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Solid organ transplant recipients (SOTR) have a high incidence of squamous cell carcinoma (SCC), for which preceding actinic keratoses (AK) are a major risk factor.1-4 We investigated whether cyclic photodynamic therapy (PDT) could reduce or delay the development of AK in renal transplant recipients (RTR) with no baseline skin dysplasia. Correspondingly, 73% ( I n i = 18) of patients had first onset of AK in untreated skin, 23% ( I n i = 5) developed AK simultaneously in untreated and PDT-treated skin, and 4% ( I n i = 1) had I de novo i AK in PDT-treated skin. Cyclic photodynamic therapy delays first onset of actinic keratoses in renal transplant recipients: a 5-year randomized controlled trial with 12-month follow-up. [Extracted from the article]

In addition to approved indications in non‐melanoma skin cancer in immunocompetent patients, topical photodynamic therapy (PDT) has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune‐suppressed patients, although sustained clearance rates are lower than for immune‐competent individuals. PDT using a nanoemulsion of ALA in a daylight or conventional PDT protocol has been approved for use in field cancerization, although evidence of the potential of the treatment to prevent new SCC remained limited. High‐quality evidence supports a strong recommendation for the use of topical PDT in photorejuvenation as well as for acne, refractory warts, cutaneous leishmaniasis and in onychomycosis, although these indications currently lack approvals for use and protocols remain to be optimized, with more comparative evidence with established therapies required to establish its place in practice. Adverse events across all indications for PDT can be minimized through the use of modified and low‐irradiance regimens, with a low risk of contact allergy to photosensitizer prodrugs, and no other significant documented longer‐term risks with no current evidence of cumulative toxicity or photocarcinogenic risk. The literature on the pharmacoeconomics for using PDT is also reviewed, although accurate comparisons are difficult to establish in different healthcare settings, comparing hospital/office‐based therapies of PDT and surgery with topical ointments, requiring inclusion of number of visits, real‐world efficacy as well as considering the value to be placed on cosmetic outcome and patient preference. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical photodynamic therapy in Dermatology prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence. [ABSTRACT FROM AUTHOR]

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas. Recurrence rates when standard treatment protocols are used are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as lesional and field therapies and has the potential to delay/reduce the development of new lesions. A protocol using daylight to treat actinic keratoses is widely practised, with conventional PDT using a red light after typically a 3‐h period of occlusion employed for other superficial skin cancer indications as well as for actinic keratoses when daylight therapy is not feasible. PDT is a well‐tolerated therapy although discomfort associated with conventional protocol may require pain‐reduction measures. PDT using daylight is associated with no or minimal pain and preferred by patient. There is an emerging literature on enhancing conventional PDT protocols or combined PDT with another treatment to increase response rates. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical PDT in dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence. [ABSTRACT FROM AUTHOR]

Summary: Background: Physical pretreatments can potentiate the efficacy of daylight photodynamic therapy (dPDT), but clinical comparative studies remain limited. Objectives: Performed in large skin areas with actinic keratoses (AKs) and photodamage, this blinded, randomized clinical trial compared the efficacy and safety of dPDT after tailored skin pretreatment using ablative fractional laser (AFL) or microdermabrasion (MD). Methods: Two ≥ 50‐cm2 side‐by‐side skin areas were randomized to receive a single treatment with AFL‐dPDT or MD‐dPDT. Pretreatment parameters were tailored according to AK grade and skin constitution to ensure standardized immediate end points. Subsequently, methyl aminolaevulinate was applied, followed by 2‐h daylight exposure. The primary outcome comprised blinded assessment of AK clearance at the 3‐month follow‐up. Results: In 18 patients with 832 AKs, AFL‐dPDT provided significantly higher AK clearance (81% vs. 60%, P < 0·001), led to fewer new AKs (P < 0·001) and showed superior improvement in dyspigmentation (P = 0·003) and skin texture (P = 0·001) vs. MD‐dPDT. Peaking at days 3–6, AFL‐PDT induced more intensified local skin responses (P = 0·004), including instances of Staphylococcus aureus infection (n = 3). Patients nonetheless preferred AFL‐dPDT (P = 0·077), due to lower pretreatment‐related pain (P = 0·002) and superior cosmesis (P = 0·035) and efficacy compared with MD‐dPDT. Conclusions: AFL‐dPDT is an effective treatment for patients with AK with extensive field cancerization, although AFL pretreatment is associated with intensified local skin reactions. What's already known about this topic? Different physical skin pretreatments have been shown to potentiate the efficacy of daylight photodynamic therapy (dPDT), but comparison studies are lacking. What does this study add? Using tailored pretreatment parameters to obtain standardized immediate end points prior to dPDT, ablative fractional laser provided superior lesional clearance and enhanced rejuvenating effects, but increased local skin reactions compared with pretreatment with microdermabrasion.Ablative fractional laser‐assisted dPDT represents a viable, intensified treatment strategy for patients with multiple actinic keratoses and large areas of photodamaged skin. Linked Editorial:Wolf. Br J Dermatol 2019; 180:697–698. Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: Topical photodynamic therapy (PDT) is an approved treatment for actinic keratosis (AK). To enhance the efficacy of PDT for AKs, physical and chemical pretreatments have been suggested. Objectives: To compare the efficacy and safety of the combination of topical calcipotriol (CAL) before methyl aminolaevulinate (MAL)‐PDT for AKs of the scalp vs. conventional MAL‐PDT in a randomized controlled clinical trial. Methods: Twenty patients with multiple AKs on the scalp were randomized to receive conventional MAL‐PDT with previous curettage on one side of the scalp and CAL‐assisted MAL‐PDT once a day for 15 days before illumination on the other side. After 3 months, patients were evaluated for clearance of AKs, side‐effects and histopathology before and after the procedure. Protoporphyrin IX (PpIX) fluorescence was measured before and after illumination on both sides. Results: All 20 patients completed the study. Overall AK clearance rates were 92·1% and 82·0% for CAL‐PDT and conventional PDT, respectively (P < 0·001). Grade 1 AKs showed similar response rates for both sides (P = 0·055). However, grade II AKs showed more improvement on the CAL‐PDT side (90%) than on the MAL‐PDT side (63%) (P < 0·001). Before illumination, PpIX fluorescence intensity was higher on the CAL‐assisted side (P = 0·048). The treatment was more painful on the CAL‐PDT side, although well tolerated. The mean visual analogue scale score was 5·4 ± 1·4 on the CAL‐PDT side and 4·0 ± 0·69 on the conventional MAL‐PDT side (P = 0·001). Side‐effects such as erythema (P = 0·019), oedema (P = 0·002) and crusts (P < 0·001) were more pronounced on the CAL‐assisted side. Histopathological analyses were obtained from five patients and both sides showed improved keratinocyte atypia following PDT, with slightly more improvement on the CAL‐assisted side. Conclusions: CAL‐assisted PDT proved to be safe and more effective than conventional MAL‐PDT for the treatment of AKs on the scalp. CAL pretreatment increased PpIX accumulation within the skin and may have enhanced the efficacy in this first human trial. What's already known about this topic? Topical vitamin D pretreatment enhances methyl aminolaevulinate (MAL)‐induced protoporphyrin IX (PpIX) in hairless mice.Topical vitamin D prior to aminolaevulinic acid photodynamic therapy (PDT) enhances treatment efficacy of nonmelanoma skin cancers in mouse skin models. What does this study add? In human skin, calcipotriol (CAL)‐assisted MAL‐PDT proved to be superior to MAL‐PDT alone and was well tolerated.Topical preconditioning of actinic keratoses with CAL‐assisted MAL induced PpIX formation to a greater extent compared with the side that was not pretreated. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult‐to‐treat premalignancies and comparison of topical therapies is therefore warranted. Objectives: In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL‐PDT) and imiquimod (IMIQ) for AKs in OTRs. Methods: OTRs (n = 35) with 572 AKs (grade I–III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL‐PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference. Results: The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I–III median 78%; range 50–100) compared with IMIQ‐treated skin areas (median 61%, range 33–100; P < 0·001). Fewer emergent AKs were seen in PDT‐treated skin vs. IMIQ‐treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ. Conclusions: Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3‐month follow‐up and achieved shorter‐lasting, but more intense, short‐term skin reactions. [ABSTRACT FROM AUTHOR]

Background Topical photodynamic therapy ( PDT) for actinic keratoses ( AK) is hampered by pain during illumination and inferior efficacy in organ-transplant recipients ( OTR). Objectives We assessed ablative fractional laser (AFL)-assisted daylight photodynamic therapy (PDT) (AFL-d PDT) compared with daylight PDT (d PDT), conventional PDT (c PDT) and AFL alone (AFL) in field treatment of AK in OTR. Methods In each patient, four areas in the same region were randomized to one treatment with AFL-d PDT, d PDT, c PDT and AFL. AFL was delivered with a 2940-nm AFL at 2·3 mJ per pulse, 1·15 W, two stacks, 50-μs pulse-duration, 2·4% density. In d PDT and AFL-d PDT, methyl aminolaevulinate (MAL) was applied for 2·5 h without occlusion during daylight exposure. For c PDT, MAL was occluded for 3 h followed by red-light (630 nm) irradiation at 37 J cm−2. The primary end-point was complete response (CR) 3 months post-treatment. Results Sixteen patients with 542 AK (grades I-III) in field-cancerized skin of the scalp, chest and extremities were treated during August and September 2012. After 3 months, CR (AK I-III) rates were 74% after AFL-d PDT, 46% after d PDT, 50% after c PDT and 5% after AFL ( P < 0·001). CR rates in AFL-d PDT, d PDT and c PDT were also significantly different ( P = 0·004). Median maximal pain scores differed significantly during AFL-d PDT (0), d PDT (0), AFL (0) and c PDT (5) ( P < 0·001). Erythema and crusting were more intense following AFL-d PDT than d PDT and c PDT, but only transient hypopigmentation was observed. Conclusions AFL-d PDT is a novel PDT modality that enhances CR with excellent tolerability compared with d PDT and c PDT in difficult-to-treat AK in OTR. [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy (PDT) is approved for selected nodular basal cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours. Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate (MAL) and may thus improve PDT outcome. Objectives To evaluate efficacy and safety of AFXL-mediated PDT (AFXL-PDT) compared with conventional PDT of high-risk nBCC. Methods Patients with histologically verified facial nBCC ( n = 32) defined as high-risk tumours were included; diameter > 15 mm, tumours located in high-risk zones, or on severely sun-damaged skin. Tumours were debulked and patients randomized to either AFXL-PDT ( n = 16) or PDT ( n = 16). Fractional CO2 laser treatment was applied at 5% density and 1000 μm (80 mJ) ablation depth. MAL was applied under occlusion for 3 h and illuminated with a 633-nm light-emitting diode source, 37 J cm−2. Clinical assessments were performed at 3, 6, 9 and 12 months and biopsies were taken at 12 months. Results Clinical cure rates at 3 months were 100% (16 of 16 AFXL-PDT) and 88% (14 of 16 PDT, P = 0·484). Recurrences tended to occur later and in lower numbers after AFXL-PDT at 6, 9 and 12 months (6%, 19%, 19%) than PDT (25%, 38%, 44%) ( P = 0·114). Histology at 12 months documented equal tumour clearance after AFXL-PDT (63%, 10 of 16) and PDT (56%, 9 of 16). Cosmetic outcomes were highly satisfactory after both treatments ( P > 0·090). Conclusions Long-term efficacy was similar after PDT and AFXL-PDT with a trend for a favourable short-term cure rate after AFXL-PDT. AFXL-PDT needs further refinement for nBCC and at present is not recommended over PDT. [ABSTRACT FROM AUTHOR]

Background Patients with Gorlin syndrome develop multiple basal cell carcinomas ( BCC), for which treatment is often difficult. Methylaminolevulinate-photodynamic therapy ( MAL- PDT) is approved for the treatment of superficial and nodular BCCs in Canada and several European countries. Objectives To establish consensus recommendations for the use of MAL- PDT in patients with Gorlin syndrome. Methods The Gorlin consensus panel was comprised of 7 dermatologists who had treated a total of 83 patients with Gorlin syndrome using MAL- PDT. Consensus was developed based on the personal experience of the expert and results of literature review (on PUBMED using the keywords ' MAL' and ' PDT' and 'Gorlin' or 'naevoid basal cell carcinoma syndrome'). Results Consensus was reached among the experts and the literature review identified 9 relevant reports. The experts considered MAL-PDT a generally effective and safe therapy for treatment of BCC in Gorlin syndrome. For superficial BCC ( sBCC), all sizes can be treated, and in nodular BCC ( nBCC), better efficacy can be achieved in thinner lesions (<2 mm in thickness). MAL-PDT treatment schedule should be performed according to labelling although in individual cases, it may be adapted and performed on a monthly basis based on clinical assessment. Follow-up should be related to frequency of recurrence, and severity, number and location of lesions. Multiple lesions and large areas may be treated during the same session; however, adequate pain management should be considered. Conclusions MAL- PDT is safe and effective in patients with Gorlin syndrome. Utilization of these recommendations may improve efficacy and clearance rates in this population. [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy ( PDT) is a well-documented treatment for actinic keratosis ( AK), but achieves inferior efficacy in organ transplant recipients ( OTRs), particularly in acral regions. Ablative fractional laser ( AFXL) intensifies the PDT response and may improve the efficacy of AK clearance when used as monotherapy. Objectives To compare the efficacy of a single treatment with AFXL-assisted PDT vs. AFXL alone for difficult-to-treat AKs and wart-like lesions ( WLLs) in OTRs. Methods Ten OTRs were included with a total of 680 AKs (severity grade I- III) and 409 WLLs on the dorsal hands. Both hands were initially treated with targeted fractional ablation of thick keratotic lesions followed by AFXL field treatment. Treatment regions were then randomized to (i) PDT ( AFXL- PDT) or (ii) no further treatment ( AFXL). The primary end point was complete response ( CR) at 4 months after treatment; secondary end points were improvement of AK severity grade, overall patient assessment of efficacy and tolerability of treatments. Results CR of AKs was significantly higher for AFXL- PDT (73%) compared with AFXL alone (31%) ( P = 0·002). AFXL- PDT improved 82% of AKs to lower lesion grades compared with 52% after AFXL alone ( P = 0·008). For WLLs, the rate of CR was 37% for AFXL- PDT compared with 14% for AFXL ( P = 0·02). Overall assessment showed a preference for AFXL- PDT compared with AFXL ( AFXL- PDT, n = 8; AFXL, n = 0; equal, n = 2). Mild pigment changes were observed in four patients ( AFXL- PDT, n = 3; AFXL, n = 1). No scarring was observed. Conclusions AFXL- PDT is more effective than AFXL in the treatment of acral AKs and WLLs in OTRs. [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy (PDT) is an effective but time-consuming and often painful treatment for actinic keratosis (AK). Home-based daylight–PDT has the potential to facilitate treatment procedure and to reduce associated pain due to continuous activation of small amounts of porphyrins. Moreover, a reduced methyl aminolaevulinate (MAL) concentration may reduce associated inflammation, making the treatment more tolerable for the patients. Objectives To compare response rates and adverse effects after PDT using conventional 16% and 8% MAL with home-based daylight exposure in treatment of AK. Methods Thirty patients with mostly thin-grade AK of the face or scalp were treated with 16% and 8% MAL–PDT in two symmetrical areas after application of sunscreen. Immediately after, patients left the hospital with instructions to spend the remaining day outside at home in daylight. Patients scored pain during treatment and light exposure was monitored with an electronic wristwatch dosimeter. Results The complete response rate after 3 months was 76·9% for 16% MAL and 79·5% for 8% MAL ( P = 0·37). Patients spent a mean of 244 min outdoors and received a mean effective light dose of 30 J cm−2. Light doses of 8–70 J cm−2 induced similar response rates ( P = 0·25). Patients experienced mild to moderate pain during daylight exposure (mean maximal pain score of 3·7). No differences in pain scores and erythema were seen between the areas treated with 16% MAL and with 8% MAL. Conclusions Home-based daylight-mediated MAL–PDT was an effective and well-tolerated treatment for AK. No differences in response rates or adverse events were found between the areas treated with 16% MAL and with 8% MAL. [ABSTRACT FROM AUTHOR]

Background  Photodynamic therapy (PDT) is a highly effective treatment for actinic keratoses (AK); however, it is time consuming and often painful for the patient. Daylight-PDT would make the treatment independent of the clinic and less painful due to the continuous activation of small amounts of porphyrins during its formation. Objectives  The objective of this randomized controlled study was to compare response rates and adverse effects after methyl aminolevulinate (MAL)-PDT using conventional red light-emitting diode (LED) light vs. daylight. Patients/methods  Twenty-nine patients with AK of the face and scalp were treated with MAL-PDT in two symmetrical areas. One area was illuminated by red LED light (37 J cm−2) after 3-h incubation with MAL under occlusive dressing. The other area was treated with daylight for 2·5 h after the MAL cream had been under occlusion for half an hour. Results  We found no significant difference in the treatment effect between the two treatments ( P = 0·13), with a reduction of AK lesions of 79% in the daylight area compared with 71% in the LED area. Treatment response in the daylight area did not depend on the intensity of the daylight. Illumination with LED was more painful than daylight ( P < 0·0001). Erythema and crusting occurred after both treatments and were similar in the two areas. Conclusions  PDT of AK by continuous activation of porphyrins by daylight proved to be as effective as conventional PDT. PDT using daylight activation will make the treatment of these extremely common premalignant tumours more time and cost effective, and more convenient for the patient. [ABSTRACT FROM AUTHOR]

Background There is a considerable need for effective and safe treatment for acne vulgaris. Objective In a systematic review with an evidence-based approach to assess the effects of optical treatments for acne vulgaris. Methods Original publications of controlled clinical trials were identified through searches in PubMed and the Cochrane Library. Results A total of 16 randomized controlled trials (RCT) and 3 controlled trials (CT) were identified, involving a total of 587 patients. Interventions included photodynamic therapy (PDT; 5 RCTs), infrared lasers (4 RCTs), broad-spectrum light sources (3 RCTs, 1 CT), pulsed dye lasers (PDL; 2 RCTs, 1 CT), intense pulsed light (IPL; 1 RCTs, 2 CTs), and potassium titanyl phosphate laser (1 RCT). The randomization method was mentioned in 6 of 16 RCTs, and one trial described adequate allocation concealment. Most trials were intraindividual trials (12 of 19), which applied blinded response evaluations (12 of 19) and assessed a short-term efficacy up to 12 weeks after treatment (17 of 19). Based on the present best available evidence, we conclude that optical treatments possess the potential to improve inflammatory acne on a short-term basis with the most consistent outcomes for PDT [up to 68% improvement, aminolevulinic acid (ALA), methyl-aminolevulinic acid (MAL) and red light]. IPL-assisted PDT seems to be superior to IPL alone. Only two trials compare optical vs. conventional treatments, and further studies are needed. Side-effects from optical treatments included pain, erythema, oedema, crusting, hyperpigmentation, pustular eruptions and were more intense for treatments combined with ALA or MAL. Conclusion Evidence from controlled clinical trials indicates a short-term efficacy from optical treatments for acne vulgaris with the most consistent outcomes for PDT. We recommend that patients are preoperatively informed of the existing evidence, which indicates that optical treatments today are not included among first line treatments. [ABSTRACT FROM AUTHOR]

Summary: Actinic keratosis (AK) is a common pre‐malignant lesion (affected patch) of the skin that affects many people worldwide, especially fair skin type people. It is more common after the age of 40 and in sun‐exposed areas of the body. It can progress into a type of skin cancer named squamous cell carcinoma (SCC). For this reason, an adequate treatment of each AK lesion is recommended. This study aimed to treat these lesions with photodynamic therapy (PDT), which is a well‐established option. Normally, topical PDT is a treatment that combines a drug (applied to the lesions) and illumination with light (blue or red). The final result is the massive killing of the cancer cells that will bring high cure rates to these patients. However, AKs on the scalp are sometimes hard to treat and the efficacy levels are lower when compared to facial lesions. Therefore, we aimed to find if the combination of PDT with a well‐known drug named Calcipotriol would bring any benefit to the patients. So we compared: one half of the scalp with CAL and PDT and the other half with PDT alone. Patients were then followed (monitored) for 3 months. We found that the combination was safe and more effective for AK treatment, especially when the lesions were thicker. Side effects were more common, but well‐tolerated by the patients. This is the first study of CAL and PDT for AKs. Linked Article: Torezan et al. Br J Dermatol 2018; 179:829–835 [ABSTRACT FROM AUTHOR]