Keloids – clinical diagnosis, pathogenesis, and treatment options

Keloids are defined as excessive scar tissue formation extending beyond the area of the original skin injury and occurring in predisposed individuals. They are considered to be a result of abnormal wound healing. The pathogenetic mechanisms that cause keloids remain unknown. Experiments with cells derived from keloid tissue revealed a number of abnormalities in cellular functions, such as in proliferation, apoptosis, or expression of growth factors and extracellular matrix proteins. Furthermore, several studies have reported altered keratinocyte‐fibroblast interactions in keloids. Despite the diverse pathological changes in cellular functions and expression profiles of cells derived from keloid tissue, recent genetic studies have provided evidence that single genes may act as major regulators of keloid formation. We provide an overview of the pathogenetic mechanisms of keloid formation in the context of their clinical characteristics and current therapeutic approaches.

[1]  R. W. Miller,et al.  Keloids and neoplasms in the Rubinstein-Taybi syndrome. , 2006, Medical and pediatric oncology.

[2]  M. Partington Rubinstein-Taybi syndrome: a follow-up study. , 2005, American journal of medical genetics. Supplement.

[3]  B. Olsen,et al.  Genome scans provide evidence for keloid susceptibility loci on chromosomes 2q23 and 7p11. , 2004, The Journal of investigative dermatology.

[4]  D. Ann,et al.  Increased vascular endothelial growth factor may account for elevated level of plasminogen activator inhibitor-1 via activating ERK1/2 in keloid fibroblasts. , 2004, American journal of physiology. Cell physiology.

[5]  A. Bayat,et al.  Description of site-specific morphology of keloid phenotypes in an Afrocaribbean population. , 2004, British journal of plastic surgery.

[6]  W. Timens,et al.  Hypertrophic scar formation is associated with an increased number of epidermal Langerhans cells , 2004, The Journal of pathology.

[7]  Tsuneki Sugihara,et al.  Keratinocytes promote proliferation and inhibit apoptosis of the underlying fibroblasts: an important role in the pathogenesis of keloid. , 2003, The Journal of investigative dermatology.

[8]  D. Ann,et al.  Mechanisms of hypoxic regulation of plasminogen activator inhibitor-1 gene expression in keloid fibroblasts. , 2003, The Journal of investigative dermatology.

[9]  T. T. Nguyen,et al.  Synchronous Activation of ERK and Phosphatidylinositol 3-Kinase Pathways Is Required for Collagen and Extracellular Matrix Production in Keloids* , 2003, Journal of Biological Chemistry.

[10]  S. Yamashita,et al.  Insulin-like growth factor-I enhances transforming growth factor-beta-induced extracellular matrix protein production through the P38/activating transcription factor-2 signaling pathway in keloid fibroblasts. , 2003, The Journal of investigative dermatology.

[11]  W. Laug,et al.  Increased plasminogen activator inhibitor-1 in keloid fibroblasts may account for their elevated collagen accumulation in fibrin gel cultures. , 2003, The American journal of pathology.

[12]  Edmond Sabo,et al.  Intralesional Cryotherapy for Enhancing the Involution of Hypertrophic Scars and Keloids , 2003, Plastic and reconstructive surgery.

[13]  Hung Huynh,et al.  Role of IGF system of mitogens in the induction of fibroblast proliferation by keloid-derived keratinocytes in vitro. , 2003, American journal of physiology. Cell physiology.

[14]  Hiko Hyakusoku,et al.  Postoperative Electron‐Beam Irradiation Therapy for Keloids and Hypertrophic Scars: Retrospective Study of 147 Cases Followed for More Than 18 Months , 2003, Plastic and reconstructive surgery.

[15]  B. Berman,et al.  Pilot study of the effect of postoperative imiquimod 5% cream on the recurrence rate of excised keloids. , 2002, Journal of the American Academy of Dermatology.

[16]  Woraphong Manuskiatti,et al.  Treatment response of keloidal and hypertrophic sternotomy scars: comparison among intralesional corticosteroid, 5-fluorouracil, and 585-nm flashlamp-pumped pulsed-dye laser treatments. , 2002, Archives of dermatology.

[17]  Hung Huynh,et al.  Fibroblasts cocultured with keloid keratinocytes: normal fibroblasts secrete collagen in a keloidlike manner. , 2002, American journal of physiology. Cell physiology.

[18]  M. Maarouf,et al.  Radiotherapy in the Management of Keloids Clinical Experience with Electron Beam Irradiation and Comparison with X-Ray Therapy , 2002, Strahlentherapie und Onkologie.

[19]  M. Tenenhaus,et al.  Alterations in Fibroblast α1β1 Integrin Collagen Receptor Expression in Keloids and Hypertrophic Scars , 2002 .

[20]  B. Olsen,et al.  Clinical genetics of familial keloids. , 2001, Archives of dermatology.

[21]  H. Kamiishi,et al.  NEW CONCEPT OF BALLOON‐COMPRESSION WEAR FOR THE TREATMENT OF KELOIDS AND HYPERTROPHIC SCARS , 2001, Plastic and reconstructive surgery.

[22]  R. Fitzpatrick,et al.  Energy density and numbers of treatment affect response of keloidal and hypertrophic sternotomy scars to the 585-nm flashlamp-pumped pulsed-dye laser. , 2001, Journal of the American Academy of Dermatology.

[23]  M. Cintra,et al.  Silicone versus Nonsilicone Gel Dressings: A Controlled Trial , 2001, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[24]  A. Martinez,et al.  Treatment of keloids by high-dose-rate brachytherapy: A seven-year study. , 2001, International journal of radiation oncology, biology, physics.

[25]  M. Longaker,et al.  Investigation of the influence of keloid-derived keratinocytes on fibroblast growth and proliferation in vitro. , 2001, Plastic and reconstructive surgery.

[26]  H. Namba,et al.  Keloid fibroblasts resist ceramide-induced apoptosis by overexpression of insulin-like growth factor I receptor. , 2000, The Journal of investigative dermatology.

[27]  N. Fusenig,et al.  c-Jun and JunB Antagonistically Control Cytokine-Regulated Mesenchymal–Epidermal Interaction in Skin , 2000, Cell.

[28]  T. Sugihara,et al.  Keloid-derived fibroblasts are refractory to Fas-mediated apoptosis and neutralization of autocrine transforming growth factor-beta1 can abrogate this resistance. , 2000, The American journal of pathology.

[29]  H. S. Shukla,et al.  In-situ irradiation of keloid scars with Nd:YAG laser. , 2000, Journal of wound care.

[30]  C. Harland,et al.  Treatment of keloid scars with pulsed dye laser and intralesional steroid , 2000, Journal of cutaneous laser therapy.

[31]  M. Longaker,et al.  Expression of transforming growth factor beta 1, 2, and 3 proteins in keloids. , 1999, Annals of plastic surgery.

[32]  P. Shenefelt,et al.  Keloids and hypertrophic scars. , 1999, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[33]  N. Fusenig,et al.  Keratinocyte growth regulation in fibroblast cocultures via a double paracrine mechanism. , 1999, Journal of cell science.

[34]  R. Fitzpatrick Treatment of inflamed hypertrophic scars using intralesional 5-FU. , 1999, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[35]  H. Namba,et al.  Overexpression of insulin-like growth factor-1 (IGF-I) receptor and the invasiveness of cultured keloid fibroblasts. , 1999, The American journal of pathology.

[36]  R. Johnson,et al.  c‐Jun regulates cell cycle progression and apoptosis by distinct mechanisms , 1999, The EMBO journal.

[37]  O. Haugen,et al.  A new hereditary conjunctivo-corneal dystrophy associated with dermal keloid formation. Report of a family. , 1998, Acta ophthalmologica Scandinavica.

[38]  Miyachi,et al.  Distinct patterns of collagen gene expression are seen in normal and keloid fibroblasts grown in three‐dimensional culture , 1998, The British journal of dermatology.

[39]  G. Lemperle,et al.  Elevated Levels of Testosterone Receptors in Keloid Tissue: An Experimental Investigation , 1997, Plastic and reconstructive surgery.

[40]  I. K. Cohen,et al.  The effect of TGF-beta on keloid fibroblast proliferation and collagen synthesis. , 1996, Plastic and reconstructive surgery.

[41]  A. Sclafani,et al.  Prevention of Earlobe Keloid Recurrence with Postoperative Corticosteroid Injections Versus Radiation Therapy A Randomized, Prospective Study and Review of the Literature , 1996, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[42]  W. Laug,et al.  Elevated levels of plasminogen activator inhibitor-1 may account for the altered fibrinolysis by keloid fibroblasts. , 1996, The Journal of investigative dermatology.

[43]  B. Berman,et al.  Adjunct Therapies to Surgical Management of Keloids , 1996, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[44]  J. Fulton Silicone Gel Sheeting for the Prevention and Management of Evolving Hypertrophic and Keloid Scars , 1995, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[45]  K. Ernst,et al.  Ergebnisse der Kryochirurgie bei 394 Patienten mit hypertrophen Narben und Keloiden , 1995, Der Hautarzt.

[46]  T. Alster,et al.  Treatment of keloid sternotomy scars with 585 nm flashlamp-pumped pulsed-dye laser , 1995, The Lancet.

[47]  Gary R. Grotendorst,et al.  Elevated levels of PDGF alpha receptors in keloid fibroblasts contribute to an enhanced response to PDGF. , 1994, The Journal of investigative dermatology.

[48]  M. Anscher,et al.  Keloids treated with excision followed by radiation therapy. , 1994, Journal of the American Academy of Dermatology.

[49]  I. K. Cohen,et al.  Morphological and immunochemical differences between keloid and hypertrophic scar. , 1994, The American journal of pathology.

[50]  N. Fusenig,et al.  Mutual induction of growth factor gene expression by epidermal-dermal cell interaction , 1993, The Journal of cell biology.

[51]  R. Bono,et al.  Use of cryotherapy in the treatment of keloids. , 1993, The Journal of dermatologic surgery and oncology.

[52]  R. Diegelmann,et al.  Keloid fibroblasts exhibit an altered response to TGF-beta. , 1992, The Journal of investigative dermatology.

[53]  R. Ward,et al.  Pressure therapy for the control of hypertrophic scar formation after burn injury. A history and review. , 1991, The Journal of burn care & rehabilitation.

[54]  T. Flotte,et al.  A controlled trial of intralesional recombinant interferon-gamma in the treatment of keloidal scarring. Clinical and histologic findings. , 1990, Archives of dermatology.

[55]  W. Larrabee,et al.  Intralesional interferon gamma treatment for keloids and hypertrophic scars. , 1990, Archives of otolaryngology--head & neck surgery.

[56]  B. Wen,et al.  The role of kilovoltage irradiation in the treatment of keloids. , 1990, International journal of radiation oncology, biology, physics.

[57]  R. Diegelmann,et al.  Fibronectin is overproduced by keloid fibroblasts during abnormal wound healing , 1989, Molecular and cellular biology.

[58]  R. Halder Pseudofolliculitis barbae and related disorders. , 1988, Dermatologic clinics.

[59]  L. Ala‐Kokko,et al.  Collagen gene expression in keloids: analysis of collagen metabolism and type I, III, IV, and V procollagen mRNAs in keloid tissue and keloid fibroblast cultures. , 1987, The Journal of investigative dermatology.

[60]  C. J. Smith,et al.  The possible role of mast cells (allergy) in the production of keloid and hypertrophic scarring. , 1987, The Journal of burn care & rehabilitation.

[61]  J. Uitto,et al.  Altered steady-state ratio of type I/III procollagen mRNAs correlates with selectively increased type I procollagen biosynthesis in cultured keloid fibroblasts. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[62]  J. Uitto,et al.  Biochemical composition of the connective tissue in keloids and analysis of collagen metabolism in keloid fibroblast cultures. , 1985, The Journal of investigative dermatology.

[63]  L. Lagasse,et al.  Increased androgen binding in keloids: a preliminary communication. , 1983, The Journal of dermatologic surgery and oncology.

[64]  A. Shons,et al.  The Treatment of Earlobe Keloids by Surgical Excision and Postoperative Triamcinolone Injection , 1983, Annals of plastic surgery.

[65]  H. Calvert,et al.  Rubinstein‐Taybi syndrome and spontaneous keloids , 1980, Clinical and experimental dermatology.

[66]  I. K. Cohen,et al.  Growth kinetics and collagen synthesis of normal skin, normal scar and keloid fibroblasts in vitro , 1979, Journal of cellular physiology.

[67]  P. Omo-Dare Genetic studies on keloid. , 1975, Journal of the National Medical Association.

[68]  M. Abdel-Fattah,et al.  Presumptive evidence of the effect of pregnancy estrogens on keloid growth. Case report. , 1975, Plastic and reconstructive surgery.

[69]  Raizada In Surgery of pterygium. , 1975 .

[70]  Ramakrishnan Km,et al.  Study of 1,000 patients with keloids in South India. , 1974, Plastic and reconstructive surgery.

[71]  Cohen Ik,et al.  Hypertrophic scars and keloids. A collective review. , 1974 .

[72]  E. Peacock,et al.  Biologic basis for the treatment of keloids and hypertrophic scars. , 1970 .

[73]  L. Goeminne A new probably X-linked inherited syndrome: congenital muscular torticollis, multiple keloids cryptorchidism and renal dysplasia. , 1968, Acta geneticae medicae et gemellologiae.

[74]  B. Cosman,et al.  THE SURGICAL TREATMENT OF KELOIDS , 1961 .

[75]  I. Lim,et al.  Synchronous activation of ERK and PI-3K pathways is required for collagen and extracellular matrix production in keloids , 2003 .

[76]  M. Tenenhaus,et al.  Alterations in fibroblast alpha1beta1 integrin collagen receptor expression in keloids and hypertrophic scars. , 2002, The Journal of investigative dermatology.

[77]  G. Yosipovitch,et al.  A comparison of the combined effect of cryotherapy and corticosteroid injections versus corticosteroids and cryotherapy alone on keloids: a controlled study. , 2001, The Journal of dermatological treatment.

[78]  K. Takehara,et al.  Effects of various growth factors and histamine on cultured keloid fibroblasts. , 1995, Dermatology.

[79]  M. Hundeiker,et al.  [Results of cryosurgery in 394 patients with hypertrophic scars and keloids]. , 1995, Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete.

[80]  Y. W. Tang,et al.  Intra- and postoperative steroid injections for keloids and hypertrophic scars. , 1992, British journal of plastic surgery.

[81]  P. Combemale,et al.  [Treatment of keloids]. , 1991, Annales de dermatologie et de venereologie.

[82]  I. Muir,et al.  On the nature of keloid and hypertrophic scars. , 1990, British journal of plastic surgery.

[83]  U. Ringborg,et al.  Treatment of keloids with surgical excision and postoperative X-ray radiation. , 1989, Scandinavian journal of plastic and reconstructive surgery and hand surgery.

[84]  J. Russell,et al.  Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[85]  R. Davey,et al.  Silicone gel: a new treatment for burn scars and contractures. , 1983, Burns, including thermal injury.

[86]  J. Oluwasanmi Keloids in the African. , 1974, Clinics in plastic surgery.

[87]  D. J. Crockett,et al.  REGIONAL KELOID SUSCEPTIBILITY. , 1964, British journal of plastic surgery.