Swiss clinical practice guidelines on field cancerization of the skin.

Actinic keratosis (AK) affects millions of people worldwide, and its prevalence continues to increase. AK lesions are caused by chronic ultraviolet radiation exposure, and the presence of two or more AK lesions along with photodamage should raise the consideration of a diagnosis of field cancerization. Effective treatment of individual lesions as well as field cancerization is essential for good long-term outcomes. The Swiss Registry of Actinic Keratosis Treatment (REAKT) Working Group has developed clinical practice guidelines for the treatment of field cancerization in patients who present with AK. These guidelines are intended to serve as a resource for physicians as to the most appropriate treatment and management of AK and field cancerization based on current evidence and the combined practical experience of the authors. Treatment of AK and field cancerization should be driven by consideration of relevant patient, disease, and treatment factors, and appropriate treatment decisions will differ from patient to patient. Prevention measures and screening recommendations are discussed, and special considerations related to management of immunocompromised patients are provided

Effect of Corticosteroid on Safety and Efficacy for Actinic Keratosis Therapy with Ingenol Mebutate

Actinic keratoses are common premalignant lesions that occur in fair-skinned individuals with high cumulative ultraviolet exposure. Monotherapy with ingenol mebutate has been known to cause local skin reactions, such as erythema, which reduces safety. Clobetasol propionate has worked well with other actinic keratosis therapies to reduce inflammation, but its role with ingenol mebutate is not well understood. The effect of concurrent application of clobetasol propionate with ingenol mebutate to reduce local skin reactions without impacting efficacy has not yet been investigated. We are proposing a superiority trial for safety as well as a non-inferiority trial for effectiveness. We will conduct an intra-individual, randomized controlled trial at the West Haven Veterans Affairs in patients with multiple actinic keratoses, and analyze local skin reactions at day 4 and efficacy at day 57. If combination therapy has significant advantages compared to monotherapy, it can improve the safety profile and tolerability of ingenol mebutate

Prevalence, discontinuation rate, and risk factors for severe local site reactions with topical field treatment options for actinic keratosis of the face and scalp

Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Actinic keratoses (AKs) are common lesions on chronically sun damaged skin, which are morphologically characterized by lower third to full thickness atypia of epidermal keratinocytes. These lesions carry a risk of progression towards invasive squamous cell carcinoma (SCC); therefore, treatment of visible lesions and the field in case of field cancerization is recommended. Treatment of AK includes the destruction of atypical keratinocytes that clinically presents with various degrees of erythema, scaling, crusting, erosion, and other visible and subjective symptoms. Such inflammatory reactions may have an impact on the patient’s social life and have shown to decrease compliance and adherence to therapy. Additionally, as various topical treatments have been proven to be effective in treating AK, tolerability of local site reactions (LSRs) might drive the decision for appropriate treatment in an individual scenario. Therefore, we aimed to review prevalence of severe LSRs among various topical treatments for AK. In addition, we summarized discontinuation rates due to LSRs and possible therapy-unrelated risk factors for the development of LSRs with increased severity.publishersversionPeer reviewe

New developments in the treatment of actinic keratosis: focus on ingenol mebutate gel

Actinic keratosis is a common disease in older, fair-skinned people, and is a consequence of cumulative ultraviolet exposure. It is part of a disease continuum in photodamaged skin that may lead to invasive squamous cell carcinoma. Treatment options frequently used include cryosurgery and topical pharmacologic agents, which are examples of lesion-directed and field-directed strategies. Ingenol mebutate gel was recently approved by the US Food and Drug Administration for topical treatment of actinic keratosis. While the mechanism of action of ingenol mebutate is not fully understood, in vitro and in vivo studies using tumor models indicate it has multiple mechanisms. Ingenol mebutate directly induces cell death by mitochondrial swelling and loss of cell membrane integrity preferentially in transformed keratinocytes. It promotes an inflammatory response characterized by infiltration of neutrophils and other immunocompetent cells that kills remaining tumor cells. The ability of ingenol mebutate to eliminate mutant p53 patches in ultraviolet-irradiated mouse skin suggests that it may have the potential to treat chronically ultraviolet-damaged skin. In human studies, ingenol mebutate achieved high clearance of actinic keratosis on the head and body after 2–3 consecutive daily treatments when measured by complete or partial clearance of lesions. Localized inflammatory skin responses were generally mild to moderate and resolved in less than a month

Actinic keratoses - a systemic review

Mainly elderly people with pale skin are affected by actinic keratoses (AK). Due to the demographic change, the prevalence of AK increased over the last years. An established risk factor is chronic UV-exposure (outdoor workers) inducing mutations of the tumor suppressor gene TP53 and the oncogene H-Ras. This leads to an intraepidermal proliferation of atypical keratinocytes. The term “field cancerization” characterises the presentation of multiple AK in UV-exposed areas. AK are also termed squamous cell carcinoma (SCC) in situ. The risk for AK turning into a SCC is 6-10%. In order to avoid invasive growth, an early treatment is recommended. During the last years multiple therapeutic options have been established. Depending on the clinical extent, lesion- or field-directed therapies with excellent clinical response and cosmetic results are available

Diclofenac gel in the treatment of actinic keratoses

Actinic keratoses are areas of intraepithelial neoplasia for which treatment is necessary. Because they arise in areas of sun damage, it is desirable to treat the entire damaged field to not only treat visible lesions, but also subclinical, emerging malignancies, ie, “field therapy”, 5-fluorouracil, imiquimod, and diclofenac are all treatment options, and are discussed and compared

Current and emerging treatment strategies for the treatment of actinic keratosis

Actinic keratoses are encountered by physicians worldwide on a daily basis. As these precancerous lesions can transform to skin carcinomas, it is important to understand the many available options to use as treatment. In recent years, new therapeutic options have emerged to treat this common condition. These treatments as well as a review of the literature of conventional therapies will be discussed

Treatment of Actinic Keratoses and Field Cancerization – Croatian perspective

Actinic keratoses (AKs) are the most common premalignant skin lesions, caused by chronic sun damage and accordingly, found on chronically sun-exposed skin, such as face, scalp, neck, hands, and forearms. Clinically, these lesions present as macules, papules or hyperkeratotic plaques on an erythematous background. In Caucasians over 60 years of age, the prevalence of AKs is up to 80%. The diagnosis is based on clinical and dermoscopic examination. The main concern with AKs is the risk of transformation into squamous cell carcinoma (SCC), therefore all lesions should be evaluated for treatment. Treatment options for AKs are divided into lesion-oriented and field-oriented treatments. Lesion-directed treatment modalities commonly involve cryosurgery/liquid nitrogen cryotherapy, surgery (shave, excision), and laser therapy, while field-directed treatments include topical agents, photodynamic therapy, chemical peels, field ablation with dermabrasion and CO2 laser resurfacing. This review outlines the different types of treatments available, the characteristics, side effects, and benefits of each modality, and highlights the best treatment options, with a reflection on possibilities and limitations in the Republic of Croatia

A New, Objective, Quantitative Scale for Measuring Local Skin Responses Following Topical Actinic Keratosis Therapy with Ingenol Mebutate

INTRODUCTION: Local skin responses (LSRs) are the most common adverse effects of topical actinic keratosis (AK) therapy. There is currently no method available that allows objective characterization of LSRs. Here, the authors describe a new scale developed to quantitatively and objectively assess the six most common LSRs resulting from topical AK therapy with ingenol mebutate. METHODS: The LSR grading scale was developed using a 0–4 numerical rating, with clinical descriptors and representative photographic images for each rating. Good inter-observer grading concordance was demonstrated in peer review during development of the tool. Data on the use of the scale are described from four phase III double-blind studies of ingenol mebutate (n = 1,005). RESULTS: LSRs peaked on days 4 (face/scalp) or 8 (trunk/extremities), with mean maximum composite LSR scores of 9.1 and 6.8, respectively, and a rapid return toward baseline by day 15 in most cases. Mean composite LSR score at day 57 was generally lower than at baseline. CONCLUSION: The LSR grading scale is an objective tool allowing practicing dermatologists to characterize and compare LSRs to existing and, potentially, future AK therapies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13555-014-0059-9) contains supplementary material, which is available to authorized users