Management Of Actinic Keratosis Research Articles

Comparative Efficacy and Tolerability of Imiquimod 3.75% Cream vs 5-Fluorouracil 4% cream in the Treatment of Actinic Keratosis: A Split-Face Study

Introduction: Actinic keratosis (AK) is a common precancerous skin lesion that arises on chronically UV-exposed skin and can progress to keratinocyte carcinoma. Objective: The aim of this study is to compare efficacy, safety, local skin reaction, time to wound closure, and patient preference of imiquimod (IMQ) 3.75% vs 5-fluorouracil (5-FU) 4% cream treatment for AKs. Methods: Two symmetrical contralateral areas of approximately 25 cm2 harboring a similar (≥5) number of AKs were selected and randomly assigned to IMQ 3.75% or 5- FU 4% cream treatment. The total number of AKs for each patient, was evaluated at baseline (T0) and 90 days after the end of treatments (T1). Local skin reaction (LSR) score was registered the day after the end of both treatments. Complete remission rate of lesions, cosmetic outcome, and patient preference of treatment were assessed after 90 days (T1). Results: The mean variation (ΔT0-T1) of AKs was not significantly different in patients treated with IMQ 3.75% and 5-FU 4% (p=0.35). The mean LSR was not significantly different for patients treated with IMQ 3.75% and 5-FU 4% (p=0.63). No difference in cosmetic outcome was observed in the 2 groups. Patient preference was equally distributed between the treatments. The mean time to wound closure after the end of the treatment was similar after IMQ 3.75% as compared to 5-FU 4% (p=0.83). Conclusions: This study reports a non-superiority of efficacy, tolerability, wound-healing time, and cosmetic outcome of topical IMQ 3.75% treatment compared to topical 5-FU 4% treatment in AK management.

Epidemiology and Management of Actinic Keratosis in France: A General Population Survey (REAKT).

The objective of this retrospective observational study was to estimate the prevalence of actinic keratosis (AK) in individuals aged ≥ 40 years in France, to describe the characteristics of affected patients, and to describe treatments. A representative panel of 20,000 households with ≥ 1 member aged ≥ 40 years were invited to participate. Participants who reported AK lesions diagnosed by a physician were eligible. The study questionnaire collected data on demographics, lesion characteristics, Fitzpatrick phototype, diagnosis, and treatments. In total, 15,246 questionnaires (78.5%) were returned and 639 responders were eligible. The adjusted prevalence of AK was 4.03% (95% CI: 3.73-4.35). Prevalence is probably underestimated due to data collection by self-report and low awareness of AK. 177 participants (27.7%) were aged < 65 years. AK was diagnosed by a dermatologist for 521 participants (81.6%). Some 200 participants (31.3%) had no lesions at the time of the survey and 243 (37.9%) had never been treated; 312 participants (78.6%) were prescribed physical treatment, principally cryotherapy; and 125 (31.5%) were prescribed topical treatment, principally 5-fluorouracil or imiquimod. In conclusion, improving diagnosis of AK in everyday clinical practice is important to ensure that all individuals with AK are treated optimally and encouraged to take sun protection measures to prevent progression to SCC.

HSD43 Pain and Lesion Count in the Clinical Management of Actinic Keratosis in the Real-World Setting

HSD43 Pain and Lesion Count in the Clinical Management of Actinic Keratosis in the Real-World Setting

Role of Nicotinamide in the Pathogenesis of Actinic Keratosis: Implications for NAD+/SIRT1 Pathway.

Actinic keratosis (AK) is a precursor to invasive squamous cell carcinoma, making early diagnosis and treatment essential to prevent progression. Among available therapeutic options, nicotinamide (NAM) has shown potential in reducing AK progression. NAM is a precursor of nicotinamide adenine dinucleotide (NAD+), which activates sirtuin (SIRT)1, a protein with anti-cancer properties. Although the role of SIRT1 in AK is still debated, no data currently exist on the systemic modulation of this protein in AK. Therefore, this study aims to evaluate whether NAM, by increasing serum NAD+ levels, may promote SIRT1 activation in peripheral blood mononuclear cells (PBMCs) in AK patients. Thirty patients were enrolled and treated with NAM for 24 months. Hematological, biochemical, and skin condition assessments were conducted, alongside the measurement of SIRT1 and NAD+ levels. A decrease in basophils, monocytes, total cholesterol, and blood glucose levels was observed in the study group, along with a reduction in AK lesions. Notably, NAM treatment significantly enhanced serum NAD+ levels, and nuclear SIRT1 activity in PBMCs. In conclusion, NAM administration significantly reduced AK progression in a NAD+/SIRT1-dependent manner, supporting its role as a chemopreventive agent in AK management.

Evolución de la terapia fotodinámica en el manejo de la queratosis actínica ¿qué tan efectiva y segura es según la evidencia actual?

Actinic keratosis is a premalignant dermatological condition characterized by the potential to progress to squamous cell carcinoma. To date, there is no treatment with an adequate benefit-risk balance. Photodynamic therapy is proposed as one of the most effective therapeutic tools. However, there is still divergence regarding the quality of available evidence. The objective of this review is to analyze the most recent evidence on the therapeutic performance of photodynamic therapy in the management of actinic keratosis. A literature search was conducted in the PubMed, Scopus, and MEDLINE databases. Based on the most recent randomized controlled trial comparing the use of dynamic phototherapy combined with aminolevulinic acid without incubation versus incubation for one hour, it was found that the intervention group had a higher percentage of lesion resolution compared to the control group (49.5% vs. 34.9%, p=0.002), as well as less pain in the intervention group (p=0.03). In addition, a similar trend was observed in other studies, suggesting that this therapy could be effective and beneficial in the management of actinic keratosis. Despite the limited and heterogeneous evidence regarding the use of dynamic phototherapy and its various combined regimens for the management of actinic keratosis, there is a clear trend towards potential benefits compared to other therapies.

The "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) Project: An Expert Panel Opinion.

Actinic keratosis (AK) is an intraepithelial condition characterized by the development of scaly, erythematous lesions after repeated exposure to ultraviolet radiation. Significant immunosuppression is a risk factor for the development of AK and subsequent lesion progression to squamous cell carcinoma. Immunocompromised patients (ICPs), particularly organ transplant recipients, often have more advanced or complex AK presentations and an increased risk of skin carcinomas versus non-ICPs with AK, making lesions more difficult to treat and resulting in worse treatment outcomes. The recent "Personalising Actinic Keratosis Treatment" (PAKT) consensus reported that delivering patient-centric care may play a role in supporting better clinical outcomes and patient satisfaction with treatments for chronic dermatologic conditions such as AK, which require repeated cycles of treatment. Additionally, currently published guidance and recommendations were considered by the PAKT panel to be overly broad for managing ICPs with their unique and complex needs. Therefore, the "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) panel was established to build upon general recommendations from the PAKT consensus. The panel identified current gaps in guidance for AK care in ICPs, offered practical care approaches based on typical ICP scenarios, and highlighted the need to adapt AK management to optimize care and improve treatment outcomes in ICPs. In particular, dermatologists should establish collaborative and transparent relationships with patients' multidisciplinary teams to enhance overall care for patients' comorbidities: given their increased risk of progression to malignancy, earlier assessments/interventions and frequent follow-ups are vital.The panel also developed a novel "triage" tool outlining effective treatment follow-up and disease surveillance plans tailored to patients' risk profiles, guided by current clinical presentation and relevant medical history. Additionally, we present the panel's expert opinion on three fictional ICP scenarios to explain their decision-making process for assessing and managing typical ICPs that they may encounter in clinical practice.

P067 A novel validated patient decision aid to enhance shared decision making for the management of actinic keratosis

P067 A novel validated patient decision aid to enhance shared decision making for the management of actinic keratosis

The Development and Validation of a Decision Aid to Enhance Shared Decision-Making for the Management of Actinic Keratosis

Abstract Actinic keratoses (AKs) are common pre-malignant lesions. There are numerous management options including active surveillance, multiple topical therapies, cryotherapy, curettage and cautery, and photodynamic therapy, each with their own risks, benefits and efficacy. Best practice currently involves shared decision-making between patient and clinician, particularly in the setting of multiple management options. Patient decision aids have been shown to be beneficial in the shared decision-making process. In view of this, we have developed and validated a decision aid for the management of AKs, in concordance with the International Patient Decision Aids Standards.

Combination of 5-fluorouracil with photodynamic therapy enhances immune responses in a murine model of actinic keratosis

SignificancePhotodynamic therapy (PDT) to treat actinic keratoses (AK) involves application of a photosensitizer followed by exposure to light, resulting in effective lesion clearance by inducing cell death and long-term immune responses. Here, we show that pretreatment of AK lesions with 5-fluorouracil (5FU) causes significant enhancement of PDT-related immune effects. ApproachSKH-1 mice with AK (generated by repeated UVB exposure) were treated topically with 5FU for three days prior to application of topical ALA followed by blue light exposure. AK lesions were harvested for time-course analyses of intra-tumoral immune responses after PDT with or without 5FU. ResultsImmunofluorescence data showed that 5FU pretreatment increased recruitment of innate immune cells, infiltration of activated T cells and of cytotoxic T cells and reduced the presence of cells expressing the immune checkpoint marker PD1. ConclusionsOur results suggest that a combination of 5FU and PDT may synergize to provide better management of AK in the dermatology clinic.

Advancements in elucidating the pathogenesis of actinic keratosis: present state and future prospects.

Solar keratosis, also known as actinic keratosis (AK), is becoming increasingly prevalent. It is a benign tumor that develops in the epidermis. Individuals with AK typically exhibit irregular, red, scaly bumps or patches as a result of prolonged exposure to UV rays. These growths primarily appear on sun-exposed areas of the skin such as the face, scalp, and hands. Presently, dermatologists are actively studying AK due to its rising incidence rate in the United States. However, the underlying causes of AK remain poorly understood. Previous research has indicated that the onset of AK involves various mechanisms including UV ray-induced inflammation, oxidative stress, complex mutagenesis, resulting immunosuppression, inhibited apoptosis, dysregulated cell cycle, altered cell proliferation, tissue remodeling, and human papillomavirus (HPV) infection. AK can develop in three ways: spontaneous regression, persistence, or progression into invasive cutaneous squamous cell carcinoma (cSCC). Multiple risk factors and diverse signaling pathways collectively contribute to its complex pathogenesis. To mitigate the risk of cancerous changes associated with long-term UV radiation exposure, prompt identification, management, and prevention of AK are crucial. The objective of this review is to elucidate the primary mechanisms underlying AK malignancy and identify potential treatment targets for dermatologists in clinical settings.

Topical Immunotherapy for Actinic Keratosis and Field Cancerization.

This comprehensive review delves into various immunotherapeutic approaches for the management of actinic keratoses (AKs), precancerous skin lesions associated with UV exposure. Although there are treatments whose main mechanism of action is immune modulation, such as imiquimod or diclofenac, other treatments, apart from their main effect on dysplastic cells, exert some immunological action, which in the end contributes to their efficacy. While treatments like 5-fluorouracil, imiquimod, photodynamic therapy, and nicotinamide are promising in the management of AKs, especially in immunocompetent individuals, their efficacy is somewhat reduced in solid organ transplant recipients due to immunosuppression. The analysis extends to optimal combination, focusing on cryoimmunotherapy as the most relevant. New immunotherapies include resimiquimod, ingenol disoxate, N-phosphonacetyl-L-aspartate (PALA), or anti-PD1 that have shown promising results, although more studies are needed in order to standardize their use.

Prevention, diagnosis and treatment of actinic keratosis

Actinic keratoses are common in the UK, especially in lighter skinned individuals and those with high lifetime UV exposure. As they are considered premalignant and can progress to squamous cell carcinoma, early identification and treatment are important. This article provides a guide to the prevention, recognition and management of actinic keratosis.

Field Cancerization Therapies for the Management of Actinic Keratosis: An Updated Review.

Field cancerization theory highlights that the skin surrounding actinic keratoses (AK) is also at increased risk for possible malignant transformation; thus, field-directed treatments may both reduce the risk of AK recurrence and potentially reduce the risk of development of cutaneous squamous cell carcinoma (cSCC). Photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL), as well as topical treatments such as 5-fluorouracil (5-FU), diclofenac gel, piroxicam, imiquimod, and ingenol mebutate, have all shown higher efficacy than vehicle treatments. PDT is widely recognized for its high efficacy; however, concerns for associated pain have driven new studies to begin using alternative illumination and pretreatment techniques, including lasers. Among topical treatments, a combination of 5-FU and salicylic acid (5-FU-SA) has shown to be the most effective but also causes the most adverse reactions. Tirbanibulin, a new topical agent approved for use in 2020, boasts a favorable safety profile in comparison with imiquimod, 5-FU, and diclofenac. Meanwhile, ingenol mebutate is no longer recommended for the treatment of AKs due to concerns for increased risk of cSCC development. Moving forward, an increasing number of studies push for standardization of outcome measures to better predict risk of future cSCC and use of more effective measures of cost to better guide patients. Here, we present an updated and comprehensive narrative review both confirming the efficacy of previously mentioned therapies as well as highlighting new approaches to PDT and discussing the use of lasers and novel topical treatments for treatment of AK.

Combination of vitamin D and photodynamic therapy enhances immune responses in murine models of squamous cell skin cancer

Improved treatment outcomes for non-melanoma skin cancers can be achieved if Vitamin D (Vit D) is used as a neoadjuvant prior to photodynamic therapy (PDT). However, the mechanisms for this effect are unclear. Vit D elevates protoporphyrin (PpIX) levels within tumor cells, but also exerts immune-modulatory effects. Here, two murine models, UVB-induced actinic keratoses (AK) and human squamous cell carcinoma (A431) xenografts, were used to analyze the time course of local and systemic immune responses after PDT ± Vit D. Fluorescence immunohistochemistry of tissues and flow analysis (FACS) of blood were employed. In tissue, damage-associated molecular patterns (DAMPs) were increased, and infiltration of neutrophils (Ly6G+), macrophages (F4/80+), and dendritic cells (CD11c+) were observed. In most cases, Vit D alone or PDT alone increased cell recruitment, but Vit D + PDT showed even greater recruitment effects. Similarly for T cells, increased infiltration of total (CD3+), cytotoxic (CD8+) and regulatory (FoxP3+) T-cells was observed after Vit D or PDT, but the increase was even greater with the combination. FACS analysis revealed a variety of interesting changes in circulating immune cell levels. In particular, neutrophils decreased in the blood after Vit D, consistent with migration of neutrophils into AK lesions. Levels of cells expressing the PD-1+ checkpoint receptor were reduced in AKs following Vit D, potentially counteracting PD-1+ elevations seen after PDT alone. In summary, Vit D and ALA-PDT, two treatments with individual immunogenic effects, may be advantageous in combination to improve treatment efficacy and management of AK in the dermatology clinic.

Needs and challenges among general practitioners in the management of actinic keratosis: a qualitative study

BackgroundBecause of the increasing incidence of actinic keratosis (AK), optimal use of limited healthcare resources is essential. Although most patients can be managed in primary care, dermatology referrals are common. More profound knowledge of general practitioners’ (GPs) considerations might assist in enhancing AK care.MethodsThe aim of the current study was to gain insight into AK management in primary care by exploring the needs and challenges among GPs in the Netherlands. A qualitative study was conducted based on semi-structured in-depth interviews with 15 conveniently sampled Dutch GPs, focusing on the needs and challenges in AK management. A literature-informed, predefined topic list guided the interviews, which were recorded, transcribed ad verbatim, and thematically analysed using the Framework Method.ResultsAll GPs reported AK to be a clinical diagnosis and most GPs indicated that most AK patients could be managed in primary care. Cryotherapy was preferred and experience with 5-FU therapy was limited. Most GPs applied cryotherapy without discussing other treatment options with patients. Reasons for dermatology referrals included an incomplete treatment response, extensive lesions, difficult-to-treat areas, and serious doubts about the diagnosis. GPs reported a need for more education, especially on 5-FU therapy. Their main challenges were dealing with diagnostic uncertainty, treating extensive lesions, managing treatment-related skin reactions, and reconciling patient misconceptions.ConclusionsThis study shows various AK management approaches among Dutch GPs with suboptimal guideline compliance due to diverse underlying barriers. It suggests that more education might contribute to a more standardised and uniform AK management and supports further transition of AK care from hospital to primary care.

Expert Recommendations on Facilitating Personalized Approaches to Long-term Management of Actinic Keratosis: The Personalizing Actinic Keratosis Treatment (PAKT) Project.

Actinic keratoses are pre-malignant skin lesions that require personalized care, a lack of which may result in poor treatment adherence and suboptimal outcomes. Current guidance on personalizing care is limited, notably in terms of tailoring treatment to individual patient priorities and goals and supporting shared decision-making between healthcare professionals and patients. The aim of the Personalizing Actinic Keratosis Treatment panel, comprised of 12 dermatologists, was to identify current unmet needs in care and, using a modified Delphi approach, develop recommendations to support personalized, long-term management of actinic keratoses lesions. Panellists generated recommendations by voting on consensus statements. Voting was blinded and consensus was defined as ≥ 75% voting 'agree' or 'strongly agree'. Statements that reached consensus were used to develop a clinical tool, of which, the goal was to improve understanding of disease chronicity, and the need for long-term, repeated treatment cycles. The tool highlights key decision stages across the patient journey and captures the panellist's ratings of treatment options for attributes prioritized by patients. The expert recommendations and the clinical tool can be used to facilitate patient-centric management of actinic keratoses in daily practice, encompassing patient priorities and goals to set realistic treatment expectations and improve care outcomes.

The Importance of Medication Adherence in the Treatment of Actinic Keratosis: An Expert Consensus Panel

Background: Actinic keratosis (AK) is one of the most common dermatologic diagnoses. While there are several treatment options, many topical therapies have poor adherence due to duration of treatment and local skin reactions (LSRs).&#x0D; Objective: To review the available literature on the most commonly used patient-administered field-directed therapies for AK and create consensus statements on the role of medication adherence in improving AK outcomes.&#x0D; Methods: A literature search of PubMed was completed for English-language original research articles reporting efficacy, safety, and tolerability data for 5-FU, diclofenac gel, imiquimod cream, and tirbanibulin. Once the articles were selected, they were distributed to a panel consisting of seven dermatologists with extensive expertise in managing AKs. Each panelist reviewed the articles and assigned them a level of evidence based on Strength of Recommendation Taxonomy (SORT) criteria. The panelists then met to review and discuss the studies and created consensus statements on the management of AKs and the importance of medication compliance. A modified Delphi process was used to approve the adoption of each statement.&#x0D; Results: The literature search produced 1,326 articles that met search criteria. After screening these articles for relevance and applying the inclusion criteria, 17 articles were chosen to be reviewed by the panel and assigned a level of evidence based on SORT criteria. The panel then created six consensus statements that received a unanimous vote for adoption.&#x0D; Conclusion: While there are several options for the treatment of AK, there is little consensus on a standard of care. Clearance rates for the most common topical field therapies vary significantly but are also difficult to directly compare due to differences in methodology for measuring and assessing outcomes. Overall, it is clear that an efficacious, tolerable, and convenient treatment for AKs is critical to optimal adherence and management and, given the results of recent studies, tirbanibulin may be the best topical option for meeting these criteria.

Clinician- and Patient-Reported Outcomes with Tirbanibulin 1% Treatment for Actinic Keratosis in Routine Clinical Practice Across the U.S. (PROAK Study)

Background: Patients' experiences regarding topical actinic keratosis (AK) treatments may optimize clinical outcomes. PROAK study aimed to evaluate patient- and clinician-reported outcomes among adult patients with AK on face or scalp who were prescribed tirbanibulin in real-world clinical practice in the United States.&#x0D; Methods: Key primary endpoint was quality of life (QoL) assessed by Skindex-16. Additional endpoints were tirbanibulin treatment effectiveness and satisfaction (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire).&#x0D; Results: 290 patients were included in this analysis. At week 8, Skindex-16 scores improved in all domains (mean change from baseline [standard deviation, SD]: -14.3 [27.8] in symptoms, -24.9 [33.0] in emotions, and -9.8 [23.7] in functioning domain). Clinicians and patients reported high global satisfaction with tirbanibulin (mean [SD] scores of 78.8 [20.1] and of 74.5 [23.5]). Overall skin appearance improved from baseline to week 8 (91.0% clinicians; 84.1% patients). In comparison with previous treatments, tirbanibulin had shorter skin reactions duration (89.2% clinicians; 73.9% patients); milder skin reaction severity (91.0% clinicians; 76.6% patients); better daily activities impact (87.4% clinicians; 64.0% patients); and was easier to use (88.3% clinicians; 71.2% patients). Investigator’s Global Assessment (IGA) success (0-1) was achieved by 73.8% of the patients. Skin photodamage severity reduction from baseline to week 8 was significant (77.4% vs. 39.6%; p&lt;0.0001).&#x0D; Conclusions: Tirbanibulin treatment demonstrated effectiveness in AK management. Moreover, tirbanibulin improved QoL, as early as week 8, and both clinicians and patients reported tirbanibulin treatment convenience, and high levels of treatment satisfaction, compared to patient’s previous treatments.

Clinical Management of Actinic Keratosis: Review and Update

Actinic keratosis is commonly seen in dermatology clinics. Age and chronic sun exposure are the essential risk factors for its pathogenesis. It is regarded as a premalignant lesion; hence, aggressive treatment is warranted. Abundant research has been published about overall management, however, extensive knowledge about actinic keratosis prevention, the cost, safety profile, and mechanism of the existing therapeutics are pivotal in optimal clinical care. In this review article, we hereby present several commonly used approaches in office settings and the current guidelines. Finally, we will discuss the limitations of the available clinical evidence.

Treatment of Actinic Keratosis: The Best Choice through an Observational Study.

Actinic keratosis (AK) is a precancerous lesion that can progress to invasive squamous cell carcinoma if untreated. However, no gold standard treatment has been established. We aimed to investigate the management of AK by comparing the effectiveness and treatment duration of treatment modalities, including cryotherapy, imiquimod (IMQ), and photodynamic therapy (PDT). We reviewed the medical records of 316 patients diagnosed with AK at Seoul St. Mary’s Hospital from February 2015 to May 2020, and a total of 195 patients were included. The clearance rate was the highest in PDT, followed by cryotherapy and IMQ (82.4%, 71.2%, and 68.0%, respectively). The recurrence rate was the lowest in cryotherapy, followed by PDT and IMQ (3.5%, 6.7%, and 10.5%, respectively, p < 0.05). The average treatment duration was shortest with PDT, followed by IMQ and cryotherapy (5.5 weeks, 6.8 weeks, and 9.1 weeks, respectively, p < 0.05). The number of hospital visits was lowest for PDT, followed by cryotherapy and IMQ (1.8, 2.8, and 3.6, respectively, p < 0.05). PDT showed the highest clearance rate, a moderate recurrence rate, the shortest treatment duration, and the least number of visits, suggesting that PDT could be the first choice for treatment of AK. Considering the advantages as a topical agent, IMQ could also be a treatment option.