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Local, Systemic, and Genetic Risk Factors for Keloids and Hypertrophic Scars and the Reset Concept of Pathological Scar Therapy

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Total Scar Management

Abstract

Keloids and hypertrophic scars are red and elevated pathological inflammatory scars that are caused by aberrant wound healing after injury or irritation to the reticular dermis. These injuries include trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster. The importance of the reticular dermis in this pathology is demonstrated by the fact that superficial injuries that do not reach the reticular dermis will never cause keloidal or hypertrophic scarring. The aberrant wound healing of these pathological scars is characterized by continuous inflammation that is mainly found in the reticular dermis. Thus, the reticular layer of these scars contains large numbers of inflammatory cells, fibroblasts, and newly formed blood vessels along with accumulations of collagen. Increasing evidence suggests that these characteristic histological features of keloids and hypertrophic scars are driven by external and/or internal stimuli that are placed on the reticular layer during the course of wound healing. These stimuli are either delivered repeatedly or are continuously present. This prolongs and amplifies the reticular dermal inflammation, thereby preventing the orderly progression of wound healing to the maturation phase. These external and internal stimuli include multiple local, systemic, and genetic factors. The nature, strength, and duration of these stimuli ultimately shape the characteristics, quantity, and progression of keloids and hypertrophic scars. Therapies should aim to extinguish the inflammation. In severe cases, surgery followed by radiotherapy and then conservative therapies will be needed to fully eliminate the inflammation and prevent recurrence: this approach resets the skin to a state that allows scar maturation (the “Reset Concept”). At that point, aesthetic and functional reconstruction can proceed.

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References

  1. Ogawa R. Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci. 2017;18(3):E606.

    Article  Google Scholar 

  2. Huang C, Murphy GF, Akaishi S, Ogawa R. Keloids and hypertrophic scars: update and future directions. Plast Reconstr Surg Glob Open. 2013;1(4):e25.

    Article  Google Scholar 

  3. Huang C, Akaishi S, Hyakusoku H, Ogawa R. Are keloid and hypertrophic scar different forms of the same disorder? A fibroproliferative skin disorder hypothesis based on keloid findings. Int Wound J. 2014;11(5):517–22.

    Article  Google Scholar 

  4. Ogawa R. Mechanobiology of scarring. Wound Repair Regen. 2011;19(Suppl 1):s2–9.

    Article  Google Scholar 

  5. Ogawa R, Akaishi S. Endothelial dysfunction may play a key role in keloid and hypertrophic scar pathogenesis: keloids and hypertrophic scars may be vascular disorders. Med Hypotheses. 2016;96:51–60.

    Article  CAS  Google Scholar 

  6. Huang C, Liu L, You Z, Zhao Y, Dong J, Du Y, Ogawa R. Endothelial dysfunction and mechanobiology in pathological cutaneous scarring: lessons learned from soft tissue fibrosis. Br J Dermatol. 2017;177:1248–55.

    Article  CAS  Google Scholar 

  7. Akaishi S, Akimoto M, Ogawa R, Hyakusoku H. The relationship between keloid growth pattern and stretching tension: visual analysis using the finite element method. Ann Plast Surg. 2008;60(4):445–51.

    Article  CAS  Google Scholar 

  8. Ogawa R, Okai K, Tokumura F, Mori K, Ohmori Y, Huang C, Hyakusoku H, Akaishi S. The relationship between skin stretching/contraction and pathologic scarring: the important role of mechanical forces in keloid generation. Wound Repair Regen. 2012;20(2):149–57.

    Article  Google Scholar 

  9. Moustafa MF, Abdel-Fattah MA, Abdel-Fattah DC. Presumptive evidence of the effect of pregnancy estrogens on keloid growth. Case report. Plast Reconstr Surg. 1975;56(4):450–3.

    Article  CAS  Google Scholar 

  10. Mendelsohn ME, Karas RH. Estrogen and the blood vessel wall. Curr Opin Cardiol. 1994;9(5):619–26.

    Article  CAS  Google Scholar 

  11. Deitch EA, Wheelahan TM, Rose MP, Clothier J, Cotter J. Hypertrophic burn scars: analysis of variables. J Trauma. 1983;23(10):895–8.

    Article  CAS  Google Scholar 

  12. Arima J, Huang C, Rosner B, Akaishi S, Ogawa R. Hypertension: a systemic key to understanding local keloid severity. Wound Repair Regen. 2015;23(2):213–21.

    Article  Google Scholar 

  13. Huang C, Ogawa R. The link between hypertension and pathological scarring: does hypertension cause or promote keloid and hypertrophic scar pathogenesis? Wound Repair Regen. 2014;22(4):462–6.

    Article  CAS  Google Scholar 

  14. Noishiki C, Takagi G, Kubota Y, Ogawa R. Endothelial dysfunction may promote keloid growth. Wound Repair Regen. 2017;25:976–83.

    Article  Google Scholar 

  15. Quong WL, Kozai Y, Ogawa R. A case of keloids complicated by Castleman’s disease: interleukin-6 as a keloid risk factor. Plast Reconstr Surg Glob Open. 2017;5(5):e1336.

    Article  Google Scholar 

  16. Miller MC, Nanchahal J. Advances in the modulation of cutaneous wound healing and scarring. BioDrugs. 2005;19(6):363–81.

    Article  CAS  Google Scholar 

  17. Baisch A, Riedel F. Hyperplastic scars and keloids. Part I: basics and prevention. HNO. 2006;54(11):893–904.

    Article  CAS  Google Scholar 

  18. Nakashima M, Chung S, Takahashi A, Kamatani N, Kawaguchi T, Tsunoda T, Hosono N, Kubo M, Nakamura Y, Zembutsu H. A genome-wide association study identifies four susceptibility loci for keloid in the Japanese population. Nat Genet. 2010;42(9):768–71.

    Article  CAS  Google Scholar 

  19. Ogawa R, Watanabe A, Than Naing B, Sasaki M, Fujita A, Akaishi S, Hyakusoku H, Shimada T. Associations between keloid severity and single-nucleotide polymorphisms: importance of rs8032158 as a biomarker of keloid severity. J Invest Dermatol. 2014;134(7):2041–3.

    Article  CAS  Google Scholar 

  20. Marneros AG, Norris JE, Watanabe S, Reichenberger E, Olsen BR. Genome scans provide evidence for keloid susceptibility loci on chromosomes 2q23 and 7p11. J Invest Dermatol. 2004;122:1126–32.

    Article  CAS  Google Scholar 

  21. Chen Y, Gao JH, Yan X, Song M, Liu XJ. Location of predisposing gene for one Han Chinese keloid pedigree. Zhonghua Zheng Xing Wai Ke Za Zhi. 2007;23:137–40.

    CAS  PubMed  Google Scholar 

  22. Ogawa R. The latest in keloid and hypertrophic scar pathophysiology and treatment strategies: keloids can be treated by employing up-to-date surgical management. Plastic surgery pulse news 5. Quality Medical Publishing, Inc.: St Louis; 2013.

    Google Scholar 

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Correspondence to Rei Ogawa .

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Ogawa, R. (2020). Local, Systemic, and Genetic Risk Factors for Keloids and Hypertrophic Scars and the Reset Concept of Pathological Scar Therapy. In: Ogawa, R. (eds) Total Scar Management. Springer, Singapore. https://doi.org/10.1007/978-981-32-9791-3_5

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  • DOI: https://doi.org/10.1007/978-981-32-9791-3_5

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  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-32-9790-6

  • Online ISBN: 978-981-32-9791-3

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