Effective Treatment For Actinic Keratoses Research Articles

Efficacy of Photodynamic Therapy in the Treatment of Actinic Keratosis: A Network Meta-Analysis.

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. 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). 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. 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. 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.

Modified Painless Photodynamic Therapy for Actinic Keratosis in China

SignificanceAminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for actinic keratosis (AK). However, the pain during illumination usually caused patient to discontinue PDT treatment and resulted lower efficacy. Previous study showed modified painless PDT (M-PDT) with short ALA incubation time and longer irradiation time can reduce pain and preserve the efficacy. If M-PDT worked in AK still need to investigate. ApproachA splie-face controlled clinical study was conducted. Eleven patients with facial AK received C-PDT (conventional PDT) on the left and M-PDT in the contralateral area. The left area was illuminated by a red LED light (a total light dose of 140 J/cm2) after applying the ALA cream for 3 hours; the other had illumination for a total light dose of 288 J/cm2 after applying the ALA cream for 0.5 hours. The primary endpoint was the lesion clearance rate at 1 month. Secondary endpoints included pain scores, the incidence of adverse events, and cosmetic outcomes. ResultsAt one month following 3 treatments, the lesion clearance rate of M-PDT was non-inferior to that of C-PDT (93.1% vs. 86.4%, respectively. The lesion clearance rate of M-PDT to reach 100% clearance earlier than C-PDT for grade I lesions and higher clearance rates for grade III lesions. 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 (GS2A2) 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. ConclusionsM-PDT is non-inferior to C-PDT in terms of efficacy for treating AK, resulting in much lower pain scores.

The impact of occlusive vs non-occlusive application of methyl aminolevulinate on the efficacy and tolerability of daylight photodynamic therapy for actinic keratosis

BackgroundConventional 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. ObjectiveTo compare the efficacy and tolerability of occlusive and non-occlusive DL-PDT. MethodsWe 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. ResultsLesions 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. ConclusionThe occlusive application of MAL improves the efficacy of DL-PDT in clearing AKs and does not increase the incidence of side effects.

Is a 4 J/cm2 PpIX-Weighted Simulated Daylight (SDL-PDT) Dose Still Efficient for Photodynamic Therapy of Actinic Keratosis?

Background: Several solutions are now proposed to provide indoor illumination with so-called artificial white light or simulated daylight (SDL-PDT), resulting in an effective treatment for actinic keratosis (AK). However, the optimal PpIX-weighted light dose is still debated. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose and is a key parameter for the efficacy of the treatment. Objectives: The paper aims to report the clinical outcomes of SDL-PDT when using the PpIX-weighted light dose of 4 J/cm2, in patients treated for AK lesions of the scalp or the face at our medical dermatology center (ClinicalTrials.gov NCT052036). Methods: A total of 30 patients (16 males, 14 females), with a mean age of 71.0 ± 10.2, with phototype 1 (16 patients) and phototype 2 (14 patients) with grade I-II AK were treated with a drug light interval (DLI) of 10 min and a light exposure of 35 min (Dermaris, Surgiris, Croix, France), corresponding to a PpIX-weighted light dose of 4 J/cm2. The primary endpoint was the cure rate of patients at six months post-treatment. Secondary endpoints included scores of pain, erythema, crusts, and discomfort during or/and post the treatment. Results: In total, 762 AK were treated. Six months following treatment, the cure rate of the patients was 77%. The median pain score was less than 1 out of 10 for most of the patients. Erythema was observed in all patients and lasted 3 days (±1.5 day). Crusts were seen in 28 patients. Discomfort was reported as mild or less in more than 97% of patients. Conclusions: The shortening of the PpIX-weighted light dose to 4 J/cm2, corresponding to an illumination duration of 35 min with the Dermaris, does not modify the efficacy of the SDL-PDT. This observation is in agreement with recent published data demonstrating that the light dose can be reduced. Furthermore, this clinical study confirmed that SDL-PDT is an effective and nearly painless treatment with minimal side effects for patients with AK lesions of the scalp.

Hemodynamic changes during conventional and daylight photodynamic therapy of actinic keratoses – a randomized controlled trial

Background Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK). However, pain and hypertension are important side effects of conventional PDT (c-PDT). Several studies have demonstrated that daylight PDT (dl-PDT) is less painful while being as effective as c-PDT. Objective To observe the effect of c-PDT and dl-PDT on different hemodynamic parameters (systolic blood pressure and diastolic blood pressure, pulse rate, and peripheral oxygen saturation). Methods Fifty patients with AK on the head were enrolled into this prospective, randomized, controlled study and treated with c-PDT or dl-PDT in a 1:1 ratio. Hemodynamic parameters were measured at four different time points during treatment. Pain was quantified using a visual analog scale. AK was counted before treatment and after one month. Results C-PDT is associated with significantly more pain, a significant increase in blood pressure and a higher rate of patients with grade 3 hypertension. Whereas dl-PDT is almost painless and does not lead to any changes in hemodynamic parameters. For both treatments, a similar lesion response rate was found after one month. Conclusions dl-PDT has a better tolerability while being as effective as c-PDT and therefore may be the more favorable treatment option in certain patient groups.

Pulse rate and blood pressure changes during low-irradiance PDT compared with conventional PDT in the treatment of facial actinic keratoses: A retrospective study.

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

Sequential treatment with calcitriol and methyl aminolevulinate-daylight photodynamic therapy for patients with multiple actinic keratoses of the upper extremities

BackgroundTopical photodynamic therapy (PDT) is a widely used and effective treatment for actinic keratoses (AKs). However, cure rates are significantly reduced for AKs on acral sites. We compared the sequential regimen of topical calcitriol and methyl aminolevulinate (MAL) daylight-PDT (CAL-DL-PDT) versus placebo and MAL-DL-PDT (P-DL-PDT) on acral AKs in an intra-individual, randomized trial. MethodsAdult patients with multiple all grade AKs of the upper extremities were treated with daily topical calcitriol or placebo for 14 days followed by 2 sessions of DL-MAL-PDT. After 3 months, patients were evaluated for lesion response rate, both overall and by AK grade, and patient ≥ 75 % clearance rate. Safety assessments included pain VAS immediately after the first DL-PDT session, side effects after calcitriol pretreatment and 7 days after the first DL-PDT session. Cosmetic outcome by the physician and patient’s preference were graded at the end of the study. ResultsForty-two patients were enrolled and 36/42 completed the study. After 3 months, the overall lesion response rate and patient ≥ 75 % clearance rate of CAL-DL-PDT were higher, albeit not significantly, than P-DL-PDT. According to grade, response rate of grouped AK II/III was significantly higher for CAL-DL-PDT than for P-DL-PDT while similar results were observed for grade I AKs. Mild erythema and itch were reported after calcitriol application. No significant difference was observed in pain intensity. Local skin reactions occurred more frequently on the CAL-DL-PDT-treated sides. Cosmetic outcome did not differ but overall subject’s preference was slightly significantly in favor of P-DL-PDT. ConclusionsCAL-DL-PDT is more effective than P-DL-PDT for thicker “difficult to treat” AKs on the upper extremities but is associated with increased local skin reactions.

Global verification of a model for determining daylight photodynamic therapy dose.

Daylight photodynamic therapy is an effective treatment for actinic keratoses and relies on a minimum PpIX-effective light exposure dose being delivered during treatment. As such, daylight dosimetry is an important aspect of this treatment. Relatively simple measurements of illuminance may be converted to PpIX-effective irradiance, and subsequently exposure dose, via a conversion model (the O'Mahoney model). This model has been verified against spectral irradiance data from the UK, however the accuracy of the model has not been determined outside the UK. In this work, we test the O'Mahoney model against spectral irradiance measurements from several global locations to within bounds of a median deviation of ±10 %. The median percentage deviations are shown to be independent of location latitude and longitude. The model can be used confidently to determine PpIX-effective irradiance from illuminance measurements irrespective of location and can be widely implemented as an effective and low-cost means of accurately measuring effective light exposure for this important treatment.

Cold Atmospheric Plasma (CAP) for the Treatment of Actinic Keratosis and Skin Field Cancerization: Clinical and High-Frequency Ultrasound Evaluation.

IntroductionCold atmospheric plasma (CAP) has been clinically demonstrated to be an effective treatment for actinic keratosis (AK) in a number of case series. In this study, we evaluated the efficacy of CAP in the treatment of multiple AKs and assessed morphological changes induced on the skin field of cancerization both clinically and by high-frequency ultrasound (HFUS).MethodsPatients with multiple grade I–II AKs of the scalp and/or face who were resistant or intolerant to conventional field-directed treatments were enrolled. CAP treatments were performed using a microwave-driven argon plasma jet. At baseline and 3 months after the last CAP session, performance indexes were determined using three-dimensional digital pictures and HFUS investigations were performed on a representative Olsen grade II AK and a small spot of clinically unaffected skin within the test area. ResultsTwelve patients were enrolled in the study. All clinical variables showed a statistically significant reduction after CAP. HFUS evaluation revealed that the total, epidermal and dermal thicknesses of the target AKs had not changed with treatment. CAP therapy significantly increased dermal density in both the target AK and the surrounding photodamaged skin and signficantly decreased the thickness of the subepidermal low-echogenic band in the perilesional skin, which is an ultrasound sign of photodamage. ConclusionsCold atmospheric plasma was found to be an effective treatment for patients with multiple AKs. CAP was not followed by skin atrophy. HFUS examiniation showed the CAP improved features of chronic photodamage of the dermis of the skin underlying and surrounding the AK spots.

17491 Utilization of an online cash-pay prescription program for topical 5-fluorouracil prescriptions in older patients

Background: High cost of prescription medications presents a challenging issue in dermatology, particularly for older adults. Such costs are associated with decreased adherence, particularly in older patients with multimorbidities. The topical antineoplastic agent, 5-fluorouracil (5-FU) is an effective treatment for actinic keratosis (AK), a highly prevalent condition in elderly, fair-skinned populations, but it is often associated with high out-of-pocket costs and insurance hurdles. One online pharmacy provides patients with direct access to branded dermatology medications at lower, predictable prices, however, the online platform may be less accessible to older adults.

Utilization of an Online Cash-Pay Pharmacy for Topical 5-Fluorouracil Prescriptions in Older Patients

High cost of prescription medications presents a challenging issue for older patients with multimorbidities. Topical 5-fluorouracil (5-FU) is an effective treatment for actinic keratoses (AK), a highly prevalent condition among elderly populations, but it is often associated with unpredictable retail prices and high out-of-pocket costs. One online pharmacy offers branded prescription medications at fixed, low prices, but it may be less accessible to older patients for numerous reasons. To determine if the number of patients receiving topical 5-FU from an online pharmacy is proportionate to the national data on expected payment types for patients prescribed topical 5-FU for AK. We conducted a cross-sectional study using weighted pooled data from the National Ambulatory Medical Care Survey (NAMCS) on topical 5-FU prescriptions for AK from 2007-2016. Data regarding online pharmacy use were provided by Dermatology.com for the year 2019. Among patients with AK prescribed topical 5-FU, the most prevalent payment source was Medicare (54%) followed by private insurance (40%). On the online pharmacy, the majority of patients had commercial insurance (71%) followed by Medicaid (12%). Data from Dermatology.com are limited. Lower-cost medications from the online pharmacy site may improve adherence and outcomes in older adults and decrease total cost associated with AK treatment. However, the online pharmacy is underutilized by this population. J Drugs Dermatol. 2020;19(4): doi:10.36849/JDD.2020.4690.

Utilization of an Online Cash-Pay Pharmacy for Topical 5-Fluorouracil Prescriptions in Older Patients

Background: High cost of prescription medications presents a challenging issue for older patients with multimorbidities. Topical 5-fluorouracil (5-FU) is an effective treatment for actinic keratoses (AK), a highly prevalent condition among elderly populations, but it is often associated with unpredictable retail prices and high out-of-pocket costs. One online pharmacy offers branded prescription medications at fixed, low prices, but it may be less accessible to older patients for numerous reasons. Objective: To determine if the number of patients receiving topical 5-FU from an online pharmacy is proportionate to the national data on expected payment types for patients prescribed topical 5-FU for AK. Methods: We conducted a cross-sectional study using weighted pooled data from the National Ambulatory Medical Care Survey (NAMCS) on topical 5-FU prescriptions for AK from 2007-2016. Data regarding online pharmacy use were provided by Dermatology.com for the year 2019. Results: Among patients with AK prescribed topical 5-FU, the most prevalent payment source was Medicare (54%) followed by private insurance (40%). On the online pharmacy, the majority of patients had commercial insurance (71%) followed by Medicaid (12%). Limitations: Data from Dermatology.com are limited. Conclusions: Lower-cost medications from the online pharmacy site may improve adherence and outcomes in older adults and decrease total cost associated with AK treatment. However, the online pharmacy is underutilized by this population. J Drugs Dermatol. 2020;19(4): doi:10.36849/JDD.2020.4690

A feasibility study of microwave therapy for precancerous actinic keratosis.

SummaryBackgroundActinic keratosis (AK) is a common premalignant skin lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Microwave therapy is an established cancer treatment and has been used for plantar viral warts.ObjectivesTo evaluate the efficacy and feasibility of microwave as a treatment for AK.MethodsStage I was a dose‐setting study, in which seven participants had the dielectric properties of 12 thick and 22 thin AKs assessed for optimization of the microwave dose used for treatment in Stage II. Stage II was a randomized, internally controlled trial evaluating 179 AKs in 11 patients (93 treated, 86 untreated controls) on the scalp/forehead or dorsal hand. Participants received one treatment initially and a repeat treatment to unresolved AKs at week 4. The response was assessed at six visits over 4 months. The primary outcome was partial or complete resolution of the treated AKs.ResultsA significantly higher proportion of treated AK areas responded than untreated (90% vs. 15%; P < 0·001). Thin AKs were more responsive than thick AKs. The site did not affect efficacy. Pain was severe, but brief (80% reported pain lasting ‘a few seconds only’). Adverse effects were minimal (erythema, n = 6; flaking, n = 3; itch, n = 3). All participants who would chose microwave therapy over their current treatment cited the shorter discomfort period.ConclusionsMicrowave therapy is a portable, safe and effective treatment for AK. An easy‐to‐deliver, acceptable therapy for AK is attractive as a prevention strategy. While these results are promising, a larger randomized controlled trial is needed against an effective comparator to confirm clinical efficacy and patient acceptability. What is already known about this topic? Actinic keratoses (AKs) are common precancerous skin lesions.Successful treatment of AK can prevent cutaneous squamous cell carcinoma (cSCC).Most topical therapies for AK require repeated application over weeks and drive local skin inflammation, leading to poor compliance.An easy‐to‐deliver and effective treatment for AK, suitable for use in primary care, could reduce cSCC. What does this study add? Microwave therapy is a feasible, effective treatment for AK.Ninety per cent of treated AKs showed full or partial resolution at 120 days post‐treatment.Microwave therapy was painful, but the pain was short‐lived (seconds) and this short discomfort period was cited as the main reason that microwave was preferred to their current treatment. Linked Comment: Samimi and Kelleners-Smeets. Br J Dermatol 2020; 183:197–199.

Efficacy and safety of photodynamic therapy with amino-5-laevulinate nanoemulsion versus methyl-5-aminolaevulinate for actinic keratosis: A meta-analysis.

Photodynamic therapy is an effective treatment for actinic keratosis. 5-aminolevulinic acid nanoemulsion (BF-200 ALA) and methyl-5-aminolevulinate (MAL) are both prodrugs for the treatment of actinic keratosis with photodynamic therapy. A comparison of the efficacy and safety between the drugs is critical for clinical practice. To investigate if photodynamic therapy in combination with BF-200 ALA is superior to photodynamic therapy with MAL for actinic keratosis. We performed a meta-analysis to investigate the combination of photodynamic therapy with BF-200 ALA and with MAL. The PubMed, Cochrane Library, Web of Science and EMBASE databases were searched to select eligible randomized controlled trials. Our search was conducted on April 1, 2019, and included the search terms "5-aminolevulinic acid nanoemulsion or BF-200 ALA", "methyl-5-aminolevulinate or methyl aminolaevulinate" and "actnic keratosis". Cochrane Risk of Bias Tool was used to estimate the risk of bias. The meta-analysis consisted of 5988 actinic keratosis lesions in five eligible randomized controlled trials, with a total of 2953 actinic keratosis lesions treated with BF-200 ALA and 3035 actinic keratosis lesions treated with MAL. BF-200 ALA in combination with photodynamic therapy showed significantly higher overall complete clearance rates (RR: 1.07, 95% CI 1.02-1.12, p = 0.01) and 3 month complete clearance rates (RR: 1.09, 95% CI 1.06-1.12, p < 0.00001) compared to MAL. A subgroup analysis was performed for photodynamic therapy combined with BF-200 ALA, revealing increased complete clearance rates of grade II-III lesions in comparison with MAL (RR: 1.24, 95% CI 1.05-1.46, p = 0.01). Compared with MAL, the pooled relative risk for the meta-analysis for recurrence was 0.67 (95% CI 0.48-0.92, p = 0.01) at 12 month after BF-200 ALA treatment. Photodynamic therapy with BF-200 ALA has a 9% better chance of complete clearance at 3 months and a 24% better chance of grade II-III lesions after treatment than with MAL for patients with actinic keratosis.

Modern aspects of photodynamic therapy of actinic keratoses

Currently, photodynamic therapy (PDT) remains the most effective treatment for actinic keratosis (AK). With the increase in the incidence of AK, mainly due to the popularization of recreation in countries with increased insolation, there is an increasing interest in developing new methods of diagnostics and treatment and improving the existing ones. Studies that are aimed at determining the final efficacy of PDT, taking into account the resulting adverse reactions and long-term cosmetic results, are becoming increasingly popular. The nature of the light needed to excite a photosensitizer (PS) opens up new possibilities in the field of experimental studies that are aimed at reducing adverse reactions with similar efficacy of the applied therapy. In the review article, we presented the results of our own and foreign studies on the diagnosis and treatment of AK for 2017–2019, namely: we determined the possibilities of using sources with natural and short-wave radiation at different depths of skin lesions; presented a classification of the growth of AK in the basal layer of the epidermis, which increases the possibility of predicting the outcomes of the disease; showed the prevailing efficiency of fluorescent diagnostics compared with traditional diagnostic methods; evaluated the advantages of PDT using natural light and artificial sources of radiation; described the possibility of using a combination of drugs to increase the effectiveness of PDT in difficult to treat areas and in AK foci with a high degree of damage to the basal layer of the epidermis.

Photodynamic therapy for actinic keratosis in vegan and omnivore patients: the role of diet on skin healing

Background: Photodynamic therapy (PDT) is an approved and effective treatment for actinic keratosis (AK). The time of complete skin healing is estimated to range between 5 and 10 days, but the role of nutrition in influencing it has never been evaluated.Objective: The aim of this study was to compare the time of skin healing and side effects in omnivores and vegans treated with PDT for AK.Materials and methods: Thirty omnivore and thirty vegan patients, treated with PDT for AK, were enrolled. Side effects, according to local skin response (LSR) score, were compared after 3, 7, and 30 days; the time of complete skin healing was recorded.Results: At day 3, day 7, and day 30 post treatment, vegan group showed higher total LSR score (p = .008, p < .001, p < .001, respectively), highlighting higher edema and vesiculation at day 3 (p < .001, p = .002, respectively), erythema, desquamation, edema, and vesiculation at day 7 (p < .001, p < .001, p < .001, p < .001, respectively) and erythema and desquamation after 30 days (p < .001, p < .001, respectively). The difference of complete skin healing was statistically significant (p < .001).Conclusions: The present study suggests that diet may have a prognostic and predictive role on PDT outcomes in term of side effects and time of skin repair.

Conventional versus daylight photodynamic therapy for actinic keratosis: A randomized and prospective study in China.

Conventional photodynamic therapy (C-PDT) is an effective treatment for actinic keratoses (AKs) in Asia, with some unmet needs. Severe PDT-associated pain results in low treatment willingness. Daylight photodynamic therapy (DL-PDT) is a more simple and tolerable treatment that has the same efficacy as C-PDT in Europe. However, few studies have been conducted with Asian patients. To evaluate the efficacy and safety of DL-PDT vs. C-PDT for treating AK patients in China. This randomized and prospective study was conducted in Shanghai, China. Sixty patients with AKs (grades I-III) were randomized into two groups (DL-PDT and C-PDT). PDT was performed once every two weeks for a total of three times. Patients were evaluated before each treatment (baseline and two weeks after the first and second treatment) and at one month after the third treatment. Endpoints included efficacy (lesion response) and safety (pain scale and adverse events). A total of 55 patients completed the study. At the first month after 3 sessions of PDT, the overall lesion clearance rate of DL-PDT (95.5%) was similar to that of C-PDT (96.8%). However, in some particular parts (eyebrow and sideburns), C-PDT resulted in higher rates of cured lesions than DL-PDT. Additionally, patients undergoing DL-PDT had nearly no pain, showing significantly lower pain scores than those undergoing C-PDT (1.7 ± 0.9 for DL-PDT vs. 5.2 ± 1.7 for C-PDT). Moreover, fewer subjects undergoing DL-PDT had related adverse events than those undergoing C-PDT (36.7% vs. 63.3%). DL-PDT was effective, better tolerated and nearly painless compared with C-PDT in AK patients in China.

Photodynamic therapy and pain: A systematic review

Photodynamic therapy (PDT) is an effective treatment for actinic keratoses and early skin cancers, and the only office procedure to control field cancerization. Procedure-associated pain limits widespread PDT use and by early termination of treatment can decrease overall therapeutic efficacy. Here we review and assess reported interventions on PDT-associated pain, in order to identify the most promising methods to manage treatment-associated pain and identify focus for future studies. Literature search was performed using MEDLINE, EMBASE, and the Cochrane Library by two independent reviewers to select publications that assessed and compared pain quantitatively during PDT treatment for actinic keratoses, basal cell carcinomas, and/or in situ squamous cell carcinomas. A total of 48 studies reporting on pain during PDT were identified and were comprised of two main categories of interventions: pain-controlling therapies and PDT parameter (photosensitizer or photo-irradiation) adjustments. Of these interventions: nerve block, subcutaneous infiltration anesthesia, cold analgesia, and transcutaneous electrical nerve stimulation, but not topical anesthetic gels, were associated with less PDT-related pain; 5-aminolevulinic acid (ALA) tended to be more painful than methyl-5-aminolevulinate (MAL); daylight PDT was less painful than conventional PDT; and lower irradiance delivery produced lower pain scores in general. There is no single crystalized protocol for management of PDT-related pain. Evidence suggests that continuous activation of low levels of PpIX with methods using lower irradiance and possibly shorter incubation times are associated with decreased pain without loss of PDT efficacy. Protocols to reduce pain should be standardized and large controlled trials are needed.

Repeated Treatments with Ingenol Mebutate Prevents Progression of UV-Induced Photodamage in Hairless Mice.

Background and AimIngenol mebutate (IngMeb) is an effective treatment for actinic keratosis. In this study, we hypothesized that repeated treatments with IngMeb may prevent progression of UV-induced photodamage, and that concurrent application of a corticosteroid may reduce IngMeb-induced local skin responses (LSR).MethodsHairless mice (n = 60; 3 groups of 20 mice) were irradiated with solar simulated ultraviolet radiation (UVR) throughout the study. Five single treatments with IngMeb were given at 4-week intervals (Days 21, 49, 77, 105, and 133). Clobetasol propionate (CP) was applied once daily for 5 days prior to each IngMeb application, as well as 6 h and 1 day post treatment. One week after IngMeb treatment No. 1, 3, and 5 (Days 28, 84, and 140), biopsies from four mice in each group were collected for histological evaluation of UV-damage on a standardized UV-damage scale (0–12). LSR (0–24) were assessed once daily (Days 1–7) after each IngMeb treatment.ResultsIngMeb prevented progression of photodamage in terms of keratosis grade, epidermal hypertrophy, dysplasia, and dermal actinic damage with a lower composite UV-damage score on day 140 (UVR 10.25 vs. UVR+IngMeb 6.00, p = 0.002) compared to UVR alone. IngMeb induced LSR, including erythema, flaking, crusting, bleeding, vesiculation, and ulceration. Concurrent CP increased LSR (max LSR Tx 1–5: UVR+IngMeb+CP 3.6–5.5 vs. UVR+IngMeb 2.6–4.3) and provided better prevention of photodamage compared to IngMeb alone (Day 140: UVR+IngMeb 6.00 vs. UVR+IngMeb+CP 3.00 p < 0.001).ConclusionRepeated field-directed treatments with IngMeb prevent progression of cutaneous photodamage in hairless mice, while CP cannot be used to alleviate IngMeb-induced LSR. The findings suggest that IngMeb may potentially serve as a prophylactic treatment for UV-induced tumors.

Daylight photodynamic therapy: The Southern California experience

Photodynamic therapy (PDT) is a safe and effective treatment for actinic keratoses (AKs) and photoactinic damage. Three elements are needed for PDT: a photosensitizer, oxygen, and a light source. Conventional PDT is performed with a variety of different laser and light sources including blue, yellow and red in addition to filtered intense pulsed lights (IPL). Daylight PDT, using ambient visible light has been reported as safe, time- and cost-efficient, and more comfortable than with other light sources. We report our experience with daylight PDT in 80 patients. Eighty patients with multiple actinic keratoses related to chronic photodamage underwent one or two sessions with daylight PDT. Anatomic locations treated included face, chest, arms, and legs. Aminolevulinic acid (ALA, Levulan, Kerastick Dusa USA) was applied one hour prior to light exposure. Thick actinic keratoses were gently curetted prior to ALA application. A chemical sunscreen was applied thirty minutes into the incubation and subsequently patients sat outside in the shade for 2.5 hours. The following day, patients applied a chemical sunscreen and went into either shaded or direct sunlight for 15-30 extra minutes depending on sensitivity. Significant pain associated with this second day exposure was an indication to return indoors immediately. After the second exposure they were instructed to stay inside for the remainder of the 48 hour post treatment period. All patients tolerated the procedure well. Patients denied any pain during the first two and half hour exposure. The second day exposure elicited a mild burning sensation that patients rated as a 2-3/10 though some patients elected to go outside protocol and 'tough it out' despite more significant discomfort. Patients and physicians noted significant reduction in photoactinic damage and actinic keratoses. Patients appreciated the convenience of the treatment. There were no significant adverse events, and no patients reported scarring. In this case series, daylight PDT achieved obvious improvement in photodamage, specifically precancerous lesions, and in photoaging with a reduction in lentigenes and other signs of aging. Patients reported significantly less pain than with conventional PDT and enjoyed the convenience of treatment generally in their backyard. It was noted to be a safe procedure with no significant adverse events such as scarring. Additionally, the cost of the procedure was significantly reduced, with ALA and its application being the only expenses.