August 26, 2009 — Keloids and hypertrophic scars result from an exuberant healing response and are often difficult to distinguish and treat, according to a review of recommendations for family practitioners regarding treatment of keloids and hypertrophic scars, published in the August 1 issue of American Family Physician.

"Keloids are elevated fibrous scars that extend beyond the borders of the original wound, do not regress, and usually recur after excision," write Gregory Juckett, MD, MPH, and Holly Hartman-Adams, MD, from West Virginia University in Morgantown. "Hypertrophic scars are similar, but are confined to the wound borders and usually regress over time. Scar hypertrophy usually appears within a month of injury, whereas keloids may take three months or even years to develop."

Risk Factors, Development of Keloids

Risk factors for keloids are age younger than 30 years, darker skin, high-risk trauma such as burns or ear piercing, and any factor that prolongs wound healing. The areas most vulnerable to development of keloids are the sternal skin, shoulders and upper arms, earlobes, and cheeks. In contrast, hypertrophic scars may arise in any location but often occur on the extensor surfaces of joints.

Keloids and hypertrophic scars are both manifestations of abnormal responses to dermal injury. There are 3 main stages of overabundant collagen deposition: inflammation in the first 3 to 10 days after trauma; proliferation during the next 10 to 14 days; and maturation or remodeling, which begins at approximately 2 weeks and continues for years.

On histologic examination, hypertrophic scars have fewer thick collagen fibers and a scanty mucoid matrix, whereas keloids have thicker collagen fibers and a mucoid matrix. Hypertrophic scars usually flatten spontaneously in time, whereas keloids remain elevated more than 4 mm. Darkly pigmented skin is associated with a 15- to 20-fold increased risk for keloids, perhaps because of melanocyte-stimulating hormone anomalies. In contrast, hypertrophic scars are less associated with skin pigmentation.

If keloid formation is anticipated, it often can be prevented with immediate silicone elastomer sheeting, taping to reduce skin tension, or corticosteroid injections. However, keloids are challenging to treat once they have developed, and recurrence rate is high regardless of treatment.

Therapy for Keloids

Based on studies and other evidence to date, recommended first-line therapy for keloids includes silicone sheeting, pressure dressings, and intralesional corticosteroid injections. In 50% to 100% of cases, intralesional corticosteroid injections eventually flatten keloids. Use of cryotherapy to the keloid immediately before injection may improve efficacy, as well as facilitating the injection procedure.

Application of silicone sheeting is started as soon as wounds heal and is maintained for 2 to 3 months, for at least 12 hours per day. Many patients cannot use pressure dressings, which must be worn for 6 to 12 months to be effective.

Cryotherapy alone may be useful in some patients, but this should be used only for smaller lesions. Unless 1 or several of these standard treatments is used concurrently, surgical removal of keloids is likely to result in recurrence.

For refractory scars, alternative postsurgical therapies include pulsed dye laser, radiation, and possibly imiquimod cream. However, potential adverse effects of radiation therapy include growth retardation in young people and a possible risk for future cancer.

For established keloids, therapies that may be helpful include intralesional verapamil, fluorouracil, bleomycin, and interferon alfa-2b injections.

Potential advantages of fluorouracil are that this therapy may effectively reduce keloid size without causing tissue atrophy or telangiectasias, which may occur with corticosteroid injections. Less than 5% of bleomycin injected into the keloid reaches the bloodstream, and regression rates of 84% have been reported. Although interferon alfa-2b injections may have a rapid onset of action, they may be painful and are costly.

Evidence is mixed for the use of over-the-counter herb-based creams, such as onion extracts, although they are widely used. Similarly, limited evidence supports any benefits of vitamin E, which may cause dermatitis.

Key Recommendations for Practice

Key clinical recommendations for practice, all rated level of evidence B (inconsistent or limited-quality patient-oriented evidence) are as follows:

• For smaller lesions, such as acne keloids, cryotherapy is helpful, especially when combined with other treatment modalities.
• For the family physician, a practical first-line approach for the prevention and treatment of keloids and hypertrophic scars is intralesional corticosteroid injections.
• For the prevention and treatment of keloids and hypertrophic scars, silicone elastomer sheeting is a noninvasive, but time-intensive, first-line option.
• Especially for burns, pressure dressings or garments can effectively prevent hypertrophic scars.
• Combination therapy with surgery, silicone sheeting, and/or corticosteroid injections is an effective second-line option after failure of first-line treatments of keloids and hypertrophic scars.
• Although there is less evidence supporting their use, intralesional verapamil, fluorouracil, bleomycin, and interferon alfa-2b injections, as well as topical imiquimod 5% cream are reasonable alternatives to corticosteroids for keloid treatment and postoperative prevention.
• In limited clinical trials to date, onion extract topical gel or topical vitamin E have not shown lasting improvement of established keloids and hypertrophic scars.

"The treatments for keloids and hypertrophic scars are similar, but hypertrophic scars have a better prognosis," the review authors write. "The large number of treatment options is a reflection of the poor quality of research on this topic, with no single proven best treatment or combination of treatments. First-line options include silicone sheeting, pressure treatment, and corticosteroid injections, but all of these require exemplary adherence and follow-up."

The review authors have disclosed no relevant financial relationships.

Am Fam Physician. 2009;80:253-260.

Clinical Context

Clinical Implications

• Risk factors for the development of keloids include dark skin and delayed wound healing. The risk for the development of keloids is greatest between ages 10 and 20 years, and keloids are most commonly encountered over the sternum, shoulders and upper arms, earlobes, and cheeks.
• The current review suggests that first-line treatment options for keloids include corticosteroid injections, silicone sheeting, and pressure treatment. Topical vitamin E preparations appear to be ineffective in the treatment of keloids.

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