Extracellular matrix alterations in inflammatory skin diseases: emerging biomarkers and clinical implications

The interaction among extracellular matrix (ECM) components (proteoglycans, elastin, laminins, collagens and metalloproteinases) is important for maintaining homeostasis of the skin. However, in chronic inflammatory diseases, tissue homeostasis is disrupted by having an uncontrolled remodelling of the ECM, resulting in an imbalance of its composition and functionality. In these pathologies, there is a dysregulation of the immune system characterized by recurrent itching, pain and inflammation in affected areas of the skin. Three of the most common inflammatory skin diseases are hidradenitis suppurativa, psoriasis and atopic dermatitis, with worldwide prevalence of 1%, 3% and 15%, respectively. The shared pathological characteristic for these diseases is an altered skin tissue structure, characterized by an excessive remodelling of ECM proteins. Despite well-documented evidence of ECM alterations in these pathologies, biomarkers reflecting ECM remodelling to aid drug development and potential treatment targets have been overlooked. There is therefore an unmet need to develop biomarkers for predicting outcomes and selecting treatment for individual patients. This review focuses on ECM dysregulation in inflammatory skin diseases, with a focus on how biomarkers can predict outcomes and monitor drug efficacy.