Treating the Elusive Keloid

Surgical excision with a scalpel, primary closure, followed by local steroid injection is the best treatment for a keloid.

The optimal management of keloids continues to be an enigma for surgeons. The best modality of treatment has been debated for many years. Keloids occur after dermal trauma, surgery, insect bites, or acne, resulting in excessive connective tissue formation. Keloids are different from hypertrophic scars in that keloids grow beyond the boundaries of the original wound area. During the healing process, it is clinically difficult to determine if a scar will develop into a keloid or hypertrophic scar. Keloids gradually grow into large, raised amorphous masses that can cause pruritus, pain, and disfigurement. Histologically, keloids consist of dense dermal connective tissue with randomly oriented collagen fibers. The etiological factors that determine how a scar becomes a keloid remain unknown. Familial predisposition and immunological causes have been implicated.

Skin wound tension plays an important role in keloid formation. Areas of the body susceptible to keloid formation are the earlobes, mandibular angle, upper back, shoulders, posterior neck, upper arms, and anterior chest.¹ Keloids and hypertrophic scars can form in all races; however, darker-pigmented individuals are more predisposed. Among the African American, Hispanic, and Asian populations, keloids occur in 6% to 16% of individuals. Hormonal factors are also thought to contribute to keloid formation. Keloids can appear during puberty and regress after menopause. Patients with cutaneous disorders that have an inflammatory or infectious component, such as cellulitis, pilonidal cysts, and foreign-body reactions, have a special predisposition for keloids.

Presently, the treatment of keloids remains challenging (Table 1). Many techniques have been tried with variable degrees of success, including surgery alone, surgery followed by corticosteroids, laser excision, cryotherapy, silicone gel sheeting, pressure devices, oral colchicine therapy, and surgery followed by radiotherapy. Unfortunately, most studies have been either retrospective or case report descriptions. Currently, no matter what form of treatment is instituted, the likelihood of keloid recurrence remains high. In addition, keloids that have been previously treated or that are greater than 2 cm are even more likely to recur.

Studies have had significant variations in study design and methods of classifying the groups, and many have combined hypertrophic scars and keloids when describing the treatment regimens. In addition, many studies have incorporated treatment results from all regions of the body (chest, back, extremities, head and neck) in retrospective reviews. Follow-up periods after treatment have also varied; however, most authors now agree that at least a 12-month follow-up is needed. Furthermore, "treatment success" needs to be clearly defined. Conducting prospective studies with keloids has been difficult because many patients have not been compliant with postoperative follow-up visits.

Simple excision of keloids alone can result in a recurrence rate of 50% to 80%.² Some surgeons advocate leaving a rim of keloid at the perimeter to limit the chance of further irritating the surrounding tissue, minimizing recurrence. Although attractive, this principle has not been proven. With the combination of surgical excision followed by postoperative intralesional steroid therapy, recurrence rates have been reported to be less than 50%.³ After surgical excision, monofilament suture is preferred to braided types to minimize microabscess formation and inflammation along the suture. Undermining the surrounding tissue in the subcutaneous plant is important to minimize tension. Z-plasties and W-plasties should be avoided to prevent further scar formation, unless the scar traverses a concavity or an area of flexion.

Simple surgical excision, primary closure, and postoperative steroid injection are the most common forms of keloid treatment. Serial steroid injections do not eradicate keloids; however, they can diminish pruritus and pain and can soften the lesions. Intralesional corticosteroids are believed to act by inhibiting fibroblast growth and decreasing α₂-macroglobulin levels, which leads to collagen degradation. Corticosteroid preparations used for intralesional injection have included hydrocortisone, triamcinolone, and dexamethasone, with none found to be more advantageous. Several concentrations between 10 and 40 mg/mL can be used. In steroid-sensitive areas (eg, nose, eyelids, lips) that can undergo dermal atrophy, 10 mg/mL should be used initially. Following surgical excision of the keloid, the wound edges can be injected with steroids; however, one should consider leaving the sutures in place several days longer to decrease the risk of incisional dehiscence. After the initial dose, the patient should return in 3 to 4 weeks, and the injection should be repeated at a similar or higher dose if required.

The local adverse effects of steroid injections are associated with the dose given. They are hypopigmentation, dermal atrophy, teleangiectasia, necrosis, and ulceration. Doses less than 120 mg per month in adults and less than 80 mg per month in children (6-10 years old) are recommended. Systemic effects of intralesional steroid therapy have not been commonly reported. When corticosteroid is inadvertently injected into the surrounding dermis, dermal atrophy and hypopigmentation can result. A major disadvantage of using intralesional corticosteroid is the pain associated with the injection, which can lead to patient noncompliance in follow-up. Thus, some physicians have supported using transcutaneous infiltration (Dermo-Jet; Robbins Instruments Inc, Chatham, NJ) of a triamcinolone diacetate and lidocaine mixture for patients who have an aversion to needles.

Lawrence⁴ reported a 70% recurrence rate for keloids treated with surgery and postoperative triamcinolone injection. Thus, radiotherapy has been proposed as a form of keloid treatment. Radiotherapy to keloids is thought to destroy the proliferating fibroblast and neovascular buds, resulting in decreased collagen production. Radiotherapy alone without surgical excision is not an effective means of keloid treatment, since recurrence rates are between 50% and 100%. However, postoperative radiotherapy following excisions can be a successful means of minimizing keloid recurrence. The timing of the radiation administration (within 1 week after excision) and total dose given (700-1500 rad) appear to be important variables to reduce keloid recurrence.⁵

Proponents of radiotherapy frequently state that with surgical excision alone, the recurrence rate is 80%. With adjuvant postoperative radiation therapy, control rates are 70% to 90%.⁶ Either low-energy photons or electrons are used to limit the radiation dose to the skin, sparing the underlying tissues. Hoffman⁷ has reported a case of medullary carcinoma of the thyroid 8 years following surgery and irradiation (600 rad) for a chin keloid. However, another recent article⁸ supports an extremely low complication rate of radiotherapy for keloids. A previous dosimetry study showed that, with appropriate shielding, 1200 rad administered to the earlobe would result in a dose of only 2 rad to the ipsilateral thyroid lobe.⁶

In a randomized, prospective trial of earlobe keloids, Sclafani et al⁸ showed that surgery followed by radiation was associated with a trend for lower keloid recurrence rates (12.5%) compared with surgery with postoperative steroid injections (33%). Although no statistically significant difference (P>.05) was found between the 2 groups in this study, the authors believed that postoperative radiotherapy was more effective than postoperative steroid injections in preventing keloid recurrence, especially in the noncompliant patient. There were no complications such as chronic dermatitis, skin pigmentation, wound dehiscence, or neoplastic changes related to the postoperative radiation treatments. In another study, by Berman and Bieley,³ external-beam radiation after excision was associated with a recurrence rate of less than 10%.

The use of postoperative interstitial radiotherapy with iridium 192 has been reported with a 79% success rate, similar to that of external-beam techniques.⁹ Clavere et al¹⁰ evaluated the efficiency of keloidectomy and postoperative interstitial radiotherapy using an iridium 192 wire. They had an overall success rate of 63% with no adverse effects observed. The main complication from interstitial radiotherapy is hypopigmentation in 14% of cases. The advantages of this technique include a limited radiation volume, ease of application, and efficacy comparable to that of external-beam radiotherapy. Many surgeons have been reluctant to institute radiation treatment to keloids that are not located on the earlobe or are not refractory in nature.

Laser therapy was initially proposed as a means to effectively excise keloids without stimulating an excessive fibroblast response. In 1982, continuous-wave carbon dioxide laser treatments were used to excise keloids; this treatment was believed to be less traumatic than scalpel excision and to have anti-inflammatory properties.⁵ Initially, several reports were supportive of laser treatment; however, later results did not show significant advantages compared with use of a scalpel. Keloids excised using a carbon dioxide laser have been reported to have recurrence rates between 50% and 70%,⁸ similar to recurrence rates with conventional surgery.

Modifications in laser technology have produced 2 groups of carbon dioxide lasers: high-energy, short-pulsed carbon dioxide lasers that produce individual high-energy pulses (up to 500 mJ) with pulse durations of less than 900 microseconds and scanned continuous-wave carbon dioxide lasers that use a computer-controlled opticomechanical scanner to direct a focused, continuous wave in a spiral shape with an exposure time of 1 millisecond. Both of these lasers induce tissue vaporization with minimal coagulation. Bernstein et al¹¹ reported improved surface scar contour when treating keloids and hypertrophic scars in 24 patients with the high-energy, short-pulsed carbon dioxide laser and the scanned continuous-wave carbon dioxide laser.¹¹ Temporary adverse effects include erythema and hypopigmentation.

Alster and West¹² reported a 57% to 83% improvement in keloids after 1 or 2 treatments using the 585-nm flashlamp pulsed dye laser and later confirmed this finding in a second study of sternotomy scars. However, the optimal time to institute laser treatment for keloids has not been determined. Some propose that when the laser treatment is begun within the first few weeks after injury, further scar proliferation can be abated. Currently, when laser therapy is used, it is usually instituted in combination with other therapies. Further studies with long-term follow-up are needed to fully evaluate the keloid recurrence rate with laser therapies.

Cryotherapy has also been used to treat keloids. Cryosurgery uses a refrigerant to induce cell and microcirculatory damage leading to tissue necrosis and sloughing. Each session involves 2 or 3 freeze-thaw cycles within 30 seconds to treat the keloid. Two to 10 sessions may be required, separated by 25 days, to achieve flattening of the keloid. Isolated cryotherapy treatments result in keloid flattening in 74% of patients; for cyotherapy used in combination with intralesional steroid therapy, an 84% keloid response has been reported.¹³ Cryotherapy has often been combined with intralesional steroid injection. Some have described administering cryotherapy before intralesional steroid injection to allow for the edema and cellular injury from cryotherapy to subside. Others have used cryotherapy as an effective form of treatment for new keloids, reporting a good response in 74% of patients.¹⁴ However, repeated treatments were required (up to 10 times) before keloid shrinkage. An adverse effect of cryotherapy is hypopigmentation due to cold sensitivity of melanocytes. Thus, darker-skinned patients are at increased risk for hypopigmentation. In addition, postprocedure healing can be prolonged, requiring several weeks.

Mechanical pressure has been another approach to manage keloids. If continuous pressure (greater than capillary pressure [24 mm Hg]) is applied to a keloid day and night for 6 to 12 months, this can help the keloid to regress. It is believed that constant pressure decreases soft-tissue cellularity, increases interstitial space, and causes collagen bundles to be more widely dispersed. However, since continuous pressure application is required (>23.5 hours per day), this regimen is difficult to institute.¹⁵

Silicone gel sheeting has been shown to be effective to decrease pruritus and pain of scars at the same time, increasing scar pliability. However, scar elevation and pigmentation usually remain unaltered. Topical silicone gel sheeting is applied for at least 12 hours daily. One study showed that 79% of revised keloid scars treated immediately with silicone gel sheeting had no recurrence at 6 months.¹⁶ It is believed to work by maintaining scar hydration, which decreases capillary activity, proinflammatory cytokines, and collagen deposition.

Other, miscellaneous pharmacological therapies used to treat keloids include topical retinoic acid, colchicine, antihistamines, lathyrogens, putrescine, zinc, beta carotene, vitamin E, and verapamil, for all of which the efficacy is yet to be determined.

Interferon therapy has been used to treat keloids, based on the finding that interferons alfa, beta, and gamma inhibit collagen synthesis (collagen types I and III) in dermal fibroblasts. Several studies investigating intralesional interferon injections have reported both positive and negative results. Initial clinical trials of intralesional interferon gamma injections by Larrabee et al¹⁷ and Granstein et al¹⁸ showed promise, with interferon gamma as a possible adjunctive treatment to decrease the size of keloids. However, after a 2.5-year follow-up, Larrabee¹⁹ later reported that recurrences were evident, requiring more conventional therapies.

Berman and Flores²⁰ reported that simple excision of keloids resulted in a 51.1% recurrence rate; keloid excision with postoperative triamcinolone acetonide injection resulted in a 58.4% recurrence rate; and keloid excision with postoperative interferon alfa-2b injection resulted in an 18.7% recurrence rate. Thus, they did not show that postoperative triamcinolone acetonide injection reduced keloid recurrences, but injection of keloid excision sites with interferon alfa-2b appeared to have a therapeutic benefit compared with simple keloid excision.

Broker et al²¹ performed a double-blind, placebo-controlled trial in patients with 2 or more keloids treated with excision and subsequent local injections of interferon gamma or placebo. They found that interferon gamma did not prevent keloid recurrence. In most instances, interferon is well tolerated; however, the injections can be painful, requiring regional anesthesia. In addition, interferon injections can result in flulike symptoms, with low-grade fevers lasting up to 48 hours. Additional studies are required to clarify the correct dosing and delivery of interferon to treat keloids.

In reviewing the current literature, most studies support the stated hypothesis. However, the optimal treatment for keloids of the head and neck remains controversial. As with any disease, the treatment must be individualized. Factors to consider when choosing the optimal keloid treatment are the site and size of the lesion, keloid duration, and previous treatment.

A combination of treatments can be used in an effort to maximize the response. Lindsey and Davis²² performed a retrospective treatment analysis of 202 patients with keloids of the head and neck with at least a 2-year follow-up over a 15-year period. For a combination of treatments that included precise surgical excision, postoperative steroid infiltration, silicone sheeting, and conservative auricular radiotherapy, Lindsey and Davis found an acceptable 15% recurrence rate.

If the keloid has never been surgically excised, the keloid can be removed and closed primarily as long as excessive tension is not transmitted to the surrounding skin. Care should be taken to remove all sources of residual inflammation, such as trapped hair follicles, epithelial cysts, and dermal sinus tracts, which can act as nidi for future keloid growth. If excessive skin tension is anticipated in the primary closure, serial excisions within the keloid can be performed in several stages, leaving behind a small perimeter of keloid. One should not make incisions beyond the boundaries of the keloid to avoid "chasing the keloid" at a later date. Corticosteroid injection can begin the day of surgery and at monthly intervals for 4 to 6 months. The choice of scalpel vs laser depends on the surgeon's personal preference.

Another option for treating large keloids that cannot be closed primarily is excising the keloid, leaving a small rim of tissue to act as a splint to decrease central tensile contraction and placing a full-thickness skin graft in the defect. The small rim of tissue that is left behind is injected with corticosteroids. One should be reluctant to perform Z-plasties or W-plasties to avoid creating a keloid beyond the defect site or applying undue tension to the surrounding skin.

For recurrent earlobe keloids that are not responsive to excision and steroid treatment, repeat surgical excision followed by radiation therapy within 1 week of excision should be an option after careful discussion with the patient. For a patient who is less likely to follow up on a monthly basis for serial steroid injections over 6 months, postoperative radiotherapy to the earlobe keloid can be a useful option for adjunctive treatment for recurrent refractory earlobe keloids.

For recurrent keloids at other head and neck sites, postoperative radiation is more controversial. If a recurrent keloid is present on the lower anterior neck, many surgeons would be more reluctant to institute postoperative radiotherapy because of the risk of radiation exposure to the thyroid gland.

After excision, application of silicone occlusive dressing over the site for 12 hours per day for 6 months is optimal. An alternative to using silicone gel sheeting is to apply silicone cream occlusive dressing. For the earlobe, pressure clip-on earrings can be used.

Promising forms of treatment include using the short-pulsed carbon dioxide laser, the scanned carbon dioxide laser, or the pulsed dye laser (585 nm) for excising keloids, followed by intralesional corticosteroid injection. However, further studies with long-term follow-up are required to evaluate the keloid recurrence rate with these forms of laser therapy. In addition, a standardized grading system is needed to measure the volume and quality of keloids to allow for more objective treatment comparisons among different institutions.

Accepted for publication June 22, 2001.

The research for this article was supported by a grant from the Lions Multiple District 5M Foundation, Minneapolis, Minn.

Corresponding author and reprints: David B. Hom, MD, Division of Facial Plastic and Reconstructive Surgery, Department of Otolaryngology–Head and Neck Surgery, University of Minnesota School of Medicine, Box 396, 420 Delaware St SE, Minneapolis, MN 55455.