New approach to the understanding of keloid: psychoneuroimmune–endocrine aspects

The skin is a dynamic and complex organ that relies on the interrelation among different cell types, macromolecules, and signaling pathways. Further, the skin has interactions with its own appendages and other organs such as the sebaceous glands and hair follicles, the kidney, and adrenal glands; systems such as the central nervous system; and axes such as the hypothalamic–pituitary–adrenal axis. These continuous connections give the skin its versatility, and when an injury is caused, some triggers start a cascade of events designed to restore its integrity. Nowadays, it is known that this psychoneuroimmune–endocrine intercommunication modulates both the homeostatic condition and the healing process. In this sense, the skin conditions before a trauma, whether of endogenous (acne) or exogenous origin (injury or surgical incision), could regulate the process of tissue repair. Most skin diseases such as psoriasis and atopic dermatitis, among others, have in their pathophysiology a psychogenic component that triggers integrated actions in the nervous, immune, and endocrine systems. However, fibroproliferative disorders of wound healing, such as hypertrophic scar and keloid, are not yet included in this listing, despite showing correlation with stress, especially with the psychosocial character. This review, by understanding the “brain–skin connection”, presents evidence that allows us to understand the keloid as a psychomediated disease.