Hypertrophic scars and keloids can be described as variations of typical wound healing. In a typical wound, anabolic and catabolic processes achieve equilibrium approximately 6-8 weeks after the original injury. At this stage, the strength of the wound is approximately 30-40% that of healthy skin. As the scar matures, the tensile strength of the scar improves as a result of progressive cross-linking of collagen fibers. At this point, the scar is usually hyperemic and it may be thickened, but it tends to subside gradually over months until a flat, white, pliable, possibly stretched, mature scar has developed. When an imbalance occurs between the anabolic and catabolic phases of the healing process, more collagen is produced than is degraded, and the scar grows in all directions. The scar is elevated above the skin and remains hyperemic. Excessive fibrous tissue is classified as either a keloid or a hypertrophic scar.
Kischer and Brody declared the collagen nodule to be the identifying structural unit of hypertrophic scars and keloids.1 The nodule, which is absent from mature scars, contains a high density of fibroblasts and unidirectional collagen fibrils in a highly organized and distinct orientation. In addition, keloids and hypertrophic scars differ from healthy skin by a rich vasculature, high mesenchymal cell density, and thickened epidermal cell layer. Attempts to clinically differentiate keloids from hypertrophic scars have proved to be difficult in the early phases of formation. Clinical differences become more apparent as lesions mature. The most consistent histologic difference is the presence of broad, dull, pink bundles of collagen in keloids, which are not present in hypertrophic scars.
Only humans are affected by keloids, and both dominant and recessive modes of inheritance have been described. Although keloids occur in all age groups, they are rarely found in newborns or elderly persons and have the highest incidence in individuals aged 10-20 years.
Keloids and hypertrophic scars located at most sites are primarily of cosmetic concern; however, some keloids or hypertrophic scars can cause contractures, which may result in loss of function if overlying a joint or in significant disfigurement if located on the face. Keloids and hypertrophic scars can be both painful and pruritic.
Keloids and hypertrophic scars are associated genetically with HLA-B14, HLA-B21, HLA-Bw16, HLA-Bw35, HLA-DR5, HLA-DQw3, and blood group A.
Keloids form more frequently in Polynesian and Chinese persons than in Indian and Malaysian persons. As many as 16% of people in a random sampling of black Africans reported having keloids. White persons are least commonly affected.
The prevalence has been reported to be higher in young females than in young males, probably reflecting the greater frequency of earlobe piercing among females. Keloids and hypertrophic scars affect both sexes equally in other age groups.
Onset occurs most commonly in individuals aged 10-30 years. Keloids occur less frequently at the extremes of age, although an increasing number of presternal keloids have resulted from coronary artery bypass operations and other similar procedures now undertaken in persons in older age groups.
Keloids and hypertrophic scars do not usually cause symptoms, but they may be tender, painful, or pruritic or they may cause a burning sensation. In addition to symptomatic relief, cosmetic concern is the primary reason patients seek medical intervention.
Origins of lesions
Keloids manifest as exaggerated growths of scar tissue, usually in areas of previous trauma. Keloids extend past the areas of trauma, projecting above the level of the surrounding skin, but they rarely extend into underlying subcutaneous tissue.
Hypertrophic scars remain limited to the traumatized area and regress spontaneously within 12-24 months, although regression may not necessarily be complete.
Clinical findings in lesions
Keloids range in consistency from soft and doughy to rubbery and hard. Studies have demonstrated how to differentiate and classify keloids according to how they feel. Early lesions are often erythematous. Lesions become brownish red and then pale as they age. Lesions are usually devoid of hair follicles and other functioning adnexal glands. Note the images below.
Keloid. Courtesy of Dirk M. Elston, MD.
Keloid. Courtesy of Dirk M. Elston, MD.
Keloid. Courtesy of Dirk M. Elston, MD.
Once lesions occur, the clinical course varies. Most lesions continue to grow for weeks to months and others grow for years. Growth is usually slow, but keloids occasionally enlarge rapidly, tripling in size within months. Once they stop growing, keloids do not usually cause symptoms and remain stable or involute slightly.
Keloids on the ears, neck, and abdomen tend to be pedunculated. Keloids on the central chest and extremities are usually raised with a flat surface, and the base is often wider than the top.
Most keloids are round, oval, or oblong with regular margins; however, some have clawlike configurations with irregular borders. Keloids overlying a joint can contract and restrict movement.
Most patients present with 1 or 2 keloids; however, a few patients, especially patients with spontaneous keloids, have multiple lesions, as do patients who develop keloids as a consequence of acne or chickenpox.
Frequency of lesion sites
In white persons, keloids tend to be present, in decreasing order of frequency, on the face (with cheek and earlobes predominating), upper extremities, chest, presternal area, neck, back, lower extremities, breasts, and abdomen.
In black persons, the descending order of frequency tends to be earlobes, face, neck, lower extremities, breasts, chest, back, and abdomen.
In Asian persons, the descending order of frequency is earlobes, upper extremities, neck, breasts, and chest.
The exact mechanisms of keloid and hypertrophic scar pathogenesis continue to be an enigma for physicians and researchers alike, and no specific gene or set of genes has been identified; however, the increased prevalence of keloids paralleling increased cutaneous pigmentation suggests a genetic basis or, at least, a genetic linkage. Trauma to the skin, both physical (eg, earlobe piercing, surgery) and pathological (eg, acne, chickenpox), is the primary cause identified for the development of keloids. The presence of foreign material, infection, hematoma, or increased skin tension can also lead to keloid or hypertrophic scar formation in susceptible individuals.
No single therapeutic modality is best for all keloids. The location, size, and depth of the lesion; the age of the patient; and the past response to treatment determine the type of therapy used.
Prevention is key, but therapeutic treatment of hypertrophic scars and keloids includes occlusive dressings, compression therapy, intralesional corticosteroid injections, cryosurgery, excision, radiation therapy, laser therapy, interferon (IFN) therapy, 5-fluorouracil (5-FU), doxorubicin, bleomycin, verapamil, retinoic acid, imiquimod 5% cream, tamoxifen, tacrolimus, botulinum toxin, and over-the-counter treatments (eg, onion extract; combination of hydrocortisone, silicon, and vitamin E).
Other promising therapies include antiangiogenic factors, including vascular endothelial growth factor (VEGF) inhibitors (eg, bevacizumab), phototherapy (photodynamic therapy [PDT], UVA-1 therapy, narrowband UVB therapy), transforming growth factor (TGF)–beta3, tumor necrosis factor (TNF)-alpha inhibitors (etanercept), and recombinant human interleukin (rhIL-10), which are directed at decreasing collagen synthesis.
Prevention is the first rule in keloid therapy. Avoid performing nonessential cosmetic surgery in patients known to form keloids; however, the risk is lower among patients who have only earlobe lesions. Close all surgical wounds with minimal tension. Incisions should not cross joint spaces. Avoid making midchest incisions, and ensure that incisions follow skin creases whenever possible.
These include occlusive dressings, compression therapy, and intralesional corticosteroid injections.
Occlusive dressings include silicone gel sheets and dressings, nonsilicone occlusive sheets, and Cordran tape. These measures have been used with varied success. Antikeloidal effects appear to result from a combination of occlusion and hydration, rather than from an effect of the silicone.
Previous studies have shown that in patients treated with silicone occlusive sheeting with pressure worn 24 h/d for up to 12 months, 34% showed excellent improvement, 37.5% showed moderate improvement, and 28% demonstrated no or slight improvement.
Of patients treated with semipermeable, semiocclusive, nonsilicone-based dressings for 8 weeks, 60% experienced flattening of keloids, 71% had reduced pain, 78% had reduced tenderness, 80% had reduced pruritus, 87.5% had reduced erythema, and 90% were satisfied with the treatment.
Cordran tape is a clear surgical tape that contains flurandrenolide, a steroid that is uniformly distributed on each square centimeter of the tape, and it has been shown to soften and flatten keloids over time.
Compression therapy involves pressure, which has long been known to have thinning effects on skin. Reduction in the cohesiveness of collagen fibers in pressure-treated hypertrophic scars has been demonstrated by electron microscopy.
Compression treatments include button compression, pressure earrings, ACE bandages, elastic adhesive bandages, compression wraps, spandex or elastane (Lycra) bandages, and support bandages. In one study, button compression (2 buttons sandwiching the earlobe applied after keloid excision) prevented recurrence during 8 months to 4 years of follow-up observation.
Other pressure devices include pressure earrings and pressure-gradient garments made of lightweight porous Dacron, spandex (also known as elastane), bobbinet fabric (usually worn 12-24 h/d), and zinc oxide adhesive plaster. Overall, 60% of patients treated with these devices showed 75-100% improvement.
Corticosteroids, specifically intralesional corticosteroid injections, have been the mainstay of treatment. Corticosteroids reduce excessive scarring by reducing collagen synthesis, altering glucosaminoglycan synthesis, and reducing production of inflammatory mediators and fibroblast proliferation during wound healing. The most commonly used corticosteroid is triamcinolone acetonide (TAC) in concentrations of 10-40 mg/mL administered intralesionally with a 25- to 27-gauge needle at 4- to 6-week intervals.
Intralesional steroid therapy as a single modality and as an adjunct to excision has been shown to be efficacious in various studies. Response rates varied from 50-100%, with recurrence rates of 9-50% in completely resolved scars. When combined with excision, postoperative intralesional TAC injections yielded a recurrence rate of 0-100%, with most studies citing a rate of less than 50%. Complications of repeated corticosteroid injections include atrophy, telangiectasia formation, and pigmentary alteration.
New treatments for keloids and hypertrophic scars include intralesional IFN; 5-FU; doxorubicin; bleomycin; verapamil; retinoic acid; imiquimod 5% cream; tacrolimus; tamoxifen; botulinum toxin; TGF-beta3; rhIL-10; VEGF inhibitors; etanercept; mannose-6-phosphate inhibitors (M6P); etanercept; onion extract; the combination of hydrocortisone, silicon, and vitamin E; PDT; intense pulsed light (IPL); UVA-1; and narrowband UVB.
Combination of therapeutic agents
A combination of therapeutic agents, created in theory to obtain a beneficial synergistic effect in the treatment of keloids and hypertrophic scars, has been developed that contains 0.5% hydrocortisone, 0.5% vitamin E, and 12% silicone. Each of the 3 components has been demonstrated, in varying degrees, to be effective for the treatment of keloids and hypertrophic scars.
Corticosteroids inhibit collagen synthesis, stimulate collagenase activity, enhance collagen degradation, decrease the proliferation of inflammatory mediators in wounds, decrease fibroblast proliferation, and decrease GAG synthesis. Silicone provides occlusion and hydration to the wound surface. Occlusion decreases collagen formation, mitogenic activity, and capillary formation. In addition, silicone induces a negative ionic charge at the wound surface, inhibiting collagen formation. Vitamin E has been postulated to inhibit collagen synthesis, stimulate collagenase expression, decrease fibroblast proliferation, and reduce inflammation in the wound.
Surgical treatments include cryotherapy, removal/excision, laser therapy, and other light therapies.