Rethinking acne vulgaris: from pathogenic mechanisms to targeted therapies

Background. Acne vulgaris is a multifactorial inflammatory skin disease whose pathogenesis has traditionally been explained by four major mechanisms: sebaceous gland hyperactivity, follicular hyperkeratinization, Cutibacterium acnes colonization, and inflammation. Recent advances in research have substantially expanded this paradigm, demonstrating that acne results from complex interactions between genetic, metabolic, immunological, hormonal, and microbiological pathways. We aimed to summarize current evidence on emerging mechanisms involved in acne pathogenesis and to discuss how these discoveries are reshaping therapeutic strategies toward mechanism-based and precision medicine approaches. Methods. A systematic literature review was conducted using PubMed, Scopus and Google Scholar databases, focusing on the latest developments in the field. Priority was given to publications indexed in PubMed, including systematic reviews, meta-analyses and randomized clinical trials. The review primarily focused on studies published within the last decade to reflect the most recent advances in acne research. Earlier landmark publications were included when they introduced concepts fundamental to the current understanding of acne pathogenesis. Results. Recent studies indicate that acne should be regarded as an immunometabolic disorder driven by interconnected biological networks rather than isolated pathogenic events. Genome-wide association studies have identified susceptibility loci involved in pilosebaceous unit development and lipid metabolism, while lipidomic analyses have demonstrated qualitative alterations in sebum composition as important drivers of inflammation. Growing evidence highlights the central role of skin and gut microbiome dysbiosis, activation of the NLRP3–IL-1β–IL-17 inflammatory axis, and insulin–IGF-1–mTORC1 signaling in disease development. These discoveries have accelerated the development of targeted therapies, including topical androgen receptor antagonists, fatty acid synthase inhibitors, microbiome-modulating strategies, and novel immunomodulatory agents, while supporting the concept of biologically distinct acne phenotypes. Conclusions. Contemporary evidence supports a transition from the classical linear model of acne pathogenesis toward an integrated network model linking genetic predisposition, lipid metabolism, microbiome composition, immune activation, and metabolic regulation. This evolving understanding provides the biological foundation for personalized treatment strategies and precision dermatology, in which therapy is selected according to the dominant pathogenic mechanism rather than clinical severity alone. Future research should focus on validating molecular biomarkers that enable phenotype-driven therapeutic decision-making.