Keloids: The paradigm of skin fibrosis - Pathomechanisms and treatment

Abstract

Keloids, fibroproliferative dermal tumors with effusive accumulation of extracellular matrix (ECM) components, particularly collagen, result from excessive expression of growth factors and cytokines. The etiology of keloids is unknown but they occur after dermal injury in genetically susceptible individuals, and they cause both physical and psychological distress for the affected individuals. Several treatment methods for keloids exist, including the combination therapy of surgical excision followed by intralesional steroid therapy, however, they have high recurrence rate regardless of the current treatment method. Improved understanding of the pathomechanisms leading to keloid formation will hopefully identify pathways that serve as specific targets to improve therapy for this devastating, currently intractable, disorder.

Keywords: Collagen; Fibrotic disease; Inflammation; Keloid; TGF-β; Wound healing.

Figure 1. Clinical and histopathologic features of keloids

Note the presence of keloid formation on the earlobe as a result of trauma (upper left panel). The lesions are histopathologically characterized by accumulation of tightly packed collagen (asterisks). Some parts of the lesions demonstrate marked cellularity, as shown in the right lower panel. (Hematoxylin-Eosin stain, bottom left and upper right panels; Masson’s Trichrome stain, lower left panel)

Figure 2. Fibrotic cell-signaling pathways in keloids

Fibroblasts are the centric cell type in the process of profibrotic events that leads to excessive ECM accumulation, inflammation and eventually keloid formation. Key cell-cell and cell-ECM interactions are depicted.