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Background: Recently, indoor daylight photodynamic therapy (idl-PDT) has been developed; however, its efficacy and tolerability remain to be assessed., Objective: This is a not-inferiority study to compare treatment outcomes of cPDT with a red LED lamp and idlPDT with a polychromatic white LED lamp in adult patients affected by symmetrical AKs of face and/or scalp., Methods: In this comparative, intra-patient, split-face, randomized clinical trial forty-three adult patients were enrolled. Two contralateral and symmetrical target areas of the face and/or scalp harboring at least 5 AKs were selected and randomized 1:1 to treatment with cPDT and idlPDT. The AKs number and cumulative area were assessed at baseline (T0). Efficacy and cosmetic outcome were assessed 3 months after treatment (T1)., Results: Total AKs number and area reduced significantly with both idlPDT ( p  < .0001) and cPDT ( p  < .0001) in comparison to baseline. cPDT was more painful ( p  < .0001) and induced a more severe inflammation ( p  < .0001). Twenty-nine patients (70.7%) gave their overall preference to idlPDT ( p  < .001)., Conclusion: idlPDT may represent an alternative treatment protocol to cPDT for in-office treatment of AKs patients with better tolerability and a not inferior efficacy.

Background: The efficacy for actinic keratosis (AK) clearance of field-directed treatments has been investigated in randomized studies against placebo, but the comparison of results is difficult for several methodological reasons., Objectives: The present study aims to compare efficacy of MAL-photodynamic therapy (MAL-PDT), ingenol mebutate gel (IMB) and diclofenac plus hyaluronate gel (DHA) on multiple AKs assessing a new performance index of efficacy, the cumulative AK area and evaluating dermoscopical and high-frequency ultrasound (HFUS) changes., Methods: Patients with ≥5 Olsen II AKs in a 25 cm 2 area of the scalp and face were enrolled and randomized to one of the treatment choices. Number of AKs and cumulative area were assessed before and after treatment. Dermoscopy and HFUS were performed on a single AK and surrounding photo-damaged skin in the treatment area., Results: Cumulative AKs area reduced significantly more with PDT compared to other treatment options and with IMB in comparison to DHA. PDT was also the only treatment option that increased at a significant level the dermal density in both target AK and the surrounding skin and decreased significantly the SLEB thickness in the perilesional skin at HFUS., Conclusions: MAL-PDT is more effective than IMB and DHA for reducing the cumulative AK area which is calculated digitally from 3D pictures and should be the preferred performance index for the evaluation of the efficacy of treatments for AKs, rolling out clinical and dermoscopy evaluation. MAL-PDT improves all HFUS features of chronic photodamages of the dermis of the skin underlying and surrounding the AK spots., (© 2019 European Academy of Dermatology and Venereology.)

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., (© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: A gel containing diclofenac and hyaluronic acid (DHA) and photodynamic therapy with methyl aminolaevulinate (MAL-PDT) are widely used treatments for actinic keratoses (AKs)., Objectives: The aim of this single-centre, open-label, prospective, nonsponsored, randomized controlled clinical trial was to compare the treatment results and cost-effectiveness of MAL-PDT and DHA., Methods: Patients with multiple AKs of the face and scalp were randomized to receive MAL-PDT or DHA. After 90 days, the overall complete remission (CR) rate of patients and the CR rate of lesions according to thickness score were assessed, and patients and an investigator scored the cosmetic outcome. In addition, patients scored their overall satisfaction with the treatment. Patients with CR of all lesions were followed up for 12 months., Results: Two hundred patients with a total of 1674 AKs were enrolled. The lesion CR rates at 3 months were 85·9% with MAL-PDT and 51·8% with DHA (P < 0·0001). AKs of all thicknesses were significantly more responsive to MAL-PDT. The patient CR rates at 3 months were 68% with MAL-PDT and 27% with DHA. At the 12-month examination, the number of patients with CR reduced to 37 with MAL-PDT and seven with DHA. Rating of cosmetic outcome was very good or excellent in the vast majority of patients with both treatments. The analysis of cost-effectiveness showed that the costs per patient with CR at 3 months and at 12 months are €566·7 and €1026·2, respectively, with MAL-PDT and €595·2 and €2295·6, respectively, with DHA., Conclusions: Efficacy, cosmetic outcome and patients' overall satisfaction with MAL-PDT are superior in comparison with DHA. MAL-PDT is more expensive but it is more cost-effective., (© 2014 British Association of Dermatologists.)

Background: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an approved noninvasive treatment option for basal cell carcinoma (BCC). In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has proved useful for in vivo real-time cytomorphological analysis of BCC cells infiltrating the epidermis., Objectives:   To investigate the use of in vivo RCM to assess the persistence of BCC cells surviving MAL-PDT., Methods: In vivo  RCM images of 20 biopsy-proven BCCs were taken before patients underwent a treatment cycle with MAL-PDT. Follow-up after 3months was performed using clinical examination, RCM and conventional dermoscopy. Treated areas also underwent a targeted 3-mm punch biopsy for standard haematoxylin and eosin histology stain to establish the clinical and instrumental correlation of the treatment outcome., Results:   Three months after PDT, clinical examination established that two out of 20 BCCs were persistent; dermoscopy found three out of 20 residual BCCs, but RCM showed that one of these lesions was a false positive, and showed persistent BCC foci in five out of 20 lesions. Histological analysis of targeted biopsies confirmed these results., Conclusions:   RCM provided noninvasive, early detection of incipient recurrences of BCC after MAL-PDT. RCM findings steered targeted biopsies and surgical removal, or a new MAL-PDT, of these subclinical recurrences with minimal invasiveness., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: Photodynamic therapy (PDT) is increasingly used in the treatment of basal cell carcinoma (BCC). However, scant information is available about the impact of both patient- and lesion-related characteristics on the effectiveness of therapy. Therefore, on the basis of the current data, it is difficult to draw clear-cut indications to use PDT for treatment of BCC in clinical practice., Objective: To investigate the clinical and pathological determinants of response of BCC to PDT with methylaminolevulinate (MAL) and red light., Methods: The clinical and pathological characteristics of 194 BCCs in 135 patients, treated with MAL-PDT, were evaluated. Lesions were treated with MAL-PDT according to established methods and the response was assessed by clinical follow-up of the patients., Results: Complete response to PDT was 62%, with a better response for superficial BCC (95/116, 82%) than nodular BCC (26/78, 33%). When determinants of response were analysed, the nodular type and the location on the limbs emerged as significant clinical predictors of failure. Among the pathological characteristics, the nodular and infiltrative histotypes, as well as ulceration and tumour thickness were associated with a lower response to therapy. Patients' age and gender, as well as the size of the lesions, were not found to be significant predictors., Conclusions: Optimization of PDT procedure for BCC requires a careful selection of the lesions. In particular, superficial BCCs, preferentially located on the trunk, show the best therapeutic response., (© 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.)

Background: Photodynamic therapy (PDT) with methylaminolaevulinate (MAL) is an approved noninvasive treatment option for actinic keratosis and Bowen's disease (BD), two precursors of invasive squamous cell carcinoma (SCC)., Objectives: To assess efficacy, prognostic features, tolerability and cosmetic outcome of MAL-PDT for the treatment of BD and SCC., Methods: In total, 112 biopsy-proven lesions of BD and SCC in 55 subjects were treated in an outpatient setting. MAL cream (160 mg g(-1)) was applied for 3 h prior to illumination with a light-emitting diode source (wavelength range 635 +/- 18 nm; light dose 37 J cm(-2)). A second MAL-PDT session was given 7 days later. Complete response rate at 3 months after the last treatment, recurrence rate at the 24-month follow-up, and cosmetic outcome were recorded., Results: The overall complete response rates were 73.2% at 3 months and 53.6% at 2 years. Clinical thickness, atypia and lesion depth were significant predictors of the response at 3 months when using a univariate analysis (P < 0.001). A multivariate logistic regression model, with robust variance estimation, showed that cell atypia was the only statistically significant independent predictor of the treatment outcome at 3 months., Conclusions: MAL-PDT may represent a valuable, effective and well tolerated treatment option with good cosmetic outcome for superficial, well-differentiated (Broders' scores I and II) BD and microinvasive SCC. In contrast, its use for superficial SCCs with a microinvasive histological pattern and for nodular, invasive lesions, particularly if poorly differentiated keratinocytes are present (Broders' scores III and IV), should be avoided.

In several randomized, controlled studies, the application of a standard preparation containing methyl-aminolevulinate (MAL; Metvix, Galderma, F), followed by red light irradiation proved effective and well tolerated in the treatment of actinic keratosis and basal cell carcinoma, and has now been approved for clinical use in European countries. A brand name aminolevulinic acid (ALA) solution (Levulan Kerastick, Dusa Pharmaceuticals Inc., Wilmington, MA) plus blue light exposure has been approved for the treatment of actinic keratosis in the USA. Randomized and controlled studies have shown that MAL as well as ALA are also effective in the treatment of Bowen's disease. In addition, a large and growing number of open studies or case reports have evaluated its use in the treatment of a broad range of other neoplastic, inflammatory and infectious skin diseases. However, efficacy and definite advantages over standard therapies remain to be clarified because the experimental design of these studies was often poor, the number of enrolled patients was generally low, and the follow-up was shorter than 12 months. However, these studies have suggested a few possible clinical applications worthy of further investigation. A growing number of laboratory and clinical findings suggest that several new synthetic sensitizers, besides ALA and MAL, may be helpful in the treatment of non-melanoma skin cancers, melanoma metastasis, and selected inflammatory and infective skin diseases. These compounds are deliverable intravenously, have short half-lives both in the blood and skin, and are highly efficient. However, they are as of yet not approved for clinical use.

Photodynamic therapy (PDT) is a two-step therapeutic technique in which the topical or systemic delivery of photosensitizing drugs is followed by irradiation with visible light. Activated photosensitizers transfer energy to molecular oxygen, generating reactive oxygen species (ROS). The subsequent oxidation of lipids, amino acids and proteins induces cell necrosis and apoptosis. In addition, ROS indirectly stimulate the transcription and release of inflammatory mediators. The photosensitizers are selective, in that they penetrate and accumulate in tumour cells or in the endothelium of newly formed vessels while generally avoiding the surrounding healthy tissue. The mechanisms of penetration through the cell membrane and the pattern of subcellular localization strongly influence the type of cellular effect. The photobiology and photoimmunology of the haematoporphyrin (Hp) derivative and its purified, lyophilized and concentrated form porfimer sodium have been investigated over the past 30 years. However, interest in PDT in dermatology was not raised until the 1990s with the availability of a simple and effective technique, the topical application of aminolaevulinic acid (ALA) and its methyl ester (methyl aminolaevulinate, MAL) followed by irradiation with broadband red light. At the same time, several new 'second-generation' synthetic sensitizers (e.g. benzoporphyrin derivatives, phthalocyanines, chlorins and porphycenes) became available. These compounds are chemically pure, highly efficient, selective and safe, while offering the advantage that the generalized skin photosensitivity they produce lasts for only a short time. They are currently under clinical evaluation but have not yet been approved for clinical use. This paper provides an overview of the chemistry of the photosensitizers, the photobiology and photoimmunology of the photodynamic reaction as well as the photophysical characteristics of the light sources available for PDT.

Photodynamic therapy (PDT) is a two-step procedure, involving the topical or systemic administration of a photosensitizer followed by selective illumination of the target lesion with visible light, which triggers the oxidative photodamage and subsequent cell death within the target area. In dermatology, PDT has proven to be a useful treatment for a variety of malignant tumors and selected inflammatory diseases. In addition, PDT of several infective viral or bacterial skin diseases has been investigated. These investigations grew out of the positive findings of studies of another important use of PDT: that of disinfection of blood products. Up to now, little has been published concerning the application of PDT to fungi, probably due to the fact that research funding has been mainly directed towards blood disinfection, and these pathogens show a low risk of transfusion transmission. However, preliminary findings have demonstrated that dermatophytes and yeasts can be effectively sensitized in vitro by administering photosensitizers belonging to four chemical groups: phenothiazine dyes, porphyrins and phthalocyanines, as well as aminolevulinic acid, which, while not a photosensitizer in itself, is effectively metabolized into protoporphyrin IX. Besides efficacy, PDT has shown other benefits. First, the sensitizers used are highly selective, i.e., fungi were killed at combinations of drug and light doses much lower than that needed for a similar effect on keratinocytes. Second, all investigated photosensitizers lack genotoxic and mutagenic activity. Finally, the hazard of selection of drug resistant fungal strains was never reported. This paper intends to provide a comprehensive overview of investigative studies about the effects of PDT on yeasts and dermatophytes, and bring attention to this application of PDT which we believe very important in that skin mycosis is so common and PDT is not only cost-effective, but also has the advantages of being highly selective and avoiding the occurrence of drug resistant strains.

Background: Findings of in vitro studies have demonstrated that dermatophytes and yeasts can be effectively photosensitized after topical delivery of 5-aminolevulinic acid (ALA). This procedure, called photodynamic therapy (PDT), seems to lack mutagenic activity and hazard of selection of drug-resistant strains., Methods: Twenty percent ALA preparation in Eucerin cream was applied under an occlusive dressing to skin lesions of nine patients with clinical and microbiological evidence of interdigital mycosis of the feet. After 4 h, lesions were irradiated with 75 J/cm(2) of broad-band red light. Interdigital lesions of the other foot served as control (treated with only light or only ALA). After 7 days from the first treatment, no further treatment was delivered if lesions were not clinically evident and direct microscopic examination was negative. Otherwise, three additional weekly treatments were delivered. Four weeks after the last treatment, patients had a final follow-up clinical and laboratory examination., Results: Clinical and microbiological recovery was seen in six out of nine patients after one (four cases) or four (two cases) treatments. However, after 4 weeks, recurrences were seen in four patients. Overall tolerability was always good., Conclusion: Under the conditions employed in the present study, ALA-PDT had good therapeutic effects on interdigital mycosis of the feet. However, recurrences were quick. In vivo environmental conditions, i.e. temperature, humidity and pH of the interdigital skin, could induce a poor cell uptake of ALA and a deficient biosynthesis of photosensitizing protoporphyrin IX. In addition, the irregular tridimensional shape of this peculiar anatomical area could lead to a non-uniform delivery of light and/or ALA cream. However, the present results can stimulate further studies on the PDT of superficial skin mycoses.

Background: Actinic keratoses (AKs) are the most common premalignant tumors. Without treatment, a significant number of patients with AK will experience squamous cell carcinoma. Photodynamic therapy (PDT) using the new highly selective photosensitizer methyl 5-aminolevulinate is a promising new treatment modality for AK., Objective: We investigated the complete response rates, cosmetic outcome, and patient satisfaction after photodynamic therapy (PDT) using methyl 5-aminolevulinate (Metvix) versus cryotherapy in the treatment of AKs., Methods: Patients were randomized to receive either cryotherapy with liquid nitrogen spray or PDT using methyl 5-aminolevulinate cream 160 mg/g, 3 hours application time, and red light (75 J/cm(2))., Results: Efficacy results from 193 patients with 699 lesions (92% face/scalp and 93% thin/moderately thick) were analyzed. Overall complete response rates after 3 months were 69% for PDT and 75% for cryotherapy. Both treatments gave higher response rates in thin lesions (PDT 75%, cryotherapy 80%). PDT gave better cosmetic results and higher patient satisfaction than cryotherapy., Conclusion: PDT using methyl 5-aminolevulinate is an attractive treatment option for patients with AK, with a response rate similar to that of cryotherapy, but with superior cosmetic results and high patient satisfaction.

We have reviewed the results of clinical investigations into the use of photodynamic therapy (PDT) with intravenous injection of hematoporphyrin derivative (HpD), Photofrin (PF) and Sn-protoporphyrin (Sn-Pp) or oral administration of delta-aminolevulinic acid in the treatment of skin cancers and/or psoriasis. Bowen's disease was highly responsive, provided that adequate light and HpD or PF doses were delivered. In contrast, poor results were shown for squamous cell carcinoma, and the rates of complete response of basal cell carcinoma ranged between 0% and 100%. Treatment failures could be related to the delivery of low drug and/or light doses, but differences in the thickness and pigmentation of the treated lesions may play a relevant role. Good palliation was almost always achieved in patients affected by primary and secondary breast carcinomas, although complete eradication of tumors was very rare. PDT is a very promising treatment modality for both Mediterranean and HIV-related Kaposi's sarcoma, because it appears to be effective, can be repeated and is not associated with immunosuppressive activity or significant systemic toxicity. PDT of psoriasis with low doses of Sn-Pp, HpD or PF plus UVA light and PF plus 630 nm light proved to be effective and was associated with mild, dose-related and reversible photosensitivity.

The photodynamic therapy of cutaneous disease is developing more rapidly than that of other organs due to the accessibility of the skin to photosensitizers and light. The use of hematoporphyrin derivative, with its prolonged photosensitivity of normal skin, is gradually being replaced by a new generation of tetrapyrrolic photosensitizers. These are designed to absorb at longer wavelengths for deeper tissue penetration. Many also feature a greatly reduced photosensitizing potential of uninvolved skin. Another major development is the topical and systemic use of aminolevulinic acid for inducing the formation of endogenous porphyrins in cells which result in photosensitivity. This regimen is currently used quite extensively due to the easy availability of both drug and suitable light sources. However, continued investigation of the underlying mechanisms and their regulation will help to improve this specific photodynamic regimen. Currently, researchers use a whole array of therapeutic regimens and schedules for the evaluation of treatment efficacy. A certain uniformity of both treatment parameters and evaluation criteria will help to improve more rapidly our understanding of photodynamic sensitization in skin disease. This will also help us to define the right place and targeting strategies for photodynamic therapy in dermatology.

Photodynamic therapy (PDT) with topical delta-aminolaevulinic acid (ALA) is considered as a valuable tool for treating non-melanoma skin tumours, but there is no consensus about the methods of treatment, where they should be used and the rates of complete responses. This study reports the treatment of 50 actinic keratoses (AKs), 23 superficial basal cell carcinomas (BCCs), 30 nodular BCCs, 4 pigmented BCCs, 12 superficial squamous cell carcinomas (SCCs), 6 nodular SCCs, 6 Bowen's diseases and 4 keratoacanthomas (KAs). A 20% ALA emulsion was applied under an occlusive dressing for 6-8 h and the skin was then irradiated with 630 nm light from a dye laser. Treatments were delivered every other day until complete clinical disappearance of the lesions was observed. ALA-PDT was interrupted in the case of a partial response if, after two additional treatments, no further improvement was observed. All AKs (50/50), superficial BCCs (23/23), Bowen's diseases (6/6) and KAs (4/4) showed a complete response. In addition, 91.6% (11/12) superficial SCCs, 80.0% (24/30) nodular BCCs and 66.7% (4/6) nodular SCCs responded completely to the treatment. All 4 pigmented BCCs were resistant to the therapy. Some (59) of the treated areas that appeared completely responsive were excised for serial histopathological examination and the remaining 63 were followed-up for 24-36 months (median value, 29 months). Comprehensively, the rates of complete responses decreased after taking into consideration the results of these histological examinations and the long-term follow-up. The final response rates are as follows: 84.0% (42/50) AKs, 86.9% (20/23) superficial BCCs, 50% (15/30) nodular BCCs, 83.3% (10/12) superficial SCCs and 33.3% (2/6) nodular SCCs. The rates of complete responses of Bowen's diseases and KAs remained at 100%.(ABSTRACT TRUNCATED AT 250 WORDS)