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2011, Number 2

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Dermatología Cosmética, Médica y Quirúrgica 2011; 9 (2)

Keloid scarring: Update on therapeutic options

Sánchez AK, Jesús SMA, Karam OM

Language: Spanish
References: 98
Page: 111-121
PDF size: 497.57 Kb.


ABSTRACT

Despite scientific advances, there is no 100% effective treatment for keloid scars, so it is still a challenge not only for cosmetic disfigurement but also because of uncomfortable symptoms such as itching and pain.
A wide range of therapies do exist, and the most commonly used modalities are intralesional steroid (71%), surgical excision (50%), cryotherapy (64%), laser therapy (10%), radiation therapy (70%) and the application of silicone gel sheets (79-90%). Other treatments that have been used with variable success rates include imiquimod, interferon-α 2b, 5-FU (50%) and calcium channel blockers (44%). Furthermore, natural products like vitamin E, onion extract, beta-sitosterol, gotu kola and Bulbine fructescens, have shown some effectiveness to prevent more than treat keloids. Some of these, however, can produce adverse effects such as contact dermatitis. It should be noted that the bulk of the evidence for these modalities is based on small open label and uncontrolled studies. Therefore, it is possible that current treatments may not have any significant effect on clinical improvement. Based on emerging information on keloid pathophysiology, there have been promising new molecular therapies primarily related to TGF-β pathway. But currently, there is a need for further studies in order to develop better therapies for this pathological scarring.
We carried out this article to review the existing treatment for keloid scarring and the new options.


REFERENCES

  1. Ladin D. “The art and science of wound care”. Plast Reconstr Surg 1995; 96: 748.

  2. Breasted JH. The Edwin Smith surgical papyrus. Hieroglyphic translation and commentary. Chicago, University of Chicago Press, 1930.

  3. Alibert JLM. Description des maladies de la peau observes a l’hôpital Saint-Louis et exposition des meilleures methods suives pour leur traitment. Paris, Barrois l’aine et fils, 1806: 113.

  4. Tuan TL, Nichter LS. “The molecular basis of keloid and hypertrophic scar formation”. Mol Med Today 1998; 4: 19-24.

  5. Wolfram D, Tzankov A, Pulzl P, Piza-Katzer H. “Hypertrophic scars and Keloids –a review of their pathophysiology, risk factors, and therapeutic management”. Dermatol Surg 2009; 35: 171.

  6. Lee TY, Chin GS, Kim WJ, et al. “Expression of transforming growth factor beta 1, 2, and 3 proteins in keloids”. Ann Plast Surg 1999; 43: 179.

  7. Colwell AS, Phan TT, Kong W, et al. “Hypertrophic scar fibroblasts have increased connective tissue growth factor expression after transforming growth factor-beta stimulation”. Plast Reconstr Surg 2005; 116: 1387.

  8. Haisa M, Okochi H, Grotendorst GR. “Elevated levels of PDGF alpha receptors in keloid fibroblasts contribute to an enhanced response to PDGF”. J Invest Dermatol 1994; 103: 560.

  9. Ohtsuru A, Yoshimoto H, Ishihara, H, et al. “Insulin-like growth factor-I (IGF-I)/IGF-I receptor axis and increased invasion activity of fibroblasts in keloid”. Endocr J 2000; 47 Suppl: S41.

  10. Campaner AB, Ferreira LM, Gragnani A, et al. “Upregulation of TGFbeta1 expression may be necessary but is not sufficient for excessive scarring”. J Invest Dermatol 2006, 126: 1168-1176.

  11. Marneros AG, Krieg T. “Keloids –clinical diagnosis, pathogenesis, and treatment options”. J Dtsch Dermatol Ges 2004; 2: 905-913.

  12. Messadi DV, Le A, Berg S, et al. “Effect of TGF-beta 1 on PDGF receptors expression in human scar fibroblasts”. Front Biosci 1998, 3: a16-22

  13. Sayah DN, Soo C, Shaw WW, et al. “Downregulation of apoptosisrelated genes in keloid tissues”. J Surg Res 1999, 87: 209-216.

  14. Fujiwara M, Muragaki Y, Ooshima A. “Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration”. Br J Dermatol 2005, 153: 295-300

  15. Satish L, Lyons-Weiler J, Hebda PA, et al. “Gene expression patterns in isolated keloid fibroblasts”. Wound Repair Regen 2006, 14: 463-470.

  16. Lim CP, Phan TT, Lim IJ, et al. “Stat3 contributes to keloid pathogenesis via promoting collagen production, cell proliferation and migration”. Oncogene 2006, 25: 5416-5425.

  17. Sayah DN, Soo C, Shaw WW, et al. “Downregulation of apoptosisrelated genes in keloid tissues”. J Surg Res 1999; 87: 209.

  18. Teofoli P, Barduagni S, Ribuffo M, et al. “Expression of Bcl-2, p53, c-jun and c-fos protooncogenes in keloids and hypertrophic scars”. J Dermatol Sci 1999; 22: 31.

  19. Marneros AG, Norris JE, Olsen BR, Reichenberger E. “Clinical genetics of familial keloids.” Arch Dermatol 2001; 137: 1429.

  20. Schierle HP, Scholz D, Lemperle G. “Elevated levels of testosterone receptors in keloid tissue: an experimental investigation”. Plast Reconstr Surg 1997; 100: 390-395.

  21. Bock O, Schmid-Ott G, Malewski P, Mrowietz U. “Quality of life of patients with keloid and hypertrophic scarring”. Arch Dermatol Res 2006; 297: 433-438.

  22. Berman B, Bieley HC. “Adjunct therapies to surgical management of keloids”. Dermatol Surg 1996; 22: 126.

  23. English RS, Shenefelt PD. “Keloids and hypertrophic scars”. Dermatol Surg 1999; 25: 631.

  24. Schaffer MR, Efron PA, Thornton FJ, Klingel K, Gross SS, Barbul. “A Nitric oxide, an autocrine regulator of wound fibroblast synthetic function”. J Immunol 1997; 158: 2375- 2381.

  25. Shaffer JJ, Taylor SC, Cook-Bolden F. “Keloidal scars: A review with a critical look at therapeutic options”. J Am Acad Dermatol 2002; 46: S63.

  26. Kauh YC, Rouda S, Mondragon G, Tokarek R, diLeonardo M, Tuan RS, et al. “Major suppression of pro-alpha1(I) type I collagen gene expression in the dermis after keloid excision and immediate intrawound injection of triamcinolone acetonide”. J Am Acad Dermatol 1997; 37: 586-589.

  27. Kang N, Sivakumar B, Sanders R, Nduka C, Gault D. “Intra-lesional injections of collagenase are ineffective in the treatment of keloid and hypertrophic scars”. J Plast Reconstr Aesthet Surg 2006; 59(7): 693-699.

  28. Mustoe TA, Cooter RD, Gold MH, Hobbs FD, Ramelet AA, Shakespeare PG, et al. “International clinical recommendations on scar management”. Plast Reconstr Surg 2002; 110: 560-571.

  29. Jalali M, Bayat A. “Current use of steroids in management of abnormal raised skin scars”. Surgeon 2007; 5: 175-180.

  30. Enríquez MJ, Caballero AM. “Opciones terapéuticas para cicatrices queloides e hipertróficas”. Rev Cent Dermatol Pascua 2007; 16(2): 80-84.

  31. Darzi MA, Chowdri NA, Kaul SK, Khan M. “Evaluation of various methods of treating keloids and hypertrophic scars: a 10-year follow-up study”. Br J Plast Surg 1992; 45: 374-379.

  32. Layton AM, Yip J, Cunliffe WJ. “A comparison of intralesional triamcinolone and cryosurgery in the treatment of acne Keloids”. Br J Dermatol 1994; 130: 498-501.

  33. Yosipovitch G, Widijanti Sugeng M, Goon A, Chan YH, Goh CL. “A comparison of the combined effect of cryotherapy and corticosteroid injections versus corticosteroids and cryotherapy alone on keloids: a controlled study”. J Dermatolog Treat 2001; 12: 87-90.

  34. 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: 1149-1155.

  35. Berman B, Pérez OA, Konda S, Kohut BE, Viera MH, Delgado S, et al. “A review of the biologic effects, clinical efficacy, and safety of silicone elastomer sheeting for hypertrophic and keloid scar treatment and management”. Dermatol Surg 2007; 33: 1291-1302.

  36. O’Brien L, Pandit A. “Silicon gel sheeting for preventing and treating hypertrophic and keloid scars”. Cochrane Database Syst Rev 2006: CD003826.

  37. Ernst K, Hundeiker M. “Results of cryosurgery in 394 patients with hypertrophic scars and Keloids”. Hautarzt 1995; 46: 462-466.

  38. Niessen FB, Spauwen PH, Schalkwijk J, Kon M. “On the nature of hypertrophic scars and keloids: a review”. Plast Reconstr Surg 1999; 104: 1435-1458.

  39. Alster TS, Williams CM. “Treatment of keloid sternotomy scars with 585 nm flashlamp-pumped pulsed-dye laser”. Lancet 1995; 345: 1198- 1200.

  40. Kumar K, Kapoor BS, Rai P, Shukla HS. “In-situ irradiation of keloid scars with Nd:YAG laser”. J Wound Care 2000; 9: 213-215.

  41. 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: 1063-1067.

  42. Panizzon RG. “Dermatologic radiotherapy”. Hautarzt 2007; 58: 701-710.

  43. Klumpar DI, Murray JC, Anscher M. “Keloids treated with excision followed by radiation therapy”. J Am Acad Dermatol 1994; 31: 225-231.

  44. Ogawa R, Mitsuhashi K, Hyakusoku H, Miyashita T. “Postoperative electron-beam irradiation therapy for keloids and hypertrophic scars: retrospective study of 147 cases followed for more than 18 months”. Plast Reconstr Surg 2003; 111: 547-553.

  45. Ragoowansi R, Cornes PG, Moss AL, Glees JP. “Treatment of keloids by surgical excision and immediate postoperative single-fraction radiotherapy”. Plast Reconstr Surg 2003; 111: 1853-1859.

  46. 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 1996; 22: 569-574.

  47. Kovalic JJ, Pérez CA. “Radiation therapy following keloidectomy: a 20- year experience”. Int J Radiat Oncol Biol Phys 1989; 17: 77-80.

  48. Doornbos JF, Stoffel TJ, Hass AC, Hussey DH, Vigliotti AP, Wen BC, et al. “The role of kilovoltage irradiation in the treatment of keloids”. Int J Radiat Oncol Biol Phys 1990; 18: 833-839.

  49. Brent B. “The role of pressure therapy in management of earlobe keloids: preliminary report of a controlled study”. Ann Plast Surg 1978; 1: 579-581.

  50. Rauscher GE, Kolmer WL. “Treatment of recurrent earlobe keloids”. Cutis 1986; 37: 67-68.

  51. 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: S209-S211.

  52. Martín-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 2005; 31: 1394-1398.

  53. Cacao FM, Tanaka V, Messina MC. “Failure of imiquimod % cream to prevent recurrence of surgically excised trunk keloids”. Dermatol Surg 2009; 35: 629-633.

  54. Mrowietz U, Seifert O. “Keloid Scarring: New Treatments Ahead”. Actas Dermosifiliogr 2009; 100(2): 75-83

  55. Jiménez SA, Freundlich B, Rosenbloom J. “Selective inhibition of human diploid fibroblast collagen synthesis by interferons”. J Clin Invest 1984; 74: 1112-1116.

  56. Berman B, Duncan MR. “Short-term keloid treatment in vivo with human interferon alfa-2b results in a selective and persistent normalization of keloidal fibroblast collagen, glycosaminoglycan, and collagenase production in vitro”. J Am Acad Dermatol 1989; 21: 694-702.

  57. Al-Khawajah MM. “Failure of interferon-alpha 2b in the treatment of mature keloids”. Int J Dermatol 1996; 35: 515-517.

  58. De Waard JW, de Man BM, Wobbes T, van der Linden CJ, Hendriks T. “Inhibition of fibroblast collagen synthesis and proliferation by levamisole and 5-fluorouracil”. Eur J Cancer 1998; 34: 162-167.

  59. Van de Kar AL, Kreulen M, van Zuijlen PP, Oldenburger F. “The results of surgical excision and adjuvant irradiation for therapy-resistant keloids: a prospective clinical outcome study”. Plast Reconstr Surg 2007; 119: 2248.

  60. Copcu E, Sivrioglu N, Oztan Y. “Combination of surgery an intralesional verapamil injection in the treatment of the keloid”. J Burn Care Rehabil 2004; 25: 1-7.

  61. Tyring S. “Imiquimod applied topically: A novel immune response modifier”. Skin Therapy Lett 2001; 6: 1.

  62. Hirshowitz B, Lindenbaum E, Har-Shai Y, et al. “Static-electric field induction by a silicone cushion for the treatment of hypertrophic and keloid scars”. Plast Reconstr Surg 1998; 101: 1173.

  63. Eishi K, Bae SJ, Ogawa F, et al. “Silicone gel sheets relieve pain and pruritus with clinical improvement of keloid: possible target of mast cells”. J Dermatolog Treat 2003; 14: 248.

  64. Chang CC, Kuo YF, Chiu HC, et al. “Hydration, not silicone, modulates the effects of keratinocytes on fibroblasts”. J Surg Res 1995; 59: 705.

  65. Fulton JE Jr. “Silicone gel sheeting for the prevention and management of evolving hypertrophic and keloid scars”. Dermatol Surg 1995; 21: 947.

  66. Zouboulis CC, Blume U, Buttner P, Orfanos CE. “Outcomes of cryosurgery in keloids and hypertrophic scars. A prospective consecutive trial of case series”. Arch Dermatol 1993; 129: 1146.

  67. 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 2006; 32: 907.

  68. Alster TS. “Laser treatment of hypertrophic scars, keloids, and striae”. Dermatol Clin 1997; 15: 419.

  69. Nanda S, Reddy BS. “Intralesional 5-fluorouracil as a treatment modality of keloids”. Dermatol Surg 2004; 30: 54.

  70. Kontochristopoulos G, Stefanaki C, Panagiotopoulos A, et al. “Intralesional 5-fluorouracil in the treatment of keloids: an open clinical and histopathologic study”. J Am Acad Dermatol 2005; 52: 474.

  71. 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: 1510.

  72. Botwood N, Lewanski C, Lowdell C. “The risks of treating keloids with radiotherapy”. Br J Radiol 1999; 72: 1222.

  73. 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) 2004; 16: 290.

  74. Khoosal D, Goldman R. “Vitamin E for treating children’s scars. Does it help reduce scarring?”. Can Fam Physician 2006; 52: 855-856.

  75. Saulis AS, Mogford JH, Mustoe TA. “Effect of Mederma on hypertrophic scarring in a rabbit ear model”. Plast Reconstr Surg 2002; 110(1): 177-183.

  76. Jackson BA, Shelton AJ. “Pilot study evaluating topical onion extract as a treatment for postsurgical scars”. Dermatol Surg 1999; 25(4): 267-269.

  77. Hosnuter M, Payasli C, Isikdemir A, Tekerekoglu B. “The effects of onion extract on hypertrophic and keloid scars”. J Wound Care 2007; 16(6): 251-254.

  78. Beuth J, Hunzelman N, Van Leendert R, Basten R, Noehle M, Schneider B. “Safety and efficacy of local administration of Contractubex to hypertrophic scars in comparison to corticosteroid treatment. Results of a multicenter, comparative epidemiological cohort study in Germany”. In Vivo 2006; 20(2): 277-283.

  79. Jurjus A, Atiyeh BS, Abdallah IM, et al. “Pharmacological modulation of wound healing in experimental burns”. Burns 2007; 33(7): 892-907.

  80. Widgerow AD, Chait LA, Stals R, Stals PJ. “New innovations in scar management”. Aesthetic Plast Surg 2000; 24(3): 227-234.

  81. Denton CP, Merkel PA, Furst DE, Khanna D, Emery P, Hs VM, et al. “Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192”. Arthritis Rheum 2007; 56: 323-333.

  82. Mead AL, Wong TT, Cordeiro MF, Anderson IK, Khaw PT. “Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery”. Invest Ophthalmo Vis Sci 2003; 44: 3394-3401.

  83. Shah M, Foreman DM, Ferguson MW. “Control of scarring in adult wounds by neutralising antibody to transforming growth factor beta”. Lancet 1992; 339: 213-214.

  84. Gary-Bobo M, Nirde P, Jeanjean A, Morere A, García M. “Mannose 6-phosphate receptor targeting and its application in human diseases”. Curr Med Chem 2007; 14: 2945-2953.

  85. Santiago B, Gutiérrez-Canas I, Dotor J, Palao G, Lasarte JJ, Ruiz J, et al. “Topical application of a peptide inhibitor o transforming growth factor-beta1 ameliorates bleomycin-induced skin fibrosis”. J Invest Dermatol 2005; 125: 450-455.

  86. Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, et al. “The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis”. Cell 1999; 96: 319-328.

  87. Ishida W, Mori Y, Lakos G, Sun L, Shan F, Bowes S, et al. “Intracellular TGF-beta receptor blockade abrogates Smad-dependent fibroblast activation in vitro and in vivo”. J Invest Dermatol 2006; 126: 1733-1744.

  88. Mori Y, Ishida W, Bhattacharyya S, Li Y, Platanias LC, Varga J. “Selective inhibition of activin receptor-like kinase 5 signaling blocks profibrotic transforming growth factor beta responses in skin fibroblasts”. Arthritis Rheum 2004; 50: 4008-4021.

  89. Krause DS, Van Etten RA. “Tyrosine kinases as targets for cancer therapy”. N Engl J Med 2005; 353: 172-187.

  90. Distler JH, Jungel A, Huber LC, Schulze-Horsel U, Zwerina J, Gay RE, et al. “Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis”. Arthritis Rheum 2007; 56: 311-322.

  91. Bock O, Yu H, Zitron S, Bayat A, Ferguson MW, Mrowietz U. “Studies of transforming growth factors beta 1-3 and their receptors I and II in fibroblast of keloids and hypertrophic scars”. Acta Derm Venereol 2005; 85: 216-220.

  92. Shah M, Foreman DM, Ferguson MW. “Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition o TGF-beta 3 to cutaneous rat wounds reduces scarring”. J Cell Sci 1995; 108 Pt 3: 985-1002.

  93. Ferguson MW, Duncan J, Bond J, Bush J, Durani P, So K, et al. “Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies”. Lancet 2009; 373: 1264-1274.

  94. Ghazizadeh M. “Essential role of IL-6 signaling pathway in keloid pathogenesis”. J Nippon Med Sch 2007; 74: 11-22.

  95. Liechty KW, Kim HB, Adzick NS, Crombleholme TM. “Fetal wound repair results in scar formation in interleukin10--deficient mice in a syngeneic murine model of scarless fetal wound repair”. J Pediatr Surg 2000; 35: 866-872.

  96. Peranteau WH, Zhang L, Muvarak N, Badillo AT, Radu A, Zoltick PW, et al. “IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation”. J Invest Dermatol 2008; 128: 1852-1860.

  97. Zhang GY, Yi CG, Li X, Zheng Y, Niu ZG, 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 keloids”. Arch Dermatol Res 2008; 300: 177-184.

  98. Nemeh AJ. “Keloids and hypertrophic scars”. J Dermatol Surg Oncol 1993; 19: 738-746.




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