On the Nature of Hypertrophic Scars and Keloids: A Review Frank Niessen;Paul Spauwen;Joost Schalkwijk;Moshe Kon; Plastic and Reconstructive Surgery

On the nature of hypertrophic scars and keloids : A review

Keloids are predominantly fibrous tumors which appear as firm, variably pruritic or tender growths near a site of injury. Usually appearing between the ages of 10 and 30, most keloids are located on the upper back, shoulders, earlobes, and anterior portion of the chest. The etiology remains unknown, but the accumulated fibrous tissue is associated with increased cellularity and increased metabolic activity of keloid fibroblasts. Isolated keloid fibroblasts demonstrate normal growth characteristics along with increased collagen and proteoglycan synthesis. Numerous keloid treatments have been attempted, but variable success has followed either single use or combinations of intralesional corticosteroid injection, surgery, pressure devices, radiation, cryosurgery, and systemic chemotherapy.

https://www.jaad.org/article/S0190-9622(81)70048-3/pdf

Keloids: A review

Six patients underwent dermabrasion while on or having recently completed isotretinoin (Accutane) therapy. All patients developed keloids in atypical locations; the keloids eventually responded to topical or intralesional steroid therapy. Retinoids have a modulatory effect on connective tissue metabolism, including suppression of collagenase, which may enhance keloid formation. Dermabrasion should be delayed in those patients taking or recently on isotretinoin therapy.

Atypical keloids after dermabrasion of patients taking isotretinoin.

Hypertrophic scars and contractures may be rapidly resolved through application of pressure and forced extension. Examination of pressure-treated scars by scanning and transmission electron microscopy demonstrates a reduction in intercollagen cohesiveness and increasing numbers of vesicular fibroblasts. Assays of chondroitin sulfate A show a decrease from the excessive levels found in untreated hypertrophic scars. It is suggested that the application of pressure increases an already present condition of hypoxia, which results in degeneration of many fibroblasts. The ratio of collagen synthesis to degradation would, then, be altered in favor of the latter, resulting in resolution of the scar.

Alteration of hypertrophic scars induced by mechanical pressure.

In predisposed individuals, wound healing can lead to hypertrophic scar or keloid formation, characterized by an overabundant extracellular matrix. It has recently been shown that hypertrophic scars are accompanied by abnormal keratinocyte differentiation and proliferation, and significantly increased acanthosis, compared with normal scars. This study addressed the question of whether the development of normal and hypertrophic scars is regulated by differences in the growth factor profiles of both the epidermis and the dermis. The presence of interleukin-1alpha (IL-1alpha), IL-1beta, tumour necrosis factor-alpha (TNF-alpha), platelet-derived growth factor (PDGF), transforming growth factor-beta1 (TGF-beta1), and basic fibroblast growth factor (bFGF) was investigated in biopsies taken from breast reduction scars at 3 and 12 months following surgery. The samples were analysed by immunohistological methods and categorized as scars that remained hypertrophic (HH), became normal (HN) or remained normal after 12 months (NN). The epidermal expression of IL-1alpha was significantly increased in NN scars compared with HN and HH scars 3 and 12 months following operation, whereas the dermal expression showed no difference. PDGF was significantly increased in the dermis of normal scars after 3 months and in both the epidermis and the dermis of hypertrophic scars after 12 months. IL-1beta, TNF-alpha, TGF-beta and bFGF showed no differences. It is hypothesized that impaired production of keratinocyte-derived growth factors, such as IL-1alpha, leads to a decrease in the catabolism of the dermal matrix, whereas augmented epidermal PDGF production leads to increased formation of the dermal matrix in hypertrophic scars. These observations support the possibility that the epidermis is involved in preventing the formation of hypertrophic scars.

Keratinocyte-derived growth factors play a role in the formation of hypertrophic scars.

SummaryA study of the hexose hexosamine, sialic acid, uronic acid, glycogen, and collagen fractions has been made on hypertrophic scars, nonhypertrophic scars, and normal skin. Hexose, hexosamine, sialic acid, uronic acid, and glycogen levels were significantly and consistently elevated in hypertrophic scars. These same components were slightly, but significantly, higher in the nonhypertrophic scars. Salt-soluble collagen of hypertrophic scars was significantly elevated, citrate-soluble and insoluble collagen fractions were not different in the three groups. From these data it is concluded that hypertrophic scars contain more glycoprotein and mucopolysaccharide and are more active metabolically.

Rebecca Villarante

Papers

The hypertrophic scar. Glycoprotein and collagen components of burn scars.