| Domain | Knowledge-Base Assertion | Suggested Ontology Terms/IDs | Evidence Type | Principal Source/Date/DOI | Limitations |
|---|---|---|---|---|---|
| **Definition & Epidemiology** | Chronic inflammatory skin disorder primarily of the centrofacial/periocular regions. Estimated global prevalence ~5.46%, with slight female predominance. | MONDO:0006604 (rosacea); UBERON:0001456 (skin of face); HP:0002716 (Erythema) | Clinical Review | Nguyen et al., Jan 2024, 10.2147/CCID.S391705 (pqac-00000002); Galluccio et al., Jan 2024, 10.3390/cosmetics11010011 (pqac-00000005) | Global prevalence estimates vary highly by population and diagnostic criteria. |
| **Phenotypes & Diagnosis** | Diagnosis requires fixed centrofacial erythema or phymatous changes OR 2+ major features (papules, pustules, flushing, telangiectasia, ocular signs). Transitions away from historic subtypes. | HP:0010783 (Erythema); HP:0200034 (Papule); HP:0200039 (Pustule); HP:0001009 (Telangiectasia); HP:0012737 (Blepharoconjunctivitis) | Consensus Guidelines; Systematic Review | Tan et al., Feb 2017, 10.1111/bjd.15122 (pqac-00000003); van Zuuren et al., Mar 2019, 10.1111/bjd.17590 (pqac-00000007) | Ocular diagnostic combinations rely on limited ophthalmologist consensus. |
| **Genetics (Susceptibility)** | Polygenic trait lacking monogenic causation. Genome-wide significant loci linked to immune/inflammatory and pigmentation pathways (HLA, IL13, IRF4, HERC2-OCA2, SLC45A2). | GO:0006955 (immune response); GO:0043473 (pigmentation) | Human GWAS (73,265 European ancestry subjects) | Aponte et al., May 2018, 10.1093/hmg/ddy184 (pqac-00000011) | Primarily European ancestry cohorts; phenotype based on self-reported symptom questionnaires. |
| **Etiology (Triggers)** | Amplified innate immune and neurovascular responses triggered by UV, heat, stress, diet, and microbiota (Demodex folliculorum density is 5-7x higher in lesions). | NCIT:C16259 (Demodex); GO:0045087 (innate immune response); GO:0050954 (sensory perception of mechanical stimulus) | Narrative Review | Galluccio et al., Jan 2024, 10.3390/cosmetics11010011 (pqac-00000001) | Difficult to distinguish primary triggers from opportunistic overgrowth (e.g., Demodex). |
| **Pathophysiology (Cellular)** | ScRNA-seq reveals expansion of pro-inflammatory fibroblasts (primary source of inflammatory/vasodilatory signals), Schwann cells, endothelial cells, and macrophages. Mast cells also increased. | CL:0000057 (fibroblast); CL:0000097 (mast cell); CL:0000235 (macrophage); CL:0002573 (Schwann cell) | scRNA-seq (9 cases, 3 controls); Mouse validation | Chen et al., Oct 2024, 10.1038/s41467-024-52946-7 (pqac-00000009) | Small human sample size, all female, inherent compositional biases in skin digestion. |
| **Pathophysiology (Molecular)** | Primary causal chain: TLR2 activation -> KLK5 induction -> cleavage of cathelicidin to LL-37 -> activation of PAR2, NF-kB, NLRP3 inflammasome, and angiogenesis. | GO:0002224 (toll-like receptor signaling); GO:0001525 (angiogenesis); GO:0032640 (tumor necrosis factor production) | Clinical Reviews | Nguyen et al., Jan 2024, 10.2147/CCID.S391705 (pqac-00000002); Shi et al., Jun 2026, 10.2147/dddt.s608151 (pqac-00000004) | Highly complex feedback loops blur upstream vs. downstream ordering. |
| **Treatments** | Phenotype-targeted approaches: Brimonidine (erythema); ivermectin, azelaic acid (papules/pustules); doxycycline 40mg MR, isotretinoin (systemic); laser/IPL (telangiectasia). | NCIT:C61702 (Brimonidine); NCIT:C616 (Azelaic Acid); NCIT:C61868 (Ivermectin); NCIT:C480 (Doxycycline) | Systematic Review (152 RCTs, 20,944 subjects) | van Zuuren et al., Mar 2019, 10.1111/bjd.17590 (pqac-00000007) | Few long-term or head-to-head active comparator trials available. |
| **Experimental Models** | Subcutaneous LL-37 injection in mice induces rosacea-like lesions (erythema, inflammation, collagen hyperplasia). Demodex-induced rabbit models also utilized. | NCIT:C14251 (Mouse); NCIT:C14264 (Rabbit); HP:0000974 (Hyperextensible skin - surrogate for collagen abnormalities) | Animal experimental models | Zhang et al., Mar 2023, 10.3390/cimb45040177 (pqac-00000008) | Induced models mimic late-stage effector pathways, not spontaneous natural disease initiation. |


*Table: A structured overview of rosacea phenotypes, genetics, mechanisms, treatments, and models mapped to ontology concepts, designed for knowledge base integration.*