Keloids are pathological scars presenting as nodular firm lesions that extend beyond the area of injury. They do not spontaneously regress, often continuing to grow over time.1 The prevalence is high in the dark phototypes with an estimated incidence of 5–16% in the Hispanic and African-American populations.1 The most frequently affected body areas are chest, shoulders, earlobes and upper back.2 Symptoms often include itching and pain. Unlike hypertrophic scars, keloids do not improve over time and commonly recur following surgical excision.3 Large lesions may lead to cosmetic disfigurement and functional impairment, thus affecting the quality of life.2
The abnormal wound-healing process underlying keloid formation results from the lack of control mechanisms regulating cell proliferation and tissue repair.4 Histologically, keloids are characterized by haphazardly arranged hyalinized collagen bundles and a tongue-like advancing edge in the papillary dermis.5 Despite many clinical, histological and in vitro findings, the pathogenic mechanisms underlying keloid formation have not been fully elucidated.6,7 To date, no specific gene has been linked to the development of keloids, and it is likely that different genes contribute to their formation in different families.7–9 Excessive matrix accumulation and cell proliferation are distinctive histological features of keloids, resulting from the increased proliferation and lower apoptotic rate of fibroblasts.7,10,11 The change in the normal balance between extracellular matrix (ECM) deposition and degradation seen during wound healing, especially along the remodeling phase, may play a role in keloid formation. Increased local levels of PAI-1 and low levels of urokinase have been reported in keloid fibroblasts, likely leading to reduced collagen degradation.7,12,13 Several other pathogenic theories have also been postulated, including genetic immune dysfunction, mechanical tension, increased hyaluronic acid production, sebum reaction, tissue hypoxia and abnormal epithelial–mesenchymal interaction.7,8,12–15 Elevated levels of cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-6 and IL-13, and growth factors, such as vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-β), were proved to be involved in keloid scar formation and proliferation.7,16 TGF-β family was associated with enhanced collagen synthesis in keloid fibroblasts. TGF-β1 treatment was shown to stimulate the production of collagen in keloid fibroblasts but not in normal skin fibroblasts.16,17 The role of TGF-β1 was further confirmed by the observation that anti-TGF-β1 antibody suppressed collagen synthesis of keloid fibroblasts.16,17 Moreover, TGF-β2 treatment enhanced collagen production of xenograft derived from human keloid specimens in athymic rats.16,18 On the other hand, TGF-β2 antibody inhibited collagen generation in a xenograft model, suggesting that it could act as a potential antiscarring agent.18 IL-13 induced a faster increase in collagen production by keloid fibroblasts compared to normal ones.16,19VEGF is one of the most important growth factors involved in angiogenesis, and it was previously implicated as crucial to both normal and pathological wound healing.6,7 In vivo and in vitro studies showed that VEGF was overexpressed in keloid tissue and may play a potential role in its formation.6,7,11VEGF induces angiogenesis both directly, by acting as a mitogen for endothelial cells, and indirectly, by increasing vascular hyperpermeability and promoting the extravascular deposition of fibrin matrix. It is also paramount in the modulation of ECM proteolysis, an essential component of the angiogenic process.7,20,21
Several strategies were suggested for keloid therapy, but, to date, no universally effective treatment was found.22 Current therapeutic approaches fall into three broad categories: alteration of the inflammatory response; modification of collagen metabolism; surgical and physical manipulation of the keloid scar.7Therapeutic approaches include surgical excision, intralesional injection of steroids, verapamil, 5-fluorouracil (5-FU), cryotherapy, laser therapy (fractionated CO2 laser, Nd:YAG laser, pulsed-dye laser), silicone sheet dressings, irradiation, retinoids, tacrolimus, imiquimod and combination therapy.
Since keloids are notoriously characterized by a high recurrence rate after surgical excision, nonsurgical approaches are recommended for primary treatment.3,16 The most common approach is intralesional corticosteroid injection alone or in combination with other treatment modalities. Triamcinolone acetonide (TAC) is the most commonly used intralesional corticosteroid.
The aim of this review was to investigate and discuss the efficacy of TAC intralesional injection in the treatment of keloids.
