After injury a dynamic process of tissue regeneration occurs, which consists of 3 wound healing phases, including inflammatory phase, proliferative phase, and remodeling phase.1
All phases contribute to the ultimate healing of the scar; however, the final remodeling stage, which begins 3 weeks after the initial injury, is responsible for differences in scar outcomes. In the normal process of wound healing, the inflammation, granulation formation, and extracellular matrix formation balance is maintained by controlling the fibroblast activity.2
Continuous collagen production and degradation occurs after an injury. Abnormal scars such as keloid scars develop as a result of an imbalance of collagen production versus degradation in the months following an injury. If control of the fibroblast activity is lost, the result is either a hypertrophic or keloid scar. The first reported keloid was in 1700 CE Egypt in the Smith Papyrus. Dermatologist Baron Jean-Louis Alibert coined the term “cheloide” (Greek chele
) in the 19th century to describe the “crab claw”-like appearance of keloids.3
Only humans are thought affected by keloids, and both dominant and recessive modes of inheritance have been described. Keloid scarring is a fibroproliferative disease that affects humans after injury and an abnormal wound healing process.
Keloids are thick growths of tissue that extend beyond the boundaries of the initial injury following scar wound healing. Hypertrophic scars present as red, itchy, raised areas overlying the boundaries of the initial wound.
The pathophysiology of keloid scar formation is not fully understood. Trauma to the skin, both physical (eg, earlobe piercing, surgery) and pathological (eg, acne, chicken pox), is the primary cause identified for the development of keloids. The presence of foreign material, infection, hematoma, or increased skin tension can also lead to keloid or hypertrophic scar formation in susceptible individuals. In other types of scars (trauma, burn, acne), scarring occurs when dermal injury occurs at a minimal depth of 0.56 ± 0.03.9
Keloids may form after any disruption of the skin integrity, including superficial injuries from scratches and insect bites. Keloids commonly occur after piercings, vaccinations, surgery, and/or skin diseases such as acne. In many cases, keloid formation is spontaneous after allergic reactions or skin disease.
Recently the National Institutes of Health called keloids a disease, and the pathology is defined by scarring. NIH—Epigenetics—identified 6 genes consistently present in all patients who develop keloids. It has been studied that genes originated in Africa, and 30% of all Caucasians have African genes. Keloid-associated genetic syndromes include Rubinstein-Taybi syndrome, Goeminne syndrome, and Ehlers-Danlos syndrome. Keloids and hypertrophic scars are associated genetically with HLA-B14, HLA-B21, HLA-Bw16, HLA-Bw35, HLA-DR5, HLA-DQw3, and blood group A.10
Keloid disease has a failure to suppress the wound healing process in a way that results in an excess growth of scar tissue. In 1962 Mancini and 1970 Peacock classified excessive scarring into hypertrophic or keloid scars. Based on these classifications, both scars grow above normal skin.11
Keloids are benign dermal fibroproliferative growths that extend beyond the original wound edges and invade adjacent normal tissue. Once a keloid is formed regression is very rare, and in fact, keloids may grow larger many years after the initial injury. The ability to grow years later is unique to keloid scars versus other types of scars. Chipev et al hypothesized this may be due to myofibroblast phenotype and apoptosis in keloid.13
Although keloids are technically classified as benign dermal growths, they often have the behavior of malignant cells with the ability to invade and have the hyperproliferative features of malignant tumor cells.7
The exact mechanism of keloid pathogenesis is still unknown.14
Abnormal cellular proliferations of fibroblasts produce the keloid. Keloid fibroblasts proliferate faster than those of hypertrophic scars and produce massive amounts of collagen and matrix metalloproteinases.15
Ehrlich et al have proposed that proinflammatory genes are upregulated via an inflammatory response in the microenvironment, which activates a series of signals to create keloids.15
Saint-Jean et al proposed in a recent study that acne scarring is revealed, even though acne is a disease of the pilosebaceous gland; however, the scarring occurred in locations far from the pilosebaceous gland. The authors hypothesized that inflammation is the single greatest reason for acne scar development and that the severity of scaring was due to the patient’s innate immunity inflammatory response.16
Fibroblasts in keloids become unregulated, and in keloid scar formation there is widespread proliferation of fibroblasts and apoptosis inhibition. Owing to the massive output of the overactive fibroblasts, there is an imbalance between collagen production and degradation of the extracellular matrix and an increase in specific cytokines.2
Several clinical studies have examined the possible role of wound tension, sebum secretion, and inflammation as possible factors of keloid scar formation.17
An interesting newer hypothesis has emerged suggesting that nutritional factors may play a role in keloid production. It has been observed that the triglyceride component in keloid scars is around 60%, which is significantly higher than in normal skin.17
Normal skin and keloids share the same ratios of cholesterol and fatty acids. This theory suggests that the alteration in lipid metabolism related to essential fatty acids stimulates the inflammatory reaction in keloids.