Aesthetic Plastic Surgery

, Volume 44, Issue 1, pp 207–218 | Cite as

Comparative Efficacy and Safety of Common Therapies in Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis

  • Yawei Bao
  • Shanshan Xu
  • Zhipeng Pan
  • Jixiang Deng
  • Xinyi Li
  • Faming Pan
  • Xiaojing LiEmail author
Review Special Topics



At present, there are many therapies for treating keloids and hypertrophic scars, but there is still a lack of treatments that are relatively balanced in efficacy and safety. The study aims to evaluate comprehensively efficacy and safety of common therapies in keloids and hypertrophic scars.


The literature search was conducted up to May 2019. The traditional meta-analysis was performed on 17 therapies. Bayesian network meta-analysis was conducted on the four most common treatments. The outcome indicators were the numbers of patients with good-to-excellent effect, Vancouver Scar Scale (VSS) and adverse events.


There was no significant difference in the efficacy of triamcinolone acetonide (TAC) compared with other monotherapies except for silicone gel sheet and neodymium-yttrium-aluminum-garnet in primary indicator. The combination therapies were superior to TAC, and the results were consistent after the pooled analysis (RR = 0.522, 95% CI 0.332–0.823). The level of VSS in TAC group was higher than that in 5-flurouracil (5-FU) and TAC + 5-FU group, but lower than that in verapamil (VER) group. And the patients treated with TAC were less safe than those treated with verapamil (P = 0.013). Surface under cumulative ranking ranked verapamil and TAC + 5-FU as the favorable efficacy therapies in terms of primary indicator and ranked TAC + 5-FU as the best therapy for VSS, while VER was ranked as the worst.


This meta-analysis showed that TAC + 5-FU may be the most effective therapy, while verapamil may be a better therapeutic strategy for safety.

Level of Evidence III

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors


Keloid Hypertrophic scar Treatment Meta-analysis 



We thank all patients and healthy subjects who provided the information necessary for our study. We would like to acknowledgement the national natural science foundation of China and Scientific Research Foundation of Translational Medicine of Anhui Province for their financial support.


The study was sponsored by the National Natural Science Foundation of China (81273169,81573218 and 81773514) and Scientific Research Foundation of Translational Medicine of Anhui Province (2017zhyx03).

Compliance with Ethical Standards

Conflict of interest

All authors state that there is no conflict of interest.

Informed Consent

For this type of study, informed consent is not required.

Statement of Human and Animal Rights, or Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Huang C, Murphy GF, Akaishi S et al (2013) Keloids and hypertrophic scars: update and future directions. Plast Reconstr Surg Glob Open 1:e25. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Slemp AE, Kirschner RE (2006) Keloids and scars: a review of keloids and scars, their pathogenesis, risk factors, and management. Curr Opin Pediatr 18:396–402. CrossRefPubMedGoogle Scholar
  3. 3.
    Ogawa R (2011) Mechanobiology of scarring. Wound Repair Regen 19(Suppl 1):s2–s9. CrossRefPubMedGoogle Scholar
  4. 4.
    Baisch A, Riedel F (2006) Hyperplastic scars and keloids. Part I: basics and prevention. HNO 54:893–905. CrossRefPubMedGoogle Scholar
  5. 5.
    Younai S, Nichter LS, Wellisz T et al (1994) Modulation of collagen synthesis by transforming growth factor-beta in keloid and hypertrophic scar fibroblasts. Ann Plast Surg 33:148–151CrossRefGoogle Scholar
  6. 6.
    Robles DT, Berg D (2007) Abnormal wound healing: keloids. Clin Dermatol 25:26–32. CrossRefPubMedGoogle Scholar
  7. 7.
    Garcia-Vidal C, Calbo E, Pascual V et al (2007) Effects of systemic steroids in patients with severe community-acquired pneumonia. Eur Respir J 30:951–956. CrossRefPubMedGoogle Scholar
  8. 8.
    Muneuchi G, Suzuki S, Onodera M et al (2006) 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 40:111–116. CrossRefPubMedGoogle Scholar
  9. 9.
    Hochman B, Locali RF, Matsuoka PK et al (2008) Intralesional triamcinolone acetonide for keloid treatment: a systematic review. Aesthetic Plast Surg 32:705–709. CrossRefPubMedGoogle Scholar
  10. 10.
    Mustoe TA, Cooter RD, Gold MH et al (2002) International clinical recommendations on scar management. Plast Reconstr Surg 110:560–571CrossRefGoogle Scholar
  11. 11.
    Asilian A, Darougheh A, Shariati F (2006) New combination of triamcinolone, 5-fluorouracil, and pulsed-dye laser for treatment of keloid and hypertrophic scars. Dermatol Surg 32:907–915. CrossRefPubMedGoogle Scholar
  12. 12.
    Darougheh A, Asilian A, Shariati F (2009) Intralesional triamcinolone alone or in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars. Clin Exp Dermatol 34:219–223. CrossRefPubMedGoogle Scholar
  13. 13.
    Khan MA, Bashir MM, Khan FA (2014) Intralesional triamcinolone alone and in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars. J Pak Med Assoc 64:1003–1007PubMedGoogle Scholar
  14. 14.
    van der Wal MB, Tuinebreijer WE, Bloemen MC et al (2012) Rasch analysis of the Patient and Observer Scar Assessment Scale (POSAS) in burn scars. Qual Life Res 21:13–23. CrossRefPubMedGoogle Scholar
  15. 15.
    Manuskiatti W, Fitzpatrick RE (2002) 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 138:1149–1155CrossRefGoogle Scholar
  16. 16.
    Tan E, Chua S, Lim J (1999) Topical silicone gel sheet versus intralesional injections of triamcinolone acetonide in the treatment of keloids—a patient-controlled comparative clinical trial. J Dermatol Treat 10:251–254CrossRefGoogle Scholar
  17. 17.
    Margaret Shanthi FX, Ernest K, Dhanraj P (2008) Comparison of intralesional verapamil with intralesional triamcinolone in the treatment of hypertrophic scars and keloids. Indian J Dermatol Venereol Leprol 74:343–348CrossRefGoogle Scholar
  18. 18.
    Sadeghinia A, Sadeghinia S (2012) Comparison of the efficacy of intralesional triamcinolone acetonide and 5-fluorouracil tattooing for the treatment of keloids. Dermatol Surg 38:104–109. CrossRefPubMedGoogle Scholar
  19. 19.
    Saha AK, Mukhopadhyay M (2012) A comparative clinical study on role of 5-flurouracil versus triamcinolone in the treatment of keloids. Indian J Surg 74:326–329. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Rossi A, Lu R, Frey MK et al (2013) The use of the 300 microsecond 1064 nm Nd:YAG laser in the treatment of keloids. J Drugs Dermatol 12:1256–1262PubMedGoogle Scholar
  21. 21.
    Ahuja RB, Chatterjee P (2014) Comparative efficacy of intralesional verapamil hydrochloride and triamcinolone acetonide in hypertrophic scars and keloids. Burns 40:583–588. CrossRefPubMedGoogle Scholar
  22. 22.
    Payapvipapong K, Niumpradit N, Piriyanand C et al (2015) The treatment of keloids and hypertrophic scars with intralesional bleomycin in skin of color. J Cosmet Dermatol 14:83–90. CrossRefPubMedGoogle Scholar
  23. 23.
    Danielsen PL, Rea SM, Wood FM et al (2016) Verapamil is less effective than triamcinolone for prevention of keloid scar recurrence after excision in a randomized controlled trial. Acta Derm Venereol 96:774–778. CrossRefPubMedGoogle Scholar
  24. 24.
    Meymandi SS, Moosazadeh M, Rezazadeh A (2016) Comparing two methods of cryotherapy and intense pulsed light with triamcinolone injection in the treatment of keloid and hypertrophic scars: a clinical trial. Osong Public Health Res Perspect 7:313–319. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Chen XE, Liu J, Bin Jameel AA et al (2017) Combined effects of long-pulsed neodymium-yttrium-aluminum-garnet laser, diprospan and 5-fluorouracil in the treatment of keloid scars. Exp Ther Med 13:3607–3612. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Abedini R, Sasani P, Mahmoudi HR et al (2018) Comparison of intralesional verapamil versus intralesional corticosteroids in treatment of keloids and hypertrophic scars: a randomized controlled trial. Burns 44:1482–1488. CrossRefPubMedGoogle Scholar
  27. 27.
    Srivastava S, Patil A, Prakash C et al (2018) Comparison of intralesional triamcinolone acetonide, 5-fluorouracil, and their combination in treatment of keloids. World J Plast Surg 7:212–219PubMedPubMedCentralGoogle Scholar
  28. 28.
    Alexander S, Girisha BS, Sripathi H et al (2019) Efficacy of fractional CO2 laser with intralesional steroid compared with intralesional steroid alone in the treatment of keloids and hypertrophic scars. J Cosmet Dermatol. CrossRefPubMedGoogle Scholar
  29. 29.
    Hietanen KE, Jarvinen TA, Huhtala H et al (2019) Treatment of keloid scars with intralesional triamcinolone and 5-fluorouracil injections—a randomized controlled trial. J Plast Reconstr Aesthet Surg 72:4–11. CrossRefPubMedGoogle Scholar
  30. 30.
    Khalid FA, Mehrose MY, Saleem M et al (2019) Comparison of efficacy and safety of intralesional triamcinolone and combination of triamcinolone with 5-fluorouracil in the treatment of keloids and hypertrophic scars: randomised control trial. Burns 45:69–75. CrossRefPubMedGoogle Scholar
  31. 31.
    Saki N, Mokhtari R, Nozari F (2019) Comparing the efficacy of intralesional triamcinolone acetonide with verapamil in treatment of keloids: a randomized controlled trial. Dermatol Pract Concept 9:4–9. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Srivastava S, Kumari H, Singh A (2019) Comparison of fractional CO2 laser, verapamil, and triamcinolone for the treatment of keloid. Adv Wound Care (New Rochelle) 8:7–13. CrossRefGoogle Scholar
  33. 33.
    Tawfik AA, Fathy M, Badawi A et al (2019) Topical 5 fluorouracil cream vs combined 5 fluorouracil and fractional erbium YAG laser for treatment of severe hypertrophic scars. Clin Cosmet Investig Dermatol 12:173–180. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ren Y, Zhou X, Wei Z et al (2017) 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 14:480–487. CrossRefPubMedGoogle Scholar
  35. 35.
    Li Z, Jin Z (2016) Comparative effect and safety of verapamil in keloid and hypertrophic scar treatment: a meta-analysis. Ther Clin Risk Manag 12:1635–1641. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Zhang Z, Cheng L, Wang R et al (2018) Effects and safety of triamcinolone acetonide-controlled common therapy in keloid treatment: a Bayesian network meta-analysis. Ther Clin Risk Manag 14:973–980. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    He Y, Deng Z, Alghamdi M et al (2017) From genetics to epigenetics: new insights into keloid scarring. Cell Prolif 50:e12326. CrossRefGoogle Scholar
  38. 38.
    Shih B, Bayat A (2010) Genetics of keloid scarring. Arch Dermatol Res 302:319–339. CrossRefPubMedGoogle Scholar
  39. 39.
    Arno AI, Gauglitz GG, Barret JP et al (2014) Up-to-date approach to manage keloids and hypertrophic scars: a useful guide. Burns 40:1255–1266. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Gauglitz GG, Korting HC, Pavicic T et al (2011) Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med 17:113–125. CrossRefPubMedGoogle Scholar
  41. 41.
    Carrillo E, Navarro SA, Ramirez A et al (2015) 5-Fluorouracil derivatives: a patent review (2012–2014). Expert Opin Ther Pat 25:1131–1144. CrossRefPubMedGoogle Scholar
  42. 42.
    Lee RC, Doong H, Jellema AF (1994) The response of burn scars to intralesional verapamil. Report of five cases. Arch Surg 129:107–111CrossRefGoogle Scholar
  43. 43.
    Fanous A, Bezdjian A, Caglar D et al (2019) Treatment of keloid scars with botulinum toxin type A versus triamcinolone in an athymic nude mouse model. Plast Reconstr Surg 143:760–767. CrossRefPubMedGoogle Scholar
  44. 44.
    Chen HC, Yen CI, Yang SY et al (2017) Comparison of steroid and botulinum toxin type A monotherapy with combination therapy for treating human hypertrophic scars in an animal model. Plast Reconstr Surg 140:43e–49e. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery 2019

Authors and Affiliations

  1. 1.Department of Plastic SurgeryFirst Affiliated Hospital of Anhui Medical UniversityHefeiChina
  2. 2.Department of Epidemiology and Statistics, School of Public HealthAnhui Medical UniversityHefeiChina
  3. 3.Department of Medical OncologyFirst Affiliated Hospital of Anhui Medical UniversityHefeiChina

Personalised recommendations