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American Journal of Clinical Dermatology

, Volume 17, Issue 3, pp 201–223 | Cite as

Keloids and Hypertrophic Scars: A Spectrum of Clinical Challenges

  • Anthony P. Trace
  • Clinton W. Enos
  • Alon Mantel
  • Valerie M. Harvey
Review Article

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.

Keywords

Connective Tissue Growth Factor Imiquimod Hypertrophic Scar Pressure Therapy Keloid Fibroblast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors would like to thank Antoinette F. Hood, MD, for the histopathology slides and Donald Glass, MD, for the clinical pictures of keloids. The authors would also like to acknowledge Meena Katdare, PhD, for her guidance throughout the writing process.

Compliance with Ethical Standards

Funding

No funding was received for this review.

Conflicts of interest

Anthony Paul Trace, Clinton Enos, Alon Mantel, and Valerie Harvey report no conflicts of interest.

References

  1. 1.
    Broughton G, Janis JE, Attinger CE. The basic science of wound healing. Plast Reconstr Surg. 2006;117(7 Suppl):12S–34S.PubMedCrossRefGoogle Scholar
  2. 2.
    Murray JC. Keloids and hypertrophic scars. Clin Dermatol. 1994;12(1):27–37.PubMedCrossRefGoogle Scholar
  3. 3.
    Robles DT, Berg D. Abnormal wound healing: keloids. Clin Dermatol. 2007;25(1):26–32.PubMedCrossRefGoogle Scholar
  4. 4.
    Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1–2):113–25.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Mancini RE, Quaife JV. Histogenesis of experimentally produced keloids. J Invest Dermatol. 1962;38:143–81.PubMedCrossRefGoogle Scholar
  6. 6.
    Peacock EE, Madden JW, Trier WC. Biologic basis for the treatment of keloids and hypertrophic scars. South Med J. 1970;63(7):755–60.PubMedCrossRefGoogle Scholar
  7. 7.
    Van den Broek LJ, Limandjaja GC, Niessen FB, Gibbs S. Human hypertrophic and keloid scar models: principles, limitations and future challenges from a tissue engineering perspective. Exp Dermatol. 2014;23(6):382–6.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Bock O, Schmid-Ott G, Malewski P, Mrowietz U. Quality of life of patients with keloid and hypertrophic scarring. Arch Dermatol Res. 2006;297(10):433–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Gold MH, McGuire M, Mustoe TA, Pusic A, Sachdev M, Waibel J, et al. Updated international clinical recommendations on scar management: part 2–algorithms for scar prevention and treatment. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2014;40(8):825–31.Google Scholar
  10. 10.
    Rabello FB, Souza CD, Júnior JAF. Update on hypertrophic scar treatment. Clinics. 2014;69(8):565–73.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Huang C, Murphy GF, Akaishi S, Ogawa R. Keloids and hypertrophic scars: update and future directions. Plast Reconstr Surg Glob Open. 2013;1(4):e25.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Davidson S, Aziz N, Rashid RM, Khachemoune A. A primary care perspective on keloids. Medscape J Med. 2009;11(1):18.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Niessen FB, Spauwen PH, Schalkwijk J, Kon M. On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg. 1999;104(5):1435–58.PubMedCrossRefGoogle Scholar
  14. 14.
    Chike-Obi CJ, Cole PD, Brissett AE. Keloids: pathogenesis, clinical features, and management. Semin Plast Surg. 2009;23(3):178–84.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Brissett AE, Sherris DA. Scar contractures, hypertrophic scars, and keloids. Facial Plast Surg FPS. 2001;17(4):263–72.PubMedCrossRefGoogle Scholar
  16. 16.
    English RS, Shenefelt PD. Keloids and hypertrophic scars. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1999;25(8):631–8.Google Scholar
  17. 17.
    Wolfram D, Tzankov A, Pülzl P, Piza-Katzer H. Hypertrophic scars and keloids—a review of their pathophysiology, risk factors, and therapeutic management. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2009;35(2):171–81.Google Scholar
  18. 18.
    Alhady SM, Sivanantharajah K. Keloids in various races. A review of 175 cases. Plast Reconstr Surg. 1969;44(6):564–6.PubMedCrossRefGoogle Scholar
  19. 19.
    The surgical treatment of keloids. Plastic and reconstructive surgery [Internet]. LWW [cited 2015 May 5]. http://journals.lww.com/plasreconsurg/Fulltext/1961/04000/THE_SURGICAL_TREATMENT_OF_KELOIDS_.1.aspx. Accessed 28 Apr 2015.
  20. 20.
    Yedomon GH, Adegbidi H, Atadokpede F, Akpadjan F, Mouto EJ, do Ango-Padonou F. Keloids on dark skin: a consecutive series of 456 cases. Méd Santé Trop. 2012;22(3):287–91.Google Scholar
  21. 21.
    Lane JE, Waller JL, Davis LS. Relationship between age of ear piercing and keloid formation. Pediatrics. 2005;115(5):1312–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Manuskiatti W, Fitzpatrick RE. Treatment response of keloidal and hypertrophic sternotomy scars: comparison among intralesional corticosteroid, 5-fluorouracil, and 585-nm flashlamp-pumped pulsed-dye laser treatments. Arch Dermatol. 2002;138(9):1149–55.PubMedCrossRefGoogle Scholar
  23. 23.
    Lawrence CM, Summerly ME. Keloid formation after BCG vaccination. The Practitioner. 1982;226(1364):326–8.PubMedGoogle Scholar
  24. 24.
    Coop CA, Schaefer SM, England RW. Extensive keloid formation and progression after each vaccination. Hum Vaccin. 2007;3(4):127–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Cohen IK, Die-gelmann RF. Wound healing: biochemical and clinical aspects. Plast Reconstr Surg. 1992;90(5):926.CrossRefGoogle Scholar
  26. 26.
    Niessen FB, Spauwen PH, Robinson PH, Fidler V, Kon M. The use of silicone occlusive sheeting (Sil-K) and silicone occlusive gel (Epiderm) in the prevention of hypertrophic scar formation. Plast Reconstr Surg. 1998;102(6):1962–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Van der Veer WM, Ferreira JA, de Jong EH, Molema G, Niessen FB. Perioperative conditions affect long-term hypertrophic scar formation. Ann Plast Surg. 2010;65(3):321–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Lee S-S, Yosipovitch G, Chan Y-H, Goh C-L. Pruritus, pain, and small nerve fiber function in keloids: a controlled study. J Am Acad Dermatol. 2004;51(6):1002–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Dréno B. Assessing quality of life in patients with acne vulgaris: implications for treatment. Am J Clin Dermatol. 2006;7(2):99–106.PubMedCrossRefGoogle Scholar
  30. 30.
    Amaral CSF do, March M de FBP, Sant’Anna CC. Quality of life in children and teenagers with atopic dermatitis. An Bras Dermatol. 2012;87(5):717–23.Google Scholar
  31. 31.
    Chamlin SL, Chren M-M. Quality-of-life outcomes and measurement in childhood atopic dermatitis. Immunol Allergy Clin N Am. 2010;30(3):281–8.CrossRefGoogle Scholar
  32. 32.
    McKenna KE, Stern RS. The impact of psoriasis on the quality of life of patients from the 16-center PUVA follow-up cohort. J Am Acad Dermatol. 1997;36(3 Pt 1):388–94.PubMedCrossRefGoogle Scholar
  33. 33.
    Kent G, Al’Abadie M. Psychologic effects of vitiligo: a critical incident analysis. J Am Acad Dermatol. 1996;35(6):895–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Furtado F, Hochman B, Ferrara SF, Dini GM, Nunes JMC, Juliano Y, et al. What factors affect the quality of life of patients with keloids? Rev Assoc Médica Bras 1992. 2009;55(6):700–4.Google Scholar
  35. 35.
    Butler PD, Longaker MT, Yang GP. Current progress in keloid research and treatment. J Am Coll Surg. 2008;206(4):731–41.PubMedCrossRefGoogle Scholar
  36. 36.
    Lee JY-Y, Yang C-C, Chao S-C, Wong T-W. Histopathological differential diagnosis of keloid and hypertrophic scar. Am J Dermatopathol. 2004;26(5):379–84.PubMedCrossRefGoogle Scholar
  37. 37.
    Moshref SS, Mufti ST. Keloid and hypertrophic scars: comparative histopathological and immunohistochemical study. J King Abdulaziz Univ-Med Sci. 2010;17(3):3–22.Google Scholar
  38. 38.
    Hunasgi S, Koneru A, Vanishree M, Shamala R. Keloid: a case report and review of pathophysiology and differences between keloid and hypertrophic scars. J Oral Maxillofac Pathol JOMFP. 2013;17(1):116–20.PubMedCrossRefGoogle Scholar
  39. 39.
    Ehrlich HP, Desmoulière A, Diegelmann RF, Cohen IK, Compton CC, Garner WL, et al. Morphological and immunochemical differences between keloid and hypertrophic scar. Am J Pathol. 1994;145(1):105–13.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Shaker SA, Ayuob NN, Hajrah NH. Cell talk: a phenomenon observed in the keloid scar by immunohistochemical study. Appl Immunohistochem Mol Morphol AIMM Off Publ Soc Appl Immunohistochem. 2011;19(2):153–9.CrossRefGoogle Scholar
  41. 41.
    Shih B, Bayat A. Genetics of keloid scarring. Arch Dermatol Res. 2010;302(5):319–39.PubMedCrossRefGoogle Scholar
  42. 42.
    Omo-Dare P. Genetic studies on keloid. J Natl Med Assoc. 1975;67(6):428–32.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Bloom D. Heredity of keloids; review of the literature and report of a family with multiple keloids in five generations. N Y State J Med. 1956;56(4):511–9.PubMedGoogle Scholar
  44. 44.
    Clark JA, Turner ML, Howard L, Stanescu H, Kleta R, Kopp JB. Description of familial keloids in five pedigrees: evidence for autosomal dominant inheritance and phenotypic heterogeneity. BMC Dermatol. 2009;9:8.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Marneros AG, Norris JE, Olsen BR, Reichenberger E. Clinical genetics of familial keloids. Arch Dermatol. 2001;137(11):1429–34.PubMedCrossRefGoogle Scholar
  46. 46.
    Chen Y, Gao J-H, Liu X-J, Yan X, Song M. Characteristics of occurrence for Han Chinese familial keloids. Burns. 2006;32(8):1052–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Nakashima M, Chung S, Takahashi A, Kamatani N, Kawaguchi T, Tsunoda T, et al. A genome-wide association study identifies four susceptibility loci for keloid in the Japanese population. Nat Genet. 2010;42(9):768–71.PubMedCrossRefGoogle Scholar
  48. 48.
    Zhu F, Wu B, Li P, Wang J, Tang H, Liu Y, et al. Association study confirmed susceptibility loci with keloid in the Chinese Han population. PLoS One. 2013;8(5):e62377.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Dong X, Mao S, Wen H. Upregulation of proinflammatory genes in skin lesions may be the cause of keloid formation (Review). Biomed Rep. 2013;1(6):833–6.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Darby IA, Laverdet B, Bonté F, Desmoulière A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014;6(7):301–11.Google Scholar
  51. 51.
    Nakaoka H, Miyauchi S, Miki Y. Proliferating activity of dermal fibroblasts in keloids and hypertrophic scars. Acta Derm Venereol. 1995;75(2):102–4.PubMedGoogle Scholar
  52. 52.
    Sayah DN, Soo C, Shaw WW, Watson J, Messadi D, Longaker MT, et al. Downregulation of apoptosis-related genes in keloid tissues. J Surg Res. 1999;87(2):209–16.PubMedCrossRefGoogle Scholar
  53. 53.
    De Felice B, Ciarmiello LF, Mondola P, Damiano S, Seru R, Argenziano C, et al. Differential p63 and p53 expression in human keloid fibroblasts and hypertrophic scar fibroblasts. DNA Cell Biol. 2007;26(8):541–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Messadi DV, Le A, Berg S, Jewett A, Wen Z, Kelly P, et al. Expression of apoptosis-associated genes by human dermal scar fibroblasts. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 1999;7(6):511–7.Google Scholar
  55. 55.
    Estrem SA, Domayer M, Bardach J, Cram AE. Implantation of human keloid into athymic mice. The Laryngoscope. 1987;97(10):1214–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Armour A, Scott PG, Tredget EE. Cellular and molecular pathology of HTS: basis for treatment. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2007;15(Suppl 1):S6–17.Google Scholar
  57. 57.
    Lee TY, Chin GS, Kim WJ, Chau D, Gittes GK, Longaker MT. Expression of transforming growth factor beta 1, 2, and 3 proteins in keloids. Ann Plast Surg. 1999;43(2):179–84.PubMedGoogle Scholar
  58. 58.
    Khoo YT, Ong CT, Mukhopadhyay A, Han HC, Do DV, Lim IJ, et al. Upregulation of secretory connective tissue growth factor (CTGF) in keratinocyte-fibroblast coculture contributes to keloid pathogenesis. J Cell Physiol. 2006;208(2):336–43.PubMedCrossRefGoogle Scholar
  59. 59.
    Schmid P, Itin P, Cherry G, Bi C, Cox DA. Enhanced expression of transforming growth factor-beta type I and type II receptors in wound granulation tissue and hypertrophic scar. Am J Pathol. 1998;152(2):485–93.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Peltonen J, Hsiao LL, Jaakkola S, Sollberg S, Aumailley M, Timpl R, et al. Activation of collagen gene expression in keloids: co-localization of type I and VI collagen and transforming growth factor-beta 1 mRNA. J Invest Dermatol. 1991;97(2):240–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009;19(2):156–72.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Van Meeteren LA, ten Dijke P. Regulation of endothelial cell plasticity by TGF-β. Cell Tissue Res. 2012;347(1):177–86.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Walraven M, Beelen RHJ, Ulrich MMW. Transforming growth factor-β (TGF-β) signaling in healthy human fetal skin: a descriptive study. J Dermatol Sci. 2015;78(2):117–24.PubMedCrossRefGoogle Scholar
  64. 64.
    Xia W, Phan T-T, Lim IJ, Longaker MT, Yang GP. Complex epithelial-mesenchymal interactions modulate transforming growth factor-beta expression in keloid-derived cells. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2004;12(5):546–56.Google Scholar
  65. 65.
    Igarashi A, Okochi H, Bradham DM, Grotendorst GR. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair. Mol Biol Cell. 1993;4(6):637–45.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Ghosh AK, Vaughan DE. PAI-1 in tissue fibrosis. J Cell Physiol. 2012;227(2):493–507.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    He S, Liu X, Yang Y, Huang W, Xu S, Yang S, et al. Mechanisms of transforming growth factor beta(1)/Smad signalling mediated by mitogen-activated protein kinase pathways in keloid fibroblasts. Br J Dermatol. 2010;162(3):538–46.PubMedCrossRefGoogle Scholar
  68. 68.
    Tuan T-L, Wu H, Huang EY, Chong SSN, Laug W, Messadi D, et al. Increased plasminogen activator inhibitor-1 in keloid fibroblasts may account for their elevated collagen accumulation in fibrin gel cultures. Am J Pathol. 2003;162(5):1579–89.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Tuan T-L, Hwu P, Ho W, Yiu P, Chang R, Wysocki A, et al. Adenoviral overexpression and small interfering RNA suppression demonstrate that plasminogen activator inhibitor-1 produces elevated collagen accumulation in normal and keloid fibroblasts. Am J Pathol. 2008;173(5):1311–25.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Lu F, Gao J, Ogawa R, Hyakusoku H. Variations in gap junctional intercellular communication and connexin expression in fibroblasts derived from keloid and hypertrophic scars. Plast Reconstr Surg. 2007;119(3):844–51.PubMedCrossRefGoogle Scholar
  71. 71.
    Hu D, Zhu X, Xu M, Chen B, Margaret AH, George WC. The inhibitory effect of tamoxifen on human dermal fibroblast-populated collagen lattices. Zhonghua Zheng Xing Wai Ke Za Zhi Zhonghua Zhengxing Waike Zazhi Chin J Plast Surg. 2002;18(3):160–2.Google Scholar
  72. 72.
    Chau D, Mancoll JS, Lee S, Zhao J, Phillips LG, Gittes GK, et al. Tamoxifen downregulates TGF-beta production in keloid fibroblasts. Ann Plast Surg. 1998;40(5):490–3.PubMedCrossRefGoogle Scholar
  73. 73.
    Carthy JM, Sundqvist A, Heldin A, van Dam H, Kletsas D, Heldin C-H, et al. Tamoxifen inhibits TGF-β-mediated activation of myofibroblasts by blocking non-Smad signaling through ERK1/2. J Cell Physiol. 2015;230(12):3084–92.PubMedCrossRefGoogle Scholar
  74. 74.
    Messadi DV, Doung HS, Zhang Q, Kelly AP, Tuan T-L, Reichenberger E, et al. Activation of NFkappaB signal pathways in keloid fibroblasts. Arch Dermatol Res. 2004;296(3):125–33.PubMedGoogle Scholar
  75. 75.
    Makino S, Mitsutake N, Nakashima M, Saenko VA, Ohtsuru A, Umezawa K, et al. DHMEQ, a novel NF-kappaB inhibitor, suppresses growth and type I collagen accumulation in keloid fibroblasts. J Dermatol Sci. 2008;51(3):171–80.PubMedCrossRefGoogle Scholar
  76. 76.
    Wynn TA. Fibrotic disease and the TH1/TH2 paradigm. Nat Rev Immunol. 2004;4(8):583–94.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Murao N, Seino K-I, Hayashi T, Ikeda M, Funayama E, Furukawa H, et al. Treg-enriched CD4+ T cells attenuate collagen synthesis in keloid fibroblasts. Exp Dermatol. 2014;23(4):266–71.PubMedCrossRefGoogle Scholar
  78. 78.
    Gupta S, Sharma VK. Standard guidelines of care: keloids and hypertrophic scars. Indian J Dermatol Venereol Leprol. 2011;77(1):94–100.PubMedCrossRefGoogle Scholar
  79. 79.
    Cotterill JA, Cunliffe WJ. Suicide in dermatological patients. Br J Dermatol. 1997;137(2):246–50.PubMedCrossRefGoogle Scholar
  80. 80.
    Gupta MA, Gupta AK. Depression and suicidal ideation in dermatology patients with acne, alopecia areata, atopic dermatitis and psoriasis. Br J Dermatol. 1998;139(5):846–50.PubMedCrossRefGoogle Scholar
  81. 81.
    McCoy BJ, Diegelmann RF, Cohen IK. In vitro inhibition of cell growth, collagen synthesis, and prolyl hydroxylase activity by triamcinolone acetonide. Proc Soc Exp Biol Med Soc Exp Biol Med N Y N. 1980;163(2):216–22.CrossRefGoogle Scholar
  82. 82.
    Ardehali B, Nouraei SAR, Van Dam H, Dex E, Wood S, Nduka C. Objective assessment of keloid scars with three-dimensional imaging: quantifying response to intralesional steroid therapy. Plast Reconstr Surg. 2007;119(2):556–61.PubMedCrossRefGoogle Scholar
  83. 83.
    Muneuchi G, Suzuki S, Onodera M, Ito O, Hata Y, Igawa HH. Long-term outcome of intralesional injection of triamcinolone acetonide for the treatment of keloid scars in Asian patients. Scand J Plast Reconstr Surg Hand Surg Nord Plast Foren Nord Klubb Handkirurgi. 2006;40(2):111–6.CrossRefGoogle Scholar
  84. 84.
    Mustoe TA, Cooter RD, Gold MH, Hobbs FDR, Ramelet A-A, Shakespeare PG, et al. International clinical recommendations on scar management. Plast Reconstr Surg. 2002;110(2):560–71.PubMedCrossRefGoogle Scholar
  85. 85.
    Gold MH, Berman B, Clementoni MT, Gauglitz GG, Nahai F, Murcia C. Updated international clinical recommendations on scar management: part 1–evaluating the evidence. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2014;40(8):817–24.Google Scholar
  86. 86.
    Darougheh A, Asilian A, Shariati F. Intralesional triamcinolone alone or in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars. Clin Exp Dermatol. 2009;34(2):219–23.PubMedCrossRefGoogle Scholar
  87. 87.
    Davison SP, Dayan JH, Clemens MW, Sonni S, Wang A, Crane A. Efficacy of intralesional 5-fluorouracil and triamcinolone in the treatment of keloids. Aesthet Surg J Am Soc Aesthetic Plast Surg. 2009;29(1):40–6.CrossRefGoogle Scholar
  88. 88.
    Apikian M, Goodman G. Intralesional 5-fluorouracil in the treatment of keloid scars. Australas J Dermatol. 2004;45(2):140–3.PubMedCrossRefGoogle Scholar
  89. 89.
    Khan MA, Bashir MM, Khan FA. Intralesional triamcinolone alone and in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars. JPMA J Pak Med Assoc. 2014;64(9):1003–7.PubMedGoogle Scholar
  90. 90.
    Sharma S, Bhanot A, Kaur A, Dewan SP. Role of liquid nitrogen alone compared with combination of liquid nitrogen and intralesional triamcinolone acetonide in treatment of small keloids. J Cosmet Dermatol. 2007;6(4):258–61.PubMedCrossRefGoogle Scholar
  91. 91.
    Hirshowitz B, Lerner D, Moscona AR. Treatment of keloid scars by combined cryosurgery and intralesional corticosteroids. Aesthetic Plast Surg. 1982;6(3):153–8.PubMedCrossRefGoogle Scholar
  92. 92.
    Weshahy AH, Abdel Hay R. Intralesional cryosurgery and intralesional steroid injection: a good combination therapy for treatment of keloids and hypertrophic scars. Dermatol Ther. 2012;25(3):273–6.PubMedCrossRefGoogle Scholar
  93. 93.
    Oliaei S, Nelson JS, Fitzpatrick R, Wong BJF. Laser treatment of scars. Facial Plast Surg FPS. 2012;28(5):518–24.PubMedCrossRefGoogle Scholar
  94. 94.
    Berman B, Bieley HC. Adjunct therapies to surgical management of keloids. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1996;22(2):126–30.Google Scholar
  95. 95.
    Lawrence WT. In search of the optimal treatment of keloids: report of a series and a review of the literature. Ann Plast Surg. 1991;27(2):164–78.PubMedCrossRefGoogle Scholar
  96. 96.
    Tang YW. Intra- and postoperative steroid injections for keloids and hypertrophic scars. Br J Plast Surg. 1992;45(5):371–3.PubMedCrossRefGoogle Scholar
  97. 97.
    Amici J-M. Early hypertrophic scar after surgery on the nasal region: value of long-acting corticosteroid injections. Ann Dermatol Vénéréol. 2014;141(1):7–13.PubMedCrossRefGoogle Scholar
  98. 98.
    Chen MA, Davidson TM. Scar management: prevention and treatment strategies. Curr Opin Otolaryngol Head Neck Surg. 2005;13(4):242–7.PubMedCrossRefGoogle Scholar
  99. 99.
    Chowdri NA, Masarat M, Mattoo A, Darzi MA. Keloids and hypertrophic scars: results with intraoperative and serial postoperative corticosteroid injection therapy. Aust N Z J Surg. 1999;69(9):655–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Juckett G, Hartman-Adams H. Management of keloids and hypertrophic scars. Am Fam Physician. 2009;80(3):253–60.PubMedGoogle Scholar
  101. 101.
    Stucker FJ, Shaw GY. An approach to management of keloids. Arch Otolaryngol Head Neck Surg. 1992;118(1):63–7.PubMedCrossRefGoogle Scholar
  102. 102.
    Friedman SJ, Butler DF, Pittelkow MR. Perilesional linear atrophy and hypopigmentation after intralesional corticosteroid therapy. Report of two cases and review of the literature. J Am Acad Dermatol. 1988;19(3):537–41.PubMedCrossRefGoogle Scholar
  103. 103.
    Kelly AP. Medical and surgical therapies for keloids. Dermatol Ther. 2004;17(2):212–8.PubMedCrossRefGoogle Scholar
  104. 104.
    Kelly AP. Update on the management of keloids. Semin Cutan Med Surg. 2009;28(2):71–6.PubMedCrossRefGoogle Scholar
  105. 105.
    Kim DY, Kim ES, Eo SR, Kim KS, Lee SY, Cho BH. A surgical approach for earlobe keloid: keloid fillet flap. Plast Reconstr Surg. 2004;113(6):1668–74.PubMedCrossRefGoogle Scholar
  106. 106.
    Lee Y, Minn KW, Baek RM, Hong JJ. A new surgical treatment of keloid: keloid core excision. Ann Plast Surg. 2001;46(2):135–40.PubMedCrossRefGoogle Scholar
  107. 107.
    Rudolph R. Wide spread scars, hypertrophic scars, and keloids. Clin Plast Surg. 1987;14(2):253–60.PubMedGoogle Scholar
  108. 108.
    Yang J-Y, Yang S-Y. Are auricular keloids and persistent hypertrophic scars resectable? The role of intrascar excision. Ann Plast Surg. 2012;69(6):637–42.PubMedCrossRefGoogle Scholar
  109. 109.
    Martin-García RF, Busquets AC. Postsurgical use of imiquimod 5 % cream in the prevention of earlobe keloid recurrences: results of an open-label, pilot study. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2005;31(11 Pt 1):1394–8.Google Scholar
  110. 110.
    Stashower ME. Successful treatment of earlobe keloids with imiquimod after tangential shave excision. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2006;32(3):380–6.Google Scholar
  111. 111.
    Urioste SS, Arndt KA, Dover JS. Keloids and hypertrophic scars: review and treatment strategies. Semin Cutan Med Surg. 1999;18(2):159–71.PubMedCrossRefGoogle Scholar
  112. 112.
    Sherris DA, Larrabee WF, Murakami CS. Management of scar contractures, hypertrophic scars, and keloids. Otolaryngol Clin N Am. 1995;28(5):1057–68.Google Scholar
  113. 113.
    Berman B, Bieley HC. Keloids. J Am Acad Dermatol. 1995;33(1):117–23.PubMedCrossRefGoogle Scholar
  114. 114.
    Sidle DM, Kim H. Keloids: prevention and management. Facial Plast Surg Clin N Am. 2011;19(3):505–15.CrossRefGoogle Scholar
  115. 115.
    Van Leeuwen MCE, Stokmans SC, Bulstra A-EJ, Meijer OWM, van Leeuwen PAM, Niessen FB. High-dose-rate brachytherapy for the treatment of recalcitrant keloids: a unique, effective treatment protocol. Plast Reconstr Surg. 2014;134(3):527–34.PubMedCrossRefGoogle Scholar
  116. 116.
    Rusciani L, Rossi G, Bono R. Use of cryotherapy in the treatment of keloids. J Dermatol Surg Oncol. 1993;19(6):529–34.PubMedCrossRefGoogle Scholar
  117. 117.
    Zimmerman EE, Crawford P. Cutaneous cryosurgery. Am Fam Physician. 2012;86(12):1118–24.PubMedGoogle Scholar
  118. 118.
    Ernst K, Hundeiker M. Results of cryosurgery in 394 patients with hypertrophic scars and keloids. Hautarzt Z Für Dermatol Venerol Verwandte Geb. 1995;46(7):462–6.CrossRefGoogle Scholar
  119. 119.
    Zouboulis CC, Blume U, Büttner P, Orfanos CE. Outcomes of cryosurgery in keloids and hypertrophic scars. A prospective consecutive trial of case series. Arch Dermatol. 1993;129(9):1146–51.PubMedCrossRefGoogle Scholar
  120. 120.
    Van Leeuwen MCE, Bulstra AEJ, Ket JCF, Ritt MJPF, van Leeuwen PAM, Niessen FB. Intralesional cryotherapy for the treatment of keloid scars: evaluating effectiveness. Plast Reconstr Surg Glob Open [Internet]. 2015 Jul 8 [cited 2015 Aug 25];3(6). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494507/. Accessed 25 Aug 2015.
  121. 121.
    Layton AM, Yip J, Cunliffe WJ. A comparison of intralesional triamcinolone and cryosurgery in the treatment of acne keloids. Br J Dermatol. 1994;130(4):498–501.PubMedCrossRefGoogle Scholar
  122. 122.
    Fikrle T, Pizinger K. Cryosurgery in the treatment of earlobe keloids: report of seven cases. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2005;31(12):1728–31.Google Scholar
  123. 123.
    Stromps J-P, Dunda S, Eppstein R-J, Babic D, Har-Shai Y, Pallua N. Intralesional cryosurgery combined with topical silicone gel sheeting for the treatment of refractory keloids. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2014;40(9):996–1003.Google Scholar
  124. 124.
    Ceilley RI, Babin RW. The combined use of cryosurgery and intralesional injections of suspensions of fluorinated adrenocorticosteroids for reducing keloids and hypertrophic scars. J Dermatol Surg Oncol. 1979;5(1):54–6.PubMedCrossRefGoogle Scholar
  125. 125.
    Mirmovich O, Gil T, Goldin I, Lavi I, Mettanes I, Har-Shai Y. Pain evaluation and control during and following the treatment of hypertrophic scars and keloids by contact and intralesional cryosurgery—a preliminary study. J Eur Acad Dermatol Venereol JEADV. 2012;26(4):440–7.PubMedCrossRefGoogle Scholar
  126. 126.
    Cook DK, Georgouras K. Complications of cutaneous cryotherapy. Med J Aust. 1994;161(3):210–3.PubMedGoogle Scholar
  127. 127.
    Van Leeuwen MCE, van der Wal MBA, Bulstra A-EJ, Galindo-Garre F, Molier J, van Zuijlen PPM, et al. Intralesional cryotherapy for treatment of keloid scars: a prospective study. Plast Reconstr Surg. 2015;135(2):580–9.PubMedCrossRefGoogle Scholar
  128. 128.
    Apfelberg DB, Maser MR, Lash H, White D, Weston J. Preliminary results of argon and carbon dioxide laser treatment of keloid scars. Lasers Surg Med. 1984;4(3):283–90.PubMedCrossRefGoogle Scholar
  129. 129.
    Henning JPH, Roskam Y, van Gemert MJ. Treatment of keloids and hypertrophic scars with an argon laser. Lasers Surg Med. 1986;6(1):72–5.CrossRefGoogle Scholar
  130. 130.
    Kantor GR, Wheeland RG, Bailin PL, Walker NP, Ratz JL. Treatment of earlobe keloids with carbon dioxide laser excision: a report of 16 cases. J Dermatol Surg Oncol. 1985;11(11):1063–7.PubMedCrossRefGoogle Scholar
  131. 131.
    Apfelberg DB, Maser MR, White DN, Lash H. Failure of carbon dioxide laser excision of keloids. Lasers Surg Med. 1989;9(4):382–8.PubMedCrossRefGoogle Scholar
  132. 132.
    Norris JE. The effect of carbon dioxide laser surgery on the recurrence of keloids. Plast Reconstr Surg. 1991;87(1):44–9 (discussion 50–3).PubMedCrossRefGoogle Scholar
  133. 133.
    Bernstein LJ, Kauvar AN, Grossman MC, Geronemus RG. Scar resurfacing with high-energy, short-pulsed and flashscanning carbon dioxide lasers. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1998;24(1):101–7.Google Scholar
  134. 134.
    Campolmi P, Bonan P, Cannarozzo G, Bassi A, Bruscino N, Arunachalam M, et al. Highlights of thirty-year experience of CO2 laser use at the Florence (Italy) department of dermatology. Sci World J. 2012;2012:546528.CrossRefGoogle Scholar
  135. 135.
    Scrimali L, Lomeo G, Nolfo C, Pompili G, Tamburino S, Catalani A, et al. Treatment of hypertrophic scars and keloids with a fractional CO2 laser: a personal experience. J Cosmet Laser Ther Off Publ Eur Soc Laser Dermatol. 2010;12(5):218–21.CrossRefGoogle Scholar
  136. 136.
    Abergel RP, Meeker CA, Lam TS, Dwyer RM, Lesavoy MA, Uitto J. Control of connective tissue metabolism by lasers: recent developments and future prospects. J Am Acad Dermatol. 1984;11(6):1142–50.PubMedCrossRefGoogle Scholar
  137. 137.
    Kumar K, Kapoor BS, Rai P, Shukla HS. In-situ irradiation of keloid scars with Nd:YAG laser. J Wound Care. 2000;9(5):213–5.PubMedCrossRefGoogle Scholar
  138. 138.
    Kwon SD, Kye YC. Treatment of scars with a pulsed Er:YAG laser. J Cutan Laser Ther. 2000;2(1):27–31.PubMedCrossRefGoogle Scholar
  139. 139.
    Koike S, Akaishi S, Nagashima Y, Dohi T, Hyakusoku H, Ogawa R. Nd:YAG laser treatment for keloids and hypertrophic scars: an analysis of 102 cases. Plast Reconstr Surg Glob Open. 2014;2(12):e272.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Nd:YAG laser treatment of keloids and hypertrophic scars [Internet]. [cited 2015 Sep 6]. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258100/. Accessed 6 Sep 2015.
  141. 141.
    Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science. 1983;220(4596):524–7.PubMedCrossRefGoogle Scholar
  142. 142.
    Reiken SR, Wolfort SF, Berthiaume F, Compton C, Tompkins RG, Yarmush ML. Control of hypertrophic scar growth using selective photothermolysis. Lasers Surg Med. 1997;21(1):7–12.PubMedCrossRefGoogle Scholar
  143. 143.
    Kuo Y-R, Jeng S-F, Wang F-S, Chen T-H, Huang H-C, Chang P-R, et al. Flashlamp pulsed dye laser (PDL) suppression of keloid proliferation through down-regulation of TGF-beta1 expression and extracellular matrix expression. Lasers Surg Med. 2004;34(2):104–8.PubMedCrossRefGoogle Scholar
  144. 144.
    Kuo Y-R, Wu W-S, Jeng S-F, Huang H-C, Yang KD, Sacks JM, et al. Activation of ERK and p38 kinase mediated keloid fibroblast apoptosis after flashlamp pulsed-dye laser treatment. Lasers Surg Med. 2005;36(1):31–7.PubMedCrossRefGoogle Scholar
  145. 145.
    Karsai S, Roos S, Hammes S, Raulin C. Pulsed dye laser: what’s new in non-vascular lesions? J Eur Acad Dermatol Venereol JEADV. 2007;21(7):877–90.PubMedCrossRefGoogle Scholar
  146. 146.
    Alster TS, Kurban AK, Grove GL, Grove MJ, Tan OT. Alteration of argon laser-induced scars by the pulsed dye laser. Lasers Surg Med. 1993;13(3):368–73.PubMedCrossRefGoogle Scholar
  147. 147.
    Alster TS. Improvement of erythematous and hypertrophic scars by the 585-nm flashlamp-pumped pulsed dye laser. Ann Plast Surg. 1994;32(2):186–90.PubMedCrossRefGoogle Scholar
  148. 148.
    Dierickx C, Goldman MP, Fitzpatrick RE. Laser treatment of erythematous/hypertrophic and pigmented scars in 26 patients. Plast Reconstr Surg. 1995;95(1):84–90 (discussion 91–2).PubMedCrossRefGoogle Scholar
  149. 149.
    Connell PG, Harland CC. Treatment of keloid scars with pulsed dye laser and intralesional steroid. J Cutan Laser Ther. 2000;2(3):147–50.PubMedCrossRefGoogle Scholar
  150. 150.
    Chan HH, Wong DSY, Ho WS, Lam LK, Wei W. The use of pulsed dye laser for the prevention and treatment of hypertrophic scars in chinese persons. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2004;30(7):987–94 (discussion 994).Google Scholar
  151. 151.
    McCraw JB, McCraw JA, McMellin A, Bettencourt N. Prevention of unfavorable scars using early pulse dye laser treatments: a preliminary report. Ann Plast Surg. 1999;42(1):7–14.PubMedCrossRefGoogle Scholar
  152. 152.
    Goldman MP, Fitzpatrick RE. Laser treatment of scars. Dermatol Surg. 1995;21(8):685–7.PubMedCrossRefGoogle Scholar
  153. 153.
    Wittenberg GP, Fabian BG, Bogomilsky JL, Schultz LR, Rudner EJ, Chaffins ML, et al. Prospective, single-blind, randomized, controlled study to assess the efficacy of the 585-nm flashlamp-pumped pulsed-dye laser and silicone gel sheeting in hypertrophic scar treatment. Arch Dermatol. 1999;135(9):1049–55.PubMedCrossRefGoogle Scholar
  154. 154.
    Gold MH. Update on fractional laser technology. J Clin Aesthetic Dermatol. 2010;3(1):42–50.Google Scholar
  155. 155.
    El-Zawahry BM, Sobhi RM, Bassiouny DA, Tabak SA. Ablative CO2 fractional resurfacing in treatment of thermal burn scars: an open-label controlled clinical and histopathological study. J Cosmet Dermatol. 2015;14(4):324–31.Google Scholar
  156. 156.
    Makboul M, Makboul R, Abdelhafez AH, Hassan SS, Youssif SM. Evaluation of the effect of fractional CO2 laser on histopathological picture and TGF-β1 expression in hypertrophic scar. J Cosmet Dermatol. 2014;13(3):169–79.PubMedCrossRefGoogle Scholar
  157. 157.
    Cavalié M, Sillard L, Montaudié H, Bahadoran P, Lacour J-P, Passeron T. Treatment of keloids with laser-assisted topical steroid delivery: a retrospective study of 23 cases. Dermatol Ther. 2015;28(2):74–8.PubMedCrossRefGoogle Scholar
  158. 158.
    Singhal M, Del Rio-Sancho S, Sonaje K, Kalia YN. fractional laser ablation for the cutaneous delivery of triamcinolone acetonide from cryomilled polymeric microparticles: creating intra-epidermal drug depots. Mol Pharm. 2016.Google Scholar
  159. 159.
    Alster TS, Tanzi EL. Hypertrophic scars and keloids: etiology and management. Am J Clin Dermatol. 2003;4(4):235–43.PubMedCrossRefGoogle Scholar
  160. 160.
    Linares HA, Larson DL, Willis-Galstaun BA. Historical notes on the use of pressure in the treatment of hypertrophic scars or keloids. Burns J Int Soc Burn Inj. 1993;19(1):17–21.CrossRefGoogle Scholar
  161. 161.
    Baur PS, Larson DL, Stacey TR, Barratt GF, Dobrkovsky M. Ultrastructural analysis of pressure-treated human hypertrophic scars. J Trauma. 1976;16(12):958–67.PubMedCrossRefGoogle Scholar
  162. 162.
    Kischer CW, Shetlar MR, Shetlar CL. Alteration of hypertrophic scars induced by mechanical pressure. Arch Dermatol. 1975;111(1):60–4.PubMedCrossRefGoogle Scholar
  163. 163.
    Staley MJ, Richard RL. Use of pressure to treat hypertrophic burn scars. Adv Wound Care J Prev Heal. 1997;10(3):44–6.Google Scholar
  164. 164.
    Costa AM, Peyrol S, Pôrto LC, Comparin JP, Foyatier JL, Desmoulière A. Mechanical forces induce scar remodeling. Study in non-pressure-treated versus pressure-treated hypertrophic scars. Am J Pathol. 1999;155(5):1671–9.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Renò F, Sabbatini M, Stella M, Magliacani G, Cannas M. Effect of in vitro mechanical compression on Epilysin (matrix metalloproteinase-28) expression in hypertrophic scars. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2005;13(3):255–61.Google Scholar
  166. 166.
    Renò F, Sabbatini M, Lombardi F, Stella M, Pezzuto C, Magliacani G, et al. In vitro mechanical compression induces apoptosis and regulates cytokines release in hypertrophic scars. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2003;11(5):331–6.Google Scholar
  167. 167.
    Haq MA, Haq A. Pressure therapy in treatment of hypertrophic scar, burn contracture and keloid: the Kenyan experience. East Afr Med J. 1990;67(11):785–93.PubMedGoogle Scholar
  168. 168.
    Ward RS. Pressure therapy for the control of hypertrophic scar formation after burn injury. A history and review. J Burn Care Rehabil. 1991;12(3):257–62.PubMedCrossRefGoogle Scholar
  169. 169.
    Atkinson J-AM, McKenna KT, Barnett AG, McGrath DJ, Rudd M. A randomized, controlled trial to determine the efficacy of paper tape in preventing hypertrophic scar formation in surgical incisions that traverse Langer’s skin tension lines. Plast Reconstr Surg. 2005;116(6):1648–56 (discussion 1657–8).PubMedCrossRefGoogle Scholar
  170. 170.
    Goldwyn RM. The ultrastructure of collagen: its relation to the healing of wounds and the management of hypertrophic scar. Arch Surg. 1977;112(1):103-103.Google Scholar
  171. 171.
    Johnson J, Greenspan B, Gorga D, Nagler W, Goodwin C. Compliance with pressure garment use in burn rehabilitation. J Burn Care Rehabil. 1994;15(2):180–8.PubMedCrossRefGoogle Scholar
  172. 172.
    Kealey GP, Jensen KL, Laubenthal KN, Lewis RW. Prospective randomized comparison of two types of pressure therapy garments. J Burn Care Rehabil. 1990;11(4):334–6.PubMedCrossRefGoogle Scholar
  173. 173.
    Cheng JC, Evans JH, Leung KS, Clark JA, Choy TT, Leung PC. Pressure therapy in the treatment of post-burn hypertrophic scar—a critical look into its usefulness and fallacies by pressure monitoring. Burns Incl Therm Inj. 1984;10(3):154–63.PubMedCrossRefGoogle Scholar
  174. 174.
    Macintyre L, Baird M. Pressure garments for use in the treatment of hypertrophic scars—an evaluation of current construction techniques in NHS hospitals. Burns J Int Soc Burn Inj. 2005;31(1):11–4.CrossRefGoogle Scholar
  175. 175.
    Leung PC, Ng M. Pressure treatment for hypertrophic scars resulting from. Burns. 1980;6(4):244–50.CrossRefGoogle Scholar
  176. 176.
    Chang P, Laubenthal KN, Lewis RW, Rosenquist MD, Lindley-Smith P, Kealey GP. Prospective, randomized study of the efficacy of pressure garment therapy in patients with burns. J Burn Care Rehabil. 1995;16(5):473–5.PubMedCrossRefGoogle Scholar
  177. 177.
    Anzarut A, Olson J, Singh P, Rowe BH, Tredget EE. The effectiveness of pressure garment therapy for the prevention of abnormal scarring after burn injury: a meta-analysis. J Plast Reconstr Aesthetic Surg JPRAS. 2009;62(1):77–84.CrossRefGoogle Scholar
  178. 178.
    Fulton JE. Silicone gel sheeting for the prevention and management of evolving hypertrophic and keloid scars. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1995;21(11):947–51.Google Scholar
  179. 179.
    Quinn KJ, Evans JH, Courtney JM, Gaylor JD, Reid WH. Non-pressure treatment of hypertrophic scars. Burns Incl Therm Inj. 1985;12(2):102–8.PubMedCrossRefGoogle Scholar
  180. 180.
    Sawada Y, Sone K. Treatment of scars and keloids with a cream containing silicone oil. Br J Plast Surg. 1990;43(6):683–8.PubMedCrossRefGoogle Scholar
  181. 181.
    De Oliveira GV, Nunes TA, Magna LA, Cintra ML, Kitten GT, Zarpellon S, et al. Silicone versus nonsilicone gel dressings: a controlled trial. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2001;27(8):721–6.Google Scholar
  182. 182.
    Gold MH. Topical silicone gel sheeting in the treatment of hypertrophic scars and keloids. A dermatologic experience. J Dermatol Surg Oncol. 1993;19(10):912–6.PubMedCrossRefGoogle Scholar
  183. 183.
    Dockery GL, Nilson RZ. Treatment of hypertrophic and keloid scars with SILASTIC Gel Sheeting. J Foot Ankle Surg Off Publ Am Coll Foot Ankle Surg. 1994;33(2):110–9.Google Scholar
  184. 184.
    Katz BE. Silicone gel sheeting in scar therapy. Cutis. 1995;56(1):65–7.PubMedGoogle Scholar
  185. 185.
    Perkins K, Davey RB, Wallis KA. Silicone gel: a new treatment for burn scars and contractures. Burns Incl Therm Inj. 1983;9(3):201–4.PubMedCrossRefGoogle Scholar
  186. 186.
    Quinn KJ. Silicone gel in scar treatment. Burns Incl Therm Inj. 1987;13(Suppl):S33–40.PubMedCrossRefGoogle Scholar
  187. 187.
    Ahn ST, Monafo WW, Mustoe TA. Topical silicone gel: a new treatment for hypertrophic scars. Surgery. 1989;106(4):781–6 (discussion 786–7).PubMedGoogle Scholar
  188. 188.
    Ahn ST, Monafo WW, Mustoe TA. Topical silicone gel for the prevention and treatment of hypertrophic scar. Arch Surg Chic Ill 1960. 1991;126(4):499–504.Google Scholar
  189. 189.
    Carney SA, Cason CG, Gowar JP, Stevenson JH, McNee J, Groves AR, et al. Cica-Care gel sheeting in the management of hypertrophic scarring. Burns J Int Soc Burn Inj. 1994;20(2):163–7.CrossRefGoogle Scholar
  190. 190.
    Gold MH, Foster TD, Adair MA, Burlison K, Lewis T. Prevention of hypertrophic scars and keloids by the prophylactic use of topical silicone gel sheets following a surgical procedure in an office setting. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2001;27(7):641–4.Google Scholar
  191. 191.
    O’Brien L, Pandit A. Silicon gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev. 2006;1:CD003826.PubMedGoogle Scholar
  192. 192.
    Poston J. The use of silicone gel sheeting in the management of hypertrophic and keloid scars. J Wound Care. 2000;9(1):10–6.PubMedCrossRefGoogle Scholar
  193. 193.
    O’Brien L, Jones DJ. Silicone gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev. 2013;9:CD003826.PubMedGoogle Scholar
  194. 194.
    Mustoe TA. Evolution of silicone therapy and mechanism of action in scar management. Aesthet Plast Surg. 2008;32(1):82–92.CrossRefGoogle Scholar
  195. 195.
    De Giorgi V, Sestini S, Mannone F, Papi F, Alfaioli B, Gori A, et al. The use of silicone gel in the treatment of fresh surgical scars: a randomized study. Clin Exp Dermatol. 2009;34(6):688–93.PubMedCrossRefGoogle Scholar
  196. 196.
    Kwon SY, Park SD, Park K. Comparative effect of topical silicone gel and topical tretinoin cream for the prevention of hypertrophic scar and keloid formation and the improvement of scars. J Eur Acad Dermatol Venereol JEADV. 2014;28(8):1025–33.PubMedCrossRefGoogle Scholar
  197. 197.
    Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1999;25(3):224–32.Google Scholar
  198. 198.
    Gupta S, Kalra A. Efficacy and safety of intralesional 5-fluorouracil in the treatment of keloids. Dermatol Basel Switz. 2002;204(2):130–2.CrossRefGoogle Scholar
  199. 199.
    Haurani MJ, Foreman K, Yang JJ, Siddiqui A. 5-Fluorouracil treatment of problematic scars. Plast Reconstr Surg. 2009;123(1):139–48 (discussion 149–51).PubMedCrossRefGoogle Scholar
  200. 200.
    Asilian A, Darougheh A, Shariati F. New combination of triamcinolone, 5-Fluorouracil, and pulsed-dye laser for treatment of keloid and hypertrophic scars. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2006;32(7):907–15.Google Scholar
  201. 201.
    Kontochristopoulos G, Stefanaki C, Panagiotopoulos A, Stefanaki K, Argyrakos T, Petridis A, et al. Intralesional 5-fluorouracil in the treatment of keloids: an open clinical and histopathologic study. J Am Acad Dermatol. 2005;52(3 Pt 1):474–9.PubMedCrossRefGoogle Scholar
  202. 202.
    Jacob SE, Berman B, Nassiri M, Vincek V. Topical application of imiquimod 5 % cream to keloids alters expression genes associated with apoptosis. Br J Dermatol. 2003;149(Suppl 66):62–5.PubMedCrossRefGoogle Scholar
  203. 203.
    Tyring S. Imiquimod applied topically: a novel immune response modifier. Skin Ther Lett. 2001;6(6):1–4.Google Scholar
  204. 204.
    Berman B, Kaufman J. Pilot study of the effect of postoperative imiquimod 5 % cream on the recurrence rate of excised keloids. J Am Acad Dermatol. 2002;47(4 Suppl):S209–11.PubMedCrossRefGoogle Scholar
  205. 205.
    Patel PJ, Skinner RB. Experience with keloids after excision and application of 5 % imiquimod cream. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2006;32(3):462.Google Scholar
  206. 206.
    Malhotra AK, Gupta S, Khaitan BK, Sharma VK. Imiquimod 5 % cream for the prevention of recurrence after excision of presternal keloids. Dermatol Basel Switz. 2007;215(1):63–5.CrossRefGoogle Scholar
  207. 207.
    Cação FM, Tanaka V, Messina MC de L. Failure of imiquimod 5 % cream to prevent recurrence of surgically excised trunk keloids. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2009;35(4):629–33.Google Scholar
  208. 208.
    Chuangsuwanich A, Gunjittisomram S. The efficacy of 5 % imiquimod cream in the prevention of recurrence of excised keloids. J Med Assoc Thail Chotmaihet Thangphaet. 2007;90(7):1363–7.Google Scholar
  209. 209.
    Prado A, Andrades P, Benitez S, Umaña M. Scar management after breast surgery: preliminary results of a prospective, randomized, and double-blind clinical study with aldara cream 5 % (imiquimod). Plast Reconstr Surg. 2005;115(3):966–72.PubMedCrossRefGoogle Scholar
  210. 210.
    Berman B, Villa A. Imiquimod 5% cream for keloid management. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2003;29(10):1050–1.Google Scholar
  211. 211.
    Aggarwal H, Saxena A, Lubana PS, Mathur RK, Jain DK. Treatment of keloids and hypertrophic scars using bleom. J Cosmet Dermatol. 2008;7(1):43–9.PubMedCrossRefGoogle Scholar
  212. 212.
    Templeton SF, Solomon AR, Swerlick RA. Intradermal bleomycin injections into normal human skin. A histopathologic and immunopathologic study. Arch Dermatol. 1994;130(5):577–83.PubMedCrossRefGoogle Scholar
  213. 213.
    Bodokh I, Brun P. Treatment of keloid with intralesional bleomycin. Ann Dermatol Vénéréol. 1996;123(12):791–4.PubMedGoogle Scholar
  214. 214.
    Payapvipapong K, Niumpradit N, Piriyanand C, Buranaphalin S, Nakakes A. The treatment of keloids and hypertrophic scars with intralesional bleomycin in skin of color. J Cosmet Dermatol. 2015;14(1):83–90.PubMedCrossRefGoogle Scholar
  215. 215.
    Naeini FF, Najafian J, Ahmadpour K. Bleomycin tattooing as a promising therapeutic modality in large keloids and hypertrophic scars. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2006;32(8):1023–9 (discussion 1029–30).Google Scholar
  216. 216.
    Saray Y, Güleç AT. Treatment of keloids and hypertrophic scars with dermojet injections of bleomycin: a preliminary study. Int J Dermatol. 2005;44(9):777–84.PubMedCrossRefGoogle Scholar
  217. 217.
    Manca G, Pandolfi P, Gregorelli C, Cadossi M, de Terlizzi F. Treatment of keloids and hypertrophic scars with bleomycin and electroporation. Plast Reconstr Surg. 2013;132(4):621e–30e.PubMedCrossRefGoogle Scholar
  218. 218.
    Camacho-Martínez FM, Rey ER, Serrano FC, Wagner A. Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars. An Bras Dermatol. 2013;88(3):387–94.PubMedPubMedCentralCrossRefGoogle Scholar
  219. 219.
    España A, Solano T, Quintanilla E. Bleomycin in the treatment of keloids and hypertrophic scars by multiple needle punctures. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2001;27(1):23–7.Google Scholar
  220. 220.
    Leventhal D, Furr M, Reiter D. Treatment of keloids and hypertrophic scars: a meta-analysis and review of the literature. Arch Facial Plast Surg. 2006;8(6):362–8.PubMedCrossRefGoogle Scholar
  221. 221.
    Perdanasari AT, Lazzeri D, Su W, Xi W, Zheng Z, Ke L, et al. Recent developments in the use of intralesional injections keloid treatment. Arch Plast Surg. 2014;41(6):620–9.CrossRefGoogle Scholar
  222. 222.
    Kloeters O, Tandara A, Mustoe TA. Hypertrophic scar model in the rabbit ear: a reproducible model for studying scar tissue behavior with new observations on silicone gel sheeting for scar reduction. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2007;15(Suppl 1):S40–5.Google Scholar
  223. 223.
    Slemp AE, Kirschner RE. Keloids and scars: a review of keloids and scars, their pathogenesis, risk factors, and management. Curr Opin Pediatr. 2006;18(4):396–402.PubMedCrossRefGoogle Scholar
  224. 224.
    Mutalik S. Treatment of keloids and hypertrophic scars. Indian J Dermatol Venereol Leprol. 2005;71(1):3–8.PubMedCrossRefGoogle Scholar
  225. 225.
    Due E, Rossen K, Sorensen LT, Kliem A, Karlsmark T, Haedersdal M. Effect of UV irradiation on cutaneous cicatrices: a randomized, controlled trial with clinical, skin reflectance, histological, immunohistochemical and biochemical evaluations. Acta Derm Venereol. 2007;87(1):27–32.PubMedCrossRefGoogle Scholar
  226. 226.
    Allen JP. N.Y. MM of A New Y. The art of medicine in ancient Egypt. Metropolitan Museum of Art; 2005. p. 117.Google Scholar
  227. 227.
    Edwin Smith Papyrus [Internet]. http://archive.nlm.nih.gov/proj/ttp/flash/smith/smith.html. Accessed 31 May 2015.
  228. 228.
    Gisquet H, Liu H, Blondel WCPM, Leroux A, Latarche C, Merlin JL, et al. Intradermal tacrolimus prevent scar hypertrophy in a rabbit ear model: a clinical, histological and spectroscopical analysis. Skin Res Technol Off J Int Soc Bioeng Skin ISBS Int Soc Digit Imaging Skin ISDIS Int Soc Skin Imaging ISSI. 2011;17(2):160–6.Google Scholar
  229. 229.
    Lu L, Saulis AS, Liu WR, Roy NK, Chao JD, Ledbetter S, et al. The temporal effects of anti-TGF-beta1, 2, and 3 monoclonal antibody on wound healing and hypertrophic scar formation. J Am Coll Surg. 2005;201(3):391–7.PubMedCrossRefGoogle Scholar
  230. 230.
    Zhang G-Y, Yi C-G, Li X, Zheng Y, Niu Z-G, Xia W, et al. Inhibition of vascular endothelial growth factor expression in keloid fibroblasts by vector-mediated vascular endothelial growth factor shRNA: a therapeutic potential strategy for keloid. Arch Dermatol Res. 2008;300(4):177–84.PubMedCrossRefGoogle Scholar
  231. 231.
    Babalola O, Mamalis A, Lev-Tov H, Jagdeo J. The Role of MicroRNAs in Skin Fibrosis. Arch Dermatol Res. 2013;305(9):763–76.PubMedPubMedCentralCrossRefGoogle Scholar
  232. 232.
    RXI-109-1202 Effect of RXI-109 on CTGF mRNA Levels—getFile.aspx [Internet]. [cited 2015 Sep 21]. https://www.aad.org/eposters/Submissions/getFile.aspx?id=1400&type=sub. Accessed 21 Sep 2015.
  233. 233.
    Nanda S, Reddy BSN. Intralesional 5-fluorouracil as a treatment modality of keloids. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2004;30(1):54–6 (discussion 56–7).Google Scholar
  234. 234.
    Sadeghinia A, Sadeghinia S. Comparison of the efficacy of intralesional triamcinolone acetonide and 5-fluorouracil tattooing for the treatment of keloids. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2012;38(1):104–9.Google Scholar
  235. 235.
    Hatamipour E, Mehrabi S, Hatamipour M, Ghafarian Shirazi HR. Effects of combined intralesional 5-Fluorouracil and topical silicone in prevention of keloids: a double blind randomized clinical trial study. Acta Med. Iran. 2011;49(3):127–30.Google Scholar
  236. 236.
    Meymandi SS, Rezazadeh A, Ekhlasi A. Studying intense pulsed light method along with corticosteroid injection in treating keloid scars. Iran Red Crescent Med J. 2014;16(2):e12464.Google Scholar
  237. 237.
    Stephanides S, Rai S, August P, Ferguson J, Madan V. Treatment of refractory keloids with pulsed dye laser alone and with rotational pulsed dye laser and intralesional corticosteroids: a retrospective case series. Laser Ther. 2011;20(4):279–86.PubMedPubMedCentralCrossRefGoogle Scholar
  238. 238.
    Akaishi S, Koike S, Dohi T, Kobe K, Hyakusoku H, Ogawa R. Nd:YAG laser treatment of keloids and hypertrophic scars. Eplasty. 2012;12:e1.PubMedPubMedCentralGoogle Scholar
  239. 239.
    Son IP, Park KY, Kim B, Kim MN. Pilot study of the efficacy of 578 nm copper bromide laser combined with intralesional corticosteroid injection for treatment of keloids and hypertrophic scars. Ann Dermatol. 2014;26(2):156–61.PubMedPubMedCentralCrossRefGoogle Scholar
  240. 240.
    Weshay AH, Hay RMA, Sayed K, El Hawary MS, Nour-Edin F. Combination of radiofrequency and intralesional steroids in the treatment of keloids: a pilot study. Dermatol Surg. 2015;41(6):731–5.PubMedCrossRefGoogle Scholar
  241. 241.
    Emad M, Omidvari S, Dastgheib L, Mortazavi A, Ghaem H. Surgical excision and immediate postoperative radiotherapy versus cryotherapy and intralesional steroids in the management of keloids: a prospective clinical trial. Med Princ Pract Int J Kuwait Univ Health Sci Cent. 2010;19(5):402–5.Google Scholar
  242. 242.
    Chan KY, Lau CL, Adeeb SM, Somasundaram S, Nasir-Zahari M. A randomized, placebo-controlled, double-blind, prospective clinical trial of silicone gel in prevention of hypertrophic scar development in median sternotomy wound. Plast Reconstr Surg. 2005;116(4):1013–20 (discussion 1021–2).PubMedCrossRefGoogle Scholar
  243. 243.
    Chernoff WG, Cramer H, Su-Huang S. The efficacy of topical silicone gel elastomers in the treatment of hypertrophic scars, keloid scars, and post-laser exfoliation erythema. Aesthetic Plast Surg. 2007;31(5):495–500.PubMedCrossRefGoogle Scholar
  244. 244.
    Al-Khawajah MM. Failure of interferon-alpha 2b in the treatment of mature keloids. Int J Dermatol. 1996;35(7):515–7.PubMedCrossRefGoogle Scholar
  245. 245.
    Berman B, Flores F. Recurrence rates of excised keloids treated with postoperative triamcinolone acetonide injections or interferon alfa-2b injections. J Am Acad Dermatol. 1997;37(5 Pt 1):755–7.PubMedCrossRefGoogle Scholar
  246. 246.
    Conejo-Mir JS, Corbi R, Linares M. Carbon dioxide laser ablation associated with interferon alfa-2b injections reduces the recurrence of keloids. J Am Acad Dermatol. 1998;39(6):1039–40.PubMedCrossRefGoogle Scholar
  247. 247.
    Davison SP, Mess S, Kauffman LC, Al-Attar A. Ineffective treatment of keloids with interferon alpha-2b. Plast Reconstr Surg. 2006;117(1):247–52.PubMedCrossRefGoogle Scholar
  248. 248.
    Ghahary A, Shen YJ, Nedelec B, Scott PG, Tredget EE. Interferons gamma and alpha-2b differentially regulate the expression of collagenase and tissue inhibitor of metalloproteinase-1 messenger RNA in human hypertrophic and normal dermal fibroblasts. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 1995;3(2):176–84.Google Scholar
  249. 249.
    Lee JH, Kim SE, Lee A-Y. Effects of interferon-alpha2b on keloid treatment with triamcinolone acetonide intralesional injection. Int J Dermatol. 2008;47(2):183–6.PubMedCrossRefGoogle Scholar
  250. 250.
    Lee JP, Jalili RB, Tredget EE, Demare JR, Ghahary A. Antifibrogenic effects of liposome-encapsulated IFN-alpha2b cream on skin wounds in a fibrotic rabbit ear model. J Interferon Cytokine Res Off J Int Soc Interferon Cytokine Res. 2005;25(10):627–31.CrossRefGoogle Scholar
  251. 251.
    Wong TW, Chiu HC, Yip KM. Intralesional interferon alpha-2b has no effect in the treatment of keloids. Br J Dermatol. 1994;130(5):683–5.PubMedCrossRefGoogle Scholar
  252. 252.
    Bailey JNR, Waite AE, Clayton WJ, Rustin MHA. Application of topical mitomycin C to the base of shave-removed keloid scars to prevent their recurrence. Br J Dermatol. 2007;156(4):682–6.PubMedCrossRefGoogle Scholar
  253. 253.
    Sanders KW, Gage-White L, Stucker FJ. Topical mitomycin C in the prevention of keloid scar recurrence. Arch Facial Plast Surg. 2005;7(3):172–5.PubMedCrossRefGoogle Scholar
  254. 254.
    Simman R, Alani H, Williams F. Effect of mitomycin C on keloid fibroblasts: an in vitro study. Ann Plast Surg. 2003;50(1):71–6.PubMedCrossRefGoogle Scholar
  255. 255.
    Stewart CE, Kim JY. Application of mitomycin-C for head and neck keloids. Otolaryngol-Head Neck Surg Off J Am Acad Otolaryngol-Head Neck Surg. 2006;135(6):946–50.CrossRefGoogle Scholar
  256. 256.
    Talmi YP, Orenstein A, Wolf M, Kronenberg J. Use of mitomycin C for treatment of keloid: a preliminary report. Otolaryngol-Head Neck Surg Off J Am Acad Otolaryngol-Head Neck Surg. 2005;132(4):598–601.CrossRefGoogle Scholar
  257. 257.
    Augusti KT. Therapeutic values of onion (Allium cepa L.) and garlic (Allium sativum L.). Indian J Exp Biol. 1996;34(7):634–40.PubMedGoogle Scholar
  258. 258.
    Chung VQ, Kelley L, Marra D, Jiang SB. Onion extract gel versus petrolatum emollient on new surgical scars: prospective double-blinded study. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2006;32(2):193–7.Google Scholar
  259. 259.
    Hosnuter M, Payasli C, Isikdemir A, Tekerekoglu B. The effects of onion extract on hypertrophic and keloid scars. J Wound Care. 2007;16(6):251–4.PubMedCrossRefGoogle Scholar
  260. 260.
    Jackson BA, Shelton AJ. Pilot study evaluating topical onion extract as treatment for postsurgical scars. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1999;25(4):267–9.Google Scholar
  261. 261.
    Koc E, Arca E, Surucu B, Kurumlu Z. An open, randomized, controlled, comparative study of the combined effect of intralesional triamcinolone acetonide and onion extract gel and intralesional triamcinolone acetonide alone in the treatment of hypertrophic scars and keloids. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2008;34(11):1507–14.Google Scholar
  262. 262.
    Biemans RG. A rare case of sarcomatous degeneration of a cheloid. Arch Chir Neerl. 1963;15:175–85.PubMedCrossRefGoogle Scholar
  263. 263.
    Bischof M, Krempien R, Debus J, Treiber M. Postoperative electron beam radiotherapy for keloids: objective findings and patient satisfaction in self-assessment. Int J Dermatol. 2007;46(9):971–5.PubMedCrossRefGoogle Scholar
  264. 264.
    Borok TL, Bray M, Sinclair I, Plafker J, LaBirth L, Rollins C. Role of ionizing irradiation for 393 keloids. Int J Radiat Oncol Biol Phys. 1988;15(4):865–70.PubMedCrossRefGoogle Scholar
  265. 265.
    Botwood N, Lewanski C, Lowdell C. The risks of treating keloids with radiotherapy. Br J Radiol. 1999;72(864):1222–4.PubMedCrossRefGoogle Scholar
  266. 266.
    Clavere P, Bedane C, Bonnetblanc JM, Bonnafoux-Clavere A, Rousseau J. Postoperative interstitial radiotherapy of keloids by iridium 192: a retrospective study of 46 treated scars. Dermatol Basel Switz. 1997;195(4):349–52.CrossRefGoogle Scholar
  267. 267.
    Hintz BL. Radiotherapy for keloid treatment. J Natl Med Assoc. 1973;65(1):71–5.PubMedPubMedCentralGoogle Scholar
  268. 268.
    Kal HB, Veen RE. Biologically effective doses of postoperative radiotherapy in the prevention of keloids. Dose-effect relationship. Strahlenther Onkol Organ Dtsch Röntgenges Al. 2005;181(11):717–23.CrossRefGoogle Scholar
  269. 269.
    Kal HB, Veen RE, Jürgenliemk-Schulz IM. Dose-effect relationships for recurrence of keloid and pterygium after surgery and radiotherapy. Int J Radiat Oncol Biol Phys. 2009;74(1):245–51.PubMedCrossRefGoogle Scholar
  270. 270.
    Kovalic JJ, Perez CA. Radiation therapy following keloidectomy: a 20-year experience. Int J Radiat Oncol Biol Phys. 1989;17(1):77–80.PubMedCrossRefGoogle Scholar
  271. 271.
    Levitt W, Gillies H. Radiotherapy in the prophylaxis and treatment of keloid. The Lancet. 1942;239(6189):440–2.CrossRefGoogle Scholar
  272. 272.
    Malaker A, Ellis F, Paine CH. Keloid scars: a new method of treatment combining surgery with interstitial radiotherapy. Clin Radiol. 1976;27(2):179–83.PubMedCrossRefGoogle Scholar
  273. 273.
    Malaker K, Vijayraghavan K, Hodson I, Al Yafi T. Retrospective analysis of treatment of unresectable keloids with primary radiation over 25 years. Clin Oncol R Coll Radiol G B. 2004;16(4):290–8.CrossRefGoogle Scholar
  274. 274.
    Ogawa R, Yoshitatsu S, Yoshida K, Miyashita T. Is radiation therapy for keloids acceptable? The risk of radiation-induced carcinogenesis. Plast Reconstr Surg. 2009;124(4):1196–201.PubMedCrossRefGoogle Scholar
  275. 275.
    Ragoowansi R, Cornes PGS, Moss AL, Glees JP. Treatment of keloids by surgical excision and immediate postoperative single-fraction radiotherapy. Plast Reconstr Surg. 2003;111(6):1853–9.PubMedCrossRefGoogle Scholar
  276. 276.
    Sclafani AP, Gordon L, Chadha M, Romo T. Prevention of earlobe keloid recurrence with postoperative corticosteroid injections versus radiation therapy: a randomized, prospective study and review of the literature. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1996;22(6):569–74.Google Scholar
  277. 277.
    Speranza G, Sultanem K, Muanza T. Descriptive study of patients receiving excision and radiotherapy for keloids. Int J Radiat Oncol Biol Phys. 2008;71(5):1465–9.PubMedCrossRefGoogle Scholar
  278. 278.
    Subedi N, Roberts F. Radiotherapy treatment of keloid scars and other benign conditions: is there a need for a database of patients treated? Br J Dermatol. 2009;161(1):194–5.PubMedCrossRefGoogle Scholar
  279. 279.
    Veen RE, Kal HB. Postoperative high-dose-rate brachytherapy in the prevention of keloids. Int J Radiat Oncol Biol Phys. 2007;69(4):1205–8.PubMedCrossRefGoogle Scholar
  280. 280.
    Viani GA, Stefano EJ, Afonso SL, De Fendi LI. Postoperative strontium-90 brachytherapy in the prevention of keloids: results and prognostic factors. Int J Radiat Oncol Biol Phys. 2009;73(5):1510–6.PubMedCrossRefGoogle Scholar
  281. 281.
    Palmieri B, Gozzi G, Palmieri G. Vitamin E added silicone gel sheets for treatment of hypertrophic scars and keloids. Int J Dermatol. 1995;34(7):506–9.PubMedCrossRefGoogle Scholar
  282. 282.
    Jenkins M, Alexander JW, MacMillan BG, Waymack JP, Kopcha R. Failure of topical steroids and vitamin E to reduce postoperative scar formation following reconstructive surgery. J Burn Care Rehabil. 1986;7(4):309–12.PubMedCrossRefGoogle Scholar
  283. 283.
    Baumann LS, Spencer J. The effects of topical vitamin E on the cosmetic appearance of scars. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1999;25(4):311–5.Google Scholar
  284. 284.
    Ehrlich HP, Tarver H, Hunt TK. Inhibitory effects of vitamin E on collagen synthesis and wound repair. Ann Surg. 1972;175(2):235–40.PubMedPubMedCentralCrossRefGoogle Scholar
  285. 285.
    Havlik RJ. Vitamin E and wound healing. Plastic Surgery Educational Foundation DATA Committee. Plast Reconstr Surg. 1997;100(7):1901–2.PubMedCrossRefGoogle Scholar
  286. 286.
    Khoosal D, Goldman RD. Vitamin E for treating children’s scars. Does it help reduce scarring? Can Fam Physician Médecin Fam Can. 2006;52:855–6.Google Scholar
  287. 287.
    Martin A. The use of antioxidants in healing. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1996;22(2):156–60.Google Scholar
  288. 288.
    Zurada JM, Kriegel D, Davis IC. Topical treatments for hypertrophic scars. J Am Acad Dermatol. 2006;55(6):1024–31.PubMedCrossRefGoogle Scholar
  289. 289.
    Lawrence WT. Treatment of earlobe keloids with surgery plus adjuvant intralesional verapamil and pressure earrings. Ann Plast Surg. 1996;37(2):167–9.PubMedCrossRefGoogle Scholar
  290. 290.
    Xu S, Teng J, Xie J, Shen M, Chen D. Comparison of the mechanisms of intralesional steroid, interferon or verapamil injection in the treatment of proliferative scars. Zhonghua Zheng Xing Wai Ke Za Zhi Zhonghua Zhengxing Waike Zazhi Chin J Plast Surg. 2009;25(1):37–40.Google Scholar
  291. 291.
    D’Andrea F, Brongo S, Ferraro G, Baroni A. Prevention and treatment of keloids with intralesional verapamil. Dermatol Basel Switz. 2002;204(1):60–2.CrossRefGoogle Scholar
  292. 292.
    Doong H, Dissanayake S, Gowrishankar TR, LaBarbera MC, Lee RC. The 1996 Lindberg Award. Calcium antagonists alter cell shape and induce procollagenase synthesis in keloid and normal human dermal fibroblasts. J Burn Care Rehabil. 1996;17(6 Pt 1):497–514.PubMedCrossRefGoogle Scholar
  293. 293.
    Lee RC, Ping JA. Calcium antagonists retard extracellular matrix production in connective tissue equivalent. J Surg Res. 1990;49(5):463–6.PubMedCrossRefGoogle Scholar
  294. 294.
    Hultén L. Dressings for surgical wounds. Am J Surg. 1994;167(1A):42S–4S (discussion 44S–45S).PubMedCrossRefGoogle Scholar
  295. 295.
    Vogt PM, Andree C, Breuing K, Liu PY, Slama J, Helo G, et al. Dry, moist, and wet skin wound repair. Ann Plast Surg. 1995;34(5):493–9 (discussion 499–500).PubMedCrossRefGoogle Scholar
  296. 296.
    Hutchinson JJ. Infection under occlusion. Ostomy Wound Manage. 1994;40(3):28–30 (32–3).PubMedGoogle Scholar
  297. 297.
    Thomas DW, Hill CM, Lewis MA, Stephens P, Walker R, Von Der Weth A. Randomized clinical trial of the effect of semi-occlusive dressings on the microflora and clinical outcome of acute facial wounds. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2000;8(4):258–63.Google Scholar
  298. 298.
    Klopp R, Niemer W, Fraenkel M, von der Weth A. Effect of four treatment variants on the functional and cosmetic state of mature scars. J Wound Care. 2000;9(7):319–24.PubMedCrossRefGoogle Scholar
  299. 299.
    Schmidt A, Gassmueller J, Hughes-Formella B, Bielfeldt S. Treating hypertrophic scars for 12 or 24 hours with a self-adhesive hydroactive polyurethane dressing. J Wound Care. 2001;10(5):149–53.PubMedCrossRefGoogle Scholar
  300. 300.
    Wigger-Albert W, Kuhlmann M, Wilhelm D, Mrowietz U, Eichhorn K, Ortega J, et al. Efficacy of a polyurethane dressing versus a soft silicone sheet on hypertrophic scars. J Wound Care. 2009;18(5):208 (210–4).PubMedCrossRefGoogle Scholar
  301. 301.
    Gauglitz GG, Pavicic T. Emerging strategies for the prevention and therapy of excessive scars. MMW Fortschr Med. 2012;154(15):55–8.PubMedCrossRefGoogle Scholar
  302. 302.
    Wang L, Tai N-Z, Fan Z-H. Effect of botulinum toxin type A injection on hypertrophic scar in rabbit ear model. Zhonghua Zheng Xing Wai Ke Za Zhi Zhonghua Zhengxing Waike Zazhi Chin J Plast Surg. 2009;25(4):284–7.Google Scholar
  303. 303.
    Xiao Z, Qu G. Effects of botulinum toxin type a on collagen deposition in hypertrophic scars. Mol Basel Switz. 2012;17(2):2169–77.Google Scholar
  304. 304.
    Yang G-L, Zhao M, Wang J-M, He C-F, Luo Y, Liu H-Y, et al. Short-term clinical effects of photodynamic therapy with topical 5-aminolevulinic acid for facial acne conglobata: an open, prospective, parallel-arm trial. Photodermatol Photoimmunol Photomed. 2013;29(5):233–8.PubMedCrossRefGoogle Scholar
  305. 305.
    Ud-Din S, Thomas G, Morris J, Bayat A. Photodynamic therapy: an innovative approach to the treatment of keloid disease evaluated using subjective and objective non-invasive tools. Arch Dermatol Res. 2013;305(3):205–14.PubMedCrossRefGoogle Scholar
  306. 306.
    Nie Z. Is photodynamic therapy a solution for keloid? G Ital Dermatol E Venereol Organo Uff Soc Ital Dermatol E Sifilogr. 2011;146(6):463–72.Google Scholar
  307. 307.
    Nie Z, Bayat A, Behzad F, Rhodes LE. Positive response of a recurrent keloid scar to topical methyl aminolevulinate-photodynamic therapy. Photodermatol Photoimmunol Photomed. 2010;26(6):330–2.PubMedCrossRefGoogle Scholar
  308. 308.
    Sebastian A, Allan E, Allan D, Colthurst J, Bayat A. Addition of novel degenerate electrical waveform stimulation with photodynamic therapy significantly enhances its cytotoxic effect in keloid fibroblasts: first report of a potential combination therapy. J Dermatol Sci. 2011;64(3):174–84.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of RadiologyEastern Virginia Medical SchoolNorfolkUSA
  2. 2.The School of MedicineEastern Virginia Medical SchoolNorfolkUSA
  3. 3.Hampton University Skin of Color Research InstituteHampton UniversityHamptonUSA
  4. 4.Department of DermatologyEastern Virginia Medical SchoolNorfolkUSA

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