Keloids – an extensive review in the light of recent literature

Sajad Ahmad Salati

Abstract


Keloids are benign but challenging wound healing ailments that manifest clinically in variable and diverse forms. Patients present with one or very few small slow growing lesions on one extreme or else with numerous and very large, life-changing and debilitating lesions covering significant portion of their skin. The keloids require a comprehensive treatment plan and approach and most lesions need more than one modality of treatment. Proper assessment requires accurate quantification of the disease’s impact on the patients in terms of physical symptoms, quality of life and psychosocial status. This review focuses on the natural history, clinical features and therapeutic update of keloids in the light of the recent literature

Keywords


Keloid, hypertrophic scars, fibroblast, collagen, treatment, prevention, biology

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References


Pruimboom T, Scheltinga M.R. Keloid Formation due to Repetitive Mammographies. Case Rep Dermatol 2018;10:257–62

Bleasdale B, Finnegan S, Murray K, Kelly S, Percival SL. The Use of Silicone Adhesives for Scar Reduction. Adv Wound Care (New Rochelle). 2015; 4(7):422-30.

Andrews JP, Marttala J, Macarak E, Rosenbloom J, Uitto J. Keloids: The paradigm of skin fibrosis - Pathomechanisms and treatment. Matrix Biol. 2016. 51:37-46

Halim A S, Emami A Salahshourifar I, Kannan T P .Keloid Scarring: Understanding the Genetic Basis -Advances, and Prospects. Arch Plast Surg 2012;39:184-9

Sidgwick GP, Bayat A. Extracellular matrix molecules implicated in hypertrophic and keloid scarring. J Eur Acad Dermatol Venereol 2012; 26:41-52.

Sen CK, Roy S. Oxygenation state as a driver of myofibroblast differentiation and wound contraction: Hypoxia impairs wound closure. J Investig Dermatol 2010; 130:2701-3.

Touchi R, Ueda K, Kurokawa N, Tsuji M. Central regions of keloids are severely ischaemic. J Plast Reconstr Aesthet Surg. 2016; 69(2): e35-41.

Zhao B, Guan H, Liu JQ, Zheng Z, Zhou Q, Zhang J, Su LL, Hu DH. Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway. Int. J.Mol. Med. 2017; 39: 153-9.

Okuno R, Ito Y, Eid N, Otsuki Y, Kondo Y, Ueda K. Upregulation of autophagy and glycolysis markers in keloid hypoxic-zone fibroblasts: Morphological characteristics and implications. Histol Histopathol. 2018; 33(10): 1075-87.

Mogili NS, Krishnaswamy VR, Jayaraman M, Rajaram R, Venkatraman A, Korrapati PS. Altered angiogenic balance in keloids: a key to therapeutic intervention. Transl Res. 2012; 159(3): 182-9.

Zhou HM, Wang J, Elliott C, Wen W, Hamilton DW, Conway SJ. Spatiotemporal expression of periostin during skin development and incisional wound healing: Lessons for human fibrotic scar formation. J. Cell Commun. Signal. 2010; 4: 99-107.

Zhang Z, Nie F, Chen X, Qin Z, Kang C, Chen B, Ma J, Pan B, Ma Y. Upregulated periostin promotes angiogenesis in keloids through activation of the ERK 1/2 and focal adhesion kinase pathways, as well as the upregulated expression of VEGF and angiopoietin-1. Mol Med Rep. 2015; 11(2): 857-64.

Luan Y, Liu Y, Liu C, Lin Q, He F, Dong X, Xiao Z. Serum miRNAs Signature Plays an Important Role in Keloid Disease. Curr. Mol. Med. 2016; 16: 504-14.

Wu Z Y, Lu L, Liang J, Guo XR, Zhang PH, Luo SJ. Keloid microRNA expression analysis and the influence of miR-199a-5p on the proliferation of keloid fibroblasts. Genet. Mol. Res. 2014; 13: 2727-38.

Kashiyama K, Mitsutake N, Matsuse M, Ogi T, Saenko VA, Ujifuku K, Utani A, Hirano A, Yamashita S. miR-196a downregulation increases the expression of type I and III collagens in keloid fibroblasts. J. Investig. Dermatol. 2012; 132: 1597-1604.

Mukhopadhyay A, Wong M Y, Chan SY, Do DV, Khoo A, Ong CT, Cheong H H, Lim I J, Phan TT. Syndecan-2 and Decorin: Proteoglycans with a difference—Implications in keloid pathogenesis. J. Trauma 2010; 68: 999-1008.

Zhang Z, Garron T M, Li X J, Liu Y, Zhang X, Li YY, Xu W S. Recombinant human decorin inhibits TGF- β 1-induced contraction of collagen lattice by hypertrophic scar fibroblasts. Burns 2009; 35: 527–37.

Dienus K, Bayat A, Gilmore BF, Seifert O. Increased expression of fibroblast activation protein-alpha in keloid fibroblasts: implications for development of a novel treatment option. Arch Dermatol Res. 2010; 302(10): 725-31.

Luo L, Li J, Liu H, Jian X, Zou Q, Zhao Q, Le Q, Chen H, Gao X, He C. Adiponectin is involved in connective tissue Growth Factor-Induced proliferation, migration and overproduction of the extracellular matrix in keloid fibroblasts. Int J Mol Sci. 2017; 18(5): 1044.

Sato M. Upregulation of the Wnt/ beta-catenin pathway induced by transforming growth factor-beta in hypertrophic scars and keloids. Acta Derm Venereol. 2006; 86(4):300-7.

Marneros AG, Krieg T. Keloids--clinical diagnosis, pathogenesis, and treatment options. J Dtsch Dermatol Ges. 2004; 2(11):905-13.

Lin-Hai Xie, Sen-Kai Li, Qiang Li. Combined treatment of penile keloid: a troublesome complication after circumcision. Asian J Androl. 2013; 15(4): 575-6.

Jung JJ, Wojno TH, Grossniklaus HE. Giant corneal keloid: case report and review of the literature. Cornea. 2010; 29(12):1455-8.

Birge O, Akbas M, Ozbey EG, Adiyeke M. Clitoral keloids after female genital mutilation/cutting. Turk J Obstet Gynecol. 2016; 13(3):154-7.

Pruimboom T, Scheltinga MR. Keloid Formation due to Repetitive Mammographies. Case Rep Dermatol. 2018; 10(3):257-62.

Tiong WHC, Basiron NH: Challenging diagnosis of a rare case of spontaneous keloid scar. J Med Cases 2014; 5:466-9.

Jfri A, Rajeh N, Karkashan E. A case of multiple spontaneous keloid scars. Case Rep Dermatol 2015;7:156-60.

Jfri A, Alajmi A. Spontaneous Keloids: A Literature Review. Dermatology. 2018; 234(3-4):127-30.

Viera MH, Vivas AC, Berman B. Update on Keloid Management: Clinical and Basic Science Advances. Adv Wound Care (New Rochelle). 2012; 1(5):200-6.

Mari W, Alsabri SG, Tabal N, Younes S, Sherif A, Simman R. Novel Insights on Understanding of Keloid Scar: article Review. J Am Coll Clin Wound Spec. 2016; 7(1-3):1-7.

Lee SS, Yosipovitch G, Chan YH, Goh CL. Pruritus, pain, and small nerve fiber function in keloids: a controlled study. J Am Acad Dermatol 2004; 51:1002-6.

Kakar A K , Shahzad M , Haroon T S . Keloids: clinical features and management. Part I. J Pak Assoc Dermatol 2006; 16:98-103.

Olaitan PB.Keloids: assessment of effects and psychosocial-impacts on subjects in a black African population. Ind J Dermatol Venereol Leprol. 2009; 75(4):368-72.

Butler PD, Longaker MT, Yang GP. Current progress in keloid research and treatment. J Am Coll Surg 2008; 206(4):731-41.

Ogawa R, Akaishi S, Hyakusoku H. Differential and exclusive diagnosis of diseases that resemble keloids and hypertrophic scars. Ann Plast Surg 2009; 62(6):660-4.

Francesconi VA, Klein AP, Santos AP, Ramasawmy R, Francesconi F. Lobomycosis: epidemiology, clinical presentation, and management options. Ther Clin Risk Manag 2014; 10:851-60.

Mehta V, Balachandran C. Persistent nodular contact dermatitis to gold: case report of two cases. Indian J Dermatol Venereol Leprol. 2010; 76(4):397-9.

Casper C, Groth W, Hunzelmann N. Sarcoidal-type allergic contact granuloma: a rare complication of ear piercing. Am J Dermatopathol. 2004; 26(1):59-62.

Marsidi N, Beijnen JH, van Zuuren EJ. Palladium-induced granulomas analysed with inductively coupled plasma mass spectrometry. Contact Dermatitis. 2018; 79(1):41-2.

Liu KL, Tsai WC, Lee CH. Cutaneous sarcoidosis: A retrospective case series and a hospital-based case-control study in Taiwan. Medicine (Baltimore). 2017; 96(40):e8158.

Chaudhuri S, Sarkar D, Mukerji R. Diagnosis and management of atypical mycobacterial infection after laparoscopic surgery. Ind J Surg. 2010; 72(6):438-42.

Secil M, Mungan U, Yorukoglu K. Suture granuloma after orchiectomy: sonography, doppler and elastography features. Int Braz J Urol. 2015; 41(4):813-6.

Glass DA. Current Understanding of the Genetic Causes of Keloid Formation. J Investig Dermatol Symp Proc. 2017; 18(2):S50-3.

Marneros AG, Norris JE, Olsen BR, Reichenberger E. Clinical genetics of familial keloids. Arch Dermatol. 2001; 137(11):1429-34.

Chen Y, Gao JH, Liu XJ, Yan X, Song M. Characteristics of occurrence for Han Chinese familial keloids. Burns. 2006; 32(8):1052-9.

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.

Brown JJ, Ollier WE, Thomson W, Bayat A. Positive association of HLA-DRB1*15 with keloid disease in Caucasians. Int J Immunogenet. 2008; 35(4-5):303-7.

Brown JJ, Ollier WE, Arscott G, Bayat A. Association of HLA-DRB1 and keloid disease in an Afro-Caribbean population. Clin Exp Dermatol. 2010; 35(3):305-10.

Lu WS, Zhang WY, Li Y, Wang ZX, Zuo XB, Cai LQ, Zhu F, Wang JF, Sun LD, Zhang XJ, Yang S. Association of HLA-DRB1 alleles with keloids in Chinese Han individuals. Tissue Antigens. 2010; 76(4):276-81.

Van de Kar AL, Houge G, Shaw AC, De Jong D, van Belzen MJ, Peters DJ, Hennekam RC. Keloids in Rubinstein-Taybi syndrome: a clinical study. Br J Dermatol. 2014; 171(3):615-21.

Bijlard E, Steltenpool S, Niessen FB. Intralesional 5-fluorouracil in keloid treatment: a systematic review. Acta Derm Venereol. 2015; 95(7):778-82.

Kontochristopoulos G, Stefanaki C, Panagiotopoulos A, Stefanaki K, Argyrakos T, Petridis A, Katsambas A. 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.

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):1264-71.

Ogawa, R. Keloid and Hypertrophic Scars Are the Result of Chronic Inflammation in the Reticular Dermis. Int J Mol Sci 2017; 18: 606.

Syed F, Singh S, Bayat A. Superior effect of combination vs. single steroid therapy in keloid disease: a comparative in vitro analysis of glucocorticoids. Wound Repair Regen. 2013; 21(1):88-102.

Tosa M, Murakami M, Hyakusoku H. Effect of lidocaine tape on pain during intralesional injection of triamcinolone acetonide for the treatment of keloid. J Nippon Med Sch. 2009; 76(1):9-12.

Wang X, Wu X, Liu K, Wang X, Wu X, Liu K, Xia L, Lin X, Liu W, Gao Z. Topical cryoanesthesia for the relief of pain caused by steroid injections used to treat hypertrophic scars and keloids. Medicine (Baltimore). 2017; 96(43): e8353.

Park KY, Lee Y, Hong JY, Chung WS, Kim MN, Kim BJ. Vibration anesthesia for pain reduction during intralesional steroid injection for keloid treatment. Dermatol Surg. 2017; 43(5):724-7.

Usanakornkul A, Burusapat C. A Topical Anesthetic and Lidocaine Mixture for Pain Relief During Keloid Treatment: A Double-Blind, Randomized Controlled Trial. Dermatol Surg. 2017; 43(1):66-73.

Park TH, Seo SW, Kim JK, Chang CH. Clinical characteristics of facial keloids treated with surgical excision followed by intra- and postoperative intralesional steroid injections. Aesthetic Plast Surg. 2012; 36(1):169-73.

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; 29:40-6.

Wang XQ, Liu YK, Qing C, Lu SL. A review of the effectiveness of antimitotic drug injections for hypertrophic scars and keloids. Ann Plast Surg. 2009; 63:688-92.

Ogawa R, Akaishi S, Huang C, Dohi T, Aoki M, Omori Y, Koike S, Kobe K, Akimoto M, Hyakusoku H. Clinical applications of basic research that shows reducing skin tension could prevent and treat abnormal scarring: The importance of fascial/subcutaneous tensile reduction sutures and flap surgery for keloid and hypertrophic scar reconstruction. J Nippon Med Sch 2011; 78: 68–76.

Zouboulis CC, Rosenberger AD, Forster T, Beller G, Kratzsch M, Felsenberg D. Modification of a device and its application for intralesional cryosurgery of old recalcitrant keloids. Arch Dermatol. 2004;140:1293-4.

Har-Shai Y, Amar M, Sabo E. Intralesional cryotherapy for enhancing the involution of hypertrophic scars and keloids. Plast Reconstr Surg. 2003; 111(6):1841-52.

van Leeuwen MC, Bulstra AE, Ket JC, Ritt MJ, van Leeuwen PA, Niessen FB. Intralesional Cryotherapy for the treatment of keloid scars: Evaluating Effectiveness. Plast Reconstr Surg Glob Open. 2015; 3(6):e437.

O'Boyle CP, Shayan-Arani H, Hamada MW. Intralesional cryotherapy for hypertrophic scars and keloids: a review. Scars Burn Heal. 2017; 3:2059513117702162.

Van Leeuwen MC, Bulstra AE, Van Leeuwen PA, Niessen FB. A new argon gas-based device for the treatment of keloid scars with the use of intralesional cryotherapy. J Plast Reconstr Aesthet Surg. 2014; 67(12):1703-10.

Ji J, Tian Y, Zhu Y Q, Zhang LY, Ji SJ, Huan J, Zhou X Z, Cao JP. Ionizing irradiation inhibits keloid fibroblast cell proliferation and induces premature cellular senescence. J Dermatol 2015; 42: 56-63.

Keeling BH, Whitsitt J, Liu A, Dunnick CA. Keloid removal by shave excision with adjuvant external beam radiation therapy. Dermatol Surg 2015; 41: 989-92.

Shen J, Lian X, Sun Y, Wang X, Hu K, Hou X, Sun S, Yan J, Yu L, Sun X, Li W, Wang X, Guan Q, Pang T, Zhang F. Hypofractionated electron-beam radiation therapy for keloids: retrospective study of 568 cases with 834 lesions. J Radiat Res. 2015; 56(5):811-7.

Vivante H , Salgueiro M J, Ughetti R, Nicolini J, Zubillaga M. 32P-patch contact brachyradiotherapy in the management of recalcitrant keloids and hypertrophic scars. Indian J. Dermatol Venereol Leprol 2007; 73:336-9.

Yan DJ, Yang HP. Efficacy of CO2 laser combined with 32P-patch contact brachyradiotherapy for the treatment of keloids. Zhonghua Zheng Xing Wai Ke Za Zhi. 2012; 28(4):282-4.

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):689-99.

Zhu R, Yue B, Yang Q, Ma Y, Huang G, Guan M, Avram MM, Lu Z. The effect of 595 nm pulsed dye laser on connective tissue growth factor (CTGF) expression in cultured keloid fibroblasts. Lasers Surg Med. 2015; 47(2):203-9.

Yang Q, Ma Y, Zhu R, Huang G, Guan M, Avram MM, Lu Z. The effect of flash lamp pulsed dye laser on the expression of connective tissue growth factor in keloids. Lasers Surg Med. 2012; 44(5):377-83.

De las Alas JM, Siripunvarapon AH, Dofitas BL. Pulsed dye laser for the treatment of keloid and hypertrophic scars: a systematic review. Expert Rev Med Devices. 2012; 9(6):641-50.

Brewin MP, Lister TS. Prevention or treatment of hypertrophic burn scarring: a review of when and how to treat with the pulsed dye laser. Burns. 2014; 40(5):797-804.

Scrimali L, Lomeo G, Nolfo C, Pompili G, Tamburino S, Catalani A, Siragò P, Perrotta RE.Treatment of hypertrophic scars and keloids with a fractional CO2 laser: a personal experience. J Cosmet Laser Ther. 2010; 12(5):218-21.

Cassuto DA, Scrimali L, Sirago P. Treatment of hypertrophic scars and keloids with an LBO laser (532 nm) and silicone gel sheeting. J Cosmet Laser Ther. 2010; 12(1):32-7.

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(3):166-70.

Scrimali L, Lomeo G, Tamburino S, Catalani A, Perrotta R. Laser CO2 versus radiotherapy in treatment of keloid scars. J Cosmet Laser Ther. 2012; 14(2):94-7.

Khatri KA, Mahoney DL, McCartney MJ. Laser scar revision: A review. J Cosmet Laser Ther. 2011; 13(2):54-62.

Kontochristopoulos G, Stefanaki C, Panagiotopoulos A, Stefanaki K, Argyrakos T, Petridis A, Katsambas A. 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.

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; 22:44-6.

Davison SP, Dayan JH, Clemens MW, et al. Efficacy of intralesional 5-fluorouracil and triamcinolone in the treatment of keloids. Aesthet Surg J. 2009; 29:40-6.

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):1003-7.

Ren Y, Zhou X, Wei Z, Lin W, Fan B, Feng S. Efficacy and safety of triamcinolone acetonide alone and in combination with 5-fluorouracil for treating hypertrophic scars and keloids: a systematic review and meta-analysis. Int Wound J. 2017; 14(3):480-487.

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: 219-23.

Srivastava S, Patil A, Prakash C, Kumari H.Comparison of Intralesional Triamcinolone Acetonide, 5-Fluorouracil, and Their Combination in Treatment of Keloids. World J Plast Surg. 2018; 7(2):212-19.

Jones CD, Guiot L, Samy M, Gorman M, Tehrani H. The Use of Chemotherapeutics for the Treatment of Keloid Scars. Dermatol Rep 2015; 7: 5880.

Saray Y, Gulec AT. Treatment of keloids and hypertrophic scars with dermojet injections of bleomycin: a preliminary study. Int J Dermatol. 2005; 44(9):777-84.

Huu ND, Huu SN, Thi XL, Van TN, Minh PPT, Minh TT, Van TH, Cam VT, Huyen ML, Hau KT, Gandolfi M, Satolli F, Feliciani C, Tirant M, Vojvodic A, Lotti T. Successful Treatment of Intralesional Bleomycin in Keloids of Vietnamese Population. Open Access Maced J Med Sci. 2019;7(2):298-9.

Naeini FF, Najafian J, Ahmadpour K. Bleomycin tattooing as a promising therapeutic modality in large keloids and hypertrophic scars. Dermatol Surg. 2006; 32(8):1023-9

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-30.

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.

Dooley S, Said HM, Gressner AM, Floege J, En-Nia A, Mertens PR. Y-box protein-1 is the crucial mediator of antifibrotic interferon-gamma effects. J Biol Chem. 2006; 281(3):1784-95.

Lee JH, Kim SE, Lee AY. Effects of interferon-alpha2b on keloid treatment with triamcinolone acetonide intralesional injection. Int J Dermatol. 2008; 47(2):183-6.

Viera MH, Vivas AC, Berman B. Update on keloid management: Clinical and basic Science advances. Adv Wound Care (New Rochelle). 2012; 1(5):200-6.

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.

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):1-7.

Wang R, Mao Y, Zhang Z, Li Z, Chen J, Cen Y. Role of verapamil in preventing and treating hypertrophic scars and keloids. Int Wound J. 2016; 13(4):461-8.

Alexandrescu D, Fabi S, Yeh LC, Fitzpatrick RE, Goldman MP. Comparative results in treatment of keloids with intralesional 5-FU/Kenalog, 5-FU/Verapamil, Enalapril alone, Verapamil alone, and Laser: A Case Report and Review of the Literature. J Drugs Dermatol. 2016; 15(11):1442-7.

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(4):343-8.

Srivastava S, Kumari H, Singh A. Comparison of fractional CO2 Laser, Verapamil, and Triamcinolone for the treatment of keloid. Adv Wound Care (New Rochelle). 2019; 8(1):7-13.

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.

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. 2005; 31(11 Pt 1):1394-8.

Chuangsuwanich A, Gunjittisomram S. The efficacy of 5% imiquimod cream in the prevention of recurrence of excised keloids. J Med Assoc Thai. 2007; 90(7):1363-7.

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.

Cacao FM, Tanaka V, Messina MC. Failure of imiquimod 5% cream to prevent recurrence of surgically excised trunk keloids. Dermatol Surg. 2009; 35(4):629-33.

Mrowietz U, Seifert O. Keloid scarring: new treatments ahead. Actas Dermosifiliogr. 2009; 100(2):75-83.

Shi J, Li J, Guan H, Cai W , Bai X , Fang X, Hu X, Wang Y, Wang H, Zheng Z, Su L, Hu D, Zhu X. Anti-fibrotic actions of interleukin-10 against hypertrophic scarring by activation of PI3K/AKT and STAT3 signaling pathways in scar-forming fibroblasts. PLoS One. 2014; 9(5):e98228.

Shi J, Wang H, Guan H, Shi S, Li Y, Wu X, Li N, Yang C, Bai X, Cai W, Yang F, Wang X, Su L, Zheng Z, Hu D. IL10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways. Cell Death Dis. 2016; 7:e2133.

Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat. Rev. Immunol. 2012; 12: 383-96.

Fang F, Huang RL, Zheng Y, Liu M, Huo R. Bone marrow derived mesenchymal stem cells inhibit the proliferative and profibrotic phenotype of hypertrophic scar fibroblasts and keloid fibroblasts through paracrine signaling. J Dermatol Sci. 2016; 83(2):95-105.

Spiekman M, Przybyt E, Plantinga JA, Gibbs S, van der Lei B, Harmsen MC. Adipose tissue-derived stromal cells inhibit TGF-β1-induced differentiation of human dermal fibroblasts and keloid scar-derived fibroblasts in a paracrine fashion. Plast Reconstr Surg. 2014; 134(4):699-712.

Seo B F, Jung S N. The Immunomodulatory effects of Mesenchymal Stem Cells in prevention or treatment of excessive scars. Stem Cells Int. 2016; 2016: 6937976.

Altman AM, Matthias N, Yan Y, Song Y H, Bai X, Chiu E S, Slakey D P, Alt E U. Dermal matrix as a carrier for in vivo delivery of human adipose-derived stem cells. Biomaterials 2008; 29: 1431-42.

Huang S P, Hsu C C, Chang S C, Wang C H, Deng S C, Dai N T , Chen T M , Chan J Y, Chen S G. Huang, S.M. Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound healing in a murine model of a full-thickness defect. Ann Plast Surg 2012; 69:656-62.

Lam M T, Nauta A, Meyer NP, Wu JC, Longaker MT. Effective delivery of stem cells using an extracellular matrix patch results in increased cell survival and proliferation and reduced scarring in skin wound healing. Tissue Eng A 2013; 19: 738-47.

Negenborn V L, Groen J W, Smit J M, Niessen F B, Mullender M G. The use of autologous fat grafting for treatment of scar tissue and scar-related conditions: a systematic review. Plast. Reconstr. Surg. 2016; 137:31e–43.

Piccolo N S, Piccolo M S, Piccolo M T. Fat grafting for treatment of burns, burn scars, and other difficult wounds. Clin Plast Surg. 2015; 42:263-83.

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

So K, McGrouther DA, Bush JA, Durani P,Taylor L, Skotny G, Mason T, Metcalfe A, O’Kane S,Ferguson MW. Avotermin for scar improvement following scar revision surgery: A randomized, double-blind, within-patient, placebo-controlled, phase II clinical trial. Plast. Reconstr. Surg. 2011; 128:163-72.

Occleston N L, O’Kane S, Laverty H G, Cooper M, Fairlamb D, Mason T, Bush JA,Ferguson MW. Discovery and development of avotermin (recombinant human transforming growth factor β 3): A new class of prophylactic therapeutic for the improvement of scarring. Wound Repair Regen. 2011; 19(S1):s38–48.

Ferguson M W, Duncan J, Bond J, Bush J, Durani P, So K, Taylor L, Chantrey J, Mason T, James G. Prophylactic administration of avotermin for improvement of skin scarring: Three double-blind, placebo-controlled, phase I/II studies. Lancet 2009 : 373:1264-74.

Austin E, Koo E, Jagdeo J. The Cellular Response of Keloids and Hypertrophic Scars to Botulinum Toxin A: A Comprehensive Literature Review. Dermatol Surg. 2018; 44(2):149-157.

Xiaoxue W, Xi C, Zhibo X. Effects of botulinum toxin type A on expression of genes in keloid fibroblasts. Aesthet Surg J. 2014; 34(1):154-9.

Shaarawy E, Hegazy RA, Abdel Hay RM. Intralesional botulinum toxin type A equally effective and better tolerated than intralesional steroid in the treatment of keloids: a randomized controlled trial. J Cosmet Dermatol. 2015; 14(2):161-6.

Gauglitz GG, Bureik D, Dombrowski Y, Pavicic T, Ruzicka T, Schauber J. Botulinum toxin A for the treatment of keloids. Skin Pharmacol Physiol. 2012; 25(6):313-8.

Sidle DM, Kim H. Keloids: prevention and management. Facial Plast Surg Clin North Am. 2011; 19(3):505-15.

Wong VW, Akaishi S, Longaker MT, Gurtner GC. Pushing back: Wound mechanotransduction in repair and regeneration. J Investig Dermatol. 2011; 131:2186-96.

Gurtner GC, Dauskardt RH, Wong VW, Bhatt K A, Wu K, Vial IN ,Padois K , Korman J M , Longaker M T. Improving cutaneous scar formation by controlling the mechanical environment: Large animal and phase I studies. Ann Surg 2011; 254: 217-25.

Hsu KC, Luan CW, Tsai YW. Review of Silicone gel sheeting and Silicone gel for the prevention of hypertrophic scars and keloids. Wounds. 2017; 29(5):154-8.

Del Toro D, Dedhia R, Tollefson TT. Advances in scar management: prevention and management of hypertrophic scars and keloids. Curr Opin Otolaryngol Head Neck Surg. 2016; 24(4):322-9.

Onselen JV. Scars: impact and management, with a focus on topical silicone-based treatments. Br J Nurs. 2018; 27(12):S36-40.

Reish RG, Eriksson E. Scar treatments: preclinical and clinical studies. J Am Coll Surg. 2008; 206:719-30.

Fabbrocini G, Marasca C, Ammad S, Brazzini B, Izzo R, Donnarumma M, Monfrecola G. Assessment of the combined efficacy of needling and the use of Silicone gel in the treatment of C-Section and other surgical hypertrophic scars and keloids. Adv Skin Wound Care. 2016; 29(9):408-11.

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. 2014; 28(8):1025-33.

Phan TT, Lim IJ, Sun L, Chan SY, Bay BH, Tan EK, Lee ST. Quercetin inhibits fibronectin production by keloid-derived fibroblasts. Implication for the treatment of excessive scars. J Dermatol Sci. 2003; 33(3):192-4.

Cho J W, Cho S Y, Lee S R, Lee K S. Onion extract and quercetin induce matrix metalloproteinase-1 in vitro and in vivo. Int J Mol Med. 2010; 25(3):347-52.

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.

Gill S.E., Parks W.C. Metalloproteinases and their inhibitors: regulators of wound healing. Int J Biochem Cell Biol. 2008; 40(6–7):1334-47.

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 2008 ; 34: 1507-14.

Reno F, Sabbatini M, Lombardi F, Stella M , Pezzuto C , Magliacani G, Cannas M. In vitro mechanical compression induces apoptosis and regulates cytokines release in hypertrophic scars. Wound Repair Regen 2003; 11: 331-6.

Ahuja R B, Chatterjee P, Deraje V .A critical appraisal of nonsurgical modalities for managing hypertrophic scars and keloids. Formosan J Surg. 2015; 48:49-56

Chamaria A, De Sousa RF, Aras MA, Mascarenhas K. Surgical excision and contoured custom made splint to treat helical keloid. Ind J Plast Surg. 2016; 49(3):410-4.

Sand M, Sand D, Boorboor P, Mann B, Altmeyer P, Hoffmann K, Bechara FG. Combination of surgical excision and custom designed silicon pressure splint therapy for keloids on the helical rim. Head Face Med. 2007; 3:14.

Hassel JC, Roberg B, Kreuter A, Voigtländer V, Rammelsberg P, Hassel AJ. Treatment of ear keloids by compression, using a modified oyster-splint technique. Dermatol Surg. 2007; 33(2):208-12.


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