Abstract
Actinic keratoses (AK), also known as solar keratoses, are precancerous hyperkeratotic papules caused by long-term exposure to ultraviolet radiation. Management of AK prior to progression to cutaneous malignancy represents an important window of intervention. This is important on a population level, given the high incidence, morbidity, financial costs, and the low but measurable risk of mortality from cutaneous neoplasia. Treatments for AK have been refined for many years with significant progress over the past decade. Those recent advancements lead to questions about current treatment paradigms and the role of harnessing the immune system in field therapies. Recent studies suggest a key interplay between vitamin D and cancer immunity; in particular, the systemic and/or topical vitamin D analogs can augment field therapies used for severe actinic damage. In this review, we will examine the literature supporting the use of vitamin D-directed therapies to improve field therapy approaches. An enhanced understanding of these recent concepts with a focus on mechanisms is important in the optimized management of AK. These mechanisms will be critical in guiding whether selected populations, including those with immunosuppression, heritable cancer syndromes, and other risk factors for skin cancer, can benefit from these new concepts with vitamin D analogs and whether the approaches will be as effective in these populations as in immunocompetent patients.
Highlights
Actinic keratoses (AK) have the potential for malignant degeneration to squamous cell carcinoma (SCC), and that risk of malignant degeneration is increased in patients with a variety of susceptibility factors including immunosuppression, Fitzpatrick phototypes, and genetic factors [1, 2]
While the AK lesions might be unsightly or minimally symptomatic, interventions are primarily intended to mitigate the risk of progression to in situ or invasive SCC [3]
Field therapy options include an array of topical therapies including 5-fluorouracil, fractional laser resurfacing, chemical peels, or topical photodynamic therapy (PDT) [5]. ough overall more effective than serially treating individual lesions, field therapies suffer from multiple side effects including pain and irritation
Summary
Actinic keratoses (AK) have the potential for malignant degeneration to squamous cell carcinoma (SCC), and that risk of malignant degeneration is increased in patients with a variety of susceptibility factors including immunosuppression, Fitzpatrick phototypes, and genetic factors [1, 2]. Areas with numerous AK lesions are termed confluent AK or field cancerization. Treatments to these entire zones of skin, termed field therapies, are used to ameliorate the risk to the entire area of skin, including normal-appearing skin adjacent to the visible AK. The effects of field therapies such as topical PDT and even 5-fluorouracil only last several years [6]. As proposed in 2002 by van den Bemd, the use of vitamin D to treat skin cancers showed. E use of vitamin D agonists was further delineated in 2017 by Cunningham and colleagues with the expansion of the role of thymic stromal lymphopoietin (thymic stromal lymphopoietin role was first proposed by Demehri et al in 2012) [9, 10]. Journal of Skin Cancer promise when used topically as monotherapy in 2009 by Seckin and colleagues [7, 8]. e use of vitamin D agonists was further delineated in 2017 by Cunningham and colleagues with the expansion of the role of thymic stromal lymphopoietin (thymic stromal lymphopoietin role was first proposed by Demehri et al in 2012) [9, 10]. e goal of this review is to update new concepts in combining vitamin D agonists with field therapies for actinic damage
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