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Introduction & Objectives: Treatment with daylight photodynamic therapy (dPDT) of actinic keratosis (AK) is associated with local skin reactions (LSR), which may affect patients' quality of life and treatment acceptability. This study explores the potential of a prebiotic and panthenol-containing Dermocosmetic Cream (DC) to enhance tolerance and mitigate post-dPDT induced LSR in the treatment of AKs., Materials & Methods: This randomized controlled, intra-individual trial included 20 patients with ≥10 AKs in two symmetrical areas on their face or décolleté, treated with a single session of artificial dPDT. After treatment, the two areas were randomized to DC twice daily for 14 days or No-DC. Primary outcomes included clinical signs of LSR graded from 0=none to 3=severe, calculated as a composite score, and assessed on Days 2, 7, 14, and 30 post-treatment, along with AK clearance rate. Secondary outcomes encompassed objectively measured erythema, and clinical and objective skin photoaging assessment., Results: Topical application of DC following dPDT significantly improved post-treatment tolerance up to two weeks. By Day 2, DC-treated skin had milder LSR (median 3.0, IQR 2.0-4.8) compared to No-DC skin (median 4.0, IQR 3.0-5.0; p=0.011). This improvement continued on Day 7 (DC median 3.0, IQR 2.0-3.8 vs. No-DC median 4.5, IQR 3.0-5.8; p<0.001) and Day 14 (DC median 1.0, IQR 0.0-1.0 vs. No-DC median 1.0, IQR 1.0-2.0; p=0.004). Objective measurements showed milder erythema in DC-treated areas on Day 2 (p=0.045) and Day 7 (p=0.005). Crusting resolved more effectively in DC-treated areas by Day 7 (40% vs. 20%; p=0.039). No significant difference in complete lesion response rate was observed between DC and No-DC skin (p=0.850). By Day 30, clinical photoaging assessment demonstrated significant improvement in dyspigmentation (p=0.004) and skin texture (p<0.001) in both locations. Moreover, objective measurements revealed reduced dyspigmentation in both DC and No-DC treated skin (p≤0.001)., Conclusion: Application of a prebiotic and panthenol-containing multipurpose DC significantly enhanced tolerance from artificial dPDT and accelerated healing time up to 14 days after treatment. The use of DC cream did not affect the overall treatment efficacy of dPDT, indicating its potential to enhance patient comfort following dPDT., (Copyright © 2024. Published by Elsevier B.V.)

Background: Actinic keratoses (AK) may progress into squamous cell carcinoma. Many combination therapies were used to improve the clearance rate. However, there are limited studies on the efficacy and safety of lesion-directed Liquid nitrogen cryotherapy combined with field-directed photodynamic therapy (PDT)., Objective: This study is aimed to determine the efficacy and safety of Liquid nitrogen cryotherapy combined with PDT in Chinese patients with actinic keratosis., Methods: A total of 61 patients with AK were selected at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College between August 2018 and August 2023. They were randomly divided into PDT plus Liquid nitrogen cryotherapy group (LN-PDT) and control PDT group (C-PDT) with 30 patients and 31 patients, respectively. 27 patients in the LN-PDT group and 28 patients in the C-PDT group completed the clinical sessions. Efficacy, adverse effects, and cosmetic outcomes were recorded and compared between the two groups., Results: 3 months after the final treatment, the clearance rates for total AK lesions were 97.4 % (449/461) in the LN-PDT group and 93.4 % (456/488) in the C-PDT group (P < 0.05). For grade I AK lesions, the clearance rates were 99.2 % (234/237) for the LN-PDT group and 98.3 % (237/241) for the C-PDT group (P >0.05). For grade II lesions, the clearance rates were 97.5 % (156/160) for the LN-PDT group and 91.9 % (172/186) for the CPDT group (P < 0.05). For grade III lesions, the clearance rates of the LN-PDT and C-PDT groups were 87.5 % (58/64) and 78.7 % (47/61), respectively (P < 0.05). The two groups had no significant differences in pain, erythema, edema, hyperpigmentation and scarring. Cosmetic outcomes mainly were excellent or good in both groups with no significant difference., Conclusion: Liquid nitrogen cryotherapy combined with PDT showed higher efficacy on grade II and grade III AK lesions than PDT alone. The two groups have similar adverse effects and cosmetic outcomes., (Copyright © 2024. Published by Elsevier B.V.)

Background: Primary endpoints of clinical studies investigating treatments for actinic keratosis (AK) are mainly based on clinical evaluation, but a recent study showed that in AK, clinical classification according to Olsen and the extent of keratinocyte atypia do not necessarily correlate. The influence of the epidermal extent of atypia on treatment efficacy is usually not investigated and therefore remains largely unknown., Objective: To evaluate whether the extent of keratinocyte atypia influences efficacy of photodynamic therapy (PDT) when treating AK., Methods: We performed a post-hoc analysis of histological (keratinocyte intraepithelial neoplasia (KIN)), and clinical (Olsen) data of biopsied lesions of three pivotal studies evaluating PDT using 10 % aminolevulinic acid (ALA) gel or vehicle and narrow- or broad-spectrum red light lamps., Results: Overall, 514 biopsied lesions were considered. Clearance rates after red light PDT with 10 % ALA gel were comparable for KIN I-III (88.2 %, 92.0 % and 87.9 %) and Olsen I-II lesions for any given lamp type. Generally, clearance rates were higher using narrow- compared to broad-spectrum lamps. For both lamp types, the variation in clearance rates from KIN I-III was low. Clearance was lower with vehicle., Limitations: Varying lesion numbers in the subgroups and a remaining risk of bias due to the biopsies are potential limitations., Conclusion: Our results suggest that red light PDT with 10 % ALA gel is an effective treatment option for AK regardless of the extent of keratinocyte atypia., Competing Interests: Declaration of competing interest R.-M.S. has received grants from Almirall, Biofrontera, Dr. Wolff-Group, Galderma, Leo Pharma, Novartis, and photonamic for clinical studies; has received consulting fees and speakers’ honoraria from Abbvie, Almirall, Eli Lilly, Galderma, Janssen, and Leo Pharma, and is Vice-President of the EURO-PDT Society; T.D. has received funding from Almirall, Biofrontera, Galderma, Meda, Schulze & Böhm GmbH for research support; has received consulting fees from Almirall, Biofrontera, GSK, Dr. Pfleger, Galderma, Janssen-Cilag, Leo, Meda, Neracare, Novartis, Scibase, smartinmedia AG, UCB, Vichy; and has received speakers honoraria from Almirall, Biofrontera, Galderma, GSK, infectopharm, Leo, Meda, Neracare, Novartis, Janssen-Cilag, Riemser; E.B. and U.R. have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Treatment-resistant actinic keratosis (AK) is of concern in clinical practice, often requiring retreatment. Microvascular assessments might help differentiate treatment-resistant from treatment-responsive AKs, enabling targeted treatment. Using dynamic optical coherence tomography, AK vascularization was investigated following daylight photodynamic therapy, comparing treatment-resistant with cleared AKs. AKs on face/scalp were graded according to the Olsen Classification Scheme and scanned with dynamic optical coherence tomography pre-treatment, and 3- and 12-months post-treatment. Employing dynamic optical coherence tomography, total vessel length, mean vessel length, mean vessel diameter, vessel area density, and branchpoint density were quantified. Thirty-eight patients with 62 AKs were enrolled, including 37 AK I, 18 AK II, and 7 AK III. Treatment-resistant AKs displayed a trend toward intensified vascularization compared with cleared AK at baseline (AKs I, II), suggested by higher total vessel length (median 144.0, IQR 104.3-186.6) and vessel area density (median 27.7, IQR 18.4-34.2) than in cleared AK (median 120.9, IQR 86.9-143.0 and median 22.9, IQR 17.3-26.8). Additionally, vascularization in treatment-resistant AK I-II appeared disorganized, with trends toward shorter mean vessel length (median 151.0, IQR 138.5-167.5) and increased branchpoint density (median 3.2, IQR 2.3-3.8) compared with cleared AK (median 160.0, IQR 152.0-169.3 and median 2.6, IQR 2.2-3.0). These findings suggest that dynamic optical coherence tomography holds potential to identify treatment-resistant AKs.

Background: Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp., Methods: We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs., Results: Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded., Conclusion: Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas., (© 2024 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) and uses different light sources as well as photosensitizers. In addition, PDT is often combined with other physical therapies or drugs., Objectives: This study was aimed to compare the efficacy of different PDTs against AK lesions based on Complete Response (CR) by conducting a network meta-analysis (NMA)., Methods: Randomized controlled trials (RCTs) using PDT for AK were screened and a Bayesian model was developed to perform an NMA of CR at 3 months after the first treatment., Results: Twenty-six trials involving 2285 patients and 14 treatments were included. The treatments were broadly divided into mono-PDT and combination therapy. The photodynamic monotherapies included methyl 5-aminolevulinic acid (MAL)-daylight (DL)-PDT, MAL-light-emitting diode (LED)-PDT, 5-aminolevulinic acid (ALA)-LED-PDT, etc. Combination therapies included ablative fractional laser (AFL)-assisted MAL-LED-PDT, calcipotriol (CAL)-assisted MAL-LED-PDT, and 5-fluorouracil (5-Fu)-assisted MAL-DL-PDT. The results of the NMA showed that there is a high probability that AFL-MAL-LED-PDT is the most effective treatment option, followed by CAL-MAL-LED-PDT and ALA-LED-PDT. The subgroup analysis showed that MAL-based PDT had better efficacy when using LED versus other light sources, while LED-based PDT was likely to have better efficacy when using ALA versus other photosensitizers., Conclusions: The results of this NMA suggest that AFL-MAL-LED-PDT may be the superior choice for achieving complete clearance of AK lesions. PDT using LED as the light source and ALA as the photosensitizer may be more effective for the treatment of AK. However, more RCTs are needed to verify the results of this analysis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Care for actinic keratosis (AK) can be improved with more knowledge on the relative of effect of indicated therapies., Objectives: Using network meta-analyses, we quantitatively determined the comparative "short-term" effects of interventions in adults with facial and scalp AK., Methods: On February 28, 2023, evidence from the peer-reviewed literature was systematically obtained from OVID, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. We analyzed data from studies published in English, of a trial design, and investigating the effect of an actinic keratosis monotherapy. Patient complete clearance, patient partial clearance or lesion-specific clearance across adults were analyzed at 8-12 weeks after therapy. Patient complete clearance pertained to proportion of participants who experienced complete clearance of actinic keratosis lesions; patient partial clearance corresponded to percentage of subjects who achieved at least 75% clearance of actinic keratosis lesions; lesion-specific clearance represented the percentage of all lesions that were cleared. In the main (i.e., base) analyses, nodes were analyzed only at the level of the agent., Results: Data from a total of 84 studies were used-across which 22 active agents were identified. Estimates of interventions' surface under the cumulative ranking curve rankings and (pairwise) relative effects were estimated. Across the three outcomes, fluorouracil 5% was ranked the most effective., Conclusions: Our work is the first to provide information on covariate-adjusted relative effects of actinic keratosis therapies- including the more recently reported treatments-for the face and scalp; this knowledge may help physicians and patients make more informed decisions., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Actinic keratosis (AK) is a common cutaneous keratinocyte dysplasia characterized by the abnormal proliferation of atypical epidermal keratinocytes; an area that presents photoinduced subclinical changes, similar to those found in AKs, on the periphery of clinically visible AKs is defined as a field of cancerization. Its treatment, rather than a treatment aimed at the single lesion, is more recommended as it manages the subclinical damage and prevents the onset of a possible squamous cell carcinoma. Among the field therapies, tirbanibulin has recently been introduced with an innovative mechanism of action that determines cellular apoptosis and consequently a poor local inflammatory reaction. We present the case of an 82-year-old patient, known for previous removals of squamous cell carcinomas at the vertex and currently suffering from a large field of cancerization in the nose and scalp, to whom we proposed a sequential treatment with three cycles of tirbanibulin in contiguous areas. The treatment was well tolerated and allowed complete clearance to be obtained on the nose and > 95% on the scalp, with a reduction of the Actinic Keratosis Area and Severity Index (AKASI) from 9.4 to 1.4.

Actinic keratoses (AK) are common precancerous lesions usually arising on chronic sun-exposed areas. Field of cancerization (FC) is a chronically UV-exposed area in which subclinical multifocal AKs are found. Therapeutic choice is mainly made according to the Olsen grade of AKs. We report the case of a 76-year-old man with numerous AKs of the face and scalp. The patient had undergone numerous topical physical and medical therapies with poor results. On the left cheek, grade I and grade II AKs were found in a large FC, so he was prescribed topical therapy with tirbanibulin 1% ointment. After 10 days erythema and crusts were objectified and a burning sensation was reported on the area of application and on surrounding areas. At 8 weeks follow-up, the patient had total resolution of disease and no residual local side effects. Although tirbanibulin 1% ointment has indication for type I AKs of face and scalp, this case reported its efficacy and benefit also on type II AKs, demonstrating safety and a minimal and manageable degree of discomfort caused to the patient. Therefore, it fits fully among the treatments of grade I AKs but numerous still may be its indications as demonstrated in our case, where efficacy, safety and compliance were combined.

A 72-year-old man presented with actinic keratosis (AK) of the scalp confirmed by line-field confocal optical coherence tomography (LC-OCT) a novel non-invasive skin imaging technique. Patient was treated with Tirbanibulin 1% ointment once a day for 5 consecutive days and, after 8 days from baseline, mild erythema and desquamation was observed on the treated area, associated with mild pruritus. At the same time-point, L'LC-OCT revealed the presence of intraepidermal "targeted-like" cells, corresponding to apoptotic keratinocytes. After 2 months, clinical and instrumental examination showed the almost total disappearance of the AK. At the same time-point, a strong improvement of photoaging was noted at the level of the treated area. At 1-year follow-up, no relapse and/or new AK were observed. In conclusion, the reported case is emblematic of the short and long-term efficacy and safety of tirbanibulin in the treatment of AK, as already reported in the literature, as well as of the usefulness of non-invasive imaging technique such as LC-OCT in the therapeutic monitoring.

This review examines the pharmacology, efficacy and safety, dosage and administration, and place in therapy of the combination of 5-fluorouracil (5-FU) and calcipotriol for the treatment of actinic keratosis. Currently, 5% 5-FU topical cream is approved for actinic keratosis treatment, while calcipotriol is indicated for plaque psoriasis in adults. The typical administration of 5-FU involves topical application twice daily for up to 4 weeks, whereas calcipotriol is applied in a thin layer once or twice daily as directed by a physician. Adverse effects of 5-FU are primarily localized, including skin irritation, ulceration, pruritus, erythema, crusting, and eczematous reactions due to minimal systemic absorption. Calcipotriol may cause burning, itching, and skin irritation. This review details clinical trials that investigate the innovative approach of combining topical 5-FU with calcipotriol for actinic keratosis treatment, highlighting the significant outcomes. Notably, the clinical trials indicate that all participants experienced either a reduction in lesion size or complete lesion clearance, with minimal adverse effects impacting treatment success. The combination of 5-FU and calcipotriol effectively treats actinic keratosis by enhancing the immune response and targeting cell overgrowth, while reducing local site reactions and the lengthy treatment time often associated with existing therapies., (© 2024. The Author(s).)

Background: Pain associated with aminolevulinic acid photodynamic therapy (ALA-PDT) for the treatment of facial dermatoses results in low patient compliance. Two-step photodynamic therapy (two-step PDT) may improve comfort by optimizing light amplitude and exposure time., Objective: To investigate the efficacy of two-step PDT in reducing the pain generated during the treatment of facial skin disorders., Methods: Twenty-six patients with AK were randomly divided into two groups; the experimental group was treated with two-step photodynamic therapy and the control group was treated with conventional photodynamic therapy. The pain intensity of the patients at different times was assessed using the pain numerical rating scale (NRS)., Results: A total of 26 patients completed three ALA-PDT treatments, 13 and 13 patients in each group, respectively. The mean NRS scores of patients in the experimental group (3.28±1.41, 3.33±1.43, 3.42±1.78) were lower than those of the control group (5.00±1.94, 5.09±1.86, 4.86±1.64) on each occasion. The incidence of certain adverse reactions was lower in the experimental group than in the control group. There was no difference between the two groups in terms of clinical outcome, recurrence rate and patient satisfaction., Conclusion: Two-step photodynamic therapy can reduce pain and the incidence of some adverse reactions, but does not affect clinical efficacy, recurrence rate and patient satisfaction., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: Actinic keratoses (AK) are increasing in incidence and represent the most common (pre-)cancerous lesion in the fair-skinned population, with a high unmet medical need. In order to increase treatment adherence, it is very important to assess patients' therapy-related evaluations of different treatment options., Patients and Methods: 100 patients with AK who were treated with at least two different treatment options were included. They rated their therapies using the Treatment Satisfaction Questionnaire for Medication (TSQM, maximum 100 points per category) and a Likert scale (LS, 1  =  very satisfied; 6  =  not satisfied). Patients were also asked about their needs in terms of treatment goal, cost, type, duration, and location of treatment., Results: 81% of the study participants were male and on average 74 years old. 95% had field cancerization. Eight frequently used therapy procedures were evaluated by the patients (surgery, cryotherapy, various topical agents, photodynamic therapy). The TSQM satisfaction scores ranged from 78.47 ± 16.07 (surgical procedures) to 53.03 ± 22.13 (diclofenac-HA). Statistically significant differences between the procedures were only found in the area of efficacy. Side effects were classified as low. Low recurrence rate and safe removal were the most important treatment goals (LS: 1.18 ± 0.44 and 1.27 ± 0.53, respectively)., Conclusions: Understanding patient preferences is essential for adherence and is therefore of great importance for the success of AK therapy. Personalized approaches should be considered in the choice of therapy., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Acral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands., Methods: We analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10 % 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction., Results: 24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9 % (lesion-based) and 76.2 % (per participant's side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0 %. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0 %) rated their satisfaction with BF-200 ALA as very good or good., Conclusion: This subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands., Competing Interests: Declaration of competing interest R.A. received honoraria as scientific advisor, trial investigator and lecturer for AbbVie, Boehringer-Ingelheim, Bristol-Myers Squibb, Incyt, Janssen, Leo, Lilly, Novartis, Sanofi-Aventis, and UCB. R.-M.S. has received grants from Almirall, Biofrontera, Dr. Wolff-Group, Galderma, Leo Pharma, Novartis, and photonamic for clinical studies; has received consulting fees and speakers’ honoraria from Abbvie, Almirall, Eli Lilly, Galderma, Janssen, and Leo Pharma, and is Vice-President of the EURO-PDT Society. T.D. has received funding from Almirall, Biofrontera, Galderma, Meda, Schulze & Böhm GmbH for research support; has received consulting fees from Almirall, Biofrontera, GSK, Dr. Pfleger, Galderma, Janssen-Cilag, Leo, Meda, Neracare, Novartis, Scibase, smartinmedia AG, UCB, Vichy; and has received speakers honoraria from Almirall, Biofrontera, Galderma, GSK, infectopharm, Leo, Meda, Neracare, Novartis, Janssen-Cilag, Riemser. R.S. and M.-T.Z. were employees of Biofrontera Bioscience GmbH at the time the manuscript was written. N.P. is an employee of Biofrontera Bioscience GmbH. U.R. and R.D. have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Actinic keratosis (AK) is a common precancerous condition found on sun-damaged skin. Tirbanibulin 1 % ointment has been approved for the topical treatment of non-hyperkeratotic facial and scalp Olsen grade I AKs over a contiguous area of 25 cm 2 with a daily application for 5 consecutive days. Our aim was to investigate the use of in vivo RCM in the assessment of the response of AKs treated with tirbanibulin, as it has never been described in the published Literature. A total of 10 AKs in 10 consecutive outpatients were enrolled in the present study in May 2023. The follow-up visit was scheduled after 30 days from last application of tirbanibulin ointment. At follow-up visit, a complete response was described by clinical, dermoscopic and in vivo RCM examination in 10 out of 10 lesions, with a recovery of stratum corneum, decrease in atypical honeycomb pattern and changes in dermal collagen. All patients were followed up for at least 8 months and further recurrences were not registered. Based on our experience, we confirm the efficacy and safety of tirbanibulin in treating AKs and the usefulness of RCM in vivo examination for the therapeutic monitoring of such lesions, even in a very early stage., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/objectives: Actinic keratoses (AK) are premalignant skin lesions caused by chronic sun exposure, topically managed by 5-fluorouracil (5-FU), diclofenac 3% gel, and imiquimod. Despite their effectiveness, long treatment duration and severe adverse local skin reactions have limited patient concordance. Calcipotriol has recently been used as a combination agent for existing topical AK treatments. A systematic review was performed to determine the clinical efficacy of 5-FU and calcipotriol for the treatment of AK, Bowen's disease, and squamous cell carcinoma (SCC)., Methods: A systematic literature search was conducted on Medline, Embase, and Cochrane Library. Among the 84 records screened, 12 were retrieved for full-text review and 8 were included in the final analysis., Results: Among the 8 studies, there were 214 control patients and 288 patients who received the intervention. The combination 5% 5-FU with calcipotriol resulted in a significant reduction in the number of AKs on the face, scalp, right upper extremity, and left upper extremity for all sites at 8 weeks ( P < .0001). No significant difference in SCC incidence was observed at 1 or 2 years, but there was a significant reduction observed at 3 years for SCC on face and scalp. No study assessed the combination for Bowen's disease., Conclusions: Combination 5% 5-FU with calcipotriol is an effective treatment for Aks; however, future trials may consider longer treatment and follow-up periods for the treatment and prevention of AK, SCC in situ, and SCC., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL)., Objective: To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC., Method: This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects., Results: After 90 days, there was complete clearance of AK in 37% (95% CI 24%-49%) and partial clearance in 85% (95% CI 76%-93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%-27%) and 78% (95% CI 66%-88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%-83%) and 64% in those treated with COL (95% CI 55%-72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012)., Study Limitations: Single-center study., Conclusions: 5-FU and COL are effective for treating CFC, with neither showing superiority regarding the reduction in AK counts., (Copyright © 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Topical tirbanibulin is a highly effective and well tolerated novel treatment option for actinic keratoses (AKs). This study aimed to characterize the mode of action of tirbanibulin in keratinocytes (NHEK) and cutaneous squamous cell carcinoma (cSCC) cell lines (A431, SCC-12) in vitro. Tirbanibulin significantly reduced proliferation in a dose-dependent manner in all investigated cell lines, inhibited migration, and induced G2/M-cell cycle arrest only in the cSCC cell lines analyzed, and induced apoptosis solely in A431, which showed the highest sensitivity to tirbanibulin. In general, we detected low basal expression of phosphorylated SRC in all cell lines analyzed, therefore, interference with SRC signaling does not appear to be the driving force regarding the observed effects of tirbanibulin. The most prominent tirbanibulin-mediated effect was on β-tubulin-polymerization, which was especially impaired in A431. Additionally, tirbanibulin induced an increase of the proinflammatory cytokines IL-1α, bFGF and VEGF in A431. In conclusion, tirbanibulin mediated anti-tumor effects predominantly in A431, while healthy keratinocytes and more dedifferentiated SCC-12 were less influenced. These effects of tirbanibulin are most likely mediated via dysregulation of β-tubulin-polymerization and may be supported by proinflammatory aspects., (© 2024. The Author(s).)

Background: Actinic keratosis (AK) is a precancerous lesion that occurs in areas that are chronically exposed to sunlight and has the potential to develop into invasive cutaneous squamous cell carcinoma (cSCC). We investigated the efficacy of 20 % 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) with LED red light for the treatment of AK in Chinese patients by examining changes in dermoscopic features, histopathology and fluorescence after treatment., Methods: Twenty-eight patients with fourty-six AK lesions from March 2022 to September 2023 were treated with 20 % ALA, and 3 h later, they were irradiated with LED red light (80-100 mW/cm 2 ) for 20 min. A session of 20 % ALA-PDT was performed once a week for three consecutive weeks, and the dermoscopic, histopathological, fluorescent and photoaging outcomes were measured one week after the treatment., Results: One week after ALA-PDT, complete remission (CR) was reached in 53.6 % of patients. The CR of Grade I AK lesions was 100 %, that of Grade II lesions was 71.4 %, and that of Grade III lesions was 38.1 %. There was a significant improvement in the dermoscopic features, epidermal thickness and fluorescence of the AK lesions. The presence of red fluorescence decreased, and there was an association between CR and post-PDT fluorescence intensity. ALA-PDT also exhibited efficacy in treating photoaging, including fine lines, sallowness, mottled pigmentation, erythema, and telangiectasias, and improved the global score for photoaging. There were no serious adverse effects during or after ALA-PDT, and 82.1 % of the patients were satisfied with the treatment., Conclusion: AK lesions can be safely and effectively treated with 20 % ALA-PDT with LED red light, which also alleviates photoaging in Chinese patients, including those with multiple AKs. This study highlights the possibility that fluorescence could be used to diagnose AK with peripheral field cancerization and evaluate the efficacy of ALA-PDT., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.&nbsp; Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24., Results: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P&lt;0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%)., Conclusions: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

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., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Oculocutaneous albinism (OCA) is a genetically inherited condition, whereby melanin is reduced or absent in the skin. A lack of melanin predisposes people to actinic damage and skin malignancies. In Tanzania, a resource-limited country, the treatment of choice for precancerous skin lesions is cryotherapy., Objectives: To investigate whether daylight photodynamic therapy (dPDT) is a safe and well-tolerated treatment for actinic field change in the OCA population in Tanzania., Methods: Twelve participants with actinic damage were recruited from a Standing Voice skin surveillance clinic and treated with dPDT. Study participants completed tolerability and acceptability questionnaires at day 5 and 3 months after treatment. A dermatologist assessed their clinical response to dPDT at 3 months., Results: dPDT was well-tolerated and acceptable to the majority of patients. Actinic damage was reduced by 25-90%. No skin cancers developed during the treatment., Conclusions: This pilot study suggests that dPDT is a safe and tolerable treatment for actinic damage in people with OCA in Tanzania. Further work is required to compare the efficacy of dPDT against other topical therapies for actinic field change., Competing Interests: Conflicts of interest A.S. is chair of the skin cancer advisory committee for Standing Voice. D.M. sits on the skin cancer advisory committee for Standing Voice. H.F. is executive director/founder of Standing Voice. The other authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Simulated daylight photodynamic therapy is a relatively new and potentially less painful alternative to conventional red light photodynamic therapy for actinic keratosis. Qualitative research exploring patient experiences of pain and skin reactions during these treatments is scarce. To address this, semi-structured interviews were conducted of 10 patients aged 60-81 years with symmetrically distributed actinic keratoses 4 weeks after split-face treatment with conventional red light photodynamic therapy and simulated daylight photodynamic therapy. The participants were recruited from an ongoing clinical randomized trial. Interviews (median length 35 min) were conducted between June 2022 and January 2023, audio-recorded, transcribed verbatim, and analysed qualitatively using content analysis, as described by Graneheim and Lundman. Participants reported that conventional red light photodynamic therapy was very painful during illumination and transiently painful in the post-treatment period, while simulated daylight photodynamic therapy was almost painless during illumination and led to minor post-treatment pain. Also, skin reactions were more intense and longer-lasting with conventional red light photodynamic therapy than with simulated daylight photodynamic therapy. Most participants expressed a treatment preference for simulated daylight photodynamic therapy but had reservations about its unestablished long-term effectiveness. This study underscores the considerable pain associated with conventional red light photodynamic therapy, and the pivotal importance of shared decision-making when selecting the most appropriate treatment.

Hybrid trials are a new trend in dermatological research that leverage mobile health technologies to decentralize a subset of clinical trial elements and thereby reduce the number of in-clinic visits. In a Phase I/IIa randomized controlled hybrid trial, the safety and efficacy of an anti-proliferative and anti-inflammatory drug inhibiting cytosolic phospholipase A2 (AVX001) was tested using 1%, 3% or vehicle gel in 60 patients with actinic keratosis (AK) and assessed in-clinic as well as remotely. Over the course of 12 weeks, patients were assessed in-clinic at baseline, end of treatment (EOT) and end of study (EOS), as well as 9 times remotely on a weekly to biweekly basis. Safety outcomes comprising local skin reactions (LSR; 0-5), adverse events (AE) and cosmesis, were graded in-clinic and remotely using patient-obtained smartphone photographs (PSPs) and questionnaires; efficacy was assessed in-clinic based on clinically visible clearance of AK target area of >50%. A total of 55 participants (91.7%) completed the treatment course. The average submission rate of PSPs was high (≥85%), of which 93% were of sufficient quality. No serious AE were reported and only two experienced temporary LSR >2 (scale 0-4) and cosmesis remained stable throughout the study. Based on the mild AE and LSR profile, daily application of AVX001 gel for 1 month appears safe, tolerable, and cosmetically acceptable for use in patients with AK. At EOT, AVX001 achieved a subtle treatment response with clearance of AK target area of >50% in 18% of patients. Remote and in-clinic assessments of LSRs were in high agreement, suggesting that the use of mobile health technologies in early-phase hybrid studies of AK does not compromise patient safety., (© 2024 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role. Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients. This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Daylight photodynamic therapy (DL-PDT) has become one of the most effective treatments for the resolution of actinic keratosis (AK) of Olsen grade 1 and 2. Generally, PDT it is carried out in a clinic setting, which involves the patient's and their caregivers commuting to the hospital as well as a significant use of resources to carry it out within the clinic setting., Objectives: To determine the efficacy and safety of a home-based treatment of AK with DL-PDT with the BF-200 ALA gel compared to a clinic-based setting., Methods: The study was performed as a randomized, single-center, non-inferiority clinical trial with two parallel groups. 9 patients received one clinic-based DL-PDT (group 1) and 11 patients received one session of home-based DL-PDT (group 2). The primary endpoints were the mean AK clearance per patient and the total AK lesion clearance rate 12 weeks after treatment. The secondary endpoints were the number of remaining AKs and new AKs appearing in the treatment field 12 weeks after one PDT session. The pain during and 24 h after PDT as well as the local skin reactions were also assessed., Results: The overall reduction of AK lesions per patient was similar in both groups with one PDT session. An overall AK clearance per patient of 10 ± 4.33 for group 1 versus 9.73 ± 2.9 for group 2 without statistically significant differences (p = 0.868). Regarding the clearance rate, although it was slightly higher in group 2 (71.58 ± 22.51 vs 82.1 ± 11.13), the analysis did not show statistically significant differences. The mild pain recorded during the treatment course and the mild local skin reactions were similar in both groups. Patient satisfaction was high for both groups without statistically significant differences., Conclusion: Self-performed home-based DL-PDT with BF-200 ALA gel is as effective as the one performed in a clinic-based setting, with a comparable safety profile, high levels of patient satisfaction and with advantages for the patients and their caregivers that can enhance patient´s adherence to the treatment., Competing Interests: Declaration of competing interest None, (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Actinic keratoses (AK) are one of the most frequent reasons for consultations in dermatology. Ultraviolet-induced fluorescence dermatoscopy (UVFD) is a new method that allows the assessment of lesions in a spectrum of light that originates from the fluorochromes emitting UV-excited luminescence. The aim of this study was to assess the UVFD features of AKs before PDT and their intensity in field cancerization and single lesions., Methods: This retrospective study was conducted from June to November 2023. Lesions were assessed with the Olsen scale clinically and dermatoscopically (DermLite DL5, 10x magnification) and photographed. UVFD fluorescence was categorized as 'none', 'weak', 'moderate', and 'intense'. A 1-mm thick layer of 10 % 5-ALA gel was applied to single lesions or cancerization field (depending on the patient) and covered with an occlusive dressing for 3 h. Prior the application of 10 % 5-ALA gel, the lesions were degreased with an alcoholic solution. The occlusion was removed, and the field was cleaned with a 0,9 % saline solution. Afterward, each lesion was photographed in polarized light and UVFD mode., Results: A total of 194 dermatoscopic images were analyzed, 111 corresponded to field cancerization and 81 to single AKs. Overall, weak fluorescence was noticed in 22 of them (11,3 %), moderate in 107 (55,15 %), and intense in 65 (33,5 %). Amongst field cancerization (111 images), weak fluorescence was seen in 11 (9.9 %), moderate in 68 (61,26 %), and intense in 32 (28,82 %). In single lesions (81 images), weak fluorescence was detected in 11 (13,2 %), moderate in 39 (46,99 %), and intense in 33 (28.83 %) of the lesions. Slightly more intense fluorescence was noticed in higher Olsen grade (p = 0.04)., Conclusions: UVFD can enhance our efficacy of pre-procedural examination and might arise as a useful device to predict the therapeutic effect of PDT., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Daylight photodynamic therapy (dPDT) and topical 5-fluorouracil (5-FU) are each effective treatments for thin grade I actinic keratosis (AKs), but less so for thicker grade II-III AKs. Prolonged topical treatment regimens can be associated with severe skin reactions and low compliance. This study compares the efficacy of sequential 4 % 5-FU and dPDT with dPDT monotherapy for multiple actinic keratoses., Methods: Sixty patients with a total of 1547 AKs (grade I: 1278; grade II: 246; grade III: 23) were treated in two symmetrical areas (mean size 75 cm 2 ) of the face or scalp, which were randomized to (i) 4% 5-FU creme twice daily for 7 days before a single dPDT procedure and (ii) dPDT monotherapy. Daylight exposure was either outdoor or indoor daylight., Results: Twelve weeks after treatment 87 % of all AKs cleared after 5-FU+dPDT compared to 74 % after dPDT alone (p<0.0001). For grade II AKs, the lesion response rate increased from 55 % with dPDT monotherapy to 79 % after 5-FU+dPDT (p<0.0056). Moderate/severe erythema was seen in 88 % 5-FU+dPDT areas compared to 41 % of dPDT areas two days after dPDT. Twelve weeks after treatment 75 % of the patients were very satisfied with both treatments., Conclusions: Sequential 5-FU and dPDT was more effective than dPDT monotherapy in the treatment of AKs, especially for grade II AKs. Local skin reactions were more pronounced after combination treatment, but no patients discontinued the treatment. The combination of 5-FU and dPDT is an effective treatment of large treatment areas with high compliance and satisfaction., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The application of photodynamic therapy (PDT) is pivotal in the management of diverse dermatologic conditions. Microneedling (MN) is a minimally invasive tool that is capable of inducing transient pores on the skin to facilitate transdermal drug delivery. Several studies have reported augmentation of PDT combined with MN. This systematic review analyzes the current studies on the efficacy and safety of MN-assisted PDT for skin diseases., Methods: The literature search using the PRISMA standard was completed through PubMed, Embase, Web of Science and CENTRAL from the establishment of the databases to November 2023. Two independent researchers finished the procedure., Results: A total of 12 articles and 413 subjects met our study criteria. This systematic review suggests that MN-assisted PDT can decrease the incubation time required for the photosensitizer and reduce skin lesions of actinic keratosis (AK) . The common side effect is pain and no serious adverse events were reported., Conclusions: MN is an effective method to increase the transdermal delivery rate of photosensitizers. For different photosensitizers and disease, MN may show different clinical effects., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Conventional photodynamic therapy (c-PDT) is an effective treatment for actinic keratoses (AKs) and nonmelanoma skin cancer which exploits the photosensitizing properties of methyl aminolaevulinate (MAL). Daylight photodynamic therapy (DL-PDT) is an alternative to c-PDT which does not require the application of MAL in occlusion and that is better tolerated by patients. The impact of occlusion on the efficacy of DL-PD has not been investigated by previous studies., Objective: To compare the efficacy and tolerability of occlusive and non-occlusive DL-PDT., Methods: We conducted a prospective intraindividual left/right comparison study. AKs of the face or scalp were marked in two symmetrical treatment areas. The two target areas were randomly assigned to DL-PDT with occlusive and non-occlusive application of MAL. The efficacy and cosmetic outcome were determined by a "blinded" investigator., Results: Lesions in occluded areas showed a better response in the clearance rate of the lesions (65.5% vs 35.0 %, p < 0.001 %), and cosmetic outcome (P < 0.001). There was no difference in phototoxicity or pain between occluded and non-occluded areas., Conclusion: The occlusive application of MAL improves the efficacy of DL-PDT in clearing AKs and does not increase the incidence of side effects., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cutaneous field cancerization in dermatology describes the anatomic region of photodamaged skin with actinic keratoses (AKs) or cutaneous squamous cell carcinoma (cSCC) that is surrounded by cellular atypia, forming a dysplastic field. The concept of field cancerization is especially relevant in dermatology, as actinic keratoses and the surrounding dysplastic region can progress to carcinomas, necessitating the treatment of the field. Recent research has focused on field-directed therapy using topical agents. This study aims to systematically review randomized controlled trials on topical treatments for actinic keratosis field cancerization, following the PRISMA guidelines. Clinical recommendations were based on the Oxford Centre for Evidence-Based Medicine. We identified 20 original randomized controlled trials for topical cutaneous field therapy. 0.5% 5-Fluorouracil/salicylic acid and 0.5% 5-fluorouracil received a clinical recommendation grade of A, while diclofenac sodium received a clinical recommendation grade of B. Calcipotriol/5-fluorouracil, Imiquimod, sunscreen combination therapies, and tirbanibulin received a recommendation grade of C. This review provides a framework for clinicians when considering topical treatments for patients with field cancerization., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Methyl aminolevulinate (MAL) photodynamic therapy (PDT) is commonly used for field treatment of actinic keratoses (AKs). In standard natural daylight PDT (n-DL-PDT) the first step, after the application of chemical solar filter, is removal of crusts and scales by curettage, followed by the application of MAL cream. Some patients experience intense pain during curettage and stinging after application of the photosensitizer to just curettaged skin., Objectives: To evaluate whether n-DL-PDT without curettage, but preceded by application of keratolytics, would maintain a similar efficacy, based on clinical, dermoscopic, reflectance confocal microscopy (RCM) assessments, safety and patient satisfaction as standard n-DL-PDT with curettage., Methods: Forty patients with multiple AKs on the face and/or scalp were enrolled in this study. Patients were randomized into two groups of treatment as follows: (i) MAL n-DL-PDT without previous curettage, preceded by skin preparation at home with keratolytics (30% urea cream, twice a day for 7 days; -Cur group) and (ii) MAL n-DL-PDT preceded by skin preparation at the hospital with curettage (+Cur group)., Results: Thirty-nine participants completed the study. Four hundred and twenty-one AKs in -Cur group and 337 AKs in +Cur group were treated. The mean reduction in the number of AK lesions 3 months after the treatment was 10.7 (-54.7%) in the -Cur and 10.4 (-58.7%) in the +Cur group. We found that the differences in terms of efficacy and patient satisfaction comparing the two treatment regimens were not statistically significant. The pain score reported during and after daylight exposure was similar and low in both groups. Moreover, no unexpected adverse events occurred during the trial period., Conclusions: According to our results, curettage is not necessary to obtain the full treatment effect of n-DL-PDT. We experienced in a real-life setting that n-DL-PDT protocol could be changed by replacing curettage with keratolytics., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Introduction: Photodynamic therapy (PDT) is a safe, non-mutagenic, and non-scarring treatment for actinic keratoses (AK)., Background: 'Painless' photodynamic therapy (p-PDT) is a regimen for AK that employs simultaneous aminolevulinate incubation and blue light illumination. The efficacy of p-PDT resembles that of traditional PDT, but detailed mechanisms of action for p-PDT are not well understood., Methods: To characterize the inflammatory effects of the p-PDT procedure 48 h following treatment and determine the association of inflammation with precancer burden, we performed a retrospective cohort study of 104 patients with AK of face or scalp treated with p-PDT between 2017 and 2019. Patients self-reported their side effects 48 h following p-PDT and took photographs of their face and scalp. Photographs were edited to define seven anatomic regions, and erythema was scored by four investigators., Results: Ninety-eight patients provided photographs suitable for erythema evaluation. Most patients experienced 2 or more side effects and some pain 48 h post-procedure. Females experienced more pain (p = 0.01) and side effects (p = 0.002) compared to males. AK burden was positively associated with post p-PDT erythema response (p < 0.0001) at all sites, but particularly in the temples (p = 0.002) and supralabial area (p = 0.009)., Discussion: This study confirms a strong clinical inflammatory response after p-PDT. Severity of inflammation is positively associated with AK tumor burden, suggesting that post-treatment inflammation may be a pre-requisite for p-PDT efficacy. Interestingly, the results also identify certain gender-related differences in the severity of side effects experienced by patients post-PDT., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier B.V.)

Tirbanibulin ointment 1% is approved in the United States and Europe for the treatment of actinic keratosis with demonstrated efficacy, safety, and tolerability when applied over a field up to 25 cm 2 . This Phase 1 maximal-use trial determines the plasma pharmacokinetics, safety, and tolerability of tirbanibulin ointment 1% applied to 100 cm 2 of the face or balding scalp in adults with actinic keratosis. Twenty-eight patients self-applied tirbanibulin once daily for a single 5-day treatment course. On Day 5, the mean maximum plasma concentration was 1.06 ng/mL and area under the plasma concentration-time curve during a dosing interval was 16.2 ng • h/mL. Systemic exposure was approximately 4-fold higher than in a previous pharmacokinetic study with a 25 cm 2 field, consistent with the increase in the treated area. Tirbanibulin applied to a 100-cm 2 treatment field showed favorable safety and tolerability. The most common treatment-emergent adverse events were application site reactions (in 35.7% of patients). All treatment-emergent adverse events and most of the tolerability signs were mild/moderate and resolved or returned to baseline by Day 29. In summary, under maximal-use conditions, tirbanibulin ointment 1% was safe and well tolerated supporting its potential use over a field up to 100 cm 2 ., (© 2024 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

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., Competing Interests: Declarations of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives : Tirbanibulin 1% ointment is a novel synthetic anti-proliferative agent that inhibits tubulin polymerization. It is approved for treating actinic keratosis (AK) on the face and scalp in adults. It has demonstrated good efficacy, an adequate safety profile and excellent patient adherence in the phase 3 clinical trials, however data about its real-life efficacy and safety are lacking. Here we report the experience of the dermatology unit of the University Hospital of Messina. Materials and Methods : We performed a spontaneous open-label, prospective non-randomized study to assess the effectiveness and safety of tirbanibulin 1% ointment for the treatment of 228 AKs in 38 consecutive patients-28 males (73%) and 10 females (26%)-aged between 52 and 92 years (mean age: 72 ± 8.92 years). Results : Total clearance was recorded in 51% of lesions, while partial clearance was recorded in 73% of lesions. An excellent tolerability profile and high compliance rate were observed, with no treatment discontinuation due to the onset of adverse events. Conclusion: Our real-life experience confirms the effectiveness and safety of tirbanibulin ointment for the treatment of AKs.

Background: The 31 st European Academy of Dermatology and Venereology (EADV) Congress took place between 7 th and 10 th of September 2022 in Milan, Italy., Objectives: We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults., Methods: Summary of presentations given at the EADV Congress., Results: Prof. Pellacani presented two post hoc analyses from two phase-III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real-life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2- to 4-month follow-up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1-2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real-world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients., Conclusions: This article provides an overview of presentations and symposium discussions, summarizing key phase-III results and real-life clinical experience with tirbanibulin shared by dermatologists across Europe., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Topical photodynamic therapy is a widely approved therapy for actinic keratoses and low-risk nonmelanoma skin cancers with a rapidly growing range of emerging indications for other cutaneous diseases. This review summarizes the best-available evidence to provide a clinical update for dermatologists on the approved and emerging indications of photodynamic therapy. The body of evidence suggests that photodynamic therapy is superior or noninferior to other available treatment modalities for actinic keratoses, low-risk basal cell carcinomas, Bowen's disease, skin field cancerization, chemoprevention of keratinocyte carcinomas in organ transplant recipients, photoaging, acne vulgaris, and cutaneous infections including verrucae, onychomycosis, and cutaneous leishmaniasis. There is emerging evidence that photodynamic therapy plays a role in the management of actinic cheilitis, early-stage mycosis fungoides, extramammary Paget disease, lichen sclerosis, and folliculitis decalvans but there are no comparative studies with other active treatment modalities. Common barriers to topical photodynamic therapy include procedural pain, costs, and the time required for treatment delivery. There is significant heterogeneity in the photodynamic therapy protocols reported in the literature, including different photosensitizers, light sources, number of treatments, time between treatments, and use of procedural analgesia. Topical photodynamic therapy should be considered in the management of a spectrum of inflammatory, neoplastic, and infectious dermatoses. However, more comparative research is required to determine its role in the treatment algorithm for these dermatologic conditions and more methodological research is required to optimize photodynamic therapy protocols to improve the tolerability of the procedure for patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) belong to the group of keratinocyte carcinomas (KC). Actinic keratosis (AK) is a precursor lesion of cSCC. The incidences of cSCC, BCC, and AK are currently strongly increasing. Different standard therapies exist for these conditions but are not always applicable or successful. Hydrophilic Viscum album extracts have been used in anthroposophic cancer therapy since 1917. Viscum album lipophilic extract (VALE) is prepared by means of supercritical CO2 extraction. This retrospective case series assessed the safety and clinical effects of a topical application of 10% VALE in individual cases of cSCC, BCC, and AK., Methods: For this retrospective case series, a positive vote was obtained from the Ethics Committee of the University of Witten/Herdecke (No. 146/2020). Eligible patients signed a declaration of consent prior to inclusion in the study. The main outcome parameters were the clinical response to treatment with VALE and adverse drug reactions. Risk factors, concomitant therapies and diseases, further diagnostic and therapeutic information were documented where available. Data analysis was performed on the level of patients and of individual lesions., Results: The study population consisted of 55 patients with 74 skin lesions. Individual case analysis accompanied by photographic documentation revealed typical and promising treatment courses. Clinical response rates (complete + partial remissions) for individual lesions were 78% for cSCC, 70% for BCC, and 71% for AK. Complete remission rates for individual lesions were 56% for cSCC, 35% for BCC, and 15% for AK. In cSCC and BCC, shorter times to best clinical response were observed. Adverse drug reactions were reported in 5 patients including erythema and inflammatory reactions of mostly moderate severity that resolved completely. In one case, therapy was temporarily paused, in four cases it was continued without interruption., Discussion/conclusion: The results of this study suggest that VALE is a safe and tolerable extract under whose application complete and partial remissions of KC could be observed. To improve and assess the efficacy of VALE, prospective investigations are necessary., Das kutane Plattenepithelkarzinom (cSCC) und das Basalzellkarzinom (BCC) gehören zur Gruppe der Keratinozytenkarzinome (KC). Die aktinische Keratose (AK) ist eine Vorstufe des cSCC. Die Häufigkeit von cSCC, BCC und AK ist derzeit stark im Steigen begriffen. Es gibt verschiedene Standardtherapien für diese Erkrankungen, die jedoch nicht immer anwendbar oder erfolgreich sind. Hydrophile Viscum album-Extrakte werden seit 1917 in der anthroposophischen Krebstherapie eingesetzt. Viscum album Lipophilic Extract (VALE) wird mittels überkritischer CO2-Extraktion hergestellt. In dieser retrospektiven Fallserie wurden die Sicherheit und die klinischen Auswirkungen einer topischen Anwendung von 10% VALE bei einzelnen Fällen von cSCC, BCC und AK untersucht.Für diese retrospektive Fallserie wurde ein positives Votum der Ethikkommission der Universität Witten/Herdecke eingeholt (Nr. 146/2020). Die in Frage kommenden Patienten unterzeichneten vor der Aufnahme in die Studie eine Einverständniserklärung. Die wichtigsten Ergebnisparameter waren das klinische Ansprechen auf die Behandlung mit VALE und unerwünschte Arzneimittelwirkungen. Risikofaktoren, Begleittherapien und -erkrankungen sowie weitere diagnostische und therapeutische Informationen wurden, soweit vorhanden, dokumentiert. Die Datenanalyse wurde für jeden einzelnen Patienten und jeder einzelnen Läsion durchgeführt.Die Studienpopulation bestand aus 55 Patienten mit 74 Hautläsionen. Die Einzelfallanalyse mit Fotodokumentation ergab typische und vielversprechende Behandlungsverläufe. Die klinischen Ansprechraten (vollständige + partielle Remissionen) für einzelne Läsionen lagen bei 78% für cSCC, 70% für BCC und 71% für AK. Die Komplettremissionsraten für einzelne Läsionen lagen bei 56% für cSCC, 35% für BCC und 15% für AK. Bei cSCC und BCC wurden kürzere Zeiten bis zum besten klinischen Ansprechen beobachtet. Bei fünf Patienten wurden unerwünschte Arzneimittelwirkungen gemeldet, darunter Erytheme und Entzündungsreaktionen von meist mäßigem Schweregrad, die vollständig abklangen. In einem Fall wurde die Therapie vorübergehend pausiert, in vier Fällen wurde sie ohne Unterbrechung fortgesetzt.Die Ergebnisse dieser Studie deuten darauf hin, dass VALE ein sicherer und verträglicher Extrakt ist, bei dessen Anwendung vollständige und partielle Remissionen von KC beobachtet werden konnten. Um die Wirksamkeit der Therapie mit VALE weiterzuentwickeln und eingehender zu beurteilen, sind prospektive Untersuchungen erforderlich., (© 2024 S. Karger AG, Basel.)

Background: Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for multiple actinic keratosis (AK). However, PDT-induced pain often discontinues the therapy to reduce its efficacy, limiting its application. If modified painless PDT schedule with shorter photosensitizer dressing and higher dose illumination could achieve good efficacy in AK, it is still unknown., Objectives: To explore the efficacy and pain tolerance of the modified painless PDT (M-PDT) in facial multiple AK., Methods: A split-face controlled clinical study including 14 patients with facial multiple AK was conducted. The patients received conventional PDT (C-PDT) on the left and M-PDT in the contralateral area. The left area (C-PDT) was illuminated by a red light-emitting diode light (144 J/cm 2 ) after applying the 10% ALA cream for 3 h; the other had illumination for a total light dose of 288 J/cm 2 after applying the 10% ALA cream for 0.5 h. The primary endpoint was the lesion clearance rate at 1-month postthree sessions of PDT. Secondary endpoints included pain scores, the incidence of adverse events during treatment, and cosmetic outcomes., Results: At 1 month following three treatments, the total lesion clearance rate was comparable between M-PDT and C-PDT (91.6% vs. 89.0%). While the lesion clearance rate of M-PDT was higher than that of C-PDT in the Grade III lesions (86.5% vs. 72.0%, respectively) (p < 0.05). M-PDT achieved a 100% lesion clearance rate for Grade I lesions earlier than C-PDT, with M-PDT treated twice and C-PDT treated thrice. Moreover, the pain score during illumination was significantly lower for M-PDT than for C-PDT (p < 0.01). Regarding photoaging, the Global Subjective Skin Aging Assessment score showed that the total and atrophy scores of C-PDT and M-PDT were significantly improved, and M-PDT also reduced discoloration. There was no significant difference in adverse reactions between C-PDT and M-PDT., Conclusions: M-PDT is comparable to C-PDT's efficacy for treating facial multiple AK, resulting in much lower pain scores., (© 2023 Wiley Periodicals LLC.)

Actinic keratosis (AK) is the most common pre-malignant cutaneous lesion of the skin, often associated with field cancerization. Daylight photodynamic therapy (DL-PDT) is used as treatment, showing good histological results. Reflectance confocal microscopy (RCM) may be useful as a non-invasive, real-time approach to monitor treatment, however, there is a lack of data on the correlation between RCM and histopathological findings in AK patients treated with DL-PDT. To correlate histological and RCM findings and evaluate the efficacy of DL-PDT in patients with AK and field cancerization treated with DL-PDT. Patients with field cancerization and a minimum of six AK lesions on the face were included in the study. A single session combining methyl aminolevulinate followed by two-hour daylight exposure of the face was performed. RCM and biopsy were performed before and after three months of the intervention to compare efficacy between patients using the Wilcoxon test, and concordance of the findings based on the different methods was analysed using the Kappa test. Twenty-four patients completed the study. An improvement in photodamage and a decrease in the number of AK lesions (45.3% reduction) was observed. Regression in atypia and dysplasia was observed via histopathology and RCM, however, there was poor agreement between the methods. No changes were observed after treatment for inflammation, fibroplasia and acantholysis. Concordance between histological and RCM findings was poor, suggesting that RCM cannot replace the histopathological examination, however, it may be used as an adjuvant test for follow-up of patients. Despite this, DL-PDT proved to be an effective method for treating AK.

Background: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AKs), but there is little information on how PDT affects skin barrier function. The objectives of this study are: To compare skin barrier function between skin with AKs and healthy skin and to evaluate the impact of PDT on skin homeostasis in patients with AKs., Methods: A prospective observational study was conducted in patients with AKs to evaluate epidermal barrier function and skin homeostasis before and 1 ek after receiving PDT., Results: A total of 21 subjects were included in the study, male/female ratio was 17:4, mean age was 75.86 years. The number of AKS observed before starting treatment was reduced with respect to those diagnosed 1 month after starting PDT (14.83 vs. 1.91, p < 0.0001). Application of PDT for treating AKs modifies epidermal barrier function. Immediately after the first session temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH) and total antioxidant capacity (TAC) increased while pH decreased on lesional skin. After 1-month follow-up, the only remained change was the increased in SCH. Higher increases in temperature were observed when using occlusive PDT compared to mixed modality. 5-ALA and M-ALA seem to have a similar impact on skin barrier., Conclusions: PDT can improve skin barrier function in patients with AKs. Skin homeostasis parameters can be used to assess efficacy and optimize dosing., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Actinic keratosis (AK) is a skin condition associated with age, sun exposure, and immunosuppression. Certain drugs, such as photosensitizing medications and calcium channel blockers (CCBs), have been linked to AK. This study explores the impact of individual, behavioral, and exposure factors on the severity of AKs on the face and scalp., Methods: A multicenter cross-sectional study was conducted on immunocompetent individuals with at least one AK on their face or scalp and assessed demographic factors, sun exposure and protection, history of skin cancer, and medication use within the last 6 months. The primary outcome was the Actinic Keratosis Area and Severity Index (AKASI) score, and a hierarchical generalized linear model was used to evaluate the variation in AKASI scores, adjusting for gender, age, and skin phototype., Results: Two hundred seventy subjects between 39 and 92 years were evaluated. The majority had phototype I or II (77%), male gender (51%), personal history of skin cancer (55%), and low adherence to sunscreen use (29%). The use of photosensitizing medications was reported by 61%. Through multivariate analysis, older age (β SE  = 0.14; P < 0.01), lighter skin phototype (β SE  = 0.15; P = 0.01), history of skin cancer (β SE  = 0.12; P < 0.01), sunburning (β SE  = 0.12; P < 0.01), and use of CCBs (β SE  = 0.11; P = 0.02) were identified as independent risk factors for AK severity. Photosensitizing drugs were not identified as risk factors., Conclusion: Older age, lower skin phototype classifications, and a personal history of skin cancer were confirmed as severity risk factors for AK, while the use of CCBs was associated with more severe AK., (© 2023 the International Society of Dermatology.)

Background: Numerous clinical studies have demonstrated the effectiveness of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) in treating actinic keratosis (AK). This therapy has achieved an average lesion clearance rate of approximately 80 % and has also shown to produce satisfactory cosmetic outcomes. However, in our clinical practice, the utilization and adherence to ALA-PDT treatment among AK patients has been lower than anticipated, possibly due to various factors., Objective: The objectives of this study are twofold: (1) To analyze the actual therapeutic effects of ALA-PDT treatment on AK lesions in clinical practice; and (2) To identify the factors that hinder acceptance of ALA-PDT therapy among AK patients with large area or multiple lesions situated on the head and face., Method: This study included a group of 20 AK patients, comprising 15 females and 5 males, with an age range of 57-87 years. All patients received a complete course of ALA-PDT therapy, consisting of 3-6 treatments. The study analyzed various factors, including the cure rate, recurrence rate, cosmetic effects, and adverse reactions following treatment. To investigate the factors affecting the acceptance of ALA-PDT treatment among AK patients with large or multiple lesions on the head and face, we also examined a separate group of 43 AK patients. This group included individuals who either had incomplete courses of ALA-PDT treatment or declined the therapy for the first time. The factors potentially influencing patients' acceptance of PDT were analyzed based on the outcomes of these investigations., Result: Among the 20 patients who completed the full course of ALA-PDT treatment, the cure rate was 95 % (19/20). The recurrence rates at 1 month, 3 months, and 6 months were 0 %, 5 %, and 10 %, respectively. Out of the 19 cured patients, only 2 experienced heavy pigmentation, and no scarring was reported 1-3 months post-treatment. Based on the survey of 43 patients who either had an incomplete course of ALA-PDT treatment or declined the therapy initially, several factors were identified as limiting their choice of PDT therapy. These factors include: (1) Intolerable adverse effects of treatment. (2) Higher treatment cost than expected. (3) Inconvenient transportation. (4) Coexistence of other senile diseases. (5) Unsatisfactory clinical efficacy observed. (6) Inadequate understanding of AK. (7) Lost to follow-up., Conclusion: The study concludes that ALA-PDT is a beneficial and aesthetically pleasing treatment for AK patients, particularly those with extensive or multiple lesions on the head and face. However, various factors can impede the selection of ALA-PDT therapy, potentially depriving patients of the most suitable option. The study aims to assist dermatologists and AK patients in considering treatment plans and exploring alternative options. Overall, the findings of this study may provide valuable guidance for improving treatment outcomes and patient satisfaction., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

A man in his 60 s with a history of actinic keratosis (AK) and relapsed IgG kappa multiple myeloma (MM) recently received VD-PACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) chemotherapy and presented with numerous haemorrhagic, scaly lesions on his scalp and face. He also had sepsis from methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. Since the lesions were only present in the areas of pre-existing AK, a diagnosis of inflammation of AK secondary to chemotherapy was made. Sepsis was treated with appropriate antibiotics, and inflammation of AK was managed with topical steroids, leading to complete recovery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Actinic keratosis is a lesion that develops in sun-exposed areas of the skin and is considered to be a precancerous condition or an early in situ squamous cell carcinoma. Treatment of actinic keratosis is important for reducing skin cancer risk, with treatment choice based on patient-, lesion- and treatment-related considerations. Of the topical treatments used for field-directed therapy, those containing 5-fluorouracil are among the most effective and widely prescribed. The most recently developed topical 5-fluorouracil preparation (Tolak®; Pierre Fabre, France) contains 4% 5-fluorouracil in an aqueous cream. This narrative review discusses data on 4% 5-fluorouracil cream to treat actinic keratosis, and provides the authors' expert opinion on issues associated with it use. The effect of the cream has been evaluated in phase 2 and 3 trials of adult patients with actinic keratosis on the face, ears or scalp. These trials included patients with severe baseline disease, defined by high lesion counts and large-size treatment fields, which possibly affected the proportion of patients who were able to achieve complete clearance. Other efficacy parameters (e.g. percentage change in lesion count, ≥ 75% clearance of lesions or clinically significant changes in validated severity scales) should also be assessed to fully evaluate 4% 5-fluorouracil treatment efficacy in these patients. Nevertheless, 4% 5-fluorouracil is associated with high efficacy, a low level of recurrence and a satisfactory safety profile.