Classification of distinct endotypes in human skin scarring: S. C. A. R. - A novel perspective on dermal fibrosis

Significance: Skin scarring is a permanent, irreversible end point of cutaneous injury and is recognized as complex with significant variability in individuals’ scar type and response to treatment. Despite these tangible differences in treatment response, to date there has been no simplified approach in defining spectrum of skin scarring in relation to prediction and outcome post-treatment. Thus, we here propose that scarring consists of distinct endotypes which is characterised by their specific pathology. Four distinct scar endotypes can be observed: (1) Stretched (flat), (2) Contracted, (3) Atrophic (depressed) and (4) Raised scarring, which can be abbreviated to S.C.A.R. endotypes. We also present a structured approach in assessment of all parameters in scar evaluation including: clinical (symptoms, & signs) & non-clinical parameters (device measurements of structural, mechanical and physiological properties of scars as well as gene/protein laboratory studies). Recent Advances: Scars can be phenotypically characterised based on a multitude of parameters assessed, however, not all scar types will share all of the same characteristics. This leads to the question of whether skin scarring is a single disease entity with varying phenotypic characteristics or should be classed as several disease entities which have certain similar parameters. We suggest the latter and propose distinct scarring phenotypes arise mainly due to genetic, and environmental susceptibilities associated with the development of each specific scar endotype. Critical Issues: The concept of identifying different endotypes is key in formulating personalised treatments with improved outcomes beyond what is achieved with current non-specific approaches in scar management. This approach has gained interest and significant traction in several other medical conditions including asthma, rheumatoid arthritis and atopic dermatitis. Future Directions: By identifying distinct endotypic features in skin scarring, this approach may lead to improved theranostic outcomes and further understanding of the pathophysiology of the complex nature of human skin scarring.