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KELOIDS AND HYPERTROPHIC SCARS

Keloids and hypertrophic scars are abnormalities in the normal wound healing characterized by greater and more sustained extracellular matrix deposition that develops after any insult in the dermis.

It can affect the patient's quality of life, both physically and psychologically.

Hypertrophic scars are raised fibrous tissue scars that remains within the boundaries of the wound. Hypertrophic scars that resulted from surgery or trauma are called linear hypertrophic scars while those from burn injuries or extensive tissue trauma and/or infections are called widespread hypertrophic scars.

Keloids are elevated fibrous scars that extend beyond the borders of the original wound. Major keloids resulted from minor trauma while for those from genetic predisposition with autosomal-predominant features are called minor keloids.

 

 

Pharmacotherapy

Silicone Therapy

  • Gold standard in scar management & first-line non-invasive treatment option for hypertrophic scars & minor keloids
    • Preferred first-line due to its non-invasiveness, availability, ease of use, lesser adverse effects, & efficacy
    • Used alone or in combination w/ add-on therapies for all mild-moderate pathologic scars
    • Also used for severe scars after surgical excision
  • It should be used as soon as the wound/suture is healed but some silicone therapies can be applied to open wounds
  • Easy to use w/ minimal side effects such as pruritus, contact dermatitis & dry skin
  • The most commonly used medical silicone is the inert polymer polydimethylsiloxane
  • Silicone sheeting consists of a soft, semi-occlusive gel sheet made from medical-grade silicone that is reinforced w/ a silicone membrane backing to give the sheet increased durability & ease of handling
    • Silicone gel sheeting has been shown to have the ability to hasten hypertrophic scar maturation & decrease associated symptoms of pain, rigidity & pruritus
      • Occlusion w/ silicone gel sheeting decreases scar hypertrophy & reduces tension or stabilization effect in scar management
    • Silicone elastomer sheeting is usually used for 12-24 hours per day for 2-3 months
  • Recently, a self-drying silicone gel has been developed wherein the fluid silicone gel is applied in thin layer to the skin & when it dries it forms a transparent, flexible, gas-permeable, water-impermeable silicone sheet
    • This preparation provides “round the clock” coverage & can be used for closed wounds
  • A film-forming silicone gel-based wound dressing has been approved for open & closed wounds & compromised skin to protect it from microbial & bacterial infection
  • Silicone-based gel is as effective as silicone gel sheeting
  • In a randomized, double blind controlled study it was found that in sternotomy wounds, silicone gel minimizes the formation of hypertrophic scars in the early postoperative stage
    • It also shows that the silicone gel reduces pigmentation, vascularity, pliability, height, pain & itchiness

Intralesional Corticosteroids (eg Triamcinolone acetonide)

  • Given intralesionally as treatment for small & younger keloids as well as hypertrophic scars
    • Usually given in 2-3 injections a month apart for 6 months
  • Provides symptomatic relief by decreasing pruritus
  • Corticosteroids have suppressive effects on the inflammatory process in the wound & mitosis while increasing vasoconstriction in the scar
  • May be combined w/ cryotherapy that has shown to improve outcome in more than one modality alone, although hypopigmentation is always a significant concern
  • Injection should be limited to the scar itself & injection into the periscar tissue must be avoided as this may cause underlying fat atrophy

Intralesional 5-Fluorouracil

  • Treatment option for therapy-refractory keloids & as intralesional injection in patients w/ linear hypertrophic scar
  • As a pyrimidine analog, it inhibits the proliferation of fibroblasts & has been shown to treat inflamed hypertrophic scars
  • Combination w/ Triamcinolone results in shrinking of keloids while avoiding tissue atrophy & telangiectasia that may occur w/ repeated corticosteroid injections

Other Dermatologicals
Onion Extract-Based Topical Preparations

  • Adjunctive therapy for active hypertrophic scars
  • May be used in widespread burn hypertrophic scars although there are few evidences available
  • Inhibits fibroblast proliferation & collagen production by the flavonoids in onion extract (extractum cepae)
  • Acts as an anti-inflammatory & bactericidal agent
  • Recent studies show that it improves scar height & associated symptoms, though further studies are needed to confirm efficacy
  • Appeared to be effective for the prevention of unpleasant scars in patients having laser removal of tattoos & in combination w/ intralesional Triamcinolone acetonide in recent studies
  • Reviews show mixed results; further studies are needed to confirm efficacy

Emerging & Investigational Therapies

Bleomycin

  • Alternative therapeutic option for severe scars
  • Inhibits collagen synthesis via decreased stimulation by TGF-beta1
  • Some studies showed significant improvement in hypertrophic scar & keloid height & pliability & decrease in erythema, pruritus, & pain
  • Side effects are depigmentation, dermal atrophy & some toxicity
  • Further studies are needed to include this as part of the treatment protocols

Botulinum Toxin A

  • May present  as a novel therapeutic option for the aesthetic improvement of post-surgical scars
  • Immobilizes local muscles, decreases tensile forces on post-surgical scars, hereby decreasing microtrauma & subsequent inflammation
  • Clinical efficacy of intralesional botulinum toxin A for the treatment of existent keloids remains uncertain

Imiquimod

  • Can be considered treatment options for refractory keloids but currently not approved in this indication
  • A topical immune response modifier that stimulates the production of interferon that leads to increased collagen breakdown

Interferon

  • A promising therapeutic option for keloids resistant to any other treatment but needs further studies to establish a role in the prevention & management of pathologic scarring
  • Findings showed that it decreases collagen synthesis that provides improvement of excessive scars
  • Option as intralesional injection in patients w/ linear hypertrophic scar
Mitomycin C
  • Can be considered treatment option for refractory keloids & severe scars
  • There are limited available studies that merit as treatment consideration for hypertrophic scarring

Moisturizers (emollients, humectants)

  • Helps relieve symptoms such as itchiness & rigidity

Retinoic acid (Vitamin A derivatives)

  • Markedly reduce fibroblast proliferation by interfering w/ DNA synthesis & exhibit an inhibitory effect on TGF-beta1-induced type 1 collagen gene expression in the fibroblasts
  • Studies have shown marked reduction in scar size & decreased pruritus of intractable scars
  • Some suggests that low-dose of Isotretinoin may be used in the treatment of acne kelodalis
  • Should not be considered as first-line therapy for keloids

Verapamil

  • A calcium channel blocker that decreases collagen synthesis & increases collagen breakdown
  • Currently have insufficient evidence to recommend use in routine clinical practice
Vitamin C
  • A recent study has shown that topical application containing Vitamin C in a silicone gel reduced permanent scar formation in an Asian population
  • A water-soluble antioxidant that regulates collagen biosynthesis & regenerates vitamin E
  • As a depigmenting agent, Vitamin C reduces formation of melanin & also acts on the perifollicular pigment
  • Glycosaminoglycan helps in the effective skin penetration of Vitamin C

Non-Pharmacological Therapy

  • Both keloids & hypertrophic scars respond to the same therapies, but hypertrophic scars are easier to treat & have a better prognosis

Pressure Therapy

  • Decreases oxygen tension in the wound by decreasing collagen synthesis limiting capillary perfusion
  • Increased pressure in the matrix regulates apoptosis of dermal fibroblasts & diminishes the hypertrophic process
  • Uses pressure suits or bandages w/ transparent plastic marks or pressure buttons in special locations
  • Alleviates edema, itchiness & pain
  • Side effects such as eczema, maceration, & odor emanating from the pressure garment may cause non-compliance to this therapy
  • It can be an alternative to intralesional corticosteroid or cryotherapy for treatment of hypertrophic scars & keloids in younger children
  • Pressure garments use showed better results in children compared w/ adults

Other Non-pharmacological Therapies

  • Massage therapy
  • Static & dynamic splints
  • Psychological counseling

Cryotherapy

  • Effective treatment for older hypertrophic scars & larger keloids when combined w/ intralesional Triamcinolone acetonide
  • It freezes the scar tissue from inside & out that decreases the scar volume
  • It also induces vascular damage that leads to anoxia & tissue necrosis
  • Alternative therapeutic option for severe scars

Laser Therapy

  • Most commonly used lasers in the treatment of hypertrophic scars & keloids are:
    • Pulsed dye laser (PDL)
    • Fractional carbon dioxide (fCO2) laser
    • Intense pulsed light (IPL)
  • Pulsed-dye laser or ablative fractional laser therapy is indicated in the following:
    • Immature or linear hypertrophic scars that have persistent erythema (>1 month) even after preventive measures were done
    • Widespread hypertrophic burn scars that have not improved despite treatment for 8-12 weeks w/ silicone gel or sheeting, pressure garments &/or onion extract preparations
    • Minor keloids that have not improved after 8-12 weeks of silicone gel sheeting & intralesional corticosteroids
    • Major keloids that have not improved after treatment w/ intralesional corticosteroids & 5-FU
  • Pulsed-dye laser showed significant improvement in erythema, pruritus, & scar height that persists for at least 6 months
    • Principal effect is on scar microvasculature, decreasing erythema & pruritus & improving skin texture
  • Has shown to improve keloids or hypertrophic scars by inducing capillary destruction which generates hypoxemia & alters local collagen production by increasing collagenase
  • Non-overlapping laser pulses are currently recommended
  • 2-6 sessions are needed to successfully improve scar color, height, pliability & texture
  • Side effects include purpura, vesicles, crusts, hyperpigmentation, erythema, & reactivation of younger keloids
  • Nd:YAG laser that is short-pulsed, low-fluence & 1064-nm has been analyzed to be safe & effective in the treatment of facial acne scarring
  • Improvements in clinical & structural features of burn scars were reported w/ fractional CO2 laser therapy & is preferred for keloids
  • The fractional ablative CO2 laser has been shown to be highly effective in the treatment of hypertrophic scars, including cosmetic & functional enhancement of traumatic scars & contractures, w/ treatment ranging between 1 & 6 sessions
  • Intense Pulsed Light (IPL), although not technically a laser, delivers focused controlled light energy through a coupling gel across the 515-1200 nm spectrum & at a fluence of up to 40 J/cm2
    • Multiple studies have shown that IPL is helpful in the management of burn scar dyschromia, long-standing hypervascularity, & chronic folliculitis without the risks or downtime of PDL photothermolysis or laser resurfacing
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