Keloids and Hypertrophic Scars: A Spectrum of Clinical Challenges

Abstract

Since their earliest description, keloids and hypertrophic scars have beleaguered patients and clinicians alike. These scars can be aesthetically disfiguring, functionally debilitating, emotionally distressing, and psychologically damaging, culminating in a significant burden for patients. Our current understanding of keloid pathophysiology has grown and continues to advance while molecular biology, genetics, and technology provide ever-deepening insight into the nature of wound healing and the pathologic perturbations thereof. Greater understanding will lead to the development and application of refined therapeutic modalities. This article provides an overview of our current understanding of keloids, highlighting clinical characteristics and diagnostic criteria while providing a comprehensive summary of the many therapeutic modalities available. The proposed mechanism, application, adverse events, and reported efficacy of each modality is evaluated, and current recommendations are summarized.

Probing endogenous collagen by laser‐induced autofluorescence in burn wound biopsies: A pilot study

“…Perturbation in dermal collagen synthesis or loss of excessive tissue collagen could lead to serious pathological conditions such as keloids and hypertrophic scars [37,38], liver cirrhosis [39], dermatofibroma [40], rheumatoid arthritis [41], lung fibrosis [42], morphea and dermal elastolysis [43]. Importantly, the incidence of keloids and hypertrophic scar are more frequent in burn wounds causing physical damage, cosmetic disfigurement and a substantial amount of physiological stress affecting the quality of life [38]. Thus timely, independent and quantitative estimation of collagen will have a significant impact on the clinical management of burn wounds and outcome of the treatment.…”

Presence of galectin-1 in the epidermal and dermal thickening of keloid tissues

“…frequently occur on the anterior portion of the chest, shoulders, upper back, arms, cheeks and earlobes [1,2,[5][6][7][8][9][10]. Histopathologically, keloids are defined as inflammatory disorders characterized by exhibiting a thickened dermis containing numerous fibroblasts, abnormal vascularization, increased inflammatory immune cells, abundant hyalinised collagen bundles (keloidal collagen) and extracellular matrix (ECM) components including collagen, elastin, fibronectin and proteoglycans such as syndecan and versican, mainly produced by activated fibroblasts [1][2][3][4][5][6][7][8][9][10][11][12][13][14].…”

“…Histopathologically, keloids are defined as inflammatory disorders characterized by exhibiting a thickened dermis containing numerous fibroblasts, abnormal vascularization, increased inflammatory immune cells, abundant hyalinised collagen bundles (keloidal collagen) and extracellular matrix (ECM) components including collagen, elastin, fibronectin and proteoglycans such as syndecan and versican, mainly produced by activated fibroblasts [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. These histological alterations proper of the keloid tissue have been associated with the elevated production of growth factors such as TGF-β, FGF-2, PDGF, EGF, IGF and VEGF which regulate fibroblast proliferation, ECM synthesis and angiogenesis, and pro-inflammatory cytokines including IL-1α, IL-1β, IL-6 and TNFα which promote fibroblast activation and consequently an excessive deposition of ECM components [1,2,[5][6][7]9,10,15,16]. This is why most studies on keloids focus on dermis and few on epidermis [4,17].…”

“…However, recent studies describe the epidermis of keloids as thickened, primarily due to hyperproliferation [4,7,17] and altered terminal differentiation [18] of keratinocytes,; some of them, indicating that keratinocytes also participate in the regulation of fibroblasts activity and might contribute to keloid pathogenesis [4,7,19]. On the other hand, several studies consider genetic predisposition as an important factor in the keloid formation and progression [2,5,9,20] whilst others deem the role of local mechanical Hematoxylin staining (H&E) from a biopsy of keloid showing reduced rete ridges, epidermal thickening, hyperkeratosis and spongiosis. Note the presence in the dermis of thin collagen bundles parallel to the epidermis, numerous fibroblasts, microvessels (arrowheads), inflammatory cells, nodule (dashed line) containing elongated fibroblasts attached to randomly oriented collagen fibers, and thick compact collagen bundles with elongated fibroblasts attached (arrows).…”

“…Moreover, there is evidence suggesting that epigenetic modifications would be involved in the pathogenesis of keloids by regulation of fibroblasts activation, proliferation and apoptosis, as well as collagen and elastin synthesis [3,[20][21][22]. Nevertheless, the etiology and pathophysiology of keloids is not fully elucidated yet [3][4][5][6][7]18].…”