Actinic Keratosis Research Articles

Actinic keratosis with severe dysplasia and Bowen disease represent distinct pathways of intraepidermal squamous neoplasia: an immunohistochemical study

Intraepidermal squamous neoplasia is a precursor to invasive cutaneous squamous cell carcinoma. The most common type of intraepidermal squamous neoplasia is actinic keratosis (AK), although there is compelling clinicopathological evidence of a second distinct pattern of squamous dysplasia termed Bowen disease (BD). The distinction between these pathways of dysplasia has been inconsistently delineated in the literature.To further investigate the biological differences between AK and BD, a cohort of cases of intraepidermal squamous dysplasia including AK with mild/moderate dysplasia (n=26), AK with severe dysplasia (n=21) and BD (n=47) was prospectively collected. Immunohistochemistry was utilised to assess the protein expression of major tumour suppressor genes including p16, RB1 and p53.Most cases of BD showed complete loss of RB-1 (∼80%), strong and diffuse positive staining for p16 (∼80%), and mutant pattern (diffusely positive or completely negative) of p53 (∼79%). However, lesions of AK showed loss of RB-1 in only 6%, strong and diffuse positive staining for p16 in 4% and mutant pattern of p53 in 85% of case (p<0.001).The statistically significant difference in RB-1 and p16 expression between AK and BD confirms that the two morphologically distinct types of intraepidermal squamous neoplasia differ in protein expression of major tumour suppressor genes and provide evidence that they represent two distinct genomic pathways of squamous neoplasia. Recognition of clinical and genomic differences between different pathways of squamous neoplasia could potentially have an important role in predicting the biological behaviour and treatment of advanced tumours arising from these precursor lesions.

International Dermatology Outcome Measures (IDEOM): A Report From the 2023 Annual Meeting.

International Dermatology Outcome Measures (IDEOM) is a non-profit organization whose mission is to improve the availability of evidence-based, consensus-driven outcome measures for dermatological diseases. IDEOM facilitates collaboration between stakeholders from various backgrounds, including researchers, patients, physicians, and industry representatives, to develop objective benchmark metrics that enable better treatment and management of dermatologic conditions. The 2023 IDEOM Annual Meeting was held June 23-24, 2023. Workgroups in psoriatic disease, hidradenitis suppurativa, geriatric dermatology, connective tissue disease, vitiligo, itch, actinic keratosis, acne, and cutaneous T-cell lymphoma discussed the progress of their respective outcome-measures research. This report summarizes each workgroup&rsquo;s updates since the 2022 annual meeting and their next steps as established during the 2023 IDEOM Annual Meeting. J Drugs Dermatol. 2024;23(12):1114-1120. doi:10.36849/JDD.8363.

463 Investigating UV-induced dynamics and microenvironmental changes in primary cells from Actinic Keratosis

463 Investigating UV-induced dynamics and microenvironmental changes in primary cells from Actinic Keratosis

The Skin-Lightening Power of Tirbanibulin 1% Ointment.

Tirbanibulin 1% ointment has been licensed to treat non-hyperkeratotic actinic keratosis (AK) on the face and scalp in adults. Recent evidence suggests that, besides the antineoplastic effect, tirbanibulin may also confer substantial cosmetic benefits to patients. We report a single-center retrospective study of patients affected by solar lentigines (SLs) and AKs in the context of field cancerization treated with tirbanibulin 1% ointment. Among 42 patients, 35% (n = 15) experienced complete clearance of SLs, while partial clearance was observed in 50% (n = 21) of patients. Regarding AKs, complete and partial clearance were observed in 52% (n = 22) and 40% (n = 17) of patients, respectively. Major study limitations are the small sample size and the absence of a control group. Our results suggest that tirbanibulin 1% ointment may offer the dual benefit of treating AKs while simultaneously lightening aesthetically bothersome and difficult-to-treat lesions like SLs with just 5 days of application.

Evaluating Difluoromethylornithine Safety and Efficacy for Non-Melanoma Skin Cancer Chemoprevention: A Systematic Review.

Recent FDA approval of difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase for the prevention of neuroblastoma in children, has renewed interest in this medication for the prevention of other cancers including keratinocyte carcinomas (KCs). It has been investigated for cancer chemoprevention, including neoplasms of the colon, breast, and prostate. We assessed the current body of literature that determines DFMO efficacy and safety in non-melanoma skin cancer prevention. A systematic search of PubMed Central, and Web of Sciences was performed. In this analysis, 12 studies were included evaluating 1618 patients. Most patients were Caucasian 90% (1452/1618) with a mean age of 61 years, and 73% (1214/1618) had previously been diagnosed with KC. For oral DFMO, reduction in KC was significant in 24% (291/1214) of patients. Nonsignificant reduction was observed in 17% (207/1214) of patients. The remaining studies, representing 59% (716/1214) of patients explored DFMO's pharmacological/biological effects without elucidating its direct impact on KC. Topical DFMO shows modest efficacy in reducing the number of actinic keratosis (AK), as indicated in 4 studies representing 38.12% (154/404) of patients. For patients taking the oral eflornithine, the most frequently reported adverse events included reversible ototoxicity (11% of patients) gastrointestinal disturbances (10.39%). For the topical DFMO transient local cutaneous eruptions were common impacting 28.76% (111/386) of patients. Current evidence highlights the lack of conclusive data supporting the efficacy of oral DFMO, making it difficult to recommend its use. Conversely, topical DFMO demonstrates more promising outcomes in preventing AKs, presenting a potentially useful alternative in select patients.

Clinical Risk Factors for Cutaneous Squamous Cell Carcinoma in Patients with Actinic Keratosis or Cutaneous Squamous Cell Carcinoma in Situ: A Retrospective Double-cohort Study.

Actinic keratosis and cutaneous squamous cell carcinoma in situ are precancerous forms of cutaneous squamous cell carcinoma. In this single-centre retrospective study, patients with histopathologically confirmed actinic keratosis (n = 121) or cutaneous squamous cell carcinoma in situ (n = 99) as their initial keratinocyte-derived lesion were compared and evaluated with regard to development of cutaneous squamous cell carcinoma during a 5-year observation period. Patients with severely dysplastic actinic keratosis or cutaneous squamous cell carcinoma in situ as their initial lesion developed cutaneous squamous cell carcinoma more rapidly than patients with actinic keratosis with mild or moderate dysplasia. With either actinic keratosis or cutaneous squamous cell carcinoma in situ as an initial lesion, advanced age, male sex, comorbidity with basal cell carcinoma, and immunosuppressive medication were associated with elevated risk of cutaneous squamous cell carcinoma development. Regarding solely patient with actinic keratosis as their initial lesion male sex, advanced age, immunosuppressive medication, location of the initial lesion, and degree of dysplasia were associated with the risk of cutaneous squamous cell carcinoma. Among patients with cutaneous squamous cell carcinoma in situ as their initial lesion, only aspirin usage was associated with increased risk of cutaneous squamous cell carcinoma. This study indicates that, among the vast and increasing population of patients with cutaneous squamous cell carcinoma precursors, male patients with immunosuppressive medication who develop basal cell carcinoma should be regarded as at heightened risk of cutaneous squamous cell carcinoma development and warrant closer surveillance.

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

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

Single Nucleotide Polymorphisms on Toll-like Receptor-4 and the Risk of Developing Skin Cancer

Exposure to solar ultraviolet (UV) radiation is an established risk factor for skin cancer. Toll-like receptor-4 (TLR4)-mediated immune dysregulation has emerged as a key mechanism for the detrimental effects of acute and chronic UV exposure and skin cancer in mice. Single nucleotide polymorphisms (SNPs) on the TLR4 gene have been reported to increase or decrease susceptibility to various cancers in other organs. There is limited information on TLR4 SNPs and susceptibility to human keratinocyte carcinomas. The study’s objective is to test the association between TLR4 SNPs and the risk of developing keratinocyte carcinomas. Skin cancer patients and controls at the University of Alabama at Birmingham completed a cross-sectional survey on personal and family history of skin cancer as well as on sunscreen use and tanning proneness. Peripheral blood samples were obtained from participants, and DNA was extracted to genotype the TLR4 SNPs. Descriptive analytics were used to describe the cohort. Multivariable logistic regression models were used to assess the association between TLR4 SNPs and skin cancer risk. The sample consisted of a cohort of 93 skin cancer patients over the age of 50 and 94 controls; 33.3% of cases and 44.7% of controls were females; 12.9% of cases and 17% of controls had a TLR4 SNP. The most common SNP was D299G/T399I in 9.7% of skin cancer patients and 13.8% of controls. We did not find a statistically significant association between the D299G/T399I SNP and skin cancer (odds ratio (OR) = 0.34, 95% CI: 0.11, 1.07, p = 0.065) adjusting for age, sex, eye color, actinic keratosis, sunscreen use and reapplication, and family history of skin cancer. Based on our findings from our limited cohort of participants, we found some protective effect for the TLR4 SNP for skin cancer, which was not statistically significant. Validation of these findings in a larger cohort is warranted.

Clinical and Dermoscopic Comparison of the Efficacy and Safety of 5% Fluorouracil Topical Cream and 1% Niacinamide Topical Gel in the Treatment of Actinic Keratosis: A Randomized Controlled Trial.

Actinic keratosis (AK) is a common skin condition treated by dermatologists; however, the effectiveness, superiority, and potential side effects of current treatment protocols are still debated. This study aimed to compare the effectiveness and safety of 5% fluorouracil topical cream and 1% niacinamide topical gel in patients with AK. In a randomized clinical trial, 26 patients with 95 AK lesions were assigned to receive either 5% fluorouracil topical cream twice daily for 4 weeks or 1% niacinamide topical gel twice daily for 3 months. Photography and dermoscopy before and after treatment were used to evaluate the outcomes. The study included 26 patients who underwent randomization and treatment. Analysis of the improvement response after treatment through photography and dermoscopy scores, as well as patients' perspectives, showed that the fluorouracil group had significantly better outcomes than the niacinamide group. However, treatment complications including burning, itching, and erythema were significantly more frequent in the fluorouracil group than in the niacinamide group. Although 5% fluorouracil cream is more effective than 1% niacinamide gel in treating AK lesions, it is also associated with more frequent side effects.

Vascular Characteristics of Treatment-resistant and -responsive Actinic Keratosis Identified with Dynamic Optical Coherence Tomography.

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.

Pigmented pathological type and depth of follicular extension as predictors of treatment failure in 5-aminolevulinic acid photodynamic therapy for actinic keratosis: A retrospective, matched nested case-control study

Background: While 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is widely used to treat actinic keratosis (AK), treatment resistance and recurrence after ALA-PDT remain significant clinical challenges. Methods: This single-site, retrospective, matched case-control study included 119 patients with histologically confirmed AK to identify clinical and pathological predictors for effectiveness of ALA-PDT. Patients received four consecutive ALA-PDT sessions at intervals of 1 or 2 weeks. Initial complete clearance (ICC) at 3 months and sustained complete clearance (SCC) at 12 months were assessed. Case patients were those with treatment-resistant or recurrent AK, matched with controls based on age, sex, and the treatment date. Baseline characteristics were collected and compared between the case and control groups. Results: ICC at 3 months was achieved in 106 out of 119 patients (89.07%), with 65 out of 82 patients (79.27%) maintaining SCC at 12 months. Pigmented AK emerged as an independent predictor of treatment resistance (OR=44.05, p=0.00). Furthermore, follicular extension to the isthmus or deeper was significantly associated with recurrence within 1 year (OR=17.26, p=0.00). Conclusion: Pigmented AK and AK with follicular extension to the isthmus or deeper may serve as independent predictors of treatment resistance and recurrence, respectively. These findings highlight the importance of these specific features when assessing prognosis and tailoring treatment strategies for individual AK patients.

Safety and Efficacy of Photodynamic Therapy with ALA 10% Topical Gel Activated by Red Light versus ALA 20% Topical Solution Activated by Blue Light for the Treatment of Actinic Keratosis on the Upper Extremities: A Blinded Randomized Study

Background: Actinic keratosis (AKs) is a pre-cancerous skin neoplasm that can appear as erythematous to pink scaly plaques at sites of ultraviolet light damage. Photodynamic therapy (PDT) using aminolaevulinic acid (ALA) 10% gel activated by red light is approved by the FDA for the treatment of AKs on the face and scalp, and ALA 20% solution activated by blue light is approved for PDT treatment of AKs on the face, scalp, and upper extremities. While both options have been proven to an effective treatment on the upper extremity, there has been no direct side-by-side comparison. This study aimed to compare the safety and efficacy of both PDT on the upper extremities. Design: This was a prospective, single-center, split-arm randomized clinical trial with 20 adult subjects presenting with 4-17 clinically confirmed mild-moderate AKs (Olsen grading) on each distal upper extremity. Subjects were treated with ALA 10% gel/red light and ALA 20% solution/blue light PDT on respective randomly selected upper extremities. Lesion complete clearance rate (LCCR) served as the primary endpoint. Secondary endpoints included complete clearance per patient side (PatCR), LCCR of moderate lesions, LCCR 12 weeks after PDT-1, PatCR 12 weeks after PDT-1, overall cosmetic outcome assessed by the investigator, and patient satisfaction. Results: The LCCR was significantly greater for ALA10% vs. ALA20% at Day 120; no significant differences were observed at the other observed time points. 30 patients were enrolled in the study and received their first treatment (PDT1). LCCRs after PDT1 were 65.4% and 58.4% for ALA10% and ALA 20%, respectively. 25 patients received a second treatment (PDT2), resulting in LCCRs of 88.2% and 72.1% respectively. 22 patients returned for follow-up 6 months after their last PDT treatment (PDT1 or PDT2), with LCCR of 83.7% (ALA10%) and 79.3% (ALA20%). 17 patients returned for follow-up 12 months after the last PDT treatment, with LCCRs of 81.5% (ALA10%) and 87.6% (ALA20%). There were no statistical differences between ALA10% and ALA20% for subject-reported pain or satisfaction ratings. ALA10% was rated as significantly easier to apply compared to ALA20% by the investigator. Conclusion: Both ALA10% and ALA20% appear to be safe and effective for PDT treatment of AKs on the upper extremities. There is a trend for increased efficacy with ALA10%, and it may be easier to apply. Additional data is in the process of being collected as the study continues.

Pilot study utilizing short contact protocols for treatment of actinic keratoses (AK) with ALA gel-red light photodynamic therapy (PDT)

Background: Red light photodynamic therapy (PDT) is an effective option for actinic keratosis (AK) lesions. However, stinging pain during illumination limits utility. Objective: To compare three modified red-light PDT regimens (short incubation, whole-face application, no occlusion) and to determine whether these can reduce pain yet still provide significant AK lesion clearance. Methods: Patients in this randomized clinical trial (n = 30) were randomized into one of three groups [incubation with 10% ALA gel, illumination with red-light]: Group A: 10 min, 20 min (75 J/cm2); Group B: 20 min, 10 min (37 J/cm2); Group C: 1 hour, 10 min (37 J/cm2). Two PDT treatments were administered 8 weeks apart. Lesions were counted at each visit, and pain was recorded on a scale from 0 – 10. Results: Patients Groups A and B (shorter incubations) experienced significantly less pain during illumination than Group C. After one treatment, the AK lesion reduction in Group A (59%) was statistically non-inferior to Group C (43%), with a noninferiority margin of ±15%. Final lesion counts after two PDT treatments showed a reduction from baseline by 82% in Group C, 76% in Group A, and 74% in Group B. Groups A and B did not meet the statistical non-inferiority endpoint relative to Group C after two treatments. Limitations: Small sample size, which limited the ability to reach statistical significance after 2 PDT treatments. Conclusion: Two short/modified red light PDT regimens were essentially painless, and all three provided AK lesion clearances comparable to conventional regimens.

Evaluating the safety and efficacy of aminolevulinic acid 20% topical solution activated by blue light in the treatment of facial cutaneous squamous cell carcinoma in situ

Background: Cutaneous squamous cell carcinoma in situ (isSCC) is a common skin cancer occurring from sun exposure and often appears on the face. Treatment is primarily surgical but less invasive treatments are desirable. Currently, aminolevulinic acid for photodynamic therapy (ALA-PDT) is approved in the US and Canada for the treatment of single and multiple non-hyperkeratotic actinic keratoses of the face and scalp. This study evaluated the safety, tolerability, and efficacy of ALA-PDT for treatment of facial isSCC.Methods: Thirty-two patients with biopsy-confirmed isSCC on the face were recruited. Lesions 0.4–1.3 cm in diameter were included. Per the actinic keratosis treatment protocol, the lesion was debrided with a 4 x 4 gauze and ALA 20% topical solution was applied to the lesion and adjacent skin and incubated for 18–24 hours, followed by blue light therapy 16 minutes 40 seconds at 10 J/cm2. Patients underwent two treatments with ALA-PDT spaced 28 +/- 3 days apart. The area of the original lesion was excised eight weeks following the second treatment for histopathological assessment. The primary efficacy endpoint was the complete absence histologically of the isSCC at end of treatment. The secondary efficacy endpoint was the achievement of clinical clearance of the skin lesion. Safety assessment was done through adverse events and local skin reactions (LSRs; erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) and site pain within 15 minutes of each treatment session.Results: Of the 32 patients enrolled, two did not complete the study. No residual SCCis was detected in 30/30 (100%) patients. Clinical clearance was achieved in 30/30 (100%) of the patients by the end of treatment. None of the patients experienced related adverse events and only 2/30 (5%) experienced an AE of hypertension and was considered to be unrelated. The most common LSRs were erythema and scaling and were primarily mild, seen to occur immediately after both treatments and diminished over time. The average median ± SD immediate post-treatment pain score was 2.56 ± 2.15 on the VAS scale.Conclusion: The ALA-PDT protocol outlined in this study appears to be a very effective, safe and well-tolerated treatment option for isSCC on the face.

Dermoscopy Training Course Improves Ophthalmologists' Accuracy in Diagnosing Atypical Pigmented Periorbital Skin Lesions.

Facial pigmented skin lesions are extremely common, starting from the fourth to fifth decades, especially in South-European countries, often located in the periorbital region. These include malignant forms, Lentigo maligna (LM) and lentigo maligna melanoma (LMM), characterized by growing incidence, and a series of benign simulators, including solar lentigo (SL), pigmented actinic keratosis (PAK), seborrheic keratosis (SK) and lichen planus-like keratosis (LPK). The clinical differential diagnosis of atypical pigmented skin lesions (aPFLs) can be difficult, even for dermatologists, leading to inappropriate skin biopsies with consequent aesthetic impacts. Dermoscopy of the facial area is a specific dermoscopic field that requires dedicated training and proved to increase diagnostic accuracy in dermatologists. Since these lesions are often seen by ophthalmologists at first, we aimed to evaluate the effect of a focused dermoscopy training course on a group of ophthalmologists naïve to the use of a dermatoscope. A set of 80 periorbital pigmented skin lesions with both clinical and dermoscopic images was selected and evaluated by six ophthalmologists before and after a one-day intensive dermoscopic training course. They were required to evaluate 80 periorbital lesions one month before and after a one-day intensive dermoscopic training course, illustrating second-level diagnostic options such as reflectance confocal microscopy (RCM), obtaining a total of 480 evaluations. Specifically, they had to provide, for each case, a punctual diagnosis and a management option among dermoscopic follow-up/skin biopsy/RCM/LC-OCT. Descriptive statistics were carried out, and the accuracy (ACC), sensitivity (SE), and specificity (SP), with their 95% confidence interval (95% CI), were estimated. In the pre-course test, ophthalmologists achieved 84.0% SP, 33.3% SE and 63.7% ACC, while after the course, SE increased by +9% (i.e., 41.7%), SP decreased by 4%, and ACC remained comparable, i.e., 64.6%. In the management study, the percentage of benign lesions for which a close dermoscopic follow-up was suggested significantly decreased (51.6% versus 22.2%), in parallel with an increase in the number of lesions referred for RCM. As for malignant cases, the reduction in responses "close dermoscopic follow-up" decreased from 37.0% to 9.9%, (-27%), in favor of RCM (+15%) and skin biopsy (+12%). The ophthalmologists proved to be very receptive in quickly metabolizing and putting into practice the concepts learned during the one-day intensive dermoscopy training course. Indeed, after only a one-day lesson, they were able to increase their SE by 9% and to improve their management strategy. The present findings highlight the importance of providing training ophthalmologists in dermoscopy during residency programs, in terms of benefits for the correct patient care.

Field therapies for actinic keratosis: an Australian cost‐effectiveness analysis

AbstractBackgroundActinic keratoses have a high prevalence in the older Australian population, with most patients presenting with field actinic damage. Despite this high prevalence, no field therapies are subsidised under the Pharmaceutical Benefits Scheme.ObjectivesTo determine which therapy for field actinic damage is the most cost‐effective when comparing 5‐fluorouracil (5‐FU), imiquimod (IMQ), and methyl‐aminolevulinate photodynamic therapy (MAL‐PDT) at 12 months post‐treatment.MethodsA decision tree was constructed using TreeAge Pro, representing the likely clinical trajectories of patients with field actinic damage treated with 5‐FU, IMQ, and MAL‐PDT. The cost‐effectiveness analysis was performed from the patient perspective, assuming an outpatient setting. Efficacy data was derived from a single‐blinded, multi‐centre prospective randomised control trial. Cost data were derived from Australian dermatology clinics and pharmacies. One‐way and probabilistic sensitivity analyses were conducted.Results5‐FU was the most cost‐effective treatment. It was cheaper and more effective than all other treatments, with a cost‐effectiveness ratio of AU$201 per patient achieving ≥75% clearance in field actinic damage. The cost‐effectiveness ratios of IMQ, and MAL‐PDT were AU$940, and AU$8058 per patient achieving ≥75% clearance respectively. Both sensitivity analyses showed certainty in 5‐FU's dominance over the other treatments.Conclusions5‐FU is the most cost‐effective treatment option for Australian patients presenting with actinic field damage on the head area.

Prebiotic and panthenol-containing dermocosmetic improves tolerance from artificial daylight photodynamic therapy: A randomized controlled trial in patients with actinic keratosis

Introduction & ObjectivesTreatment 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 & MethodsThis 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. ResultsTopical 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). ConclusionApplication 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.

The Application of High-Frequency Ultrasonography in Post-Therapeutic Assessment of Actinic Keratosis After Photodynamic Therapy.

Actinic keratoses (AKs) are one of the most common reasons for consultation in the elderly population. This study aimed to assess the efficacy of 5-ALA PDT in AK treatment using high-frequency ultrasonography (HFUS) to evaluate skin layer changes during therapy. In our study, we included 44 AK patients aged 53 to 89 years. All patients had lesions clinically evaluated with the Olsen and AKASI scale. HFUS imaging was performed on seemingly healthy skin and lesions before and at 4, 8, and 12 weeks of therapy. Ultrasound markers such as skin thickness, echogenicity, and pixel intensity were measured. 5-ALA was applied under occlusion for 3 h. After removing the occlusive dressing, 5-ALA was removed with a saline solution and a directed therapy with a BF-200 lamp. Full follow-ups of 56 markers of suitable quality were selected. The thickness of SLEB significantly decreased in the following weeks compared to the pre-therapy results, reaching its lowest values after 12 weeks. The average pixel intensity significantly increased in each skin layer after therapy (p < 0.01). For SLEB, there were statistically significant differences in LEP, MEP and contrast. The AKASI score before and after treatment was determined for the 39 patients who underwent follow-up at week 12. The median AKASI score was 3.2 (1.2-8.6) before treatment and 0.6 (0-2.8) after. According to the literature data, this is the first study describing the ALA-PDT treatment efficacy in different AK severities evaluated in HFUS. HFUS provides a valuable non-invasive tool for monitoring the efficacy of PDT in AK treatment, showing significant improvements in skin texture and structure.

Transforming Skin Cancer Diagnosis: A Deep Learning Approach with the Ham10000 Dataset

Skin cancer (SC) is one of the three most common cancers worldwide. Melanoma has the deadliest potential to spread to other parts of the body among all SCs. For SC treatments to be effective, early detection is essential. The high degree of similarity between tumor and non-tumors makes SC diagnosis difficult even for experienced doctors. To address this issue, authors have developed a novel Deep Learning (DL) system capable of automatically classifying skin lesions into seven groups: actinic keratosis (AKIEC), melanoma (MEL), benign keratosis (BKL), melanocytic Nevi (NV), basal cell carcinoma (BCC), dermatofibroma (DF), and vascular (VASC) skin lesions. Authors introduced the Multi-Grained Enhanced Deep Cascaded Forest (Mg-EDCF) as a novel DL model. In this model, first, researchers utilized subsampled multigrained scanning (Mg-sc) to acquire micro features. Second, authors employed two types of Random Forest (RF) to create input features. Finally, the Enhanced Deep Cascaded Forest (EDCF) was utilized for classification. The HAM10000 dataset was used for implementing, training, and evaluating the proposed and Transfer Learning (TL) models such as ResNet, AlexNet, and VGG16. During the validation and training stages, the performance of the four networks was evaluated by comparing their accuracy and loss. The proposed method outperformed the competing models with an average accuracy score of 98.19%. Our proposed methodology was validated against existing state-of-the-art algorithms from recent publications, resulting in consistently greater accuracies than those of the classifiers.

Artificial daylight photodynamic therapy using methyl aminolevulinate in a real-world setting in Germany - Results from the non-interventional study ArtLight.

Artificial daylight photodynamic therapy (ADL-PDT) is an alternative, all-year applicable, nearly painless treatment approach for actinic keratoses (AK) with comparable effectiveness to daylight or conventional PDT. At the time this study was initiated, methyl aminolevulinate (MAL) was the only photosensitizer approved for ADL-PDT in Germany. To gain comprehensive insights into the practicability of MAL-ADL-PDT in patients with AK using different artificial daylight sources under real-world conditions. This prospective, non-interventional, multicenter study (ArtLight, NCT05725213) enrolled patients with Olsen grade 1 or 2 AK on the face and scalp in Germany. Patients were treated with MAL-ADL-PDT (160mg/g MAL cream). The primary outcome measure was the practicability of MAL-ADL-PDT assessed as rate of resolved AK lesions in the focus area (10x10 cm area within the treatment area). Secondary outcomes included treatment-associated pain (numeric rating scale, NRS-11), Actinic Keratosis Area and Severity Index (AKASI), total lesion count over time, skin preparation, safety, overall assessment of effectiveness, tolerability, adherence, and patient satisfaction. In total, 224 patients (median age: 75.0 years (range 50-91), 85.3% male, 62.5% AK Olsen grade 2, 55.4% treatment-naïve) were included and treated with MAL-ADL-PDT. Three months after treatment, lesion counts were reduced in the focus area by 71% (p<0.001) indicating practicability of the treatment. Nearly all patients (93.3%) experienced none or mild pain during PDT (NRS score 0-3). Median AKASI decreased from 6.2 at baseline to 3.4 at month 3 (95% CI 2.4-3.0; p<0.001). The majority of investigators (82.8%) and patients (80.0%) were satisfied with the treatment. No new safety signals were reported. The clinical practicability of MAL-ADL-PDT was demonstrated under real-world conditions by effective lesion reduction and predominantly none to mild procedural pain. Thus, MAL-ADL-PDT is a convenient way for healthcare professionals to deliver PDT treatment to patients with AK located on the face and scalp.