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Pain perception during photodynamic therapy: why is daylight PDT with methyl aminolevulinate almost pain-free? A review on the underlying mechanisms, clinical reflections and resulting opportunities
摘要： Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is an established and efficacious method for the treatment of non-melanoma skin cancer. However, treatment of especially larger areas often leads to pain, stinging and burning sensation during illumination. the use of daylight (dl) during mal incubation was investigated in clinical trials and compared to conventional illumination with red leds. all clinical trials on MAL DL-PDT show it to be considerably and statistically significantly less associated with pain than conventional PDT while being as efficacious. Fluence rate and light dose seem to be the strongest indicators for pain during PDT. The article summarizes the current knowledge base and shows that the model is able to explain why activation by dl produces less to no pain. recent clinical trials performed in other latitudes than Northern Europe or Australia confirm that MAL DL PDT is applicable also in regions closer to the equator. MAL DL-PDT carries the potential of mal self-application by the patient. in several clinical trials, mal dl-Pdt has been compared to topical preparations being administered by the patients themselves. the results show that mal dl-Pdt is superior or at least non-inferior to the tested topical preparations and that its tolerability is better.
关键词： Photochemotherapy,actinic keratosis,methyl 5-aminolevulinate
更新于2025-09-23 15:22:29
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An Update on Topical Photodynamic Therapy for Clinical Dermatologists
摘要： Photodynamic therapy (PDT) involves the application of a topical photosensitizer, irradiation with light, and oxygen to produce cytotoxic reactive oxygen species that selectively destroy damaged cells while leaving normal skin intact. Topical PDT is a commonly used treatment for non-melanoma skin cancers (NMSCs) due to its excellent clearance rate and cosmetic outcomes. However, PDT is emerging as an off-label treatment modality for many dermatological conditions. A literature review using MEDLINE was performed to identify randomized controlled trials conducted for currently approved and off-label clinical indications and photosensitizers for PDT between 2012 and 2018. The photosensitizer indole-3 acetic acid reduces the incubation time (<30 minutes), avoids the need for photoprotection after irradiation, and inflicts minimal pain. Cyclic PDT in individuals with evidence of field cancerization delays the mean time of actinic keratosis appearance and reduces the total number of new actinic keratoses. Substantial evidence exists outlining the utility of PDT in photorejuvenation due to its ability to improve skin texture, wrinkles, and firmness. The addition of microdermabrasion, microneedling, curettage, or various lasers improves clinical efficacy and cosmetic outcomes. PDT applications are expanding rapidly. Clinicians must stay up to date regarding the efficacy and safety of PDT applications.
关键词： non-melanoma skin cancer,daylight PDT,dermatology,PDT,actinic keratosis,photodynamic therapy
更新于2025-09-23 15:22:29
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Efficacy of different photoprotection strategies in preventing actinic keratosis new lesions after photodynamic therapy. The ATHENA study: A two-center, randomized, prospective, assessor-blinded pragmatic trial
摘要： Background: Treatment of actinic keratosis (AK) and field cancerization with photodynamic therapy (PDT) is an effective therapeutic approach with a significant reduction in the number of AK lesions (-75% or more) associated with a significant cosmetic improvement of the photodamaged skin. Recently, also the daylight PDT (DL-PDT) has proven to be as effective as the conventional PDT (C-PDT) but with a better tolerability. After C-PDT and DL-PDT it is advised to use photoprotection strategies to improve the clinical evolution and prevent appearance of new AK lesions that usually appear 3-6 months after the last phototherapy session. However, there are no robust clinical data regarding the type of photoprotection to be used (SPF level, duration of treatment ect.) after successful PDT. Study Aim: In the present study (ATHENA trial) we evaluated the efficacy and tolerability of a topical product based on 0.8% piroxicam and 50+ solar filters (ACTX), applied twice a day as sequential therapy after C-PDT) or day-light photodynamic therapy (DL-PDT) on the evolution of AK lesions number compared to the use of very high photoprotection products commonly used in this clinical setting (SPF50+ or SPF100+ associated with photolyase) (Standard Sunscreens: SS group). Subjects and Methods: We conducted a multicenter, randomized, two-arm, prospective controlled, assessor-masked outcome evaluation, parallel group (1:1), pragmatic study of 6 months duration in patients with multiple AK lesions suitable for photodynamic therapy. The objectives of the study were the evaluation of the evolution of the number of AK lesions during the period of treatment/application of the study products, and the Investigator global clinical assessment score (IGA score; 4: marked improvement, 3: good, 2: moderate; 1 no improvement; 0: worsening) after 2, 3 and 6 months after the last PDT session. A total of 68 subjects (50 men, 18 women; mean age 70 years), 34 assigned to treatment with ACTX and 34 to treatment with SS (17 treated with a SPF50+ and 17 with a photolyase-containing SPF100+ products), were enrolled in the study. Results: The number of AK lesions present before C-PDT/DL-PDT was 11.8±5.8 in the ACTX group and 12.4±6.9 in the SS group. In both groups, there was a progressive reduction of AK lesions observed at baseline (-86% and -87% after 2 months and -88% and -83% at month 3 in ACTX and in the SS group, respectively). At month 6, AK mean lesion number was 1.8±1.6 in the ACTX and 3.2±2.3 in the SS group; this difference was statistically significant (p=0.03). The IGA score at the end of the study was 3.2 in ACTX and 2.7 in the SS group (p=0.05). The percentage of subjects with an IGA score of 4/3 (very good or good) was 81% in the ACTX and 55% in the SS group (p=0.06). Conclusion: in subjects with AK treated with C- or DL-PDT, a "medicalized" photoprotection treatment is associated with a favorable clinical outcome with progressive reduction of lesions. In contrast to a very high photoprotection (SPF50+or SPF100+/photolyase), the use of piroxicam 0.8%/SPF 50 + is associated with a significant greater improvement in clinical evolution of AK lesions. (Trial number: ISRCTN16168548).
关键词： Actinic Keratosis,Piroxicam,Cancerization Field,Photodynamic Therapy
更新于2025-09-23 15:21:21
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A Randomized, Vehicle-Controlled Phase 3 Study of Aminolevulinic Acid Photodynamic Therapy for the Treatment of Actinic Keratoses on the Upper Extremities
摘要： BACKGROUND Blue-light aminolevulinic acid photodynamic therapy (ALA-PDT) after broad-area application and 3-hour incubation is ef?cacious for actinic keratosis (AK) lesion clearance on upper extremities, with use of occlusive dressing signi?cantly increasing ef?cacy. OBJECTIVE To prove the safety and ef?cacy of ALA-PDT versus vehicle (VEH-PDT) in the spot treatment of multiple AKs on upper extremities. METHODS Aminolevulinic acid or VEH was spot applied only to lesions on one upper extremity 3 hours before blue-light exposure. Treated extremity was covered with occlusive dressing during incubation. Identical treatment was repeated at Week 8 if AK lesions were present in the treated area. RESULTS Thirty-one percent (42/135) of subjects treated with ALA-PDT had complete clearance at Week 12, compared with 13% (17/134) of the subjects treated with VEH-PDT (p = .0001). The mean AK lesion clearance rate for ALA-treated subjects at Weeks 8 and 12 was 53% and 69%, respectively, compared with 26% and 30% for the VEH-treated group (p < .0001, linear mixed model). Safety pro?le observed in this study is consistent with previous studies/reports in the literature, and the therapy was well tolerated overall. CONCLUSION Aminolevulinic acid-PDT spot treatment using a 3-hour occluded incubation was superior to VEH-PDT for AK lesion clearance of the upper extremity.
关键词： actinic keratosis,photodynamic therapy,aminolevulinic acid,upper extremities,blue light
更新于2025-09-16 10:30:52
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2125. Staphylococcus Species Identification by Fourier Transform Infrared (FTIR) Spectroscopic Techniques: A Cross-Lab Study
摘要： Staphylococcus aureus is well known to be associated with atopic dermatitis. Recent studies also report S. aureus presence in lesional skin of squamous cell carcinoma (SCC) and its precursor lesion, actinic keratosis (AK). Therefore, it is of potential clinical interest to monitor skin S. aureus colonization on AK lesions. Fourier transform infrared (FTIR) spectroscopy is a cost-effective, nondestructive, and reagent-free technique for rapid microbial identification. It is based on the use of spectral databases developed with well-characterized strains in conjunction with the application of multivariate statistical analysis to elaborate classification models. In the present cross-lab study, spectral databases containing FTIR spectra of over 1000 staphylococcal isolates obtained from reference and clinical microbiology laboratories across Canada were employed in the FTIR spectroscopic identification of Staphylococcus spp. isolated from AK, SCC and perilesional skin of patients at the Princess Alexandra Hospital Dermatology Clinic in Brisbane, Australia.
关键词： atopic dermatitis,actinic keratosis,squamous cell carcinoma,microbial identification,Staphylococcus aureus,Fourier transform infrared spectroscopy
更新于2025-09-16 10:30:52
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Nonablative fractional laser therapy for treatment of actinic keratosis with 3a??months followa??up
摘要： Background: Actinic keratosis (AK) is a common skin disorder that is treated with different treatment modalities. Aims: The aim of this study was to assess the therapeutic effect of a 1540-nm non- ablative fractional laser on the AK. Methods: Ten patients with 31 AK were included in the study according to the inclu- sion and exclusion criteria. Treatment with nonablative fractional laser (1540 nm) 3 times at 4 weeks intervals in a noncontact mode was applied. Clinical severity was as- sessed at each session and 3 months after the last session. It is pertinent to mention that the patients were also involved in the assessment of improvement. Results: The results of present study showed that in comparison to the baseline, 3-session AK therapy with nonablative fractional laser significantly not only im- proved the AK severity by 79%, but also reduced the AK counts (from 31 to 17). On the other hand, the patients consented to the therapeutic effect. Conclusion: According to the obtained results and available studies, it seems that therapy with a 1540-nm nonablative fractional laser could be considered as a safe and effective alternative therapeutic option for the treatment of AK.
关键词： actinic keratosis,nonablative fractional laser
更新于2025-09-16 10:30:52
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Fractional 1,927?nm Thulium Laser Plus Photodynamic Therapy Compared and Combined for Photodamaged Décolleté Skin: A Side‐by‐Side Randomized Controlled Trial
摘要： Background and Objectives: Décolleté photodamage is a common condition typically treated with light and energy‐based devices. This study investigated the efficacy and safety of a fractional 1,927 nm thulium laser (TL) alone and combined with photodynamic therapy (PDT). Study Design/Materials and Methods: In a 12‐week follow‐up study, participant décolletés were divided into four treatment areas and randomized to receive a single treatment with field‐directed TL, PDT, combination TL‐PDT, or lesion‐directed curettage control. All actinic keratoses (AKs) underwent lesion‐directed curettage before randomization. TL was delivered at 20 mJ/mb, 500 mJ/cm2 fluence, 5 W, and 8 (n = 6 pts.) or 16 (n = 6 pts.) passes. PDT was performed with 16% methyl aminolevulinate (MAL) creme incubated for 3 h, followed by red light‐emitting diode light at 37 J/cm2. Outcome measures included clinical assessment of overall photodamage and specific subcomponents, assisted by optical coherence tomography (OCT) imaging. Results: Twelve women with moderate to severe photodamage on the décolleté and a cumulative total of 184 thin grade I AKs were included. Field‐directed treatments TL and combination TL‐PDT equally improved the overall photodamage, mottled pigmentation, and rhytides compared with lesion‐directed control (P < 0.05). The skin texture improved by TL alone and was further improved by combining TL and PDT (P < 0.05). Median AK complete responses were similar for field‐directed interventions TL‐PDT (100%), TL (90%), PDT (82%), and lesion‐directed curettage control (52%) (P = 0.464). Patients presented with mild local skin responses, slightly more pronounced when combining TL with PDT versus individual treatments (P < 0.05). No scarring or adverse events were observed. Conclusions: The 1,927 nm fractional thulium laser is an effective, tolerable, and safe field‐directed treatment for décolleté photodamage. Provided alone, TL proved to be as effective as combined TL‐PDT for overall photodamage, while a greater improvement in skin texture was achieved using TL and PDT in combination.
关键词： décolleté,optical coherence tomography,skin photodamage,thulium laser,non‐ablative laser,actinic keratosis,skin rejuvenation,photodynamic therapy
更新于2025-09-12 10:27:22
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Application of photodynamic therapy with the use of superluminescent light-emitting diode (sLED) lamp in actinic keratosis
摘要： Introduction. Actinic keratosis is a chronic disease that often requires many treatment cycles. The choice of a treatment method depends on the thickness and number of lesions as well as their extent. An efficient method of treatment, especially in the case of superficial and moderately thick lesions, is photodynamic therapy. Objective. Assessment of the photodynamic therapy with the use of a superluminescent light-emitting diode lamp after previous application of 5-aminolevulinic acid based on the observations of selected cases of patients with actinic keratosis. Material and methods. The study included patients diagnosed with actinic keratosis. After debridement of scales and crusts from the affected skin area 16% 5-aminolevulinic acid cream was applied. The irradiation was performed with the use of the superluminescent light-emitting diode matrix illuminator Medlight that sent out pulsed red light. The clinical evaluation was carried out before, immediately after the procedure as well as after 1 and 3 weeks. Results. In one case, after many years of ineffective treatment with a cryosurgery, the treatment with application of superluminescent light-emitting diode therapy lead to disease remission. In the second case early therapy with the superluminescent light-emitting diode lamp lead to complete resolution of lesions. In the case of a patient with disseminated actinic keratosis, lesion-directed therapy was possible. Conclusions. Observation results indicate a beneficial effect of superluminescent light-emitting diodes and no recurrence of actinic keratosis lesions in 3 months after the procedure.
关键词： photodynamic therapy,actinic keratosis,LED
更新于2025-09-12 10:27:22
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A Comparison of the Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy according to the Density of Ablative Laser Channel in the Treatment of Actinic Keratosis: A Prospective, Randomized, Controlled Trial
摘要： Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is effective in the treatment of actinic keratosis (AK). Protoporphyrin IX (PpIX) transformed from MAL is accumulated in abnormal AK cells, which are destroyed by light irradiation during PDT. However, AK hyperkeratosis is known to reduce the PDT treatment response, and pretreatment with ablative fractional laser (AFL) has been successfully used to overcome this barrier. AFL treatment creates microscopic ablation zones (MAZs), allowing easy absorption of MAL and direct evaporation of abnormal cells. We evaluated whether AFL pretreatment with different laser channel densities impacts the efficacy, PpIX accumulation, side effects, and cosmetic outcomes in AFL-PDT for facial AK. This study followed a previous study comparing the efficacy of AFL-PDT according to ablative depth for AK. Patients were randomly assigned to three different AFL density groups with other parameters being fixed. Each lesion was photographed and graded according to Olsen et al. Three hours after MAL application, fluorescence intensity was measured to assess PpIX accumulation and each area was irradiated with a red light-emitting diode lamp (peak emission 630; total light dose 37 J/cm2). Forty-seven Korean patients with 312 AK lesions completed the study (5.5-, 11-, and 22%-density AFL-PDT groups, 16 patients, n=110; 15 patients, n=96; and 16 patients, n=106, respectively). The three groups had no statistical differences in sex, age, Fitzpatrick score, number of lesions, or Olsen grade. However, the complete response (CR) rate was different between the 3 groups at months 3 and 12 (P=0.037; P=0.003, respectively) and the 22%-density AFL-PDT group showed a significantly higher CR rate than the 5.5%-density group (3 months, 88.7% vs. 80.0%; 12 months, 81.1% vs. 60.9%). The CR rate of the different laser densities was investigated for each Olsen grade, and the 22%-density group showed a significantly higher CR rate than the 5.5%-density group (3 months, 81.3% vs. 55.9%; 12 months, 68.8% vs. 38.2%) in Olsen grade III AK lesions. The fluorescence intensities measured and calculated from the photographs were not different among the three groups, and side effects and cosmetic outcomes showed no significant difference. In this study, the CR rate of AFL-PDT was different among the 3 groups, though there were no differences in PpIX accumulation. A recent study also demonstrated that PpIX accumulation showed no difference at laser densities above 5% when AFL is performed in normal skin. However, higher laser density AFL evaporates AK tissues more, and another study showed that AFL treatment temporarily reduced AKs and showed a trend toward decreased development of new lesions. This study had limitations with the small sample size in a single ethnic group, and more studies on AFL-PDT laser density, especially density > 22%, are needed. In conclusion, the group treated with AFL-PDT with higher laser density showed a better CR rate with reduced recurrence, especially for AK with higher Olsen grade. We recommend pretreatment with AFL at a higher laser density when AFL-PDT is used to treat AK with severe hyperkeratosis.
关键词： actinic keratosis,photodynamic therapy,laser parameter,ablative factional laser,laser channel density
更新于2025-09-12 10:27:22
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Laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound with short incubation time for field cancerization treatment: a left-right comparison
摘要： Background: Laser-assisted MAL-PDT has been reported to increase the effectiveness of conventional PDT. Nonetheless, clinical effects of this association when reducing MAL is poorly discussed. Furthermore, the association of acoustic pressure wave ultrasound with laser-assisted MAL-PDT with short incubation time for field cancerization had not been reported before. Objectives: To compare clinical effects of ablative fractional laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound (IMPACT US) with 1-hour field cancerization on the forearms, as well as the impact on safety and tolerability. Methods: Fifteen patients with 638 AK (grade I-III) with field cancerized-skin on the forearms were enrolled in this left-right trial. Two protocols were randomly chosen. One side was treated with conventional MAL-PDT, whereas the other with laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound with 1-hour incubation time. Actinic keratoses were quantitively measured, and the other signs of sun-damaged skin, like pigmentation and texture, in field cancerized skin were qualitatively evaluated before and after six months. Side effects were assessed subjectively during the procedure and one week after. Results: All patients completed the study. At six months after treatment, both protocols reduced the number of AK (72%; CO2 + PDT, and 65%; MAL-PDT). The difference between these two protocols was not statistically significant (p = 0.77). The improvement of pigmentation and texture of field cancerized skin was more significant on the side treated with laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound. Both protocols were well tolerated and without significant difference in adverse events. Conclusion: Laser-assisted MAL-PDT using CO2 laser and acoustic pressure wave ultrasound with short incubation time of 1 hour was as effective as conventional MAL-PDT for field-cancerized skin with actinic keratosis in forearms with better cosmetic outcome.
关键词： Incubation time,Skin field cancerization,Actinic keratosis,Ablative fractional laser assisted photodynamic therapy,laser-assisted drug delivery
更新于2025-09-12 10:27:22