Recent Developments in the Use of Intralesional Injections Keloid Treatment

 

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Keloid scars are often considered aesthetically unattractive and frustrating problems that occur following injuries. They cause functional and cosmetic deformities, displeasure, itching, pain, and psychological stress and possibly affect joint movement. The combination of these factors ultimately results in a compromised quality of life and diminished functional performance. Various methods have been implemented to improve keloid scars using both surgical and non-surgical approaches. However, it has proven to be a challenge to identify a universal treatment that can deliver optimal results for all types of scars. Through a PubMed search, we explored most of the literature that is available about the intralesional injection treatment of hypertrophic scars and keloids and highlights both current (corticosteroid, 5-fluorouracil, bleomycin, interferon, cryotherapy and verapamil) and future treatments (interleukin-10 and botulinum toxin type A). The reference lists of retrieved articles were also analysed. Information was gathered about the mechanism of each injection treatment, its benefits and associated adverse reactions, and possible strategies to address adverse reactions to provide reliable guidelines for determining the optimal treatment for particular types of keloid scars. This article will benefit practitioners by outlining evidence-based treatment strategies using intralesional injections for patients with hypertrophic scars and keloids.

^*The first two authors equally contributed to this work.

Publication History

Received: 21 May 2014

Accepted: 12 September 2014

Article published online:
05 May 2022

© 2014. The Korean Society of Plastic and Reconstructive Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonCommercial License, permitting unrestricted noncommercial use, distribution, and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes. (https://creativecommons.org/licenses/by-nc/4.0/)

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• References

• 1 Huang C, Murphy GF, Akaishi S. et al. Keloids and hypertrophic scars: update and future directions. Plast Reconstr Surg Glob Open 2013; 1: e25
  CrossrefPubMedGoogle Scholar
• 2 Ogawa R. The most current algorithms for the treatment and prevention of hypertrophic scars and keloids. Plast Reconstr Surg 2010; 125: 557-568
  CrossrefPubMedGoogle Scholar
• 3 Klinger M, Marazzi M, Vigo D. et al. Fat injection for cases of severe burn outcomes: a new perspective of scar remodeling and reduction. Aesthetic Plast Surg 2008; 32: 465-469
  CrossrefPubMedGoogle Scholar
• 4 Park TH, Park JH, Chang CH. Clinical features and outcomes of foot keloids treated using complete surgical excision and full thickness skin grafting followed by corticosteroid injections. J Foot Ankle Res 2013; 6: 26
  CrossrefPubMedGoogle Scholar
• 5 Martin MS, Collawn SS. Combination treatment of CO2 fractional laser, pulsed dye laser, and triamcinolone acetonide injection for refractory keloid scars on the upper back. J Cosmet Laser Ther 2013; 15: 166-170
  CrossrefPubMedGoogle Scholar
• 6 Camacho-Martinez FM, Rey ER, Serrano FC. et al. Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars. An Bras Dermatol 2013; 88: 387-394
  CrossrefPubMedGoogle Scholar
• 7 Son IP, Park KY, Kim B. et al. 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: 156-161
  CrossrefPubMedGoogle Scholar
• 8 Emad M, Omidvari S, Dastgheib L. et al. Surgical excision and immediate postoperative radiotherapy versus cryotherapy and intralesional steroids in the management of keloids: a prospective clinical trial. Med Princ Pract 2010; 19: 402-405
  CrossrefPubMedGoogle Scholar
• 9 Sadeghinia A, Sadeghinia S. Comparison of the efficacy of intralesional triamcinolone acetonide and 5-fluorouracil tattooing for the treatment of keloids. Dermatol Surg 2012; 38: 104-109
  CrossrefPubMedGoogle Scholar
• 10 Al Aradi IK, Alawadhi SA, Alkhawaja FA. et al. Earlobe keloids: a pilot study of the efficacy of keloidectomy with core fillet flap and adjuvant intralesional corticosteroids. Dermatol Surg 2013; 39: 1514-1519
  CrossrefPubMedGoogle Scholar
• 11 Anthony ET, Lemonas P, Navsaria HA. et al. The cost effectiveness of intralesional steroid therapy for keloids. Dermatol Surg 2010; 36: 1624-1626
  CrossrefPubMedGoogle Scholar
• 12 Niessen FB, Spauwen PH, Schalkwijk J. et al. On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg 1999; 104: 1435-1458
  CrossrefPubMedGoogle Scholar
• 13 Davison SP, Dayan JH, Clemens MW. et al. Efficacy of intralesional 5-fluorouracil and triamcinolone in the treatment of keloids. Aesthet Surg J 2009; 29: 40-46
  CrossrefPubMedGoogle Scholar
• 14 Gupta S, Sharma VK. Standard guidelines of care: Keloids and hypertrophic scars. Indian J Dermatol Venereol Leprol 2011; 77: 94-100
  CrossrefPubMedGoogle Scholar
• 15 Chen MA, Davidson TM. Scar management: prevention and treatment strategies. Curr Opin Otolaryngol Head Neck Surg 2005; 13: 242-247
  CrossrefPubMedGoogle Scholar
• 16 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
  CrossrefPubMedGoogle Scholar
• 17 Mustoe TA, Cooter RD, Gold MH. et al. International clinical recommendations on scar management. Plast Reconstr Surg 2002; 110: 560-571
  CrossrefPubMedGoogle Scholar
• 18 Wu WS, Wang FS, Yang KD. et al. Dexamethasone induction of keloid regression through effective suppression of VEGF expression and keloid fibroblast proliferation. J Invest Dermatol 2006; 126: 1264-1271
  CrossrefPubMedGoogle Scholar
• 19 Boyadjiev C, Popchristova E, Mazgalova J. Histomorphologic changes in keloids treated with Kenacort. J Trauma 1995; 38: 299-302
  CrossrefPubMedGoogle Scholar
• 20 Muneuchi G, Suzuki S, Onodera M. et al. 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 2006; 40: 111-116
  CrossrefPubMedGoogle Scholar
• 21 Atiyeh BS. Nonsurgical management of hypertrophic scars: evidence-based therapies, standard practices, and emerging methods. Aesthetic Plast Surg 2007; 31: 468-492
  CrossrefPubMedGoogle Scholar
• 22 Park TH, Seo SW, Kim JK. et al. Clinical characteristics of facial keloids treated with surgical excision followed by intra-and postoperative intralesional steroid injections. Aesthetic Plast Surg 2012; 36: 169-173
  CrossrefPubMedGoogle Scholar
• 23 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-S97
  CrossrefPubMedGoogle Scholar
• 24 Ogawa R, Akaishi S, Izumi M. Histologic analysis of keloids and hypertrophic scars. Ann Plast Surg 2009; 62: 104-105
  CrossrefPubMedGoogle Scholar
• 25 Alster TS, Williams CM. Treatment of keloid sternotomy scars with 585 nm flashlamp-pumped pulsed-dye laser. Lancet 1995; 345: 1198-1200
  CrossrefPubMedGoogle Scholar
• 26 Boutli-Kasapidou F, Tsakiri A, Anagnostou E. et al. Hypertrophic and keloidal scars: an approach to polytherapy. Int J Dermatol 2005; 44: 324-327
  CrossrefPubMedGoogle Scholar
• 27 Apikian M, Goodman G. Intralesional 5-fluorouracil in the treatment of keloid scars. Australas J Dermatol 2004; 45: 140-143
  CrossrefPubMedGoogle Scholar
• 28 Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg 1999; 25: 224-232
  CrossrefPubMedGoogle Scholar
• 29 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: 474-479
  CrossrefPubMedGoogle Scholar
• 30 Haurani MJ, Foreman K, Yang JJ. et al. 5-Fluorouracil treatment of problematic scars. Plast Reconstr Surg 2009; 123: 139-148
  CrossrefPubMedGoogle Scholar
• 31 Wang XQ, Liu YK, Wang ZY. et al. Antimitotic drug injections and radiotherapy: a review of the effectiveness of treatment for hypertrophic scars and keloids. Int J Low Extrem Wounds 2008; 7: 151-159
  CrossrefPubMedGoogle Scholar
• 32 Liu W, Wu X, Gao Z. et al. Remodelling of keloid tissue into normal-looking skin. J Plast Reconstr Aesthet Surg 2008; 61: 1553-1554
  CrossrefPubMedGoogle Scholar
• 33 Wu XL, Liu W, Cao YL. Clinical study on keloid treatment with intralesional injection of low concentration 5-fluorouracil. Zhonghua Zheng Xing Wai Ke Za Zhi 2006; 22: 44-46
  PubMedGoogle Scholar
• 34 Wang XQ, Liu YK, Qing C. et al. A review of the effectiveness of antimitotic drug injections for hypertrophic scars and keloids. Ann Plast Surg 2009; 63: 688-692
  CrossrefPubMedGoogle Scholar
• 35 Vivas AC, Tang JC, Maderal AD. et al. Hypertrophic scars and keloids, part 1: conventional treatments. Cosmet Dermatol 2012; 25: 309-316
  Google Scholar
• 36 Bodokh I, Brun P. Treatment of keloid with intralesional bleomycin. Ann Dermatol Venereol 1996; 123: 791-794
  PubMedGoogle Scholar
• 37 Espana A, Solano T, Quintanilla E. Bleomycin in the treatment of keloids and hypertrophic scars by multiple needle punctures. Dermatol Surg 2001; 27: 23-27
  PubMedGoogle Scholar
• 38 Aggarwal H, Saxena A, Lubana PS. et al. Treatment of keloids and hypertrophic scars using bleom. J Cosmet Dermatol 2008; 7: 43-49
  CrossrefPubMedGoogle Scholar
• 39 Saray Y, Gulec AT. Treatment of keloids and hypertrophic scars with dermojet injections of bleomycin: a preliminary study. Int J Dermatol 2005; 44: 777-784
  CrossrefPubMedGoogle Scholar
• 40 Naeini FF, Najafian J, Ahmadpour K. Bleomycin tattooing as a promising therapeutic modality in large keloids and hypertrophic scars. Dermatol Surg 2006; 32: 1023-1029
  PubMedGoogle Scholar
• 41 Templeton SF, Solomon AR, Swerlick RA. Intradermal bleomycin injections into normal human skin. A histopathologic and immunopathologic study. Arch Dermatol 1994; 130: 577-583
  CrossrefPubMedGoogle Scholar
• 42 Xu SJ, Teng JY, Xie J. et al. Comparison of the mechanisms of intralesional steroid, interferon or verapamil injection in the treatment of proliferative scars. Zhonghua Zheng Xing Wai Ke Za Zhi 2009; 25: 37-40
  PubMedGoogle Scholar
• 43 Tredget EE, Shankowsky HA, Pannu R. et al. Transforming growth factor-beta in thermally injured patients with hypertrophic scars: effects of interferon alpha-2b. Plast Reconstr Surg 1998; 102: 1317-1328
  CrossrefPubMedGoogle Scholar
• 44 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
  CrossrefPubMedGoogle Scholar
• 45 Larrabee Jr WF, East CA, Jaffe HS. et al. Intralesional interferon gamma treatment for keloids and hypertrophic scars. Arch Otolaryngol Head Neck Surg 1990; 116: 1159-1162
  CrossrefPubMedGoogle Scholar
• 46 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: 755-757
  CrossrefPubMedGoogle Scholar
• 47 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: 1039-1040
  CrossrefPubMedGoogle Scholar
• 48 al-Khawajah MM. Failure of interferon-alpha 2b in the treatment of mature keloids. Int J Dermatol 1996; 35: 515-517
  CrossrefPubMedGoogle Scholar
• 49 Jones GJ, Itri LM. Safety and tolerance of recombinant interferon alfa-2a (Roferon-A) in cancer patients. Cancer 1986; 57: 1709-1715
  CrossrefPubMedGoogle Scholar
• 50 Kelly AP. Medical and surgical therapies for keloids. Dermatol Ther 2004; 17: 212-218
  CrossrefPubMedGoogle Scholar
• 51 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
  CrossrefPubMedGoogle Scholar
• 52 Har-Shai Y, Amar M, Sabo E. Intralesional cryotherapy for enhancing the involution of hypertrophic scars and keloids. Plast Reconstr Surg 2003; 111: 1841-1852
  CrossrefPubMedGoogle Scholar
• 53 Zouboulis CC, Rosenberger AD, Forster T. et al. Modification of a device and its application for intralesional cryosurgery of old recalcitrant keloids. Arch Dermatol 2004; 140: 1293-1294
  PubMedGoogle Scholar
• 54 Tziotzios C, Profyris C, Sterling J. Cutaneous scarring: Pathophysiology, molecular mechanisms, and scar reduction therapeutics Part II. Strategies to reduce scar formation after dermatologic procedures. J Am Acad Dermatol 2012; 66: 13-24
  CrossrefPubMedGoogle Scholar
• 55 Copcu E, Sivrioglu N, Oztan Y. Combination of surgery and intralesional verapamil injection in the treatment of the keloid. J Burn Care Rehabil 2004; 25: 1-7
  CrossrefPubMedGoogle Scholar
• 56 Giugliano G, Pasquali D, Notaro A. et al. Verapamil inhibits interleukin-6 and vascular endothelial growth factor production in primary cultures of keloid fibroblasts. Br J Plast Surg 2003; 56: 804-809
  CrossrefPubMedGoogle Scholar
• 57 Yang JY, Huang CY. The effect of combined steroid and calcium channel blocker injection on human hypertrophic scars in animal model: a new strategy for the treatment of hypertrophic scars. Dermatol Surg 2010; 36: 1942-1949
  CrossrefPubMedGoogle Scholar
• 58 Lawrence WT. Treatment of earlobe keloids with surgery plus adjuvant intralesional verapamil and pressure earrings. Ann Plast Surg 1996; 37: 167-169
  CrossrefPubMedGoogle Scholar
• 59 D'Andrea F, Brongo S, Ferraro G. et al. Prevention and treatment of keloids with intralesional verapamil. Dermatology 2002; 204: 60-62
  CrossrefPubMedGoogle Scholar
• 60 Margaret Shanthi FX, Ernest K, Dhanraj P. Comparison of intralesional verapamil with intralesional triamcinolone in the treatment of hypertrophic scars and keloids. Indian J Dermatol Venereol Leprol 2008; 74: 343-348
  CrossrefPubMedGoogle Scholar
• 61 Liechty KW, Kim HB, Adzick NS. et al. Fetal wound repair results in scar formation in interleukin-10-deficient mice in a syngeneic murine model of scarless fetal wound repair. J Pediatr Surg 2000; 35: 866-872
  CrossrefPubMedGoogle Scholar
• 62 Hanasono MM, Kita M, Mikulec AA. et al. Autocrine growth factor production by fetal, keloid, and normal dermal fibroblasts. Arch Facial Plast Surg 2003; 5: 26-30
  CrossrefPubMedGoogle Scholar
• 63 Liu RK, Li CH, Zou SJ. Reducing scar formation after lip repair by injecting botulinum toxin. Plast Reconstr Surg 2010; 125: 1573-1574
  PubMedGoogle Scholar
• 64 Viera MH, Amini S, Valins W. et al. Innovative therapies in the treatment of keloids and hypertrophic scars. J Clin Aesthet Dermatol 2010; 3: 20-26
  PubMedGoogle Scholar
• 65 Gassner HG, Brissett AE, Otley CC. et al. Botulinum toxin to improve facial wound healing: a prospective, blinded, placebo-controlled study. Mayo Clin Proc 2006; 81: 1023-1028
  CrossrefPubMedGoogle Scholar
• 66 Zhibo X, Miaobo Z. Botulinum toxin type A affects cell cycle distribution of fibroblasts derived from hypertrophic scar. J Plast Reconstr Aesthet Surg 2008; 61: 1128-1129
  CrossrefPubMedGoogle Scholar
• 67 Zhibo X, Miaobo Z. Intralesional botulinum toxin type A injection as a new treatment measure for keloids. Plast Reconstr Surg 2009; 124: 275e-277e
  CrossrefPubMedGoogle Scholar
• 68 Xiao Z, Zhang F, Lin W. et al. Effect of botulinum toxin type A on transforming growth factor beta1 in fibroblasts derived from hypertrophic scar: a preliminary report. Aesthetic Plast Surg 2010; 34: 424-427
  CrossrefPubMedGoogle Scholar
• 69 Xiao Z, Zhang F, Cui Z. Treatment of hypertrophic scars with intralesional botulinum toxin type A injections: a preliminary report. Aesthetic Plast Surg 2009; 33: 409-412
  CrossrefPubMedGoogle Scholar
• 70 Haubner F, Leyh M, Ohmann E. et al. Effects of botulinum toxin A on patient-specific keloid fibroblasts in vitro. Laryngoscope 2014; 124: 1344-1351
  CrossrefPubMedGoogle Scholar
• 71 Maderal AD, Tang JC, Vivas AC. et al. Hypertrophic scars and keloids, part 2: newer and investigational therapies. Cosmet Dermatol 2012; 25: 373-379
  Google Scholar