A Closer Look at Keloids
Keloids are abnormal scars characterized by excessive scar tissue formation. Clinically, these elevated scars demonstrate extension beyond the original border of the wound. Hypertrophic scars differ from keloids in that they remain within the confines of the wound and are only slightly raised.
Who’s Affected and
How Do These Lesions Form?
Keloids are most commonly seen in African-American, Asian and Hispanic populations. Statistics on the incidence of keloids in specific populations vary greatly; however, an incidence of 4.5% to 16% has been reported in black and Hispanic patients. Keloids are least common in Caucasians and albinos.1
Patients with keloids usually present in the second or third decade. There is an equal risk between women and men. Although most keloids occur sporadically, many cases are familial. These cases appear to have an autosomal dominant pattern with incomplete penetrance and variable expression.2
Commonly affected sites for keloids include earlobes, shoulders, the upper back and the chest. Keloids are also rarely seen on the cornea. Unlike hypertrophic scars, which can improve with time, keloids do not spontaneously regress. Once excised, they tend to recur. Patients with keloids often complain of pruritus and tenderness at the site of the keloid. These symptoms are most severe in new scars and tend to diminish with time.
Histopathology of keloidal tissue reveals a thickened dermis consisting of hypereosiniphilic, hyalinized collagen. Few adnexal structures or elastic fibers are observed. Hypertrophic scars are more cellular than keloids and hyalinized collagen is less
prominent.3
The mechanism behind keloid formation has not yet been found; however, abnormal fibroblast metabolism and enhanced response to growth factors have been implicated. Other theories propose aberrant apoptosis in keloid fibroblasts.4 Abnormal epidermis-dermis interaction has also been suggested.5 Hypoxia has been proposed to play a role in keloid formation due to occluded microvessels in keloid tissue.6 Others suggest that excess nitric oxide, a free radical that stimulates collagen synthesis, is an inciting factor.7 Unfortunately, despite multiple investigations a clear understanding of keloid biology has not yet been realized.
Examining Treatment Options
Due to the recalcitrant nature of keloids and an unclear understanding of their cause, many different therapies have been utilized in the treatment of keloids. Traditional treatment options include excision and intralesional steroids.
Excision. If only this method of removal is performed, keloids have a recurrence rate of approximately of 45% to 100%.8 As a result, adjunctive therapy is recommended once keloids are excised. Recurrence rates after excision correlate closely with the location of the keloid. Areas of high stretch tension such as the chest and scapular region have much higher recurrence rates than areas of low tension such as the earlobe and face.9 Excision of keloids in the presternal chest area should be approached with caution due to the extremely high risk of recurrence even with adjunctive therapy.
Steroid therapy. Corticosteroids downregulate collagen production and have been a mainstay in the treatment of keloids.10 Intralesional steroids are especially helpful in alleviating the symptoms of itching and pain. Doses range from 20 mg to 120 mg of triamcinolone acetonide (Kenalog, Aristocort) per treatment performed at 2- to 4-week intervals. The higher doses can be utilized to flatten and soften some keloids; however, these benefits are limited in large, nodular lesions. Side effects include epidermal atrophy and overlying telangiectasias. In darker-skinned patients, transient hypopigmentation invariably occurs. There have been reports of Cushing’s syndrome after intralesional steroid injections for keloids. Although a few cases were described in adults, this phenomenon appears to be more common in children.11 Based on these reports, dosing of intralesional steroids for the treatment of keloids should be conservative in children.
Topical steroids are most commonly used to alleviate symptoms of keloids. Steroid impregnated flurandrenolone tape may be helpful as an adjunctive therapy for excised keloids.12
Cryotherapy. This method has been used in keloids to induce necrosis and subsequently debulk keloidal tissue. Cryotherapy can flatten small keloids, however, traditional cryotherapy has limitations with its ability to flatten larger lesions. Additionally, the extensive hypopigmentation following cryotherapy is undesirable. For these reasons, intralesional cryosurgery with hypodermic and lumbar puncture needles has been utilized to treat large bulky keloids and to decrease the extent of hypopigmentation observed with traditional cryotherapy.
The investigators inserted the needle directly through the keloid until it emerged on the other side and sprayed liquid nitrogen through the needle. They performed two freeze-thaw cycles per session for a total of 5 to 10 sessions. Hypopigmentation was noted along the course of the needle, which improved during follow-up in most patients. Additionally, 7 out of 12 patients showed greater than 75% flattening. This mode of cryotherapy may offer a novel treatment option for large bulky recalcitrant keloids.13
Occlusive dressings. Silicone is the most widely used and reported occlusive dressing in the treatment of keloids. Although there has been conflicting data on the efficacy of other types of occlusive dressings, it appears that most occlusive dressings decrease symptoms in patients with keloids.
Cytokine mRNA changes have been demonstrated in hypertrophic scars treated with both silicone and nonsilicone gel dressings. This study suggests that there may be molecular evidence for the clinical improvement observed with occlusion therapy.14
Radiation. Radiation is commonly used in the treatment of recalcitrant keloids. Radiation has been utilized both as monotherapy and as an adjunct to excision in treating keloids. Superficial X-rays are most commonly used; however, other forms of radiation such as electron beam therapy have also been utilized. Most studies report favorable outcomes with adjunctive radiation therapy.9,15
Lasers. Lasers treatments have offered moderate success in the management of keloids. The carbon dioxide laser has been used to excise keloids, but recurrence rates were high.16 Consequently, carbon dioxide laser excision appears to have no advantage over traditional surgery. The pulsed dye laser has been shown to be effective in treating existing hypertrophic scars and keloids. After treatment of sternotomy scars with the 585 nm pulsed dye laser, investigators noted improvement in erythema, pruritus, scar height and scar texture.17
Other therapies. Other reported therapies include intralesional verapamil, intralesional 5-fluorouracil, and intralesional interferon.18,19,20 Topical imiquimod (Aldara) applied daily for 6 weeks after surgery was effective in decreasing the recurrence rate in excised keloids.21 Bleomycin has also been reported topically in the treatment of keloids with some success.22
Most recently, researchers have been able to accomplish gene transfer into keloid tissue. The adeno-associated virus vector was successfully transfected into human keloid specimens. Transfection of a functional gene into deficient keloid tissue may prove to be most helpful in the treatment of keloids in the future.23 However, finding the dysfunctional gene or genes in these disfiguring scars remains the biggest challenge. Further elucidation of keloid biology will surely lead to more effective treatment of this condition.
References
1. Berman B. Bieley HC. Keloids. J Am Acad Dermatol. 1995;33(1):117-23.
2. Marneros A, Norris J, Olsen B, Reichenberger E. Clinical genetics of familial keloids. Arch of Dermatol. 2001;137(11):1429-34.
3. McKee P. Tumors of the Dermis and Subcutaneous Fat. In:
Pathology of the Skin with Clinical Correlations. 2nd edition. London, UK: Mosby. 1996, pp. 16.8-16.9.
4. Chodon T. Sugihara T. Igawa HH. Funayama E. Furukawa H. Keloid-derived fibroblasts are refractory to Fas-mediated apoptosis and neutralization of autocrine transforming growth factor-beta1 can abrogate this resistance. Am J Path. 2000;157(5):1661-9.
5. Lim IJ. Phan TT. Song C. Tan WT. Longaker MT. Investigation of the influence of keloid-derived keratinocytes on fibroblast growth and proliferation in vitro. Plast Reconstr Surg. 2001;107(3):797-808.
6. Steinbrech DS. Mehrara BJ. Chau D. Rowe NM. Chin G. Lee T. Saadeh PB. Gittes GK. Longaker MT. Hypoxia upregulates VEGF production in keloid fibroblasts. Annals Plast Surg. 1999;42(5):514-9; discussion 519-20.
7. Cobbold CA. The role of nitric oxide in the formation of keloid and hypertrophic lesions. Medical Hypotheses. 2001;57(4):497-502.
8. Shaffer JJ. Taylor SC. Cook-Bolden F. Keloidal scars: a review with a critical look at therapeutic options J Am Acad Dermatol. 2002;46(2 Suppl Understanding):S63-97.
9. Ogawa R. Mitsuhashi K. Hyakusoku H. Miyashita T. Postoperative electron-beam irradiation therapy for keloids and hypertrophic scars: retrospective study of 147 cases followed for more than 18 months. Plast Reconstr Surg. 2003;111(2):547-53; discussion 554-5.
10. Kauh YC. Rouda S. Mondragon G. Tokarek R. diLeonardo M. Tuan RS. Tan EM. Major suppression of pro-alpha1(I) type I collagen gene expression in the dermis after keloid excision and immediate intrawound injection of triamcinolone acetonide. J Am Acad Dermatol. 1997;37(4):586-9.
11. Teelucksingh S. Balkaran B. Ganeshmoorthi A. Arthur P. Prolonged childhood Cushing’s syndrome secondary to intralesional triamcinolone acetonide. Annals of Tropical Paediatrics. 2002;22(1):89-91.
12. Rauscher GE. Kolmer WL. Treatment of recurrent earlobe keloids. Cutis. 1986;37(1):67-8.
13. Gupta S. Kumar B. Intralesional cryosurgery using lumbar puncture and/or hypodermic needles for large, bulky, recalcitrant keloids. Int J of Dermatol. 2001;40(5):349-53.
14. Ricketts CH. Martin L. Faria DT. Saed GM. Fivenson DP. Cytokine mRNA changes during the treatment of hypertrophic scars with silicone and nonsilicone gel dressings. Dermatol Surg. 1996;22(11):955-9.
15. Klumpar DI. Murray JC. Anscher M. Keloids treated with excision followed by radiation therapy. J Am Acad Dermatol. 1994;31(2 Pt 1):225-31.
16. Norris JE. The effect of carbon dioxide laser surgery on the recurrence of keloids. Plast Reconstr Surg. 1991;87(1):44-9; discussion 50-3.
17. Alster TS. Williams CM. Treatment of keloid sternotomy scars with 585 nm flashlamp-pumped pulsed-dye laser. Lancet. 1995;345(8959):1198-200.
18. D’Andrea F. Brongo S. Ferraro G. Baroni A. Prevention and treatment of keloids with intralesional verapamil. Dermatol. 2002;204(1):60-2.
19. Gupta S. Kalra A. Efficacy and safety of intralesional 5-fluorouracil in the treatment of keloids. Dermatol. 2002;204(2):130-2.
20. Berman B, Duncan MR. Short-term keloid treatment in vivo with human interferon alfa-2b injections results in a selective and persistent normalization of keloidal fibroblast collagen, glycosaminoglycan, and collagenase production in vitro. J Am Acad Dermatol 1989;21:694-702.
21. Berman B. Kaufman J. Pilot study of the effect of postoperative imiquimod 5% cream on the recurrence rate of excised keloids. J Am Acad Dermatol.2002;47(4 Suppl):S209-11.
22. Espana A. Solano T. Quintanilla E. Bleomycin in the treatment of keloids and hypertrophic scars by multiple needle punctures. Dermatol Surg.2001;27(1):23-7.
23. Ma H. Xu R. Cheng H. Kuo HS. During M. Fang RH. Gene transfer into human keloid tissue with adeno-associated virus vector. J of Trauma-Injury Infection & Critical Care. 2003;54(3):569-73.
















