Keloids are benign fibroproliferative growths distinguished by excessive collagen deposition in the dermis. The exact etiology of these lesions remains unknown. They are considered a derailment of the normal wound healing process with a higher prevalence in darker pigmented races.
Keloids are often described as benign fibroproliferative growths resulting from a connective tissue response to a variety of insults, such as surgery, burns, trauma, inflammation, foreign-body reactions, endocrine dysfunction. However, they occasionally occur without apparent external cause. They are characterized by excessive collagen and glycosaminoglycan deposition within the dermis, an increase in collagen turnover, and micro-vasculature regeneration [6
]. Clinically, keloids may not appear for several months and can be delayed for several years after initial injury. Minor injuries can produce a fairly large, deep, and reddish-purple indurated lesion that rarely subsides. They can range in size from small papules limited to only a few millimeters in diameter to football size and larger. Their texture can vary between a soft and dough-like to a hard and rubbery consistency. These lesions most commonly affect areas of increased skin tension. Very rarely, keloids may develop on the palms of the hands, soles of the feet, and the genitalia [5
Keloid formation can be found in all ethnicities, but has a higher predilection for darker pigmented populations. Why occurrence rates are higher among these groups as opposed to others is inconclusive. Inheritance patterns may offer clues as to who could be at a greater risk of being predisposed to forming these types of lesions. Several reports have suggested that keloids follow an autosomal dominant or autosomal recessive inheritance pattern, although the exact mode of inheritance remains unknown. Maneros et al
. report observing 14 pedigrees with familial keloids that spanned 3 generations [5
]. While most families in the study where African-American, the report concludes that this may be associated more ethnicity rather than skin pigment, since some lighter-skinned members of the families had the more severe lesions. Through the use of a genome wide linkage screen, plausible gene loci for these keloid pedigrees were identified [6
]. Their results found a pattern consistent with an autosomal dominant mode of inheritance. Subsequent linkage analysis has revealed two distinct gene loci which may serve as specific susceptibility genes [11
In keloid lesions, the therapy chosen is predicated upon several factors, including: size of lesion, location, depth of lesion, age of patient, and past response to treatment. Surgical excision, radiation, pressure therapy, cryotherapy, intralesional injections of corticosteroids, interferon and fluorouracil, topical silicone and other dressings, and pulse-dye laser treatment have all been found to induce some degree of regression [12
]. Despite the broad range of treatment modalities, there is no universally accepted treatment protocol. In most instances these therapies are used as an adjuvant to surgical excision.
Radiation therapy has been a rather controversial issue in keloid treatment. Surgery-alone and adjuvant intralesional corticosteroid approaches exhibit literature reported recurrence rates of 45-100% and under 50%, respectively [7
]. Comparatively, extant radiotherapy series have demonstrated recurrence rates which are markedly better than surgery alone or adjuvant corticosteroid injection. A brief summary of selected English language series of teletherapy treatment for keloids are collated in Table . However, the only prospective randomized trial of any kind for keloids demonstrated greater control rates for surgical excision and radiotherapy compared to surgery and corticosteroid injection, with recurrence rates of 12.5% after surgery and radiation therapy, versus 33% after surgery and steroid injections, though with a statistically non-significant mean differential [8
]. The favorable outcomes with this approach are attributable to destruction of keloid fibroblasts by ionizing radiation, which has been shown to enhance apoptosis when given in small to moderate doses. In a study by Luo et al
., gamma radiation was found to cause a 2-fold increase in the density of apoptotic cells in both normal and keloid tissue [13
]. According to a study by Ragoowansi et al., using 60 kV photon irradiation of 10 Gy in a single fraction to treat 80 keloids in 80 patients, the majority of keloids can be controlled by a single operation with immediate adjuvant single-fraction radiotherapy [14
]. Unresectable keloids can also be treated satisfactorily with radiotherapy, as Malaker et al
. demonstrated by treating 64 patients with 86 unresectable keloids with 37.5 Gy was given in 5 fractions over a 5-week period[15
]. By 18 months 97% of patients had complete regression and 3% had partial regression. Surveyed, 63% of patients were happy with the outcome. Additional series have concurred that recurrent keloids may be successfully treated with the radiotherapy post-excision [16
], and have also explored brachytherapy as an option for patients failing primary therapy [17
]. Electron radiotherapy has also been used with good result. Maarouf et al. report a series of 134 keloids treated following surgical excision, with an 84% control rate) and minimal side effects, with a mean follow-up period of 7.2 years [9
]. Ogawa et al followed 129 keloid cases for 18 or more months after post-operative irradiation with 4-MeV electron beam radiation of 15 Gy [19
]. With a median follow-up period of 24 months, there was an overall 32.7% recurrence rate. The most common side effects of radiotherapy consist of hyperpigmentation, pruritis, and erythema. Additionally, there is a small, but notable, stochastic risk for future secondary malignancy inherent in any radiation exposure. However, at present, few series have exhibited notable secondary carcinogenesis[10
]; Dinh et al
] note that in a cumulative review by Ragoowansi [12
] five (5) possible
secondary malignancies were noted in 6,741 treated keloids, for crude risk of 1/1,348 patients, according to the literature. Consequently, patients must be informed and radiotherapy used judiciously, and with careful follow-up of patients over the course of their lives.
Summary of selected literature (WLE = wide local excision; RT = radiotherapy; Fx = fraction).
While no optimum treatment modality has been demonstrated for recurrent keloids in adults, surgical resection and adjuvant radiation therapy may provide an effective option, with notable clinical success rates. In summary, radiotherapy is, while not without risk, an exceedingly effective primary adjuvant or salvage therapy for some keloids (particularly large and recurrent tumors). Radiotherapy has been shown in extant series to exhibit better results than the other notable adjuvant therapy of choice, corticosteroid injection [8
], with a secondary malignancy risk that is minimal enough such that it should not preclude utilization [10