Elsevier

Burns

Volume 40, Issue 7, November 2014, Pages 1255-1266
Burns

Review
Up-to-date approach to manage keloids and hypertrophic scars: A useful guide

https://doi.org/10.1016/j.burns.2014.02.011Get rights and content

Abstract

Keloids and hypertrophic scars occur anywhere from 30 to 90% of patients, and are characterized by pathologically excessive dermal fibrosis and aberrant wound healing. Both entities have different clinical and histochemical characteristics, and unfortunately still represent a great challenge for clinicians due to lack of efficacious treatments. Current advances in molecular biology and genetics reveal new preventive and therapeutical options which represent a hope to manage this highly prevalent, chronic and disabling problem, with long-term beneficial outcomes and improvement of quality of life. While we wait for these translational clinical products to be marketed, however, it is imperative to know the basics of the currently existing wide array of strategies to deal with excessive scars: from the classical corticotherapy, to the most recent botulinum toxin and lasers. The main aim of this review paper is to offer a useful up-to-date guideline to prevent and treat keloids and hypertrophic scars.

Introduction

Cutaneous scar management has relied mainly on the experience of practitioners rather than on the results of large-scale randomized, controlled trials and evidence-based studies [1].

Patients with keloids or hypertrophic scars suffer a severe impairment of quality of life, by causing physical, psychological and social sequelae [2]. Even normal visible scars may represent an important stigma [3]. The prevalence of hypertrophic scarring following burns is about 67%, but further epidemiological research is still necessary. Excessive scarring represents the first morbidity cause in burn survivors [4].

The formation of a scar is the normal physiologic response to wounding in adults. However, an alteration of extracellular matrix (ECM) metabolism – an imbalance between its destruction and deposition – may lead to excessive scarring [5]. Wound healing, and therefore scar formation, involves three distinct phases: inflammation (the first 48–72 h after trauma, supposed to be started by the release of IL-1 by keratinocytes) [6], proliferation (which may last for up to 6 weeks) and remodeling or maturation (scars mature during a period of at least 1 year [5]).

A prolonged or excessive inflammatory phase is believed to be the onset of excessive scarring, with hypertrophic scars and keloids as minor and major clinical signs (Table 1).

Still to date, it remains much more efficient to prevent excessive scars than to treat them. The most successful treatment of a hypertrophic scar or keloid is achieved when the scar is immature but the overlying epithelium is intact. In the past, the most recommended treatment strategy has been prophylaxis using silicone gel sheeting or paper tape starting on the second week after wounding, combined with other treatments, including massage, pressure therapy and intralesional corticotherapy, depending on each patient and scar's origin and type [1].

Generally, most of the therapeutic approaches may be used for both hypertrophic scars and keloids. Nevertheless, it is important to differentiate them before performing any surgery or laser treatment [5]. Briefly, keloids (Fig. 1) extend beyond the original wound borders, in contrast to hypertrophic scars (Fig. 2). Blood type A, hyper-Immunoglobulin (Ig) E syndrome (high allergy risk), hormone peaks (puberty, pregnancy), age 10–30 years old, and Hispanic, Afro-American or Asian (but not albino) background have all been associated with high risk of developing keloid scars [5], [7]. Keloid pathophysiology is still complex, with both genetic and environmental factors involved. Abnormal fibroblasts have been shown to play a key role, but new lines of research have driven attention to keratinocytes and altered signaling crosstalks [8], [9]. Furthermore, increased number of mast cells have been associated with enhanced HIF-1α (hypoxia inducible factor-1α), VEGF (vascular endothelial growth factor) and PAI-1 (plasminogen activator inhibitor-1) expression, all well known fibrosis promoters. TGF-β signaling with preponderance of TGF-β1 or 2 expression due to alteration of POMC (proopiomelanocortin) gene expression among other mechanisms and epithelial-to-mesenchymal transition have also been shown to play a major role in keloid formation [10], [11]. Increased interleukin-6 (IL-6), PDGF (platelet derived growth factor), α1β1-integrin and Ig A, G and M expression have all also been linked to keloid pathogenesis [3]. Besides that, keloid formation has been associated with immune alteration of sebaceous glands and enhanced androgen receptors expression with enhanced sebum secretion and lipid metabolism alteration, neurogenic inflammation, infection and mechanotransduction [12]. Regarding hypertrophic scars pathophysiology, activation of myofibroblasts has been classically reported to play a key role. This has been shown to be driven by an orchestrated interplay of platelets, macrophages, T-lymphocytes, mast cells, Langerhans cells, keratinocytes and fibroblasts. The net reported result mainly consists of an alteration of ECM (extracellular matrix) metabolism: excessive production and altered remodeling of ECM, with enhanced expression of types I and III collagen and cutaneous profibrotic pathological crosslink of collagen, in the form of pyridinoline type with increased LH2b (telopeptide lysyl hydroxylase-2b). Furthermore, hemostasis alteration (due to enhanced expression of PAI-1 and chronic fibronectin deposition), increased neovascularization and time of re-epithelialization have also been involved in hypertrophic scar pathogenesis. Decreased apoptosis and increased inflammation have also been described to play a major role. Regarding this latter, increased expression of T helper 2 cells, IL-4, IL-5, IL-6, IL-13 and IL-21, but decreased levels of IL-12 and interferon-γ (IFN-γ), have also been shown to be related in the literature [13], [14]. More detailed description about both types of excessive scarring scapes from the scope of this review, which will focus on offering an evidence based description of the currently used strategies to manage keloids and hypertrophic scars, from the classical corticotherapy to the most recent botulinum toxin and lasers.

Section snippets

Massage therapy

Massage therapy, manual or mechanical (i.e., compressed air, threadlike showers, vacuotherapy, etc.), is standard therapy in rehabilitation centers specializing in the treatment of scars and burns [15].

Although there is no scientific evidence, it has been shown that massage therapy not only reduces scar-related pain and itching [16], but also increases range of motion, reveals patients’ anxiety and improves their mood and mental status [17].

A recent meta-analysis including 144 patients from 10

Special cases

As it has been aforementioned, scar clinical research is still far of providing sufficient accurate and unbiased studies, although a growing concern is detected and this may prompt to design new, high-quality clinical trials. Having said that, and taking into account the few controversial scientific evidence often encountered surrounding this topic, some recommendations could be suggested in special cases. Regarding keloids, patients suffering of generalized multiple keloids or very large

Conclusions

Hypertrophic scars and keloids represent old but still unresolved challenges. From the classical scar management strategies, corticosteroids keep playing a predominant role, especially if combined with 5-FU and PDL in a triple therapy, to enhance results and diminish their side effects. Lasers and light-based therapies are becoming more and more used nowadays and appear promising in the management of scars for many reasons: depending on the laser technology chosen, they can be used to enhance

Conflict of interest statement

None of the authors has any financial interest whatsoever in any of the drugs, treatments, techniques or instruments mentioned in this article.

Acknowledgements

This manuscript was supported by the NIH Grant RO1 GM087285-01, the CFI Leader's Opportunity Fund (Project # 25407), and the Physician's Services Incorporated Foundation – Health Research Grant Program.

References (113)

  • S. Yossi et al.

    Adjuvant treatment of keloid scars: electrons or brachytherapy?

    Cancer Radiother

    (2013)
  • M. Lebwohl

    From the literature: intralesional 5-FU in the treatment of hypertrophic scars and keloids: clinical experience

    J Am Acad Dermatol

    (2000)
  • S. Dooley et al.

    Y-box protein-1 is the crucial mediator of antifibrotic interferon-gamma effects

    J Biol Chem

    (2006)
  • T. Hasegawa et al.

    IFN-gamma fails to antagonize fibrotic effect of TGF-beta on keloid-derived dermal fibroblasts

    J Dermatol Sci

    (2003)
  • U. Mrowietz et al.

    Keloid scarring: new treatments ahead

    Actas Dermosifiliogr

    (2009)
  • N.L. Occleston et al.

    New therapeutic for the prevention and reduction of scarring

    Drug Discov Today

    (2008)
  • A. Carruthers et al.

    A exotoxin use in clinical dermatology

    J Am Acad Dermatol

    (1996)
  • M.F. Freshwater

    Botulinum toxin for scars: can it work, does it work, is it worth it?

    J Plast Reconstr Aesthet Surg

    (2013)
  • H.G. Gassner et al.

    Botulinum toxin to improve facial wound healing: a prospective, blinded, placebo-controlled study

    Mayo Clin Proc

    (2006)
  • P.D. Butler et al.

    Current progress in keloid research and treatment

    J Am Coll Surg

    (2008)
  • K.K. Lee et al.

    Surgical revision

    Dermatol Clin

    (2005)
  • T.A. Mustoe et al.

    International clinical recommendations on scar management

    Plast Reconstr Surg

    (2002)
  • D. Leventhal et al.

    Treatment of keloids and hypertrophic scars

    Arch Facial Plast Surg

    (2006)
  • O. Seifert et al.

    Keloid scarring: bench and bedside

    Arch Dermatol Res

    (2009)
  • G.G. Gauglitz et al.

    Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies

    Mol Med

    (2011)
  • F.B. Niessen et al.

    Hypertrophic scar formation is associated with an increased number of epidermal Langerhans cells

    J Pathol

    (2004)
  • P.B. Love et al.

    Keloids: an update on medical and surgical treatments

    J Drugs Dermatol

    (2013)
  • A.G. Marneros et al.

    Keloids: clinical diagnosis, pathogenesis and treatment options

    J Detsch Dermatol Ges

    (2004)
  • J.M. Hahn et al.

    Keloid-derived keratinocytes exhibit an abnormal gene expression profile consistent with a distinct causal role in keloid pathology

    Wound Repair Regen

    (2013)
  • B. Shih et al.

    Molecular dissection of abnormal wound healing processes resulting in keloid disease

    Wound Repair Regen

    (2010)
  • A.I. Arno et al.

    New molecular medicine-based scar management strategies

    Burns

    (2014)
  • C. Huang et al.

    Roles of lipid metabolism in keloid development

    Lipids Health Dis

    (2013)
  • W.M. van der Veen et al.

    Potential cellular and molecular causes of hypertrophic scar formation

    Burns

    (2009)
  • A. Armour et al.

    Cellular and molecular pathology of HTS: basis for treatment

    Wound Repair Regen

    (2007)
  • C. Roques

    Massage applied to scars

    Wound Repair Regen

    (2002)
  • T. Field et al.

    Postburn itching: pain, and psychological symptoms are reduced with massage therapy

    J Burn Care Rehabil

    (2000)
  • O. Patiño et al.

    Massage in hypertrophic scars

    J Burn Care Rehabil

    (1999)
  • T.M. Shin et al.

    The role of massage in scar management: a literature review

    Dermatol Surg

    (2012)
  • B.S. Atiyeh

    Nonsurgical management of hypertrophic scars: evidence-based therapies, standard practices, and emerging methods

    Aesth Plast Surg

    (2007)
  • W.H. Reid et al.

    Hypertrophic scarring and pressure therapy

    Burns

    (1987)
  • H. Giele et al.

    Anatomical variations in pressures generated by pressure garments

    Plast Reconstr Surg

    (1998)
  • P. Chang et al.

    Prospective, randomized study of the efficacy of pressure garment therapy in patietns with burns

    J Burn Care Rehabil

    (1995)
  • G.V. De Oliveira et al.

    Silicone versus nonsilicone gel dressings: a controlled trial

    Dermatol Surg

    (2001)
  • T.A. Mustoe

    Evolution of silicone therapy and mechanism of action in scar management

    Aesthetic Plast Surg

    (2008)
  • J.A. Atkinson et al.

    Randomized: controlled trial to determine the efficacy of paper tape in preventing hypertrophic scar formation in surgical incision that traverse Langer's skin tension lines

    Plast Reconstr Surg

    (2005)
  • A. Baisch et al.

    Hyperplastische Narben un Keloide

    HNO

    (2006)
  • H. Hamanova et al.

    Topigel in the treatment of hypertrophic scars after burn injuries

    Acta Chir Plast

    (2002)
  • L. Steinstraesser et al.

    Pressure garment therapy alone and in combination with silicone for the prevention of hypertrophic scarring: randomized controlled tiral with intraindividual comparison

    Plast Reconstr Surg

    (2011)
  • M.A. Musgrave et al.

    The effect of silicone gel sheets on perfusion of hypertrophic burn scars

    J Burn Care Rehabil

    (2002)
  • Cited by (268)

    • Burn Injury Complications Impacting Rehabilitation

      2023, Physical Medicine and Rehabilitation Clinics of North America
    View all citing articles on Scopus
    View full text