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Copyright of Zentralblatt fuer Arbeitsmedizin, Arbeitsschutz und Ergonomie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Given the importance of peroxisome proliferator-activated receptor (PPAR)-gamma in epidermal inflammation and carcinogenesis, we analyzed the transcriptomic changes observed in epidermal PPARγ-deficient mice (Pparg-/-epi). A gene set enrichment analysis revealed a close association with epithelial malignancy, inflammatory cell chemotaxis, and cell survival. Single-cell sequencing of Pparg-/-epi mice verified changes to the stromal compartment, including increased inflammatory cell infiltrates, particularly neutrophils, and an increase in fibroblasts expressing myofibroblast marker genes. A comparison of transcriptomic data from Pparg-/-epi and publicly available human and/or mouse actinic keratoses (AKs) and cutaneous squamous cell carcinomas (SCCs) revealed a strong correlation between the datasets. Importantly, PPAR signaling was the top common inhibited canonical pathway in AKs and SCCs. Both AKs and SCCs also had significantly reduced PPARG expression and PPARγ activity z-scores. Smaller reductions in PPARA expression and PPARα activity and increased PPARD expression but reduced PPARδ activation were also observed. Reduced PPAR activity was also associated with reduced PPARα/RXRα activity, while LPS/IL1-mediated inhibition of RXR activity was significantly activated in the tumor datasets. Notably, these changes were not observed in normal sun-exposed skin relative to non-exposed skin. Finally, Ppara and Pparg were heavily expressed in sebocytes, while Ppard was highly expressed in myofibroblasts, suggesting that PPARδ has a role in myofibroblast differentiation. In conclusion, these data provide strong evidence that PPARγ and possibly PPARα represent key tumor suppressors by acting as master inhibitors of the inflammatory changes found in AKs and SCCs. [ABSTRACT FROM AUTHOR]

Opinion statement: Skin tumors commonly seen in dermatology are involved in all layers of the skin and appendages. While biopsy of affected skin remains an essential method to confirm diagnosis and to predicate tumor prognosis, it has its limitations. Recently, photodynamic diagnosis (PDD) has demonstrated high sensitivity in detecting affected skin and mucosal tissues, providing valuable guidance for precision surgery to resect skin and mucosal tumors. In this review, we summarized the literatures concerning the applications of PDD in diagnostic process and treatment of skin and mucosal conditions such as actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen's disease (BD) and extramammary Paget's disease (EMPD). The findings suggest that PDD holds substantial promise for expanding clinical applications and deserves further research exploration. [ABSTRACT FROM AUTHOR]

Actinic keratoses (AKs) are common skin lesions found on sun-exposed areas and are considered potential precursors to squamous cell carcinomas (SCCs). This observational case-control study evaluates the efficacy of combining traditional daylight photodynamic therapy (DL-PDT) with pre-treatment using 0.005% calcipotriol (CAL) ointment. Twenty immunocompetent male patients with grade I-II AKs on the scalp and/or face were randomized into two groups: the case group received a 14-day pretreatment with CAL ointment before DL-PDT, while the control group used a moisturizing cream. Both groups underwent a series of three DL-PDT sessions. The study utilized the Actinic Keratosis Area Severity Index (AKASI) scoring system to measure the actinic damage at baseline, 3 months, and 6 months post-treatment. Results showed a significant reduction in AKASI scores in the CAL group compared to controls, indicating that CAL pretreatment enhances the efficacy of DL-PDT. This combination treatment was well tolerated, with minimal discomfort reported. The findings suggest that incorporating CAL into the treatment regimen can improve the clearance of AKs and potentially prevent their progression to SCCs.

Actinic keratosis (AK) is a frequent precancerous skin lesion that mostly affects chronically sun-exposed areas. Chronic sun damage leads to various mutations in onco-suppressor and oncogenic genes which cause an uncontrolled proliferation of atypical keratinocytes. Untreated AKs may evolve in cutaneous squamous cell carcinoma (cSCC), with the consequent need for dermato-surgical excision or even for systemic immunotherapy in case of invasive/metastatic cSCCs. Epidemiology data on AK prevalence are various, however, the literature unanimously reports an increasing prevalence due to the aging of the population. Clinically AKs appear as a scaly, erythematous macule or papule or hyperkeratotic plaque. Management of AKs and the field of cancerization is important to avoid the natural evolution into squamous cell carcinomas (SCCs). Both physical and topical treatments are approved for managing AKs. Patient compliance with topical regimens is usually low due to the length of the posology and frequent skin adverse events. A recently approved tirbanibulin-based ointment, showed potential for inhibiting cell proliferation and blocking SRC-kinases, implicated in the progression of AKs in SCCs. The advantage of this new treatment is the practical posology, with a daily application for 5 consecutive days on AKs of the face-scalp area. Local skin reactions are usually mild and do not require treatment discontinuation. The short course of this new therapy and its excellent tolerance massively increased patient compliance. This article reviews what is currently known about this new therapy from its mechanism of action to clinical trial outcomes regarding safety, effectiveness, and patient adherence to the treatment.

Actinic keratosis (AK) is one of the most frequent tumors of the skin; the diagnosis is basically clinical although in some cases it may be difficult to distinguish it from other keratinocytic or even melanocytic neoplasms when it presents in pigmented form. Over the years several clinical classifications and scores to objectify the burden of disease have been created. In this review the most frequent scores and classification systems are summarized along with dermoscopic criteria that allow diagnosis with greater sensitivity and specificity.

Actinic keratoses (AKs) represent a common skin cancer in situ associated with chronic sun exposure. Early diagnosis and management of AKs are crucial to prevent their progression to invasive squamous cell carcinoma. Therefore, we investigated AK PRO score assessment using ex vivo confocal laser microscopy (EVCM) coupled with a novel fluorescent dye, FCF Fast Green, to explore its potential for the precise imaging and discrimination of collagen fibers. AK PRO assessment using EVCM demonstrated excellent conformity (95.8%) with histopathologic examination. The additional utilization of FCF Fast Green dye had no impact on AK visualization but showed a high affinity for collagen fibers enabling clear differentiation of collagen alterations between healthy and sun-damaged skin. The enhanced visualization of collagen fiber changes may aid clinicians in accurately identifying AKs and differentiating them from benign skin lesions. [ABSTRACT FROM AUTHOR]

Actinic keratoses are common pre-malignant lesions of the skin that have been documented to become inflamed after the use of chemotherapy. Several agents, such as 5-fluorouracil, capecitabine, pentostatin, dactinomycin, vincristine, dacarbazine, cytarabine, 6-thioguanine, sorafenib, paclitaxel, and docetaxel have been documented to cause this reaction. This case report aims to describe the inflammation of actinic keratoses in response to docetaxel plus cyclophosphamide. A 64-year-old woman undergoing chemotherapy for breast cancer presented to the clinic with multiple scaly, erythematous papules covering her shoulders, arms, chest, and back. This occurred 15 days after treatment with IV docetaxel plus cyclophosphamide. The results of the shave biopsies done at the visit were consistent with inflammation. She was treated with topical triamcinolone ointment and the inflammation greatly improved within one month. The inflammation was completely resolved two months after completing therapy with docetaxel plus cyclophosphamide. Documentation of cutaneous adverse events help provide awareness of this reaction and thereby prevent cessation of necessary cancer treatments. Further research is needed to determine which patients undergoing chemotherapy may be susceptible to inflammation of actinic keratoses.

Given the importance of peroxisome proliferator-activated receptor (PPAR)-gamma in epidermal inflammation and carcinogenesis, we analyzed the transcriptomic changes observed in epidermal PPARγ-deficient mice (Pparg-/-epi). A gene set enrichment analysis revealed a close association with epithelial malignancy, inflammatory cell chemotaxis, and cell survival. Single-cell sequencing of Pparg-/-epi mice verified changes to the stromal compartment, including increased inflammatory cell infiltrates, particularly neutrophils, and an increase in fibroblasts expressing myofibroblast marker genes. A comparison of transcriptomic data from Pparg-/-epi and publicly available human and/or mouse actinic keratoses (AKs) and cutaneous squamous cell carcinomas (SCCs) revealed a strong correlation between the datasets. Importantly, PPAR signaling was the top common inhibited canonical pathway in AKs and SCCs. Both AKs and SCCs also had significantly reduced PPARG expression and PPARγ activity z-scores. Smaller reductions in PPARA expression and PPARα activity and increased PPARD expression but reduced PPARδ activation were also observed. Reduced PPAR activity was also associated with reduced PPARα/RXRα activity, while LPS/IL1-mediated inhibition of RXR activity was significantly activated in the tumor datasets. Notably, these changes were not observed in normal sun-exposed skin relative to non-exposed skin. Finally, Ppara and Pparg were heavily expressed in sebocytes, while Ppard was highly expressed in myofibroblasts, suggesting that PPARδ has a role in myofibroblast differentiation. In conclusion, these data provide strong evidence that PPARγ and possibly PPARα represent key tumor suppressors by acting as master inhibitors of the inflammatory changes found in AKs and SCCs.

Actinic Cheilitis (AC), also known as “sailor's lips”, is a premalignant pathology, and although it is easy to diagnose and prevent, late diagnosed cases may progress to lip carcinoma. Since its main etiological factor is exposure to ultraviolet rays, individuals often exposed to the sun, including military personnel, can be considered a risk group for the disease. The aim of this study was to describe the main risk and prognostic factors of AC and to create a clinical protocol for dental surgeons, making easier to identify and conduct each case. For this purpose, a search for articles relevant to the topic was carried out in Medline, Lilacs, SciELO and PubMed databases, from 1987 to 2022. The following AC patient profile was identified: male, in the fifth decade of life, fair skinned, with lesions on the lower lip and with a long history of outdoor occupational activities/intense sun exposure. The dentist has a fundamental role in identifying risk groups, early recognition of the disease and in more advanced cases, making the correct diagnosis and recommendation to specialized care.

Optical spectroscopy is studied to contribute to skin cancer diagnosis. Indeed, optical spectra are modified along cancer progression and provide complementary information (e.g., on metabolism and tissue structure) to clinical examination for surgical guidance [1,2]. The current original dataset is made of autofluorescence and diffuse reflectance spectra acquired in vivo on 131 patients’ skin with the SpectroLive device [3,4]. Spatially-resolved spectroscopy measurements were performed using a multi-fiber optic probe featuring 4 distances (0.4–1 mm) between excitation and collection optical fibers: spatial resolution allows spectra acquired at different distances to carry information from different depths in skin tissues. Five types of autofluorescence spectra were acquired using five different wavelength excitations (on the 365–415 nm spectral range) in order to collect information on several skin endogenous fluorophores (e.g., flavins, collagen). A sixth light source (white broadband) was used to acquire diffuse reflectance spectra carrying information about skin scattering properties and skin endogenous absorbers such as melanin and hemoglobin. Patients were proposed to be included into the clinical trial if they were suspected of suffering from actinic keratoses (precancerous skin lesions) or from basal or squamous cell carcinomas: in all cases, complete diagnostics is provided in the dataset. To increase the interest of the dataset and evaluate the dependence of optical spectra (intensity, shape) not only on pathological states but also on healthy skin features (civil age, skin age, gender, phototype, anatomical site), spectra were acquired for all 131 patients on two so-called “reference” skin sites known to rarely suffer from skin cancer: palm of the hand (featuring a thick skin type) and inner wrist (featuring thin skin). Spectra are available in .tab files: first column displays the spectral range on which intensity spectra were recorded (317–788 nm) and each following column provides an intensity spectrum acquired by each spectrometer for a given combination of light source excitation and distance. Each of the 131 folders corresponding to each of the 131 patients contains a .json file providing patients clinical features: gender, civil age, skin age, phototype score and class. All .tab files names include anatomical site and anatomopathological diagnostics of the skin site on which spectra were acquired: codes were defined to match a letter or an acronym to each diagnostic and anatomical site. To ensure quality control, a spectrum was acquired on the same calibration standard before starting spectra acquisition on each patient. It is therefore possible to follow the impact of the acquisition optical chain ageing during the 4.5 years that the patients were included. This dataset can be used by epidemiologists for the characterization of populations affected by skin cancers (gender ratio, mean age, anatomical sites typically affected, etc.); it may also be used by researchers in artificial intelligence to develop innovative methods to process such data and contribute to non-invasive diagnostics of skin cancers whose incidence is steadily increasing.

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. [ABSTRACT FROM AUTHOR]

Background: Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products. It participates in cellular energy metabolism and modulates multiple cellular survival and death pathways. Nicotinamide has been widely studied as a safe chemopreventive agent that reduces actinic keratosis (AKs) and non-melanoma skin cancers (NMSC). Methods: We used the Medline, EMBASE, PubMed, and Cochrane databases to search the concepts "nicotinamide", "chemoprevention", and "skin cancer" up to August 2023. Three independent authors screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. The primary outcome was the impact of oral nicotinamide on the incidence of NMSC in high-risk patients. We also conducted a systematic search to identify relevant epidemiological studies published evaluating dietary niacin intake and the risk of NMSC. Results: Two hundred and twenty-five studies were reviewed, and four met the inclusion criteria. There was no association between NAM consumption and risk for squamous cell carcinoma (SCC) (rate ratio (RR) 0.81, 95% CI 0.48–1.37; I2 = 0%), basal cell carcinoma (BCC) (RR 0.88, 95% CI 0.50–1.55; I2 = 63%), and NMSC (RR 0.82, 95% CI 0.61–1.12; I2 = 63%). Adverse events were rare and acceptable, allowing optimal compliance of patients to the treatment. We found only one article evaluating the association between niacin dietary intake and NMSC risk, supporting a potential beneficial role of niacin intake concerning SCC but not BCC or melanoma. Conclusions: The present meta-analysis shows, by pooling immunocompetent and immunosuppressed patients, that there is insufficient evidence that oral nicotinamide therapy significantly reduces the number of keratinocyte cancers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Actinic keratoses (AKs) are precancerous, dysplastic, epidermal lesions caused by chronic sun exposure that may progress to squamous cell carcinoma. Aminolevulinic acid 20% solution with blue light photodynamic therapy (ALA-PDT) has previously been shown to be superior to vehicle plus PDT (VEHPDT) for treatment of AKs of the face, scalp, and upper extremities. OBJECTIVE: We report detailed patient satisfaction data for ALA-PDT. METHODS: Patient satisfaction for ALA-PDT versus VEH-PDT and patient-reported acceptability of ALA-PDT versus previous treatments for AKs were assessed in three randomized, vehicle-controlled studies (two Phase II and one Phase III) in adults. Patients in the Phase II studies were treated on the scalp and/or face, and those in the Phase III study were treated on the upper extremities. RESULTS: A total of 234, 166, and 269 patients were enrolled in the two Phase II studies and one Phase III study, respectively; overall, 79.8 percent of patients were male. Overall treatment satisfaction ranged from 79 to 88 percent for ALA-PDT, compared to 35 to 56 percent for VEH-PDT. Patients generally considered ALA-PDT to be equivalent to or more acceptable than prior treatments, including cryotherapy, 5-fluorouracil, imiquimod, previous PDT, and surgery. Similar proportions of patients receiving ALA-PDT or VEH-PDT on the upper extremities considered in-office time, side effects/adverse events (AEs), and duration of side effects/AEs to be acceptable. LIMITATIONS: The majority of patients were male, and no statistical comparisons were conducted. CONCLUSION: Patients were generally satisfied with ALA-PDT for the treatment of AKs of the face, scalp, and upper extremities and considered ALA-PDT to be equal to or more acceptable than previous treatments. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background and Objectives: The histological PRO score (I–III) helps to assess the malignant potential of actinic keratoses (AK) by grading the dermal‐epidermal junction (DEJ) undulation. Line‐field confocal optical coherence tomography (LC‐OCT) provides non‐invasive real‐time PRO score quantification. From LC‐OCT imaging data, training of an artificial intelligence (AI), using Convolutional Neural Networks (CNNs) for automated PRO score quantification of AK in vivo may be achieved. Patients and Methods: CNNs were trained to segment LC‐OCT images of healthy skin and AK. PRO score models were developed in accordance with the histopathological gold standard and trained on a subset of 237 LC‐OCT AK images and tested on 76 images, comparing AI‐computed PRO score to the imaging experts' visual consensus. Results: Significant agreement was found in 57/76 (75%) cases. AI‐automated grading correlated best with the visual score for PRO II (84.8%) vs. PRO III (69.2%) vs. PRO I (66.6%). Misinterpretation occurred in 25% of the cases mostly due to shadowing of the DEJ and disruptive features such as hair follicles. Conclusions: The findings suggest that CNNs are helpful for automated PRO score quantification in LC‐OCT images. This may provide the clinician with a feasible tool for PRO score assessment in the follow‐up of AK. [ABSTRACT FROM AUTHOR]

The observations of a beneficial effect of 5-fluorouracil-induced actinic keratoses (AK) inflammation led to the development of topical fluorouracil, a product registered for the management of AK. A conscientious surveillance of AK inflammation during chemotherapy may conceivably lead to the development of further drugs for treatment of AK. A number of other chemotherapeutics have thus been linked to similar reactions without ensuing development. Here, we describe two further cases linking chemotherapy with carboplatin and paclitaxel to possible anti-AK effects, identifying them as potential treatments. Whether multidrug chemotherapy leads to stronger AK inflammation or cure AK more successfully is currently unknown.

Photoprotection is a critical health prevention strategy to reduce the deleterious effects of ultraviolet radiation (UVR) and visible light (VL). Methods of photoprotection are reviewed in this paper, with an emphasis on sunscreen. The most appropriate sunscreen formulation for personal use depends on several factors. Active sunscreen ingredients vary in their protective effect over the UVR and VL spectrum. There are dermatologic diseases that cause photosensitivity or that are aggravated by a particular action spectrum. In these situations, sunscreen suggestions can address the specific concern. Sunscreen does not represent a single entity. Appropriate personalized sunscreen selection is critical to improve compliance and clinical outcomes. Health care providers can facilitate informed product selection with awareness of evolving sunscreen formulations and counseling patients on appropriate use. This review aims to summarize different forms of photoprotection, discuss absorption of sunscreen ingredients, possible adverse effects, and disease-specific preferences for chemical, physical or oral agents that may decrease UVR and VL harmful effects. [ABSTRACT FROM AUTHOR]

Actinic keratoses (AKs) represent a common skin cancer in situ associated with chronic sun exposure. Early diagnosis and management of AKs are crucial to prevent their progression to invasive squamous cell carcinoma. Therefore, we investigated AK PRO score assessment using ex vivo confocal laser microscopy (EVCM) coupled with a novel fluorescent dye, FCF Fast Green, to explore its potential for the precise imaging and discrimination of collagen fibers. AK PRO assessment using EVCM demonstrated excellent conformity (95.8%) with histopathologic examination. The additional utilization of FCF Fast Green dye had no impact on AK visualization but showed a high affinity for collagen fibers enabling clear differentiation of collagen alterations between healthy and sun-damaged skin. The enhanced visualization of collagen fiber changes may aid clinicians in accurately identifying AKs and differentiating them from benign skin lesions.

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 decisionmaking 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. [ABSTRACT FROM AUTHOR]

Introduction: Photodynamic therapy (PDT) is a combined method of light and light-activated chemicals that are called photosensitizers (PSs). PDT is recommended as a high cure rate method with fewer side effects and a noninvasive tool to treat cancer. This study aimed to evaluate PDT efficacy as a therapeutic method against actinic keratoses in patients via protein-protein interaction (PPI) network analysis by using the gene expression profiles of Gene Expression Omnibus (GEO). Methods: Twenty-one gene expression profiles were extracted from GEO and analyzed by GEO2R to determine the significant differentially expressed genes (DEGs). The significant DEGs were included in PPI networks via Cytoscape software. The networks were analyzed by the "Network Analyzer", and the elements of the main connected components were assessed. Results: There were three main connected components for the compared sets of the gene expression profiles including the lesional region of skin before (Before set) and after (After set) PDT versus healthy (healthy set) skin and before versus after. The before-health comparison showed a partial similarity with the After-Healthy assessment. The before-after evaluation indicated that there were not considerable differences between the gene expression profile of the lesional region before and after PDT. Conclusion: In conclusion, PDT was unable to return the gene expression pattern of the actinic keratoses skin to a healthy condition completely. [ABSTRACT FROM AUTHOR]

Inflammation of actinic keratoses (AK) was originally described with systemic 5-fluorouracil, and led to the development of topical fluorouracil. Similar observations using different chemotherapeutics may point to other drugs with a potential for repositioning. This systematic review aims to evaluate chemotherapeutic agents linked to inflammation-induced cure of AK. This systematic review was registered in PROSPERO (CRD42022346168) and followed PRISMA guidelines. A comprehensive literature search for eligible original articles written in English and published in peer-reviewed journals until July 13, 2022 was conducted in MEDLINE and Embase. 28 articles met inclusion criteria accounting for 36 patients (mean age 68.4 ± 8.3 years) with inflamed AK, exposed to 21 different chemotherapeutic agents – 21/36 (58.3%) received monotherapy and 15/36 (41.7%) received multidrug combinations. Regression was complete in 13/28 (46.4%) and partial in 14/28 (50.0%) of inflamed AK. Cure rates of inflamed AK in multidrug combinations were not superior to monotherapies (p =.252), leading to the observation that the majority of the former (14/15; 93.3%) encompassed one of five chemotherapeutic agents linked to AK inflammation also as a monotherapy. Overall, inflammation partially/completely cured AK in 96.4% of patients (27/28). Taxanes, pemetrexed, and doxorubicin might have the potential for the management of AK. [ABSTRACT FROM AUTHOR]

Background: Since recurrences and new AKs commonly are observed after treatment long-term effects of field-directed therapies for AKs are crucial. Thus, we evaluated the 6- and 12-month efficacy and satisfaction of sequential topical 5-fluorouracil (5-FU) and daylight PDT (dPDT) with dPDT alone., Methods: In a randomized intra-individual study patients with multiple AKs in the face and scalp were treated with 4 % 5-fluorouracil cream twice daily for 7 days on one side of the scalp/face, followed by dPDT on both sides. Lesion clearance rate, lesion recurrence rate and number of new lesions were evaluated at 6- and 12-month after treatment., Results: 58/60 completed 6-month and 55/60 completed 12-month follow-up. Pre-treatment with topical 5-FU improved the long-term efficacy of dPDT, especially for moderately thick AKs, with a lesion clearance of 72 % at 12-month compared to 48 % after dPDT alone (p = 0.017). The recurrence rate at 12-month was 15 % for combination treatment and 20 % for dPDT alone (0.042). Most patients were highly satisfied with both treatments., Conclusions: Sequential treatment with short-term topical 5-FU followed by dPDT maintained a higher complete lesion clearance than dPDT alone at both 6- and 12-month follow-ups, with fewer new AKs developing after combination therapy., Competing Interests: Declaration of competing interest SRW has been a member of advisory board for Pierre Fabre and received travel grants from GME Medical for attending congresses. MH served as a consultant for Galderma and received honoraria for speaking. GF, FA, PB and UP declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

The observations of a beneficial effect of 5-fluorouracil-induced actinic keratoses (AK) inflammation led to the development of topical fluorouracil, a product registered for the management of AK. A conscientious surveillance of AK inflammation during chemotherapy may conceivably lead to the development of further drugs for treatment of AK. A number of other chemotherapeutics have thus been linked to similar reactions without ensuing development. Here, we describe two further cases linking chemotherapy with carboplatin and paclitaxel to possible anti-AK effects, identifying them as potential treatments. Whether multidrug chemotherapy leads to stronger AK inflammation or cure AK more successfully is currently unknown. [ABSTRACT FROM AUTHOR]

Background: Conventional photodynamic therapy (c‐PDT) is a highly effective treatment for actinic keratoses. Besides pain as the main side effect, blood pressure (BP) increases and hypertensive crises may occur during treatment. Reducing the irradiation intensity while keeping the total dose constant (low‐irradiance PDT) can achieve a clinically relevant reduction in pain. This study aimed to evaluate the influence of li‐PDT on the BP and pulse (PR) during therapy and the incidence of post‐interventional hypertension compared with c‐PDT. Methods: We retrospectively analyzed the treatment data of 79 patients (39 c‐PDT and 40 li‐PDT). BP and PR measurements were performed in all patients before PDT, at mid‐exposure, and immediately after PDT. In addition, the pain was assessed by using the visual analog scale. Results: Patients treated with li‐PDT reported significantly lower pain than those receiving c‐PDT (p <.0005). Additionally, they showed less systolic (SBP) and diastolic (DBP) BP increase (∆SBP: p <.0005, ∆DBP: p =.015) and overall lower absolute BP values (SBP: p <.0005, DBP: p =.008) compared with c‐PDT. They were also significantly less likely to develop post‐interventional hypertension (p =.037) or higher stages of arterial hypertension. Regarding PR, there was no difference in absolute values between both groups, but the increase from onset to half irradiation duration was significantly higher in c‐PDT (p =.013). Conclusions: Li‐PDT is an excellent option to reduce the elevation of arterial BP and decrease the incidence of post‐interventional hypertension and hypertensive crisis. This finding has considerable relevance, especially with the risk profile of many PDT patients in mind (advanced age and cardiovascular history). [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a highly effective and widely adopted treatment strategy for many skin diseases, particularly for multiple actinic keratoses (AKs). However, PDT is ineffective in some cases, especially if AKs occur in the acral part of the body. Several methods to improve the efficacy of PDT without significantly increasing the risks of side effects have been proposed. In this study, we reviewed the combination-based PDT treatments described in the literature for treating AKs; both post-treatment and pretreatment were considered including topical (i.e., diclofenac, imiquimod, adapalene, 5-fluorouracil, and calcitriol), systemic (i.e., acitretin, methotrexate, and polypodium leucotomos), and mechanical–physical (i.e., radiofrequency, thermomechanical fractional injury, microneedling, microdermabrasion, and laser) treatment strategies. Topical pretreatments with imiquimod, adapalene, 5-fluorouracil, and calcipotriol were more successful than PDT alone in treating AKs, while the effect of diclofenac gel was less clear. Both mechanical laser treatment with CO2 and Er:YAG (Erbium:Yttrium–Aluminum–Garnet) as well as systemic treatment with Polypodium leucotomos were also effective. Different approaches were relatively more effective in particular situations such as in immunosuppressed patients, AKs in the extremities, or thicker AKs. Conclusions: Several studies showed that a combination-based approach enhanced the effectiveness of PDT. However, more studies are needed to further understand the effectiveness of combination therapy in clinical practice and to investigate the role of acitretin, methotrexate, vitamin D, thermomechanical fractional injury, and microdermabrasion in humans. [ABSTRACT FROM AUTHOR]

Background: The suspected link between human papillomavirus (HPV) and the development of premalignant and malignant skin lesions remains inadequately examined in clinical settings. This case series describes HPV vaccination as an off-label adjuvant therapy for actinic keratosis (AK). Methods: Twelve immunocompetent AK patients underwent HPV vaccination at a private dermatology clinic in Naestved, Denmark. Prior to vaccination, all patients demonstrated a high AK burden that required regular control visits. At 0, 2, and 6 months, the patients received an intramuscular injection of a commercially available 9-valent HPV vaccine. Concurrently, patients continued conventional AK therapies at 3-month intervals. Clinical response, consisting of reduction in AK number and general change in skin appearance, was assessed by a dermatologist over 12 months following first vaccination. Results: All patients (mean age 76.2 years; 10 M and 2 F) completed the vaccine schedule. Overall, an average 85% reduction in total AK burden was recorded 12 months after beginning vaccination. Median AK burden thus fell from 56 (IQR: 44–80) to 13.5 (IQR: 1–18) lesions after 12 months. Lesion reduction was observable by the second inoculation at month 2 (34 AKs; IQR 22–80), continuing steadily until month 6 (15 AKs; IQR 5–30) and plateauing between 6 and 12 months. Clinically, HPV vaccination elicited fading of lesions’ erythematous background after the first dose, often followed by sloughing of hyperkeratotic elements in subsequent weeks. Patients reported no adverse effects related to HPV vaccination. Conclusion: This case series introduces the possibility that 9-valent HPV vaccination in combination with conventional treatments may be used as a therapeutic strategy for AK.

IntroductionThe high incidence of actinic keratoses among both the elderly population and immunocompromised subjects and the considerable risk of progression from in situ to invasive neoplasms makes it essential to identify new prevention, treatment, and monitoring strategies.ObjectiveThe aim of this study was to evaluate the efficacy on AKs of a topical product (®Rilastil AK Repair 100 +) containing high-protection sunscreens, a DNA Repair Complex with antioxidant and repairing action against UV-induced DNA damage, and nicotinamide, a water-soluble derivative of vitamin B3 that demonstrated several photoprotective effects both in vitro and in vivo.MethodsThe study enrolled 74 Caucasian patients, which included 42 immunocompetent and 32 immunosuppressed subjects. The efficacy of the treatment has been evaluated through the clinical index AKASI score and the non-invasive Near-Infrared Spectroscopy method.ResultsThe AKASI score proved to be a valid tool to verify the efficacy of the product under study, highlighting an average percentage reduction at the end of treatment of 31.37% in immunocompetent patients and 22.76% in organ transplant recipients, in comparison to the initial values, with a statistically significant reduction also in the single time intervals (T0 vs. T1 and T1 vs. T2) in both groups. On the contrary, the Near-Infrared Spectroscopy (a non-invasive technique that evaluates hemoglobin relative concentration variations) did not find significant differences for O2Hb and HHb signals before and after the treatment, probably because the active ingredients of the product under study can repair the photo-induced cell damage, but do not significantly modify the vascularization of the treated areas.ConclusionThe results deriving from this study demonstrate the efficacy of the product under study, confirming the usefulness of the AKASI score in monitoring treated patients. Near-Infrared Spectroscopy could represent an interesting strategy for AK patients monitoring, even if further large-scale studies will be needed.

Despite the superior efficacy of topical therapies for the treatment of actinic keratoses in clinical trials, cryosurgery remains a frequent treatment modality in clinical practice. Little is known about patients' experience of real-world use of topical therapy. To determine the real-world effectiveness and tolerability of 5-fluorouracil and imiquimod in the treatment of actinic keratoses. A phone survey and chart review was conducted among 51 patients prescribed 5-fluorouracil (N = 27) or imiquimod (N = 24) for actinic keratoses. Six patients (22%) in the 5-fluorouracil group and five patients (21%) in the imiquimod group reported severe local skin reactions, and three patients in both groups (11% and 13%, respectively) were unwilling to use the respective topical therapies again. Patients in the 5-fluorouracil group had, on average, 3.3 fewer cryosurgery spot treatments following topical treatment. Patients in the imiquimod group averaged 2.0 fewer spot treatments. While this study provides information on real-world experiences, patients' responses were limited by the ability to recall treatment and potential adverse effects. High rates of skin reactions, prolonged discomfort, and the continued need for procedural treatments may make patients less willing to use topical 5-fluorouracil or imiquimod for actinic keratoses. [ABSTRACT FROM AUTHOR]

We describe a patient with erythema multiformefollowing a local site reaction after the use of topicalimiquimod 5% cream and review the literature forprevious reports of this cutaneous adverse effect.

Objective: Actinic keratoses (AKs) are cutaneous lesions that arise in sun-damaged skin. AKs may transform into squamous cell carcinoma in situ. Tirbanibulin 1% ointment is a new topical treatment for AKs, recently approved by the Food and Drug Administration. Data Sources: The PubMed database was searched for articles published from 1960 to March 31, 2021, using the keywords tirbanibulin and Klisyri. Data Extraction: Phase 2 and phase 3 clinical trials were reviewed. Data Synthesis: In phase 2 clinical trials, 43% of patients treated with tirbanibulin experienced complete clearance by day 57 (43% [95% CI = 32, 54]). Across two phase 3 clinical trials (pooled data), complete (100%) clearance occurred in 49% of patients in tirbanibulin groups and in only 9% of the vehicle groups (difference, 41% points; 95% CI = 35 to 47; P < 0.001). Although no comparative studies are available, tirbanibulin is applied for a shorter duration (5 days) compared with diclofenac 3% gel, fluorouracil 5% cream, and imiquimod 3.75% cream. Adverse events were mild and included pruritus, application site pain, and local skin reactions. Systemic adverse events such as necrosis and angioedema, observed with other AK treatments such as fluorouracil and imiquimod, were not observed with tirbanibulin, thus giving tirbanibulin a favorable safety profile. Relevance to Patient Care and Clinical Practice: Tirbanibulin effectively reduces AK burden and recurrence and has a favorable safety profile with mild adverse events. In comparison, imiquimod, 5-flourouracil, and diclofenac can result in necrosis, angioedema, and arthralgias. Conclusion: With a favorable safety profile and short regimen, tirbanibulin is an efficacious treatment for clinicians to utilize in their treatment toolbox when treating AKs on the face and scalp. [ABSTRACT FROM AUTHOR]

Background: Between 2003 and 2016, 546 patients in our clinic discontinued outpatient treatment for actinic keratoses (AKs) using conventional photodynamic therapy (PDT) because of intolerable pain, thereby necessitating the use of a less painful procedure. Therefore, we developed a novel off-label PDT protocol: 'PDT light'., Methods: Laser-assisted low irradiance PDT (li-PDT) was performed beginning in 2014. The dosage was gradually lowered to 8-12 J/cm² in 2018, so that we achieved considerable pain reduction while maintaining comparable therapeutic efficacy. A further considerable reduction in pain was achieved from 2018 onwards by combining the advantages of li-PDT with daylight PDT (DLPDT), thereby resulting in 2018 in the new technique 'PDT light'. Patients with AK Olsen grades 1 or 2 and field cancerization initially received a mild-fractionated CO2 laser pretreatment prior to MAL-incubation (methyl aminolaevulinate, Metvix ®) under occlusion for 1.5-3 h. Then, patients were illuminated on average for 1.02 min with the Aktilite-LED and, after application of an UV-screen on the illuminated area, sent out into daylight for 1 h., Results: Between March and November 2019, we successfully treated 152 cases using the enhanced 'PDT light' procedure, with 137 cases achieving at follow-up 1 (on average after 8.14 months) good-to-excellent clearance rates (CLA and CLB together 90%) and minimal adverse effects., Conclusions: The novel 'PDT light' protocol proved to be an excellent and nearly painless method with an average visual-analogue scale (VAS) score of 1.19. Additional advantages included reduced illumination time, shorter outpatient stays in the clinic, fewer adverse effects, and better patient compliance than with DLPDT alone., Competing Interests: Declaration of competing interest The authors have no current or potential conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Among the tirbanibulin-treated patients with complete clearing of AKs by day 57, 47% had recurrence of >=1 lesions at 1 year and 42% had new AKs in the treated area. For many, a regimen of cryotherapy or other "spot therapy" every several months is instituted, with high recurrence rates for treated AKs and inevitable development of new lesions in the sun-exposed areas. Keywords: actinic keratoses; dermatology; tirbanibulin EN actinic keratoses dermatology tirbanibulin 1126 1129 4 10/08/21 20211001 NES 211001 The Clinical Need 1-3 Actinic keratoses (AKs) are highly prevalent precancerous skin lesions affecting primarily middle-aged and elderly White individuals. A large but unknown percentage of such patients fail to curtail their ongoing sun damage sufficiently, however, and continue to develop new AKs and progression of their existing AKs. [Extracted from the article]

Photodynamic therapy (PDT) is widely used in skin diseases; the response rate of PDT treatment varies widely. The limited penetration in the tissue of photosensitizers influenced the penetration depth of PDT, which obviously impacts the therapeutic effect. The studies have improved the efficacy of PDT through various pretreatment applications; especially, the physical pretreatment had achieved significant outcomes. We will review the physical pretreatment to optimize the efficacy of PDT in skin diseases by searching the literature on this topic. The types of physical pretreatment commonly used in the clinical practice are discussed: curettage, superficial shaving, laser, surgical resection, plum-blossom needles, and microneedles. Compared with PDT alone, the physical pretreatment before PDT application was generally improved the efficacy and reduced the recurrence, especially in actinic keratoses (AK), Bowen disease (BD), basal cell carcinoma (BCC), and viral warts. The application of the physical pretreatments before PDT may improve the efficacy of PDT in various skin diseases. However, each kind of physical pretreatment has the benefit and shortcoming, and the applicable situation is different. [ABSTRACT FROM AUTHOR]

Background: The suspected link between human papillomavirus (HPV) and the development of premalignant and malignant skin lesions remains inadequately examined in clinical settings. This case series describes HPV vaccination as an off-label adjuvant therapy for actinic keratosis (AK). Methods: Twelve immunocompetent AK patients underwent HPV vaccination at a private dermatology clinic in Naestved, Denmark. Prior to vaccination, all patients demonstrated a high AK burden that required regular control visits. At 0, 2, and 6 months, the patients received an intramuscular injection of a commercially available 9-valent HPV vaccine. Concurrently, patients continued conventional AK therapies at 3-month intervals. Clinical response, consisting of reduction in AK number and general change in skin appearance, was assessed by a dermatologist over 12 months following first vaccination. Results: All patients (mean age 76.2 years; 10 M and 2 F) completed the vaccine schedule. Overall, an average 85% reduction in total AK burden was recorded 12 months after beginning vaccination. Median AK burden thus fell from 56 (IQR: 44–80) to 13.5 (IQR: 1–18) lesions after 12 months. Lesion reduction was observable by the second inoculation at month 2 (34 AKs; IQR 22–80), continuing steadily until month 6 (15 AKs; IQR 5–30) and plateauing between 6 and 12 months. Clinically, HPV vaccination elicited fading of lesions' erythematous background after the first dose, often followed by sloughing of hyperkeratotic elements in subsequent weeks. Patients reported no adverse effects related to HPV vaccination. Conclusion: This case series introduces the possibility that 9-valent HPV vaccination in combination with conventional treatments may be used as a therapeutic strategy for AK. [ABSTRACT FROM AUTHOR]

Abstract Background Actinic keratoses (AK) are common precancerous lesions of the skin due to cumulative sun exposure. A variety of interventions are available for the treatment; however, the majority of randomised controlled trials (RCTs) and meta-analyses focus on short-term efficacy outcomes. This network meta-analysis aims to investigate the long-term (> 12 months) efficacy of interventions for AK. Methods To identify relevant studies, we will perform a systematic literature research in MEDLINE, Embase, and CENTRAL and hand-search pertinent trial registers. Two authors will independently screen titles and abstracts for eligibility. We will include RCTs with an inter-individual (parallel arm) design. The study population includes patients with a clinical or histopathologic diagnosis of AK. Eligibility will be restricted to the following interventions: surgical approaches, cryosurgery, ablative laser treatment, topical drug treatment with 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac, or photodynamic therapy. As outcomes, we will consider the following endpoints: (1) the participant complete clearance rate, (2) the participant partial clearance rate, (3) the lesion-specific clearance, (4) the mean lesion reduction per patient, and (5) the number of withdrawals due to adverse events after at least 12 months after the end of treatment. Monotherapy or placebo will serve as a comparison. Estimates of effects from individual studies will be pooled using a random-effects model. Heterogeneity will be evaluated based on I 2 and chi-square test. The risk of bias will be estimated with the Cochrane Risk of Bias Tool by two review authors independently. The quality of evidence of the outcomes will be assessed with the GRADE approach. A network meta-analysis will be performed to combine direct and indirect evidence from the included RCTs. Discussion The potential of interventions to achieve a sustained clearance of AK has not been assessed to date. To investigate the long-term efficacy of interventions is important as the natural disease course is highly variable and relapses occur frequently even after initial lesion clearance. This review will help to set a framework for clinical decision making in patients with AK. Systematic review registration CRD42018095903 (PROSPERO)

Squamous cell carcinoma (SCC) is the second most common skin cancer worldwide, and exposure to ultraviolet (UV) light is a major cause of SCC. UV nail lamps can be used for drying and hardening acrylic or gel nail polish. We report a case of a 52-year-old Caucasian woman with an 18-year history of UV nail lamp use every 3 weeks and an 18-year history of weekly tanning bed use who presented with over 25 actinic keratoses and two SCC in situ on her dorsal hands. Of note, this patient has never had any previous biopsies, skin cancer or precancers, or skin cancer or precancer treatment at any time in the past and on skin examination had no precancers or cancers elsewhere on her body. We also review the existing research regarding nail lamp use, which overall suggests that the risk of carcinogenesis is low, and discuss ways dermatologists can educate patients regarding proper UV nail lamp use to minimize risks. This patient’s extensive UV nail lamp use coupled with UVA exposure from tanning beds may have put her at particular risk and exacerbated the effects of the nail lamp alone.