Daylight photodynamic therapy - Experience and safety in treatment of actinic keratoses of the face and scalp in low latitude and high brightness region

ABSTRACT Daylight photodynamic therapy has been used in countries with high latitudes during the summer for actinic keratoses treatment with reports of similar efficacy to conventional photodynamic therapy. We evaluate its safety in 20 patients in the city of Fortaleza, a local with low latitude and high brightness. Sixteen patients did not report any discomfort due to the procedure. Daylight photodynamic therapy is an easy application method with great tolerability by the patient and has the possibility of being performed throughout the year in these regions. It can mean a promising tool in the control of skin cancer.

Long-term recurrence of nonmelanoma skin cancer after topical methylaminolevulinate photodynamic therapy in a dermato-oncology department

Abstract: BACKGROUND: Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE: To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS: The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. RESULTS: A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. CONCLUSIONS: Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients.

Efficacy of red light alone and methyl-aminolaevulinate-photodynamic therapy for the treatment of mild and moderate facial acne.

Background: Photodynamic therapy (PDT) has been shown to be an effective alternative for acne. However, there is little information comparing the efficacy of red light alone and methyl aminolaevulinate (MAL)-PDT. Aims: To compare the efficacy and tolerability of red light alone and MAL-PDT in patients with mild to moderate facial acne. Methods: Thirty six patients with mild to moderate acne were enrolled. Eighteen patients recieved MAL-PDT and 18 received red light alone in two sessions, 2 weeks apart. Acne grade and lesion counts were assessed by blinded evaluators at baseline, 2, 4 and 10 weeks. Results: At week 2, clinical improvement from acne grade II-IV to 0-I was observed in 82.3% of MAL-PDT group and 14.2% of red light alone group. Red light alone group had a gradual clinical improvement over time with a 77% response at week 10. In contrast, MAL-PDT group had a rapid clinical improvement with total response at week 10. Both treatments were significantly effective for improving acne lesions. However, MAL-PDT group had a greater response (P < 0.001). Histologically, decreased amounts of sebocytes and lipids along with atrophic sebaceous glands were observed after MAL-PDT. Conclusion: MAL-PDT has a quicker onset of action with a higher response than red light alone. MAL-PDT may induce a reduction in the size of the sebaceous glands and then long-term acne remission.

Terapia fotodinámica en queilitis actínica, experiencia de hospital clínico Universidad de Chile / Photodynamic therapy in actinic cheilitis, clinical hospital of the University Chile experience

Introducción: La queilitis actínica (QA) es una lesión pre-neoplásica secundaria al fotodaño solar, que afecta al labio inferior. La Terapia fotodinámica (TFD) es un tratamiento promisorio en QA con buenos resultados tanto clínicos, que se han confirmado con hallazgos histopatológicos, así como cosméticos. Material y método: Serie de casos. Se presentan 3 casos de pacientes de sexo femenino tratados con TFD, en donde se utilizó ácido metil aminolevulínico en forma oclusiva y con protección de la luz 3 horas antes de la aplicación de la luz roja con lámpara Aktilite™, en el Hospital clínico de la Universidad de Chile entre los años 2008 y 2012. Se realizaron biopsias de control al final de la TFD para confirmar curación. Resultados: Se obtuvo el 100 por ciento de respuesta clínica en los 3 pacientes con un máximo de seguimiento de 33 meses en uno, sin evidencia de recidiva clínica ni histopatológica, con escasos efectos colaterales, buena aceptación y conformidad por parte de los pacientes. Conclusión: La TFD es una buena alternativa en el manejo de la QA con excelentes resultados y mínimos efectos colaterales. Los excelentes resultados clínicos se confirman con la histopatología, por lo cual se recomendaría su uso, previa biopsia, que descarte un carcinoma invasor concurrente. Queda aún por definir los intervalos de tratamiento y su duración.

Introduction: Actinic cheilitis (AC) is a pre-neoplasic lesion secondary to sun photodamage, that affect the inferior lip. Photodinamic therapy (PDT) is a promissory way of treatment inAC which has proven to be successful both clinical, and by histopatologic findings, as well as in cosmetic results. Materials and methods: Case series. Three cases are presented; female patients treated with PDT using methyl aminolevulinic acid in an occlusive way and protected from the light three hours before the application of red light using the Aktilite™ lamp. The trial was perfomed at the Clinical hospital of the University Chile of between the years 2008 and 2012. Control biopsies were made at the end of the PDT to confirm resolution. Results: 100 percent of clinical response was obtained in the three patients with a maximal follow-up of 33 months in one of the patients. No evidence of neither clinical nor histopathological reappearance was found fewer side effects, good reception and acceptance from the patients. Conclusion: PDT is a good alternative for the management of the AC with excellent results and minimal side effects. The outstanding clinical results are confirmed by histopathology, suggesting its use prior ruling out concurrent invasive carcinoma. Nevertheless, still reminds to define the treatments intervals and its duration.

Terapia fotodinâmica em carcinoma basocelular periocular: relato de caso / Photodynamic therapy in periocular basal cell carcinoma: case report

Os autores descrevem a aplicação de terapia fotodinâmica com cloridrato de aminolevulinato de metila (Metivix®) em uma paciente com carcinoma basocelular padrão misto (nodular e infiltrativo) em pálpebra inferior de olho direito. Os efeitos colaterais sobre o olho foram avaliados semanalmente. Foi submetida à biòpsia incisional com punch de 2 mm para controle de cura após 12 semanas de tratamento. O anátomopatológico revelou ausência de neoplasia. O tratamento padrão ouro reconhecido mundialmente é a exérese da lesão, porém a terapia fotodinâmica com cloridrato de aminolevulinato de metila (MAL) surge como uma opção terapêutica à cirurgia.

The authors report the use of photodynamic therapy with methyl aminolevulinate (Metvix®) in a patient with nodular and infiltrative basal cell carcinoma in the right lower eyelid. Side effects on the eye were evaluated weekly. After 12 weeks of treatment, to confirm cure the patient was submitted to a 2-mm punch biopsy, the anatomopathological findings of which were negative for neoplasia. Photodynamic therapy with methyl aminolevulinate was shown to be an attractive alternative to surgical excision¯the current gold standard treatment worldwide.

Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

Photodynamic therapy (PDT) mediated by oxidative stress causes direct tumor cell damage as well as microvascular injury. To improve this treatment new photosensitizers are being synthesized and tested. We evaluated the effects of PDT with 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin (TMPP) and its zinc complex (ZnTMPP) on tumor levels of malondialdehyde (MDA), reduced glutathione (GSH) and cytokines, and on the activity of caspase-3 and metalloproteases (MMP-2 and -9) and attempted to correlate them with the histological alterations of tumors in 3-month-old male Wistar rats, 180 ± 20 g, bearing Walker 256 carcinosarcoma. Rats were randomly divided into five groups: group 1, ZnTMPP+irradiation (IR) 10 mg/kg body weight; group 2, TMPP+IR 10 mg/kg body weight; group 3, 5-aminolevulinic acid (5-ALA+IR) 250 mg/kg body weight; group 4, control, no treatment; group 5, only IR. The tumors were irradiated for 15 min with red light (100 J/cm², 10 kHz, 685 nm) 24 h after drug administration. Tumor tissue levels of MDA (1.1 ± 0.7 in ZnTMPP vs 0.1 ± 0.04 nmol/mg protein in control) and TNF-α (43.5 ± 31.2 in ZnTMPP vs 17.3 ± 1.2 pg/mg protein in control) were significantly higher in treated tumors than in controls. Higher caspase-3 activity (1.9 ± 0.9 in TMPP vs 1.1 ± 0.6 OD/mg protein in control) as well as the activation of MMP-2 (P < 0.05) were also observed in tumors. These parameters were correlated (Spearman correlation, P < 0.05) with the histological alterations. These results suggest that PDT activates the innate immune system and that the effects of PDT with TMPP and ZnTMPP are mediated by reactive oxygen species, which induce cell membrane damage and apoptosis.

Terapêutica fotodinâmica com ácido delta-aminolevulínico e luz de diodos em ceratoses actínicas / Photodynamic therapy with delta-aminolevulinic acid and light-emitting diodes in actinic keratosis

FUNDAMENTOS: A terapêutica fotodinâmica é técnica de tratamento em que se aplica uma substância fotossensibilizante nos tecidos ativada por uma fonte de luz de comprimento de onda específico, gerando destruição celular seletiva. Estudam-se novas fontes de luz que possam ser usadas no tratamento de ceratoses actínicas. OBJETIVOS: Avaliar a efetividade da terapêutica fotodinâmica com ácido delta-aminolevulínico utilizando como fonte de luz um aparelho emissor de luz de diodos no tratamento de ceratoses actínicas de face e membros superiores. MÉTODOS: Dezoito pacientes com ceratoses actínicas na face ou membros superiores realizaram uma aplicação de creme de ácido delta-aminolevulínico a 20 por cento e foram submetidos à exposição de luz de diodos, comprimento de onda de 630 nm. RESULTADOS: Foram tratadas 328 ceratoses actínicas, obtendo-se cura clínica completa em 210 (64,0 por cento) após 24 semanas. Lesões do dorso das mãos apresentaram cura clínica completa em 49,2 por cento; nas demais áreas esse valor foi de 81,4 por cento. Não houve registro de efeitos adversos graves, e obteve-se bom grau de satisfação dos pacientes com os resultados. CONCLUSÃO: A terapêutica fotodinâmica com fonte de emissão de luz de diodos mostrou-se eficaz e bem tolerada para tratamento de ceratoses actínicas, com resultados semelhantes aos encontrados na literatura utilizando outras fontes luminosas.

BACKGROUND: Photodynamic therapy is a form of treatment in which a photosensitizing substance is applied to tissue and activated by a light source at a specific wavelength, thus selectively destroying cells. New light sources are being evaluated for use in the treatment of actinic keratoses. OBJECTIVES: To evaluate the efficacy of photodynamic therapy with delta-aminolevulinic acid using a light emitting diode device as a light source in the treatment of actinic keratoses of the face and upper limbs. METHODS: Eighteen patients with actinic keratoses of the face or upper limbs received an application of a 20 percent delta-aminolevulinic acid cream and were submitted to diode light irradiation at a wavelength of 630 nm. RESULTS: A total of 328 actinic keratoses were treated, obtaining complete cure in 210 (64.0 percent) after 24 weeks. Lesions situated on the back of the hands were clinically cured in 49.2 percent of cases compared to 81.4 percent in the cases of lesions in other areas. There was no record of any severe adverse effects and patient satisfaction with the results was high. CONCLUSION: Photodynamic therapy with a diode light emitting source proved effective and well-tolerated for the treatment of actinic keratoses, with results similar to those reported in the literature with other light sources.

Terapia fotodinâmica: revisão da literatura e documentação iconográfica / Photodynamic therapy: a review of the literature and image documentation

A terapia fotodinâmica é uma reação química ativada por luz usada para destruição seletiva de um tecido e requer um agente fotossensibilizante no tecido-alvo, uma fonte de luz e oxigênio. Estão disponíveis, no momento, o ácido 5-aminolevulínico para tratamento de ceratoses actínicas e o metilaminolevulinato, aprovado para tratamento de ceratoses actínicas, carcinoma basocelular e doença de Bowen. As fontes de luz utilizadas para a terapia fotodinâmica devem emitir comprimentos de onda no espectro de absorção do fotossensibilizante escolhido. As lâmpadas LED (light emitting diode) são as indicadas para terapia fotodinâmica tópica no tratamento do câncer de pele não melanoma. A terapia fotodinâmica deve ser considerada, em particular, para pacientes que apresentam lesões superficiais, múltiplas, disseminadas e para pacientes imunossuprimidos. Mais recentemente, a terapia fotodinâmica tem sido indicada no tratamento do fotoenvelhecimento, acne, hidrosadenite, esclerodermia, psoríase, verrugas, leishmaniose, entre outras. Por este trabalho será possível ter acesso a uma extensa revisão da literatura sobre terapia fotodinâmica, seus mecanismos, indicações e resultados, seguida de comentários e críticas pertinentes ao assunto.

Photodynamic therapy (PDT) consists of a chemical reaction activated by light energy that is used to selectively destroy tissue. The reaction requires a photosensitizer in the target tissue, a light source and oxygen. The most extensively studied photosensitizing agents for PDT are 5-aminolevulinic acid for the treatment of actinic keratosis and methyl-aminolevulinate, which has been approved for the treatment of actinic keratosis, basal cell carcinoma and Bowen's disease. The light sources used in photodynamic therapy should emit light at wavelengths within the absorption spectrum of the photosensitizer used in PDT treatment. Light emitting diode (LED) lamps are indicated for the photodynamic treatment of nonmelanoma skin cancer. PDT should be considered as a therapeutic option, particularly in the case of patients with superficial, multiple or disseminated lesions and for immunosuppressed patients. More recently, PDT has been indicated for a wide range of dermatological conditions such as photo-damaged skin, acne, hidradenitis, scleroderma, psoriasis, warts and leishmaniosis, among others. This article provides an extensive review of photodynamic therapy, its mechanisms, indications and results.

Terapia fotodinâmica para tratamento de múltiplas lesões no couro cabeludo na síndrome do nevobasocelular: relato de caso / Photodynamic therapy for treatment of multiple lesions on the scalp in nevoid basal cell carcinoma syndrome: case report

A terapia fotodinâmica é uma alternativa eficaz de tratamento para neoplasias cutâneas não melanoma e tem como princípio a utilização de substâncias fotossensibilizantes que, após serem irradiadas com uma fonte de luz de comprimento de onda adequado, destroem seletivamente as células neoplásicas. A Síndrome do Nevobasocelular é uma genodermatose que cursa com o desenvolvimento de inúmeros carcinomas basocelulares em uma idade precoce, submetendo os pacientes a vários procedimentos cirúrgicos, muitas vezes desfigurantes. Este artigo tem como objetivo demonstrar o excelente resultado do tratamento de carcinomas basocelulares no couro cabeludo de uma paciente com a Síndrome do Nevobasocelular.

Photodynamic therapy is an effective alternative for the treatment of non-melanoma skin cancer, selectively destroying the neoplastic cells through the use of photosensitizer substances that are irradiated with a source of light of adequate wave length. Nevoid Basal Cell Carcinoma Syndrome is a genodermatosis characterized by multiples basal cell carcinomas occurring at an early age, compelling patients to various surgeries, some of them disfiguring. The aim of this article is to show the excellent result of the treatment of multiple basal cell carcinomas on the scalp of a patient suffering from Nevoid Basal Cell Carcinoma Syndrome.

Terapia fotodinámica en pacientes con acné inflamatorio facial leve a moderadamente severo: estudio abierto en 30 pacientes chilenos / Photodynamic therapy in patients with inflammatory mild to moderate-severe acne

Introducción: La terapia fotodinámica es un procedimiento útil en el manejo del acné inflamatorio. Diversos esquemas terapéuticos se han usado. Objetivo: Demostrar eficacia y tolerancia de una sesión de TFD-MAL en el manejo del acné inflamatorio. Métodos: Una sesión de TFD-MAL y luz roja por cuatro minutos e incubación de tres horas fue realizada en 30 pacientes portadores de acné inflamatorio, leve, o moderadamente severo. Resultados: Resolución clínica de las lesiones o las seis semanas fue considerada buena (mejoría > 50%) en un 70% según evaluación médica y en un 66,6% según evaluación por el paciente. Se consignaron efectos adversos de eritema, descamación y rezumación leves dentro de las primeras 48 horas de la terapia en una gran proporción de pacientes. No se presentaron efectos adversos residuales o la semana 6. La encuesta de satisfacción relacionada a tolerancia y rapidez de acción demostró aceptación de la terapia en un 56% de los casos. Conclusión: La TFD-MAL con una sesión, incubación de tres horas y cuatro minutos de iluminación con luz roja constituye una buena alternativa terapéutica para el manejo del acné inflamatorio recalcitrante o en pacientes con contraindicaciones a terapias habituales.

Introduction: Photodynamic therapy is useful in the treatment of inflammatory acne. Several modalities have been used. Objective: To prove efficacy and tolerance of one session of PDT-MAL in the management of inflammatory acne. Methods: One session of PDT-MAL, for 4 minutes of red light, with an incubation period of 3 hours was performed in 30 patients with inflammatory mild to moderate-severe acne. Results: Clinical resolution at 6 weeks was considered good (resolution > 50%) in 70% of the patients under dermatologist evaluation and in 66.6% under patient evaluation. Adverse effects such as erythema, desquamation, oozoning were light and present in the first 48 hrs in o great proportion of cases. No adverse effects were seen at week 6. Satisfaction interview related to tolerance and speed of action showed good therapy acceptance in 56% of the patients. Conclusion: One session of PD T-MAL after 3 hours of incubation period and 4 minutes of red light is o good therapeutic option for the management of resistant inflammatory acne or to be used in patients with contraindication of common therapies for acne.

Terapia fotodinâmica: relato de caso / Photodynamic therapy: case report

A terapia fotodinâmica (PDT) utiliza um agente fotossensibilizante, luz e oxigênio molecular para matar seletivamente certos tipos de células. Na Dermatologia, utiliza-se o PDT com sucesso no tratamento de câncer de pele não melanoma e lesões prémalignas. A introdução do ácido aminolevulínico (ALA) diminuiu a morbidade do PDT e isso despertou novos interesses para seu uso, como o tratamento de dermatoses inflamatórias e um adjuvante nos tratamentos de fotorrejuvenescimento. Este artigo avalia uma paciente fotoenvelhecida tratada com o PDT.

Influence of ceramide 2 on in vitro skin permeation and retention of 5-ALA and its ester derivatives, for photodynamic therapy / Influência da ceramida 2 sobre a permeação cutânea in vitro e retenção de 5-ALA e seus derivados de ésteres, para terapia fotodinâmica

Photodynamic therapy (PDT) based on topical 5-aminolevulinic acid (5-ALA), an endogenous precursor of protoporphyrin, is an interesting approach for the treatment of skin cancer. However, 5-ALA is a hydrophilic molecule and such a characteristic limits its appropriate cutaneous penetration and retention. In this way, more lipophilic molecules, such as esterified 5-ALA derivatives, have been under investigation in order to improve the skin penetration of this molecule. Drug formulation can also alter 5-ALA skin penetration. Therefore, the aim of this work was to study the influence of ceramide 2 - the main lipid of the SC- on the cutaneous delivery of 5-ALA and its ester derivatives in vitro, using Franz diffusion cell. The skin permeation of all studied drugs was decreased in the presence of ceramide, representing a desirable characteristic in order to avoid the risk of systemic side effects. Nevertheless, the SC and [epidermis + dermis] retention after 16 h has also been decreased in the presence of ceramide, as compared to control. In conclusion, ceramide was not a good adjuvant, meaning that research of other vehicles could be useful to improve cutaneous delivery of 5-ALA.

A Terapia Fotodinâmica (TFD) tópica com um precursor das porfirinas endógenas, o ácido 5-aminolevulínico (5-ALA), constitui uma nova modalidade para o tratamento do câncer de pele. Entretanto, o 5-ALA é uma molécula hidrofílica, o que limita sua penetração e retenção cutânea apropriadas. Moléculas mais lipofílicas, tais como derivados esterificados do 5-ALA, estão sob intensa investigação para melhorar a penetração cutânea desta molécula. A formulação que contém o fármaco também pode alterar a penetração cutânea do 5-ALA. Desta forma, o objetivo deste trabalho foi estudar a influência da ceramida 2 - o principal lipídeo do EC- sobre a penetração cutânea de 5-ALA e seus derivados esterificados usando células de difusão de Franz. A permeação de todas as drogas estudadas através da pele foi diminuída na presença de ceramida, o que é desejável, evitando riscos de efeitos colaterais sistêmicos. Entretanto, a retenção no EC e [epiderme + derme] também foi diminuída na presença da ceramida, após 16 horas, comparado ao controle. Concluindo, a ceramida não foi um bom adjuvante, sendo necessária a pesquisa de outros veículos para melhorar a liberação cutânea do 5-ALA.

Terapia fotodinámica con metil aminolevulinato tópico en dos casos de carcinoma basocelular del pabellón auricular / Methyl-aminolevulinate photodynamic therapy for basal cell carcinoma of the ear

La cirugía dermatológica sigue siendo la mejor indicación para el carcinoma basocelular; sin embargo, cuando afecta a áreas de compleja reparación quirúrgica, existen tipos histológicos que se benefician con nuevas terapias, como la terapia fotodinámica con metil aminolevulinato. Esto es de gran importancia para lesiones en el oído externo, principalmente en el pabellón auricular, ya que muchas veces su tratamiento requiere de colgajos o injertos de piel completa con gran dificultad técnica y resultados estéticamente insatisfactorios. La TFD usando metil aminolevulinato (MAL) tópico ha mostrado ser tan efectiva como la crioterapia o la resección quirúrgica en el CBC primario, pero con la ventaja agregada de una cosmética superior. En el presente artículo se muestran dos casos de CBC de pabellón auricular tratados con MAL tópico, cuyos resultados, tanto cosméticos como oncológicos, han sido plenamente satisfactorios a 19 meses de seguimiento.

Dermatologic surgery is still the best choice for basal cell carcinoma treatment. But, when the lesion is present in difficult to treat areas, there are histological types that benefit from therapies such as topical photodynamic therapy (PDT) using methyl aminolevulinate (MAL). This is of great importance for injuries in the external ear, mostly in the helix, as it often requires treatments or flaps of full-thickness skin grafts with great technical difficulty and aesthetically unsatisfactory results. PDT with MAL has proven to be as effective as cryotherapy or surgical resection in primary BCC, but with the added advantage of superior cosmetic results. We present two cases of BCC of the ear treated with topical MAL, whose results, both cosmetic as oncologic, have been fully satisfactory for over 19 months of follow-up.

Tratamiento de verruga plantar recalcitrante con terapia fotodinámica / Treatment of recalcitrant verruca plantaris with photodynamic therapy

Se presenta el caso de un paciente de sexo masculino, de 55 años de edad, portador de una verruga plantar recalcitrante de casi dos años de evolución. El paciente fue tratado con terapia fotodinámica utilizando metil aminolevulinato y una fuente de luz roja de 630 mm, con una dosis de 37 J/cm2. Luego de tres sesiones de terapia fotodinámica, el paciente presentó una remisión completa de la verruga plantar, lo que ha persistido luego de ocho meses de seguimiento y con excelente resultado cosmético.

We present the case of a 55-year-old male patient with recalcitrant verruca plantaris for almost two years. The patient was treated with photodynamic therapy using aminolevulinic acid and a red light source (630 nm), with a 37 J/cm2 dose. After three photodynamic therapy sessions, the patient showed a complete remission and is still free of the lesion after 8 months of follow-up, evidencing an excellent cosmetic outcome.