INTRODUCTION
As one of the most common benign lesions, over 83 million Americans are estimated to be affected by seborrheic keratoses (SKs).1,2 The prevalence of SKs increases with age – nearly 100% of patients over 50 years old have SKs, with the average number per patient ranging from 9 to 23.3,4 Excluding the palms, soles, and mucous membranes, SKs can occur anywhere on the body.5 These benign epithelial tumors present as round to oval, sharply demarcated papules or plaques that appear “stuck on.”6
Despite being prevalent, the pathogenesis of SKs is not fully elucidated. Investigation of the molecular mechanisms identified at least two mutations, in fibroblast growth factor receptor 37 and the oncogenic phosphoinositide 3-kinase pathway,8 that may influence the development of SKs. Additionally, increased cyclin-dependent kinase inhibitor p16 and anti-apoptotic bcl-2 may mediate inhibition of apoptosis in seborrheic keratinocytes.9,10 The human papillomavirus (HPV) has also been proposed to influence the formation of SKs given one study found HPV DNA in 76% of non-genital SKs, but the authors were skeptical about HPV being a true causative factor given multiple HPV types were found in one specimen.11 Further, HPV can be found in normal skin.10 Similar to the pathogenesis, the etiologic risk factors for SKs are not completely understood. Increasing age is a known risk factor as demonstrated by numerous prevalence studies.3,4 Ultraviolet light exposure may also increase the risk of SKs, but the evidence is conflicting with two studies showing that SKs are associated with sun exposure,3,4 but another study finding that they are not.12 Finally, friction may contribute to the development of SKs as they often occur in intertriginous areas.5
Patients often desire treatment for SKs out of concern that the skin finding is something serious, for cosmetic reasons, or for symptomatic relief as they can become irritated, painful, or pruritic.5,13 SKs are typically diagnosed clinically, but histologic confirmation is recommended for atypical, inflamed, or changing lesions.6 In these cases, a shave excision should be done to preserve tissue for diagnosis.5 Table 1 presents the current treatment options for SKs, including cryotherapy, surgical techniques, and topical therapies. Cryotherapy is the most common treatment,5 however, this therapy and the surgical techniques presented in Table 1 can lead to pigmentary changes, especially in patients with Fitzpatrick Skin Type IV-VI.5 Cryotherapy and surgical techniques can also cause bleeding, pruritus, or scarring.5,14–21 To avoid these adverse effects, various topical therapies have been utilized to treat SKs (Table 1). The efficacies of keratolytics including ammonium lactate, imiquimod, and tazarotene have been examined but overall, these therapies had limited success in small clinical trials.2,22,23 Topical vitamin D analogs have also been used, but similarly, these had limited efficacy for treating SKs.2,24 Given the inadequacy of existing topical therapies, safe and effective non-invasive therapies are still needed. One novel therapy is BL-5010, a combination of trichloroacetic acid and formic acid. In a phase I/II open-label trial, a single treatment with BL-5010 resulted in a complete response in 90% of patients and partial response in 7% of patients six months after application (n=60).25 The medication was well-tol
Despite being prevalent, the pathogenesis of SKs is not fully elucidated. Investigation of the molecular mechanisms identified at least two mutations, in fibroblast growth factor receptor 37 and the oncogenic phosphoinositide 3-kinase pathway,8 that may influence the development of SKs. Additionally, increased cyclin-dependent kinase inhibitor p16 and anti-apoptotic bcl-2 may mediate inhibition of apoptosis in seborrheic keratinocytes.9,10 The human papillomavirus (HPV) has also been proposed to influence the formation of SKs given one study found HPV DNA in 76% of non-genital SKs, but the authors were skeptical about HPV being a true causative factor given multiple HPV types were found in one specimen.11 Further, HPV can be found in normal skin.10 Similar to the pathogenesis, the etiologic risk factors for SKs are not completely understood. Increasing age is a known risk factor as demonstrated by numerous prevalence studies.3,4 Ultraviolet light exposure may also increase the risk of SKs, but the evidence is conflicting with two studies showing that SKs are associated with sun exposure,3,4 but another study finding that they are not.12 Finally, friction may contribute to the development of SKs as they often occur in intertriginous areas.5
Patients often desire treatment for SKs out of concern that the skin finding is something serious, for cosmetic reasons, or for symptomatic relief as they can become irritated, painful, or pruritic.5,13 SKs are typically diagnosed clinically, but histologic confirmation is recommended for atypical, inflamed, or changing lesions.6 In these cases, a shave excision should be done to preserve tissue for diagnosis.5 Table 1 presents the current treatment options for SKs, including cryotherapy, surgical techniques, and topical therapies. Cryotherapy is the most common treatment,5 however, this therapy and the surgical techniques presented in Table 1 can lead to pigmentary changes, especially in patients with Fitzpatrick Skin Type IV-VI.5 Cryotherapy and surgical techniques can also cause bleeding, pruritus, or scarring.5,14–21 To avoid these adverse effects, various topical therapies have been utilized to treat SKs (Table 1). The efficacies of keratolytics including ammonium lactate, imiquimod, and tazarotene have been examined but overall, these therapies had limited success in small clinical trials.2,22,23 Topical vitamin D analogs have also been used, but similarly, these had limited efficacy for treating SKs.2,24 Given the inadequacy of existing topical therapies, safe and effective non-invasive therapies are still needed. One novel therapy is BL-5010, a combination of trichloroacetic acid and formic acid. In a phase I/II open-label trial, a single treatment with BL-5010 resulted in a complete response in 90% of patients and partial response in 7% of patients six months after application (n=60).25 The medication was well-tol
