Answer:
Hypertrophic scars and keloids are forms of excessive healing. They are found only in humans. They occur in 5% to 15% of wounds and are seen 5 to 15 times more frequently in nonwhites. Hypertrophic scars are defined as those that remain within the borders of the original scar, whereas keloids extend beyond the original scar margins. Wounds that cross skin tension lines, in thick skin or in susceptible locations such as the earlobe, presternal, and deltoid regions, are more prone to abnormal healing. Other anatomic locations, such as the genitalia, eyelids, palms, and soles, seem to be spared. Hypertrophic scars generally begin to develop in the weeks after injury, whereas keloids can develop up to 1 year later.
Histologically, there are subtle differences between keloids and hypertrophic scars. Both differ from normal skin and scar by their rich vasculature, high mesenchymal density, and thickened epidermal layer. Collagen fibers are organized in swirls. Mucinous ground substance is present in large amounts in keloids, but fibroblast density is less than in hypertrophic scars. Scanning electron microscopy shows ultrastructural morphologic differences in that hypertrophic scars have collagen fibers that are flatter and less clearly demarcated than in normal skin or scar. In addition, the collagen fibers in hypertrophic scars are fragmented and shortened and are loosely arrayed in a wavy pattern. Keloids are even less organized with larger and more irregular collagen fibers and smaller interfibrillar distance than seen in hypertrophic scars. The collagen nodule is absent from mature scars but is present in hypertrophic scars and keloids. It contains a high density of fibroblasts and unidirectional collagen fibrils aligned in a highly stressed orientation.
Biochemically, differences have been found between normal skin, mature scars, and abnormal scars. Collagen synthesis is 3 times higher in keloids than in hypertrophic scars and 20 times higher in keloids than in normal skin. The absolute amount of soluble collagen is also increased in keloids, indicative of increased collagen synthesis, increased degradation, or decreased cross-linking. Mature scars have been found to have a higher content of cross-linked collagen than exists in keloids. Collagenase activity is 14 times greater in keloids than in normal scar while hypertrophic scars show a fourfold increase compared to normal skin. There is also a decrease in the serum proteinase inhibitors (a1 antitrypsin and a2 macroglobulin) in abnormal scars, which may contribute to a net increase in the deposition of collagen in both keloids and hypertrophic scars. Biochemical evaluation of the extracellular matrix indicates an increase in fibronectin and hyaluronic acid in patients with abnormal scarring when compared to normal skin.
The type of collagen present also differs in patients with abnormal scarring. Keloid tissues contain 32% type III collagen as compared with 21% type III collagen in normal dermis. The type III collagen in keloids is also immaturely cross-linked, indicating a pathologic process in which the extracellular matrix fails to mature and therefore does not achieve normal stability.
The influence of growth factors on the formation of abnormal scars is still unclear. Hypertrophic scar-derived fibroblast proliferation decreases in response to EGF but not to TNF-a or PDGF. Unlike normal fibroblasts, fibroblasts from hypertrophic scars show no increase in the rate of collagen synthesis when exposed to TGF-b.