Keloids and Hypertrophic Scars

Overview of Presentation

• Discussion of and definition of hypertrophic and keloid scars.
• Review of the normal wound healing process.
• Aberrant healing in keloid and hypertrophic scar formation.
• Current treatment options.

Definitions of Keloid Scars

·         Scar tissue that progressively invades surrounding tissue, characterized by overabundant collagen deposition.

·         Benign dermal tumors secondary to abnormal wound healing.

·         Thick scars of human skin or cornea, produced by deposition of excessive amounts of collagen over prolonged periods.

Definition of Hypertrophic Scars

• Scar tissue which remains confined to the area of tissue damaged by the original injury, and increases in size by pushing out the margins of the scar, not by invasion of surrounding normal tissue.

Features of Keloids

• Only affects humans.
• Genetic link probable but mode of inheritance is unclear.
• Higher incidence with dark pigmented races
• Increased incidence associated with HLA types B14, BW16, and blood group A.
• Association with concentration of melanocytes in skin.
• No sex predilection.
• Can occur at any age, highest frequency at ages 10-30.
• Can occur up to 1 year post injury, with a reported 24 year lag time in the literature.
• Size of the lesion does not correlate to the initial injury.
• Lesion margin extends beyond margin of original injury.
• Regression is rare.

Clinical Features with Keloids

• Presternal area, upper back, and post neck are most susceptible, followed by ears, deltoid, anterior chest and beard areas.
• Varied clinical appearance: pedunculated and multilobular to smooth with regular margins.
• Rarely penetrate subcutaneous tissues.
• Can project above surrounding skin from a few millimeters to 2-3 cm’s.
• Consistency from firm and rubbery to rock hard.
• Seldom associated with pin.
• Pruritus is commonly noted.
• Contracture and loss of range of motion is reported.
• May continue to increase in size over time.

Features of Hypertrophic Scars

• Affect only humans.
• No genetic predisposition noted.
• No sex or age predilection.
• No racial predilection noted.
• Frequently develops in 2nd and 3rd degree burns.
• Can affect any body area but more common in the extremities and the trunk.
• Wounds crossing joints and at right angles to skin creases are more susceptible.
• Size of lesion commensurate with original injury.
• Scarring is limited to boundaries of original injury.
• May regress spontaneously in 12-18 months.
• Tends to improve with surgical correction.

Histopathology of Keloid Scars

• Haphazard deposition of collagen fibers in the dermis.
• Extracellular matrix is mucinous with eosinophils, mast cells, plasma cells, and lymphocytes.
• Collagen appears as thick hyalinized bands in nodular formation.
• Nodules are a dense mass of fibroblasts and collagen encircled by small vessels.

Histopathology of Keloid Scars

• Electron microscopy shows partial to full occlusion of the vessels secondary to excessive endothelial proliferation.

Histopathology of Hypertrophic Scars

• Increased collagen bundles, in parallel relation to the skin surface.
• Increase numbers of fibroblasts.
• No increase extracellular matrix.
• No nodules, however this is debated.
• Microvascular occlusion is common.

Overview of Normal Wound Healing

• Phase One: Inflammation
• Phase Two: Tissue formation
• Phase Three: Tissue remodeling
• Characterized by a balance between collagen deposition and lysis.

Phase One: Inflammation

• Begins immediately and lasts for approximately 2-3 days (uncomplicated scenario).
• Goal to remove damaged tissue and foreign debris and reestablish immunologic control.
• Numerous inflammatory mediators are stimulators of collagen formation.

Phase Two: Tissue Formation

• Begins at approximately 72 hrs and continues for 3 - 6 weeks.
• Objective: reestablish functional structural integrity of the injured tissue ASAP.
• Predominated by macrophages, fibroblasts and capillary endothelial cells.

Phase Three: Remodeling

• Characterized by a replacement of the previously randomly deposited collagen fibers into an organized array.
• Macrophages and fibroblasts predominate.
• Can last from 6-12 months.

What Goes Wrong?

• Increased collagen production as opposed to decreased collagen breakdown appears to be the key element in keloids and hypertrophic scars.
• Keloids: 20x greater than normal collagen synthesis.
• Hypertrophic scars: 7x greater collagen production than normal.
• In both types of aberrant scarring there is also an increase in collagenase activity, yet this fails to provide the needed collagen lysis.
• IgE and histamine have been implicated in the enhanced collagen production associated with keloids.
• Increases in growth factors in both scar types have also been implicated (sp. TGF- ).

Treatment Options

• Surgery
• Radiation therapy
• Pressure
• Silicone Gel Sheets
• Laser Surgery
• Corticosteroids
• Cryotherapy
• Interferon
• Cryotherapy
• Interferon therapy
• Other Pharmacologic agents
• Combination therapy

Surgery

• Hypertrophic scar: can obtain acceptable results, need to adhere to solid surgical principles.
• Keloids: reported 50-80% recurrence with surgery alone.
• Reorientation of scar along skin tension lines is crucial.
• Tension free closure essential.
• Combined therapy with steroids is common.

Radiation Therapy

• Controversial treatment modality.
• Usual dose 1500-2000 rads.
• Recurrence rate alone 50-100%, combined with surgery decreases to 12%.
• Uncertain of long term effects of radiation therapy, possible carcinogenic effect.
• Brachytherapy has been used.
• In general, radiation therapy is used as a second or third line treatment modality.

Pressure Dressings

• Multiple mechanisms of action proposed.
• Technique sensitive: must have greater than 24 mm Hg pressure (capillary pressure).
• Must be maintained 24 hrs/day for 6-12 months.
• Patient compliance is crucial.

Silicone Gel Sheeting

• Mechanism of action through scar hydration, postulated that hydration via decreased evaporation results in decreased capillary action thus decreased collagen production secondary to decrease in cytokine delivery.
• Silicone has no direct action.

Laser Surgery

• Pulsed dye laser seems to be effective in the treatment of both types of scars.
• Probable mechanism is through elimination of neovascularization.
• Other laser systems seem to have increased risks.
• Can be utilized in a combination treatment with corticosteroids.

Corticosteroids

• Mechanism of action through inhibition of fibroblast growth and inhibiting  2 -macroglobulin, resulting in collagen degradation.
• Injected directly into the lesion.
• Not curative alone, thus used in combo therapy.
• Pain is associated with injection.
• Side-effects include skin atrophy, depigmentation, and telangiectasias.

Corticosteroid Regimen

• 10 - 80 mg of triamcinolone injected into the lesion at 4-6 week intervals.
• Duration of treatment based on clinical response.
• Multiple regimens have been utilized.

Interferon

• Interferon ( ,  ,  ) inhibits type I and III collagen synthesis in dermal and synovial fibroblasts.
• Painful injections and flu like symptoms post-injection.
• 10-200 g injected 2x/week for four weeks.
• Not a widely utilized treatment modality.

Cryosurgery

• Mechanism of action via direct cell and circulatory damage. Providing stasis, thrombus, and anoxia, and resultant necrosis and sloughing, then a flattening of the scar.
• 2-3 freeze cycles at each treatment visit, 2-10 visits separated by 20-30 days.
• 50-70% success rate.

Other Pharmocologic Treatments

• 5-FU
• Topical Retinoic Acid
• Topical Putrescine
• Injected Verapamil

The End