopoietin 2 in the endothelial cells of the dermal vessels in rosacea skin vs. non-lesional skin (100% and 33.3% for Tie2, and 100% and 50% for Angiopoietin 2) was observed."
    explanation: >-
      This provides direct biopsy-level immunohistochemical evidence for
      altered dermal vascular endothelium in rosacea lesions.
- name: Early dermal fibrotic remodeling
  finding_term:
    preferred_term: fibrosis
    term:
      id: NCIT:C3044
      label: Fibrosis
  description: >-
    Fibrotic remodeling is detectable in rosacea skin biopsies even at
    inflammation-dominant stages, indicating that tissue-remodeling changes
    begin before fully developed phymatous disease.
  context: Inflammation-dominant rosacea skin biopsies
  evidence:
  - reference: PMID:41800255
    reference_title: "Targeting Macrophage-to-Myofibroblast Transition Mitigates Progression from Inflammation to Fibrosis in Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and histological staining of skin biopsies demonstrated that fibrotic remodeling was already evident at inflammation-dominant stages"
    explanation: >-
      This study directly supports fibrosis as an observable tissue-level
      change in rosacea biopsies, not only in late rhinophyma.
- name: Sebaceous gland and surrounding soft tissue hyperplasia with fibrosis
  subtype: Phymatous Rosacea
  description: >-
    Rhinophyma shows hypertrophic remodeling of sebaceous glands and adjacent
    soft tissue accompanied by fibrosis, forming the core microscopic pattern
    of phymatous rosacea.
  context: Rhinophyma / phymatous rosacea
  evidence:
  - reference: PMID:19428039
    reference_title: "[Rhinophyma in a black African male patient]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rhinophyma is an irregular and progressive nasal hypertrophy, due to hyperplasia and fibrosis of the sebaceous glands and surrounding soft tissues."
    explanation: >-
      This abstract directly supports sebaceous gland hyperplasia with
      fibrosis as a defining microscopic tissue-remodeling feature of
      rhinophyma.
- name: Leaky vascular architecture in rhinophyma tissue
  subtype: Phymatous Rosacea
  description: >-
    Rhinophyma tissue shows an abnormal vascular architecture with leaky
    vessel profiles rather than the stromal-enveloped vascular pattern seen
    in hypertrophic scars.
  context: Rhinophyma tissue
  evidence:
  - reference: PMID:41909715
    reference_title: "Distinct diversity of skin cell populations of rhinophyma and hypertrophic scar illustrated by scRNA-seq."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Vascular structures in hypertrophic scar tissues are enveloped by a significant number of stromal cells, in contrast to the leaky vascular profiles observed in rhinophyma tissues."
    explanation: >-
      This study supports a distinctive vascular tissue architecture in
      rhinophyma that fits the disease's vascular-remodeling phenotype.
- name: Immune-cell-rich rhinophyma tissue
  subtype: Phymatous Rosacea
  description: >-
    Rhinophyma tissue contains a relatively expanded immune-cell compartment,
    consistent with persistent inflammatory remodeling in phymatous disease.
  context: Rhinophyma tissue
  evidence:
  - reference: PMID:41909715
    reference_title: "Distinct diversity of skin cell populations of rhinophyma and hypertrophic scar illustrated by scRNA-seq."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the number of immune cells in rhinophyma is significantly higher than in hypertrophic scar tissues."
    explanation: >-
      This supports immune-cell enrichment as a tissue-level feature of
      rhinophyma.
- name: Eyelid tissue lymphoedema in ocular rosacea
  subtype: Ocular Rosacea
  description: >-
    In rare ocular rosacea with persistent peri-orbital swelling, eyelid
    debulking biopsy can show rosacea-associated inflammatory change with
    superimposed lymphoedematous tissue remodeling.
  context: Ocular rosacea with persistent peri-orbital edema
  evidence:
  - reference: PMID:41058755
    reference_title: "Unilateral Peri-Orbital Oedema and Mechanical Ptosis: An Unusual Case Presentation of Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Histopathological analysis of the debulking biopsy confirmed the diagnosis of rosacea, with additional features indicative of lymphoedema."
    explanation: >-
      This provides direct biopsy-level support for lymphoedematous tissue
      change in a rare ocular rosacea presentation.
genetic:
- name: IRF1
  gene_term:
    preferred_term: IRF1
    term:
      id: hgnc:6116
      label: IRF1
  association: MR-supported druggable gene
  notes: >-
    Integrative MR/SMR analysis prioritized IRF1 as a rosacea-linked
    druggable gene and connected it to immune-cell activation and interferon
    signaling.
  evidence:
  - reference: PMID:40635520
    reference_title: "Integrated Genomic and GEO Data Analysis Reveals Therapeutic Targets for Rosacea."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "MR and SMR analyses identified IRF1 and SLC22A5 as druggable genes for rosacea, with Bayesian colocalization strongly supporting shared causal variants."
    explanation: >-
      This directly supports IRF1 as a genetically prioritized therapeutic
      target in rosacea.
- name: SLC22A5
  gene_term:
    preferred_term: SLC22A5
    term:
      id: hgnc:10969
      label: SLC22A5
  association: MR-supported druggable gene
  notes: >-
    SLC22A5 emerged from integrative MR/SMR analysis as a rosacea-linked
    druggable gene, with proposed relevance to transport and lipid
    homeostasis.
  evidence:
  - reference: PMID:40635520
    reference_title: "Integrated Genomic and GEO Data Analysis Reveals Therapeutic Targets for Rosacea."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "MR and SMR analyses identified IRF1 and SLC22A5 as druggable genes for rosacea, with Bayesian colocalization strongly supporting shared causal variants."
    explanation: >-
      This directly supports SLC22A5 as a genetically prioritized
      therapeutic target in rosacea.
- name: GZMK
  gene_term:
    preferred_term: GZMK
    term:
      id: hgnc:4711
      label: GZMK
  association: MR-supported drug target
  notes: >-
    Multi-omics prioritization identified GZMK as a rosacea-linked target and
    functionally connected it to inflammatory fibroblast activation.
  evidence:
  - reference: PMID:41139274
    reference_title: "Integrated Multi-Omics and Experimental Validation Unveil the GZMK/NF-κB Axis Driving Inflammation and Fibroblast Proliferation in Rosacea: A Novel Drug Target Selection Strategy."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "MR and colocalization identified Granzyme K (GZMK) as a drug target, whose expression increased in the affected samples."
    explanation: >-
      This supports GZMK as a genetically prioritized rosacea target with
      increased expression in disease-associated samples.
- name: MSR1
  gene_term:
    preferred_term: MSR1
    term:
      id: hgnc:7376
      label: MSR1
  association: MR-supported risk-promoting biomarker
  notes: >-
    Integrative proteomic and Mendelian-randomization analysis identified
    MSR1 as a rosacea-promoting protein target.
  evidence:
  - reference: PMID:40890957
    reference_title: "Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "Further refinement through SMR and differential expression analysis reduced this to five key proteins, including four (ABHD14B, CHMP6, DBNL and MCFD2) that inhibit rosacea onset and one (MSR1) that promotes it."
    explanation: >-
      This directly supports MSR1 as the risk-promoting protein among the
      final MR-prioritized rosacea biomarkers.
- name: ABHD14B
  gene_term:
    preferred_term: ABHD14B
    term:
      id: hgnc:28235
      label: ABHD14B
  association: MR-supported protective biomarker
  notes: >-
    ABHD14B was among the final proteins whose genetically informed analyses
    suggested an inhibitory relationship with rosacea onset.
  evidence:
  - reference: PMID:40890957
    reference_title: "Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "Further refinement through SMR and differential expression analysis reduced this to five key proteins, including four (ABHD14B, CHMP6, DBNL and MCFD2) that inhibit rosacea onset and one (MSR1) that promotes it."
    explanation: >-
      This supports ABHD14B as one of the final MR-prioritized proteins
      associated with lower rosacea risk.
- name: CHMP6
  gene_term:
    preferred_term: CHMP6
    term:
      id: hgnc:25675
      label: CHMP6
  association: MR-supported protective biomarker
  notes: >-
    CHMP6 was among the final proteins whose genetically informed analyses
    suggested an inhibitory relationship with rosacea onset.
  evidence:
  - reference: PMID:40890957
    reference_title: "Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "Further refinement through SMR and differential expression analysis reduced this to five key proteins, including four (ABHD14B, CHMP6, DBNL and MCFD2) that inhibit rosacea onset and one (MSR1) that promotes it."
    explanation: >-
      This supports CHMP6 as one of the final MR-prioritized proteins
      associated with lower rosacea risk.
- name: DBNL
  gene_term:
    preferred_term: DBNL
    term:
      id: hgnc:2696
      label: DBNL
  association: MR-supported protective biomarker
  notes: >-
    DBNL was among the final proteins whose genetically informed analyses
    suggested an inhibitory relationship with rosacea onset.
  evidence:
  - reference: PMID:40890957
    reference_title: "Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "Further refinement through SMR and differential expression analysis reduced this to five key proteins, including four (ABHD14B, CHMP6, DBNL and MCFD2) that inhibit rosacea onset and one (MSR1) that promotes it."
    explanation: >-
      This supports DBNL as one of the final MR-prioritized proteins
      associated with lower rosacea risk.
- name: MCFD2
  gene_term:
    preferred_term: MCFD2
    term:
      id: hgnc:18451
      label: MCFD2
  association: MR-supported protective biomarker
  notes: >-
    MCFD2 was among the final proteins whose genetically informed analyses
    suggested an inhibitory relationship with rosacea onset.
  evidence:
  - reference: PMID:40890957
    reference_title: "Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "Further refinement through SMR and differential expression analysis reduced this to five key proteins, including four (ABHD14B, CHMP6, DBNL and MCFD2) that inhibit rosacea onset and one (MSR1) that promotes it."
    explanation: >-
      This supports MCFD2 as one of the final MR-prioritized proteins
      associated with lower rosacea risk.
environmental:
- name: Ultraviolet B radiation
  description: >-
    Ultraviolet B exposure is a recognized favoring factor that can worsen
    rosacea activity and amplify inflammatory and vascular responses.
  effect: TRIGGERS
  evidence:
  - reference: PMID:34035646
    reference_title: "Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Microorganisms, genetic predisposition, corticosteroid treatment, and ultraviolet B (UVB) radiation are favoring factors."
    explanation: >-
      This review explicitly identifies UVB radiation as an important
      rosacea-promoting exposure.
- name: Corticosteroid treatment
  description: >-
    Corticosteroid exposure can favor rosacea expression and is a recognized
    exacerbating factor in susceptible patients.
  effect: TRIGGERS
  evidence:
  - reference: PMID:34035646
    reference_title: "Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Microorganisms, genetic predisposition, corticosteroid treatment, and ultraviolet B (UVB) radiation are favoring factors."
    explanation: >-
      This review explicitly identifies corticosteroid treatment as a
      favoring factor for rosacea.
treatments:
- name: Trigger avoidance and photoprotection
  description: >-
    Baseline management includes avoidance of provoking exposures, gentle skin
    care, moisturization, and sun protection to reduce flares.
  role: Foundational nonpharmacologic management
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "While standard measures, including avoidance of triggers, gentle cleansers, and moisturizers in combination with sun protection, may mitigate flares, control signs and symptoms in some patients"
    explanation: >-
      This review supports trigger avoidance, gentle skin care, and
      photoprotection as foundational rosacea management.
- name: Papulopustular-directed pharmacotherapy
  description: >-
    Papulopustular rosacea is commonly treated with topical metronidazole,
    azelaic acid, or ivermectin, and in more inflammatory disease with oral
    doxycycline or isotretinoin.
  role: Mainstay treatment for papulopustular disease
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: metronidazole
      term:
        id: CHEBI:6909
        label: metronidazole
    - preferred_term: azelaic acid
      term:
        id: NCIT:C47407
        label: Azelaic Acid
    - preferred_term: ivermectin
      term:
        id: CHEBI:6078
        label: ivermectin
    - preferred_term: doxycycline
      term:
        id: CHEBI:50845
        label: doxycycline
    - preferred_term: isotretinoin
      term:
        id: NCIT:C603
        label: Isotretinoin
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "topical metronidazole, azelaic acid, ivermectin, or oral doxycycline and isotretinoin for papulopustules of rosacea"
    explanation: >-
      This review summarizes standard pharmacologic options used for
      papulopustular rosacea.
- name: Topical brimonidine therapy
  description: >-
    Persistent background erythema can be treated with topical brimonidine to
    reduce visible vasodilatory erythema.
  role: Pharmacologic treatment for the vascular erythema phenotype
  treatment_term:
    preferred_term: topical pharmacotherapy
    term:
      id: MAXO:0001573
      label: topical pharmacotherapy
    therapeutic_agent:
    - preferred_term: brimonidine
      term:
        id: CHEBI:3175
        label: brimonidine
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "topical brimonidine or intense pulsed light (IPL) for background persistent erythema"
    explanation: >-
      This review identifies brimonidine as a targeted therapy for
      persistent background erythema.
- name: Vascular light-based therapy
  description: >-
    Persistent vascular erythema may also be treated with light-based therapy
    such as intense pulsed light.
  role: Procedural treatment for the vascular erythema phenotype
  treatment_term:
    preferred_term: vascular light-based therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: phototherapy
        term:
          id: NCIT:C15301
          label: Phototherapy
  notes: >-
    Local OAK searches in MAXO for phototherapy, light therapy, laser
    therapy, and intense pulsed light did not return a suitable non-ionizing
    light-treatment term. This remains an NTR candidate, so the entry is
    represented with a free-text preferred term and an NCIT phototherapy
    qualifier rather than the incorrect radiotherapy term.
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "topical brimonidine or intense pulsed light (IPL) for background persistent erythema"
    explanation: >-
      This review identifies light-based vascular therapy as another
      targeted approach for persistent erythema.
- name: Cyclosporine eye drops
  description: >-
    Ocular rosacea may require targeted ophthalmic anti-inflammatory therapy
    such as cyclosporine eye drops.
  role: Pharmacologic treatment for ocular rosacea
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: cyclosporine
      term:
        id: CHEBI:4031
        label: cyclosporin A
  evidence:
  - reference: PMID:28150107
    reference_title: "Acne and Rosacea."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "cyclosporine eye drops for ocular rosacea"
    explanation: >-
      This review identifies cyclosporine eye drops as a treatment option
      for ocular rosacea.
- name: Morbihan disease-directed pharmacotherapy
  description: >-
    Rosacea-associated solid facial edema may require individualized
    combination pharmacotherapy centered on isotretinoin and intralesional
    corticosteroid treatment, with ketotifen used in selected refractory
    cases.
  role: Targeted treatment for rosacea-associated solid facial edema
  target_phenotypes:
  - preferred_term: facial edema
    term:
      id: HP:0000282
      label: Facial edema
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: isotretinoin
      term:
        id: NCIT:C603
        label: Isotretinoin
    - preferred_term: triamcinolone
      term:
        id: NCIT:C901
        label: Triamcinolone
    - preferred_term: ketotifen
      term:
        id: CHEBI:92511
        label: ketotifen
  evidence:
  - reference: PMID:41426892
    reference_title: "Multimodal Management of Morbihan Disease: Isotretinoin, Intralesional Triamcinolone, and Ketotifen in a Recalcitrant Case."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient reported partial improvement, most notably with higher isotretinoin dosing and intralesional corticosteroid injections, though intermittent flares persisted."
    explanation: >-
      This supports isotretinoin and intralesional corticosteroid treatment
      as active components of Morbihan disease management.
  - reference: PMID:41222206
    reference_title: "Unilateral presentation of Morbihan's disease: a comprehensive case report and review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Successful treatment with a series of triamcinolone injections to the upper and lower eyelids was achieved after several unsuccessful therapies."
    explanation: >-
      This independently supports intralesional triamcinolone as a useful
      treatment option for rosacea-associated solid facial edema.
- name: Laser surgical debulking for rhinophyma
  description: >-
    CO2 laser or blue-laser debulking can remove phymatous nasal tissue and
    improve function and cosmesis in selected rhinophyma.
  role: Procedural treatment for phymatous rosacea
  target_phenotypes:
  - preferred_term: rhinophyma
    term:
      id: HP:0000414
      label: Bulbous nose
  treatment_term:
    preferred_term: laser surgical procedure
    term:
      id: MAXO:0001578
      label: laser surgical procedure
  evidence:
  - reference: PMID:41918801
    reference_title: "CO(2) Laser Resection of Giant Rhinophyma Under Local Anesthesia: A Case Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "we emphasize the surgical value of local anesthesia with CO2 laser for rhinophyma, reducing blood loss, operation time, and the need for secondary surgery."
    explanation: >-
      This case report supports CO2 laser debulking as an effective
      rhinophyma procedure with practical operative advantages.
  - reference: PMID:40791837
    reference_title: "Rhinophyma Treatment with Blue Laser."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The use of blue laser to treat rhinophyma has shown to be an effective and safe procedure with very promising results."
    explanation: >-
      This provides additional support for laser-based debulking in
      rhinophyma.
- name: Excisional reconstruction for advanced rhinophyma
  description: >-
    Severe rhinophyma may require excision with reconstructive approaches
    such as graft-based resurfacing when tissue overgrowth is extensive.
  role: Reconstructive procedural treatment for advanced phymatous rosacea
  target_phenotypes:
  - preferred_term: rhinophyma
    term:
      id: HP:0000414
      label: Bulbous nose
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: skin graft
        term:
          id: NCIT:C12842
          label: Skin Graft
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: reconstructive surgery
        term:
          id: NCIT:C25351
          label: Reconstructive Surgery
  evidence:
  - reference: PMID:40860281
    reference_title: "Rhinophyma treated by skin graft: a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Surgical excision is the primary treatment, and various techniques are available."
    explanation: >-
      This supports excisional surgery as the primary treatment framework
      for advanced rhinophyma, including graft-based reconstruction.
clinical_trials:
- name: NCT01493947
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Phase III comparative topical trial of ivermectin 1% cream versus
    metronidazole 0.75% cream in papulopustular rosacea, with an extension
    period assessing relapse-related outcomes.
  target_phenotypes:
  - preferred_term: erythematous papule
    term:
      id: HP:0030350
      label: Erythematous papule
  - preferred_term: pustule
    term:
      id: HP:0200039
      label: Pustule
  evidence:
  - reference: clinicaltrials:NCT01493947
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "To compare efficacy and safety of Ivermectin 1% cream versus metronidazole 0.75% cream in subjects with papulopustular rosacea after 16-week topical treatment."
    explanation: >-
      This registry summary supports a pivotal interventional trial focused
      on papulopustular rosacea lesion control.
- name: NCT00126399
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Phase III placebo-controlled trial of once-daily 40 mg doxycycline
    controlled-release capsules for rosacea.
  target_phenotypes:
  - preferred_term: erythematous papule
    term:
      id: HP:0030350
      label: Erythematous papule
  - preferred_term: pustule
    term:
      id: HP:0200039
      label: Pustule
  evidence:
  - reference: clinicaltrials:NCT00126399
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The objective of this study is to evaluate the safety and efficacy of 40 mg doxycycline controlled-release capsules administered once daily for the treatment of rosacea compared with a placebo."
    explanation: >-
      This registry entry supports controlled clinical evaluation of
      subantimicrobial-dose doxycycline for rosacea.
- name: NCT03380390
  phase: PHASE_IV
  status: COMPLETED
  description: >-
    Phase IV open-label study of oxymetazoline 1.0% cream used adjunctively
    with energy-based therapy for persistent facial erythema in rosacea.
  target_phenotypes:
  - preferred_term: persistent centrofacial erythema
    term:
      id: HP:0001041
      label: Facial erythema
  evidence:
  - reference: clinicaltrials:NCT03380390
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This study will evaluate the safety and tolerability of oxymetazoline HCl cream 1.0% when used as an adjunctive treatment to energy-based therapy for participants with moderate to severe persistent facial erythema associated with rosacea."
    explanation: >-
      This trial directly targets the persistent erythema phenotype that
      anchors erythematotelangiectatic rosacea.
- name: NCT05616923
  phase: PHASE_I
  status: COMPLETED
  description: >-
    Early-phase vehicle-controlled trial evaluating topical MEK inhibition in
    erythematotelangiectatic rosacea.
  target_phenotypes:
  - preferred_term: persistent centrofacial erythema
    term:
      id: HP:0001041
      label: Facial erythema
  - preferred_term: flushing
    term:
      id: HP:0031284
      label: Flushing
  evidence:
  - reference: clinicaltrials:NCT05616923
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This is a prospective, vehicle controlled, double blinded study to evaluate the safety and potential efficacy of a topical formulation of a MEK inhibitor in patients with erythematotelangiectatic rosacea"
    explanation: >-
      This registry entry supports a mechanism-oriented interventional study
      in the vascular erythematotelangiectatic phenotype.
datasets:
- accession: geo:GSE65914
  title: Th1/Th17 Immune Response in Rosacea
  description: >-
    Human facial biopsy transcriptomic dataset spanning rosacea subtypes and
    healthy controls, used to define adaptive immune and inflammatory cell
    programs across erythematotelangiectatic, papulopustular, and phymatous
    disease.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: MICROARRAY
  sample_count: 58
  conditions:
  - erythematotelangiectatic rosacea
  - papulopustular rosacea
  - phymatous rosacea
  - healthy control facial skin
  evidence:
  - reference: GEO:GSE65914
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The T cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFNγ or IL-17, for example."
    explanation: >-
      This GEO series directly supports subtype-spanning adaptive immune
      polarization in human rosacea tissue.
- accession: geo:GSE155141
  title: Paired transcriptomic and proteomic analysis implicates IL-1β in the pathogenesis of papulopustular rosacea explants [RNA-seq]
  description: >-
    Human RNA-seq dataset from paired non-lesional and lesional
    papulopustular rosacea explants, linked to paired proteomic profiling and
    inflammatory pathway analysis.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 15
  conditions:
  - non-lesional papulopustular rosacea skin
  - lesional papulopustular rosacea skin
  - IL-1beta-treated non-lesional rosacea skin
  evidence:
  - reference: GEO:GSE155141
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our study suggests that MAPK and TNF signaling pathways are the most significantly upregulated pathways in lesional papulopustular rosacea human skins, highlighting IL-1β as a potential central mediator."
    explanation: >-
      This dataset captures lesion-associated inflammatory pathway activity
      in papulopustular rosacea.
- accession: geo:GSE303282
  title: Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway
  description: >-
    Human keratinocyte microarray dataset modeling LL-37-driven rosacea-like
    inflammation in vitro to resolve chemokine and JAK-STAT signaling outputs
    downstream of cathelicidin exposure.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: MICROARRAY
  sample_count: 6
  conditions:
  - LL-37-treated primary keratinocytes
  - untreated primary keratinocytes
  evidence:
  - reference: GEO:GSE303282
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Mechanistically, LL-37 induced CXCL10 production relied on JAK-1/STAT-1 signaling pathway."
    explanation: >-
      This in vitro transcriptomic dataset is directly relevant to the
      cathelicidin and STAT-linked mechanism nodes in rosacea.
- accession: geo:GSE277020
  title: Effect of eyelid UVB irradiation on gene expression of rat meibomian gland
  description: >-
    Rat bulk RNA-seq dataset from a UVB-induced ocular rosacea model focused
    on meibomian gland dysfunction, ocular surface injury, and downstream
    inflammatory and keratinization pathways.
  organism:
    preferred_term: Rattus norvegicus
    term:
      id: NCBITaxon:10116
      label: Rattus norvegicus
  data_type: BULK_RNA_SEQ
  sample_count: 7
  conditions:
  - UVB-irradiated rat eyelids and meibomian glands
  - non-irradiated rat controls
  evidence:
  - reference: GEO:GSE277020
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "We have developed a rat model of UVB-induced ocular surface and eyelid damages mimicking ocular rosacea, a common chronic inflammatory and neurovascular ocular surface disease associated with meibomian gland dysfunction."
    explanation: >-
      This dataset provides an ocular/meibomian model aligned to the ocular
      rosacea subgraph in this entry.
differential_diagnoses:
- name: Acne
  disease_term:
    preferred_term: acne
    term:
      id: MONDO:0011438
      label: acne
  description: >-
    Acne can overlap clinically with papulopustular rosacea because both
    produce inflammatory papules and pustules on the face.
  distinguishing_features:
  - Acne more often shows open or closed comedones and broader sebaceous facial or truncal involvement.
  - Rosacea more often centers on persistent centrofacial erythema, flushing, and telangiectasia without comedones.
  evidence:
  - reference: PMID:11582639
    reference_title: "[Rosacea in the year 2001]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It can be difficult to distinguish acne vulgaris, seborrheic eczema, perioral dermatitis and lupus erythematosus from rosacea."
    explanation: >-
      This review explicitly lists acne vulgaris among the core differential
      diagnoses for rosacea.
- name: Seborrheic dermatitis
  disease_term:
    preferred_term: seborrheic dermatitis
    term:
      id: MONDO:0006608
      label: seborrheic dermatitis
  description: >-
    Facial seborrheic dermatitis can mimic rosacea when patients present with
    chronic erythema in sebaceous facial regions.
  distinguishing_features:
  - Seborrheic dermatitis more often has greasy yellow-white scale involving the eyebrows, nasolabial folds, and scalp.
  - Rosacea more often has flushing, telangiectasia, and papulopustular lesions without prominent greasy scale.
  evidence:
  - reference: PMID:11582639
    reference_title: "[Rosacea in the year 2001]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It can be difficult to distinguish acne vulgaris, seborrheic eczema, perioral dermatitis and lupus erythematosus from rosacea."
    explanation: >-
      This review explicitly identifies seborrheic eczema as a major
      rosacea mimic; the corresponding MONDO disease term used here is
      seborrheic dermatitis.
- name: Lupus erythematosus
  disease_term:
    preferred_term: lupus erythematosus
    term:
      id: MONDO:0004670
      label: lupus erythematosus
  description: >-
    Lupus erythematosus can resemble rosacea when facial erythema or a
    butterfly-pattern eruption predominates.
  distinguishing_features:
  - Lupus erythematosus more often has photosensitivity, scale, dyspigmentation, scarring plaques, or systemic autoimmune features.
  - Rosacea more often has trigger-provoked flushing, telangiectasia, and papulopustular centrofacial inflammation.
  evidence:
  - reference: PMID:11582639
    reference_title: "[Rosacea in the year 2001]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It can be difficult to distinguish acne vulgaris, seborrheic eczema, perioral dermatitis and lupus erythematosus from rosacea."
    explanation: >-
      This review explicitly lists lupus erythematosus among disorders that
      can be difficult to distinguish from rosacea.
  - reference: PMID:41695827
    reference_title: "Rosacea overlapping the malar rash: A diagnostic challenge in early systemic lupus erythematosus."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The coexistence of rosacea and lupus-like lesions delayed diagnosis, highlighting the need for clinicopathological correlation."
    explanation: >-
      This case report reinforces lupus erythematosus as a real-world
      rosacea mimic and overlap diagnosis.
- name: Systemic sclerosis
  disease_term:
    preferred_term: systemic sclerosis
    term:
      id: MONDO:0005100
      label: systemic sclerosis
  description: >-
    Rosacea-associated solid facial edema can mimic systemic sclerosis when
    facial induration or swelling dominates the presentation.
  distinguishing_features:
  - Systemic sclerosis more often has Raynaud phenomenon, acral involvement, and broader connective-tissue disease manifestations.
  - Morbihan-type rosacea edema may remain centered on the face with sparing of the hands and feet.
  evidence:
  - reference: PMID:41694889
    reference_title: "Facial Swelling in a Young Adult With Type 1 Diabetes: Morbihan Disease as a Scleroderma Mimic."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Scleredema diabeticorum and Morbihan disease (solid facial edema) can mimic scleroderma, creating diagnostic challenges for rheumatologists."
    explanation: >-
      This directly supports systemic sclerosis-spectrum disease as a
      differential diagnosis for edematous rosacea presentations.
- name: Coccidioidomycosis
  disease_term:
    preferred_term: coccidioidomycosis
    term:
      id: MONDO:0005706
      label: coccidioidomycosis
  description: >-
    Cutaneous coccidioidomycosis can mimic rosacea-like dermatitis,
    particularly in immunocompromised patients living in endemic regions.
  distinguishing_features:
  - Coccidioidomycosis is favored by endemic exposure, immunosuppression, and biopsy evidence of fungal infection.
  - Rosacea lacks an infectious tissue diagnosis and more typically follows a chronic trigger-responsive vascular-inflammatory course.
  evidence:
  - reference: PMID:41017054
    reference_title: "Cutaneous Coccidioidomycosis Mimicking Rosacea in Immunosuppressed Patient, Arizona, USA, 2024."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "An immunocompromised patient in Arizona, USA, experienced cutaneous coccidioidomycosis mimicking rosacea-like dermatitis"
    explanation: >-
      This directly documents cutaneous coccidioidomycosis as a rosacea
      mimic in the appropriate epidemiologic context.
- name: Lymphomatoid papulosis
  disease_term:
    preferred_term: lymphomatoid papulosis
    term:
      id: MONDO:0020326
      label: lymphomatoid papulosis
  description: >-
    Recurrent periocular nodules can be misclassified as papulopustular
    rosacea before biopsy reveals a CD30-positive lymphoproliferative lesion.
  distinguishing_features:
  - Lymphomatoid papulosis shows recurrent papulonodules with diagnostic CD30-positive atypical lymphoid infiltrates on histopathology.
  - Rosacea more typically produces diffuse erythema, papules, pustules, and telangiectasia rather than isolated recurrent nodules.
  evidence:
  - reference: PMID:40827152
    reference_title: "Recurrent Periocular Nodules: Lymphomatoid Papulosis in an Uncommon Anatomic Site."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "he was subsequently diagnosed with papulopustular rosacea and impetigo. However, despite multiple treatment trials, he still experienced recurrent flares with nodules"
    explanation: >-
      This case report documents an initial rosacea diagnosis later revised
      to lymphomatoid papulosis after biopsy.
references:
- reference: PMID:41918801
  title: "CO(2) Laser Resection of Giant Rhinophyma Under Local Anesthesia: A Case Report."
  findings: []
- reference: PMID:41695827
  title: "Rosacea overlapping the malar rash: A diagnostic challenge in early systemic lupus erythematosus."
  findings: []
- reference: PMID:41694889
  title: "Facial Swelling in a Young Adult With Type 1 Diabetes: Morbihan Disease as a Scleroderma Mimic."
  findings: []
- reference: PMID:41426892
  title: "Multimodal Management of Morbihan Disease: Isotretinoin, Intralesional Triamcinolone, and Ketotifen in a Recalcitrant Case."
  findings: []
- reference: PMID:41222206
  title: "Unilateral presentation of Morbihan's disease: a comprehensive case report and review."
  findings: []
- reference: PMID:41058755
  title: "Unilateral Peri-Orbital Oedema and Mechanical Ptosis: An Unusual Case Presentation of Rosacea."
  findings: []
- reference: PMID:41017054
  title: "Cutaneous Coccidioidomycosis Mimicking Rosacea in Immunosuppressed Patient, Arizona, USA, 2024."
  findings: []
- reference: PMID:40860281
  title: "Rhinophyma treated by skin graft: a case report."
  findings: []
- reference: PMID:40827152
  title: "Recurrent Periocular Nodules: Lymphomatoid Papulosis in an Uncommon Anatomic Site."
  findings: []
- reference: PMID:40791837
  title: "Rhinophyma Treatment with Blue Laser."
  findings: []
- reference: PMID:41909715
  title: "Distinct diversity of skin cell populations of rhinophyma and hypertrophic scar illustrated by scRNA-seq."
  findings: []
- reference: PMID:41800255
  title: "Targeting Macrophage-to-Myofibroblast Transition Mitigates Progression from Inflammation to Fibrosis in Rosacea."
  findings: []
- reference: PMID:41562711
  title: "Increased Expression of Angiopoietin 2 and Tie2 in Rosacea."
  findings: []
- reference: PMID:41203722
  title: "Lipidomic profiling of skin surface lipids in a cohort of Chinese patients with rosacea."
  findings: []
- reference: PMID:41139274
  title: "Integrated Multi-Omics and Experimental Validation Unveil the GZMK/NF-κB Axis Driving Inflammation and Fibroblast Proliferation in Rosacea: A Novel Drug Target Selection Strategy."
  findings: []
- reference: PMID:41087666
  title: "LAPTM5 exacerbates STING-mediated inflammation induced by LL-37 through stabilizing STING in rosacea."
  findings: []
- reference: PMID:40890957
  title: "Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation."
  findings: []
- reference: PMID:40835085
  title: "Cathelicidin LL-37-Induced Transcriptome of Human Keratinocyte Identifies Chemokine CXCL10 Link to T-Cell-Mediated Rosacea Pathogenesis through Jak1/STAT1 Pathway."
  findings: []
- reference: PMID:40635520
  title: "Integrated Genomic and GEO Data Analysis Reveals Therapeutic Targets for Rosacea."
  findings: []
- reference: PMID:40567003
  title: "Novel Molecular Subtyping Revealed Molecular Pathways That Contribute to the Pathogenesis of Rosacea."
  findings: []
- reference: PMID:11582639
  title: "[Rosacea in the year 2001]."
  findings: []
- reference: PMID:27718519
  title: "Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel."
  findings: []
- reference: PMID:28150107
  title: "Acne and Rosacea."
  findings: []
- reference: PMID:34035646
  title: "Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models."
  findings: []
- reference: PMID:35392024
  title: "Multi-Transcriptomic Analysis and Experimental Validation Implicate a Central Role of STAT3 in Skin Barrier Dysfunction Induced Aggravation of Rosacea."
  findings: []
- reference: PMID:37626650
  title: "Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates."
  findings: []
- reference: PMID:39823143
  title: "Unveiling the Molecular Mechanisms of Rosacea: Insights From Transcriptomics and In Vitro Experiments."
  findings: []
- reference: PMID:40522449
  title: "[Ocular rosacea : Clinical aspects, diagnostics, management and treatment]."
  findings: []
- reference: PMID:25151931
  title: "[Physiopathology of rosacea]."
  findings: []
- reference: PMID:19428039
  title: "[Rhinophyma in a black African male patient]."
  findings: []

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