A Holistic Approach to Unravel Keloid Pathogenesis and Optimize Therapeutic Outcomes

Although tremendous progress has been made over the past decades in elucidating the mechanisms of keloid formation and developing therapeutic interventions, keloid remains challenging to cure and prone to recurrence. Historically, keloid has been regarded as a benign skin tumor, with mechanistic investigations and therapeutic efforts focused primarily on keloid tissue and cells themselves. In contrast, Traditional Chinese Medicine (TCM) posits that skin diseases manifest from internal bodily dysfunction or dysregulation. Inspired by the holistic principles of TCM, together with the literature reports and clinical evidence of keloid constitution (a systemic condition characterized by an individual's predisposition to keloid formation), we propose that keloid is likely a pseudo-skin tumor profoundly influenced by its pathological microenvironment. Accordingly, we propose keloid as a persistent inflammation-driven proliferative skin disorder, and elimination of the inflammatory microenvironment may be essential for curing keloid and preventing relapse. Based on this concept, we developed a holistic therapeutic approach that combines systemic treatment targeting keloid constitution with local therapies, including surgery, chemo/radiotherapy, and compression therapy, for the keloid lesion itself. The systemic component encompasses lifestyle and dietary modifications, stress management, physical exercise, as well as the oral administration of TCM herbal medicines and small chemical compounds to suppress systemic inflammatory and fibrotic status, thereby improving keloid constitution. This article introduces this novel holistic approach along with supportive case studies.