Acne and Rosacea: Distinct Disorders Sharing a Sebum–Microbiome–Inflammation–Barrier Axis

Acne vulgaris and rosacea are traditionally classified as distinct inflammatory facial dermatoses. Nevertheless, accumulating mechanistic and translational evidence suggests that these conditions share partially overlapping biological domains including preferential localization of sebaceous gland-rich facial skin, alterations in sebaceous function, microbiota dysregulation, innate immune activation and epidermal barrier impairment. This review evaluates the pilosebaceous unit and its surrounding ecosystem as a shared anatomical and functional platform from which these disorders may diverge into distinct clinical phenotypes. Evidence on sebum quantity and composition, microbial ecology, biofilm and quorum-sensing biology, barrier integrity and immuno-inflammatory signaling is synthesized. Acne is more consistently linked to seborrhea, follicular hyperkeratinization, comedogenesis, and Cutibacterium acnes-associated inflammation. Rosacea is more strongly associated with barrier fragility, Demodex overabundance, dysregulated TLR2/KLK5/cathelicidin signaling, neurovascular reactivity and persistent centrofacial inflammation. This review proposes that acne and rosacea are distinct clinical entities arising from partially overlapping but differentially weighted perturbations along a shared sebum–microbiome–inflammation–barrier axis. This framework may help explain mixed facial presentations, improve differential diagnosis and support therapeutic strategies that target biological networks while preserving disease-specific clinical distinctions. The strength of the supporting evidence is, however, unequal across these domains, being more robust for sebaceous and microbial mechanisms in acne than in rosacea. The proposed axis is therefore presented as a conceptual and hypothesis-generating framework rather than as an established disease continuum.