Triamcinolone acetonide intralesional injection for the treatment of keloid scars: patient selection and perspectives

Marco Morelli Coppola, Rosa Salzillo, Francesco Segreto, Paolo Persichetti, Marco Morelli Coppola, Rosa Salzillo, Francesco Segreto, Paolo Persichetti

Abstract

Keloids are pathological scars presenting as nodular lesions that extend beyond the area of injury. They do not spontaneously regress, often continuing to grow over time. The abnormal wound-healing process underlying keloid formation results from the lack of control mechanisms self-regulating cell proliferation and tissue repair. Keloids may lead to cosmetic disfigurement and functional impairment and affect the quality of life. Although several treatments were reported in the literature, no universally effective therapy was found to date. The most common approach is intralesional corticosteroid injection alone or in combination with other treatment modalities. Triamcinolone acetonide (TAC) is the most commonly used intralesional corticosteroid. The aim of this article was to review the use of TAC, alone or in combination, in the treatment of keloid scars. The response to corticosteroid injection alone is variable with 50-100% regression and a recurrence rate of 33% and 50% after 1 and 5 years, respectively. Compared to verapamil, TAC showed a faster and more effective response even though with a higher complication rate. TAC combined with verapamil was proved to be effective with statistically significant overall improvements of scars over time and long-term stable results. TAC and 5-fluorouracil (5-FU) intralesional injections were found to achieve comparable outcomes when administered alone, although 5-FU was more frequently associated with side effects. Conversely, the combination of 5-FU and TAC was more effective and showed fewer undesirable effects compared to TAC or 5-FU alone. Several kinds of laser treatments were reported to address keloids; however, laser therapy alone was burdened with a high recurrence rate. Better results were described by combining CO2, pulsed-dye or Nd: YAG lasers with TAC intralesional injections. Further options such as needle-less intraepidermal drug delivery are being explored, but more studies are needed to establish safety, feasibility and effectiveness of this approach.

Keywords: intralesional corticosteroid injections; keloids; scars.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

References

    1. Kraeva E, Ho D, Jagdeo J. Successful treatment of keloid with fractionated carbon dioxide (CO2) laser and laser-assisted drug delivery for triamcinolone acetonide ointment in an African-American man. J Drugs Dermatol. 2017;16(9):925–927.
    1. Robles DT, Berg D. Abnormal wound healing: keloids. Clin Dermatol. 2007;25(1):26–32.
    1. Mustoe TA, Cooter RD, Gold MH, et al. International Advisory Panel on Scar Management International clinical recommendations on scar management. Plast Reconstr Surg. 2002;110(2):560–571.
    1. Gao Z, Wang Z, Shi Y, et al. Modulation of collagen synthesis in keloid fibroblasts by silencing Smad2 with siRNA. Plast Reconstr Surg. 2006;118(6):1328–1337.
    1. Jumper N, Paus R, Bayat A. Functional histopathology of keloid disease. Histol Histopathol. 2015;30(9):1033–1057.
    1. Wu WS, Wang FS, Yang KD, Huang CC, Kuo YR. Dexamethasone induction of keloid regression through effective suppression of VEGF expression and keloid fibroblast proliferation. J Invest Dermatol. 2006;126(6):1264–1271.
    1. Salem A, Assaf M, Helmy A, et al. Role of vascular endothelial growth factor in keloids: a clinicopathologic study. Int J Dermatol. 2009;48(10):1071–1077.
    1. Bayat A, Arscott G, Ollier WE, Ferguson MW, McGrouther DA. “Aggressive keloid”: a severe variant of familial keloid scarring. J R Soc Med. 2003;96(11):554–555.
    1. Robles DT, Moore E, Draznin M, Berg D. Keloids: pathophysiology and management. Dermatol Online J. 2007;13(3):9.
    1. Saed GM, Ladin D, Olson J, Han X, Hou Z, Fivenson D. Analysis of p53 gene mutations in keloids using polymerase chain reaction-based single-strand conformational polymorphism and DNA sequencing. Arch Dermatol. 1998;134(8):963–967.
    1. Tanaka A, Hatoko M, Tada H, Iioka H, Niitsuma K, Miyagawa S. Expression of p53 family in scars. J Dermatol Sci. 2004;34(1):17–24.
    1. Shaffer JJ, Taylor SC, Cook-Bolden F. Keloidal scars: a review with a critical look at therapeutic options. J Am Acad Dermatol. 2002;46(2 suppl Understanding):S63–S97.
    1. Butler PD, Longaker MT, Yang GP. Current progress in keloid research and treatment. J Am Coll Surg. 2008;206(4):731–741.
    1. Al-Attar A, Mess S, Thomassen JM, Kauffman CL, Davison SP. Keloid pathogenesis and treatment. Plast Reconstr Surg. 2006;117(1):286–300.
    1. Akaishi S, Ogawa R, Hyakusoku H. Keloid and hypertrophic scar: neurogenic inflammation hypotheses. Med Hypotheses. 2008;71(1):32–38.
    1. Wong T-S, Li JZ-H, Chen S, Chan JY-W, Gao W. The efficacy of triamcinolone acetonide in keloid treatment: a systematic review and meta-analysis. Front Med (Lausanne) 2016;3:71.
    1. Younai S, Nichter LS, Wellisz T, Reinisch J, Nimni ME, Tuan TL. Modulation of collagen synthesis by transforming growth factor-beta in keloid and hypertrophic scar fibroblasts. Ann Plast Surg. 1994;33(2):148–151.
    1. Wang X, Smith P, Pu LL, Kim YJ, Ko F, Robson MC. Exogenous transforming growth factor beta(2) modulates collagen I and collagen III synthesis in proliferative scar xenografts in nude rats. J Surg Res. 1999;87(2):194–200.
    1. Oriente A, Fedarko NS, Pacocha SE, Huang SK, Lichtenstein LM, Essayan DM. Interleukin-13 modulates collagen homeostasis in human skin and keloid fibroblasts. J Pharmacol Exp Ther. 2000;292(3):988–994.
    1. Chau CH, Clavijo CA, Deng HT, et al. Etk/Bmx mediates expression of stress-induced adaptive genes VEGF, PAI-1, and iNOS via multiple signaling cascades in different cell systems. Am J Physiol Cell Physiol. 2005;289(2):C444–C454.
    1. 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(8):804–809.
    1. Trisliana Perdanasari A, Lazzeri D, Su W, et al. Recent developments in the use of intralesional injections keloid treatment. Arch Plast Surg. 2014;41(6):620–629.
    1. Roques C, Tèot L. The use of corticosteroids to treat keloids: a review. Int J Low Extrem Wounds. 2008;7(3):137–145.
    1. 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):362–368.
    1. Carroll LA, Hanasono MM, Mikulec AA, Kita M, Koch RJ. Triamcinolone stimulates bFGF production and inhibits TGF-beta1 production by human dermal fibroblasts. Dermatol Surg. 2002;28(8):704–709.
    1. 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. 2006;40(2):111–116.
    1. Rahban S, Garner W. Fibroproliferative scars. Clin Plast Surg. 2003;30(1):77–89.
    1. 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.
    1. Acosta S, Ureta E, Yanez R, Oliva N, Searle S, Guerra C. Effectiveness of intralesional triamcinolone in the treatment of keloids in children. Pediatr Dermatol. 2016;33(1):75–79.
    1. Finken MJ, Mul D. Cushing’s syndrome and adrenal insufficiency after intradermal triamcinolone acetonide for keloid scars. Eur J Pediatr. 2010;169(9):1147–1149.
    1. Kumar S, Singh RJ, Reed AM, Lteif AN. Cushing’s syndrome after intra-articular and intradermal administration of triamcinolone acetonide in three pediatric patients. Pediatrics. 2004;113(6):1820–1824.
    1. Liu MF, Yencha M. Cushing’s syndrome secondary to intralesional steroid injections of multiple keloid scars. Otolaryngol Head Neck Surg. 2006;135(6):960–961.
    1. Teelucksingh S, Balkaran B, Ganeshmoorthi A, Arthur P. Prolonged childhood Cushing’s syndrome secondary to intralesional triamcinolone acetonide. Ann Trop Paediatr. 2002;22(1):89–91.
    1. Epstein E. Triamcinolone and keloids. West J Med. 1980;133(3):257–258.
    1. Vo A, Doumit M, Rockwell G. The biomechanics and optimization of the needle-syringe system for injecting triamcinolone acetonide into keloids. J Med Eng. 2016;2016:8. 5162394.
    1. 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.
    1. Boggio RF, Freitas VM, Cassiola FM, Urabayashi M, Machado-Santelli GM. Effect of a calcium-channel blocker (verapamil) on the morphology, cytoskeleton and collagenase activity of human skin fibroblasts. Burns. 2011;37(4):616–625.
    1. Ahuja RB, Chatterjee P. Comparative efficacy of intralesional verapamil hydrochloride and triamcinolone acetonide in hypertrophic scars and keloids. Burns. 2014;40(4):583–588.
    1. Danielsen PL, Rea SM, Wood FM, et al. Verapamil is less effective than triamcinolone for prevention of keloid scar recurrence after excision in a randomized controlled trial. Acta Derm Venereol. 2016;96(6):774–778.
    1. Kant SB, van den Kerckhove E, Colla C, Tuinder S, van der Hulst RRWJ, Piatkowski de Grzymala AA. A new treatment of hypertrophic and keloid scars with combined triamcinolone and verapamil: a retrospective study. Eur J Plast Surg. 2018;41(1):69–80.
    1. Ghoshal K, Jacob ST. An alternative molecular mechanism of action of 5-fluorouracil, a potent anti-cancer drug. Biochem Pharmacol. 1997;53(11):1569–1575.
    1. Blumenkranz MS, Claflin A, Hajek AS. Selection of the therapeutic agents for intraocular proliferative disease: cell culture evaluation. Arch Ophthalmol. 1984;102(4):598–604.
    1. Wendling J, Marchand A, Mauviel A, Verrecchia F. 5-Fluorouracil blocks transforming growth factor-beta-induced alpha 2 type I collagen gene (COL1A2) expression in human fibroblasts via c-Jun NH2-terminal kinase⁄activator protein-1 activation. Mol Pharmacol. 2003;64(3):707–713.
    1. Saha AK, Mukhopadhyay M. A comparative clinical study on role of 5-flurouracil versus triamcinolone in the treatment of keloids. Indian J Surg. 2012;74(4):326–329.
    1. 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(1):104–109.
    1. Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg. 1999;25(3):224–232.
    1. Khan MA, Bashir MM, Khan FA. Intralesional triamcinolone alone and in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars. J Pak Med Assoc. 2014;64(9):1003–1007.
    1. 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. 2009;29(1):40–46.
    1. Gupta S, Sharma VK. Standard guidelines of care: keloids and hypertrophic scars. Indian J Dermatol Venereol Leprol. 2011;77(1):94–100.
    1. Nanda S, Reddy BS. Intralesional 5-fluorouracil as a treatment modality of keloids. Dermatol Surg. 2004;30(1):54–56. discussion 56–57.
    1. Apikian M, Goodman G. Intralesional 5-fluorouracil in the treatment of keloid scars. Australas J Dermatol. 2004;45(2):140–143.
    1. Mamalis AD, Lev-Tov H, Nguyen DH, Jagdeo JR. Laser and light-based treatment of Keloids – a review. J Eur Acad Dermatol Venereol. 2014;28(6):689–699.
    1. Bass LS, Moazami N, Pocsidio J, Oz MC, LoGerfo P, Treat MR. Changes in type I collagen following laser welding. Lasers Surg Med. 1992;12(5):500–505.
    1. Schober R, Urlich F, Sander T, Durselen H, Hessel S. Laser induced alteration of collagen substructure allows microsurgical tissue welding. Science. 1986;232(4756):1421–1422.
    1. Dierickx C, Goldmann MP, Fitzpatrick RE. Laser treatment of erythematous/hypertrophic and pigmented scars in 26 patients. Plast Reconstr Surg. 1995;95(1):84–90. discussion 91–92.
    1. Nouri K, Vidulich K, Rivas MP. Lasers for scars: a review. J Cosmet Dermatol. 2006;5(1):14–22.
    1. Driscoll B. Treating keloids with carbon dioxide lasers. Arch Otolaryngol Head Neck Surg. 2001;127(9):1145.
    1. Stern JC, Lucente FE. Carbon dioxide laser excision of ear lobule keloid. Arch Otolaryngol Head Neck Surg. 1989;115(9):1107–1111.
    1. Apfelberg DB, Maser MR, White DN, Lash H. Failure of carbon dioxide laser excision of keloids. Lasers Surg Med. 1989;9(4):382–388.
    1. Norris JE. The effect of carbon dioxide laser surgery on the recurrence of keloids. Plast Reconstr Surg. 1991;87(1):44–49. discussion 50–53.
    1. Verma KK, Garg T, Raj T. Carbon dioxide laser for the treatment of keloids. Indian J Dermatol. 2002;47(2):91–93.
    1. Kumar K, Kapoor BS, Rai P, Shukla HS. In situ irradiation of keloid scars with Nd:YAG laser. J Wound Care. 2000;9(5):213–215.
    1. Rossi A, Lu R, Frey MK, Kubota T, Smith LA, Perez M. The use of the 300 microsecond 1064 nm Nd:YAG laser in the treatment of keloids. J Drugs Dermatol. 2013;12(11):1256–1262.
    1. Kassab AN, El Kharbotly A. Management of ear lobule keloids using 980-nm diode laser. Eur Arch Otorhinolaryngol. 2012;269(2):419–423.
    1. Singhal M, Del Río-Sancho S, Sonaje K, Kalia YN. Fractional laser ablation for the cutaneous delivery of triamcinolone acetonide from cryomilled polymeric microparticles: creating intraepidermal drug depots. Mol Pharm. 2016;13(2):500–511.
    1. Perkins K, Davey RB, Walis KA. Silicone gel: a new treatment for burns and contractures. Burns. 1982;9:406–410.
    1. Gold MH. A controlled clinical trial of topical silicone gel sheeting in the treatment of hypertrophic scars and keloids. J Am Acad Dermatol. 1994;30(3):506–507.
    1. Wood LC, Elias PM, Sequeira-Martin SM, Carl G, Feingold KR. Occlusion lowers cytokine mRNA levels in essential fatty acid-deficient and normal mouse epidermis, but not after acute barrier disruption. J Invest Dermatol. 1994;103(6):834–838.
    1. Duncan MR, Beman B. Stimulation of connective tissue related biosynthetic functions of cultured human adult dermal fibroblasts by recombinant human interleukin 6. J Invest Dermatol. 1991;97(4):686–692.
    1. Fulton JE., Jr Silicone gel sheeting for the prevention and management of evolving hypertrophic and keloid scars. Dermatol Surg. 1995;21(11):947–951.
    1. Katz BE. Silicone gel sheeting in scar therapy. Cutis. 1995;56(1):65–67.
    1. Tan E, Chua S, Lim J. Topical silicone gel sheet versus intralesional injections of triamcinolone acetonide in the treatment of keloids – a patient-controlled comparative clinical trial. J Dermatol Treat. 1999;10(4):251–254.
    1. Sproat JE, Dalcin A, Weitauer N, Roberts RS. Hypertrophic sternal scars: silicone gel sheet versus Kenalog injection treatment. Plast Reconstr Surg. 1992;90(6):988–992.
    1. Kelemen O, Kollár L. Current methods of treatment and prevention of pathologic scars. Magy Seb. 2007;60(2):63–70.
    1. Yamawaki S, Naitoh M, Ishiko T, Muneuchi G, Suzuki S. Keloids can be forced into remission with surgical excision and radiation, followed by adjuvant therapy. Ann Plast Surg. 2011;67(4):402–406.
    1. Kuo YR, Wu WS, Jeng SF, et al. Activation of ERK and p38 kinase mediated keloid fibroblast apoptosis after flashlamp pulsed-dye laser treatment. Lasers Surg Med. 2005;36(1):31–37.
    1. Bodokh I, Brun P. Treatment of keloid with intralesional bleomycin (French) Ann Dermatol Venereol. 1996;123(12):791–794.
    1. 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.
    1. Espana A, Solano T, Quintanilla E. Bleomycin in the treatment of keloids and hypertrophic scars by multiple needle punctures. Dermatol Surg. 2001;27(1):23–27.
    1. Farahnaz FN, Jamshid N. Bleomycin tattooing as a promising therapeutic modality in large keloids and hypertrophic scars. Dermatol Surg. 2006;32(8):1023–1029. discussion 1029–1030.
    1. 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.
    1. Hackert I, Aschoff R, Sebastian G. The treatment of keloids. Hautarzt. 2003;54(10):1003–1015.
    1. Savion Y, Sela M, Sharon-Buller A. Pressure earring as an adjunct to surgical removal of earlobe keloids. Dermatol Surg. 2009;35(3):490–492.
    1. Akoz T, Gideroglu K, Akan M. Combination of different techniques for the treatment of earlobe keloids. Aesthetic Plast Surg. 2002;26(3):184–188.
    1. Chrisostomidis C, Konofaos P, Chrisostomidis G, et al. Management of external ear keloids using form-pressure therapy. Clin Exp Dermatol. 2008;33(3):273–275.
    1. Niessen FB, Spauwen PH, Schalkwijk J, Kon M. On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg. 1999;104(5):1435–1458.
    1. Carvalhaes SM, Petroianu A, Ferreira MA, de Barros VM, Lopes RV. Assessment of the treatment of earlobe keloids with triamcinolone injections, surgical resection, and local pressure. Rev Col Bras Cir. 2015;42(1):9–13.
    1. Bran GM, Brom J, Hörmann K, Stuck BA. Auricular keloids: combined therapy with a new pressure device. Arch Facial Plast Surg. 2012;14(1):20–26.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit