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.

Photodynamic therapy - a non-invasive treatment modality for precancerous lesions

Introduction: Oral premalignant lesions are conditions having high potential tendency for transformation into malignancy. The use of a conservative and effective treatment modality is one of the best strategies for cancer prevention. Photodynamic therapy [PDT] is a non-invasive method for topical and selective treatment of oral precancerous lesions. The present study was taken up to determine the efficacy of PDT in oral precancerous lesions

Methods: The study consisted 13 patients with 24 oral leukoplakia [OL] lesions and 8 with 20 oral lichen planus [OLP] lesions, divided into control and study groups. These lesions were affecting various intraoral sites, the buccal mucosa being the most common site followed by tongue and gingiva. The treatment regimen of PDT included 98% 5-aminolevulinic acid [5-ALA] which is topical applied and irradiated with light emitting diode [LED] of 420 nm wavelengths at several sessions

Results: In OL 16.6% of cases showed complete response, 66.6% partial response and 16.6% no response of the lesions to the treatment. In OLP 80% and 20% of the lesions showed partial and no response respectively. The differences with control groups for OL + OLP were found to be significant [P<0.001]

Conclusion: Based on the results of the present study, we can conclude that PDT appears to be a feasible alternative to conventional therapy for oral premalignant lesions

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.

Cell accumulation and antileishmanial effect of exogenous and endogenous protoporphyrin IX after photodynamic treatment / Acumulación celular y efecto anti- Leishmania de la protoporfirina IX exógena y endógena después del tratamiento fotodinámico

Introduction: Photodynamic therapy (PDT) using 5-aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX) constitutes an interesting alternative for cutaneous leishmaniasis treatment. Objective: To evaluate the production of PpIXbased on the administration of ALA and MAL and the effect of ALA-PDTat cellular level on non-infected and infected THP-1 cells using Leishmania ( Viannia ) panamensis or Leishmania ( Leishmania ) infantum (syn Leishmania chagasi ) parasites. Materials and methods: Protoporphyrin IX (PpIX) production and mitochondrial colocalization were evaluated by confocal microscopy. Cell toxicities were evaluated after treatment with the compounds, followed by light irradiation (597-752 nm) at 2.5 J/cm 2 fluency using a colorimetric MTT assay for THP-1 cells and a standard microscopic analysis of parasites. Results were expressed as compound concentration activity against 50% of cells or parasites (CC 50 or IC 50 ). Results: ALA or MAL induced an endogenous PpIX with a red fluorescence localized mainly in the mitochondria inside human cells. ALA and MAL-PDT induced a similar range of toxicities on THP-1 cells (CC 50 0.16±0.01mM and 0.33±0.019 mM, respectively) without any apparent inhibition of intracellular parasites in the infected cells as compared to untreated controls. Exogenous PpIX-PDT was toxic to THP-1 cells (CC 50 0.00032±0.00002 mM), L. (L.) infantum (IC 50 0.003±0.0001 mM) and L. (V.) panamensis (IC 50 0.024±0.0001 mM) promastigotes. Conclusions: Despite the effectiveness of exogenous PpIX on promastigotes and the production of PpIX by human infected cells, treatment with ALA or MAL before irradiation was unable to completely destroy L. (L.) infantum or L. (V.) panamensis intracellular amastigotes.

Introducción. El tratamiento fotodinámico con ácido 5-aminolevulínico como inductor de la protoporfirina IX (ALA-PpIX) constituye una alternativa interesante en el tratamiento de la leishmaniasis cutánea. Objetivo. Evaluar la producción de protoporfirina IX (PpIX) a partir de la administración de ALA o MAL y el efecto de la PDT con ALA a nivel celular en células THP-1 no infectadas e infectadas con Leishmania ( Viannia ) panamensis o Leishmania ( Leishmania ) infantum (syn. Leishmania chagasi ). Materiales y métodos. La producción de protoporfirina IX y su ‘colocalización´ mitocondrial se evaluaron mediante microscopía ‘confocal´. Se evaluó la toxicidad celular después del tratamiento con los compuestos y la aplicación de irradiación de luz (597-752 nm) en una fluencia de 2,5 J/cm 2 mediante el empleo de la prueba colorimétrica con metil-tiazol-tetrazolio (MTT) en las células, y de métodos microscópicos estándar en los parásitos. Los resultados se expresaron como la concentración del compuesto activo en el 50 % de las células o parásitos (CC 50 o CI 50 ). Resultados. El ácido aminolevulínico o el metil-5-aminolevulinato indujeron la protoporfirina IX endógena en células humanas, y se observó fluorescencia de color rojo en las mitocondrias. La actividad del ácido aminolevulínico y del metil-5-aminolevulinato utilizados con terapia fotodinámica fue similar en las células THP-1 (CC 50 0,16±0,01 mM y 0,33±0,019 mM, respectivamente) y, aparentemente, no inhibió los parásitos en las células infectadas, en comparación con los controles. El tratamiento exógeno con protoporfirina IX y terapia fotodinámica fue tóxico para las células THP-1 (CC 50 0,00032 ±0,00002 mM) y para los promastigotes de L. (L .) infantum (IC 50 0,003±0,0001 mM) y L. ( V .) panamensis (CI 50 0,024±0,0001 mM). Conclusiones. A pesar de la ‘fotoactividad´ del tratamiento con protoporfirina IX en promastigotes y de su producción después del tratamiento con ácido aminolevulínico y metil-5-aminolevulinato en las células infectadas con Leishmania , no se observó daño en los amastigotes presentes en las células de L. ( L .) infantum o L . ( V .) panamensis .

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.

Photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients / Tratamento de queilite actínica com terapia fotodinâmica: avaliação clínica e anatomopatológica de 19 pacientes

BACKGROUND: Actinic cheilitis, a common disease caused by chronic solar exposure and tobacco use, is considered a premalignant lesion with potential to develop into squamous cell carcinoma. Some of the available treatments are invasive, have unaesthetic results and require multiple sessions. OBJECTIVE: To assess the efficacy of a therapy and its cosmetic results. METHODS: In this uncontrolled clinical trial a single photodynamic therapy (PDT) session using 16% methyl-aminolevulinate was performed on actinic cheilitis of the lower lip. A standardized questionnaire was applied in order to assess the clinical improvement from the patients' point of view and the satisfaction with the treatment. Anatomopathological evaluation was performed before the treatment and two months afterwards. RESULTS: The sample was composed of 19 patients (10 males and 9 females), phototypes I to III, with average age of 62 years. Main adverse effects were: sudden pain, scabs, herpes flare-up, and edema. The average score of pain during the procedure was 5,8+2,9. At the final assessment the patients reported improvement of 80% and satisfaction of 85% (p<0.01). Anatomopathological analysis showed a significant decrease of dysplasia (p=0.03) in spite of its presence in 84% of cases. There was no significant correlation between the level of dysplasia with either the subjective impression of clinical improvement (p=0.82) or with the patients' final satisfaction (p=0.96). CONCLUSION: PDT is effective in the treatment of actinic cheilitis, but it is associated with a significant level of pain. Due to the persistence of dysplasia, more research needs to be done in order to define the ideal number of sessions for the effective treatment of these lesions.

FUNDAMENTOS: Queilite actínica, afecção causada por exposição solar crônica e tabagismo, é considerada lesão pré-maligna com possibilidade de transformação para carcinoma espinocelular. Alguns tratamentos descritos são invasivos, têm resultados inestéticos e requerem múltiplas aplicações. OBJETIVO: Verificar o uso de tratamento efetivo com resultado esteticamente aceitável. MÉTODOS: Ensaio clínico não controlado, utilizando terapia fotodinâmica com cloridrato de aminolevulinato de metila creme 16%, única aplicação, na queilite actínica de lábio inferior. Aplicação de questionário padronizado para avaliar melhora clínica da lesão subjetiva do paciente e satisfação com tratamento. Avaliação anatomopatológica antes da aplicação e dois meses após. RESULTADOS: Amostra compreendeu 19 pacientes (10 homens e 9 mulheres), fototipos I a IH, idade média 62 anos. Principais efeitos adversos: dor imediata, crostas, herpes labial e edema. Escore médio de dor referida durante o procedimento foi 5,8±2,9. Na avaliação final, os pacientes referiram melhora de 80% das lesões e apresentaram mediana de 85% de satisfação (p<0,01). Análise anatomopatológica mostrou diminuição significativa de displasia (p=0,03), apesar da persistência em 84% dos casos. Não houve correlação significativa da redução no grau de displasia com impressão subjetiva de melhora clínica (p=0,82) ou com satisfação final do paciente (p=0,96). CONCLUSÃO: TFD é efetiva no tratamento da queilite actínica, porém associada a grau significativo de dor. Devido à persistência de displasia, mais estudos são necessários para definir o número ideal de aplicações para tratamento efetivo destas lesões.

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 con metil aminolevulinato y ácido 5-aminolevulínico en acné inflamatorio leve y moderado: experiencia clínica / Photodynamic therapy with 5-aminolevulinic acid and methyl aminolevulinate for mild to moderate inflammatory acne: clinical experience

Introducción: La terapia fotodinámica (TFD) con ácido 5-aminolevulínico (ALA) y metil aminolevulinato (MAL) ha mostrado utilidad en el manejo del acné inflamatorio. Métodos: Dos grupos de cuatro pacientes cada uno, portadores de acné inflamatorio leve o moderado. Se realizaron dos sesiones de TFD separadas por dos semanas: un grupo fue tratado con MAL y luz roja y el otro, con ALA y luz azul. Se midió la severidad del acné con escala de 6 puntos y se consideró éxito clínico los grados 0 y 1. Resultados: En ambos grupos se observó éxito clínico a las 12 semanas post tratamiento, quedando con pigmentación residual, escasos comedones y menos de 10 pápulas. Se observaron efectos adversos tolerables, siendo los más importantes el eritema y la descamación. Conclusión: La TFD con ALA y MAL es una buena alternativa terapéutica para aquellos pacientes con acné inflamatorio leve y moderado que no responden o tienen contraindicación a los tratamientos convencionales.

Introduction: Photodynamic therapy with methyl aminolevulinate (MAL) and 5-aminolevulinic acid (ALA) has shown to be useful in the management of inflammatory acne. Methods: Two groups of 4 patients each with mild to moderate inflammatory acne. Two PDT sessions were performed within a 2 week interval; one group was treated with MAL and red light, and the other with ALA and blue light. Acne severity was measured with a 6-point scale and clinical success was considered between grades 0 and 1. Results: In both groups, clinical success was observed at 12 weeks post treatment, leaving residual pigmentation, scarce comedones and less than 10 papules. Tolerable side effects were observed, being the most important erythema and desquamation. Conclusion: PDT with ALA and MAL is a good therapeutic option for patients with mild to moderate inflammatory acne who do not respond or have contraindications to conventional treatments.

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.

Diagnóstico por fluorescencia o fotodinámico: fotografía con luz ultravioleta / Fluorescence and photodynamic diagnosis: photography with ultraviolet light

La capacidad de ciertas sustancias de emitir fluorescencia puede ser captada fácilmente mediante sistemas adaptados de fotografía digital. La aplicación tópica sobre la piel de derivados porfíricos como el ácido aminolevulánico ALA y el ácido metilaminolevulinato MAL provoca una fluorescencia roja característica en ciertas lesiones tumorales e inflamatorias que ayuda para el diagnóstico de las mismas; es lo que se ha denominado como diagnóstico fotodinámico o diagnóstico de fluorescencia. Otras sustancias como las tetraciclinas también han sido utilizadas en el diagnóstico, con buenos resultados. Las aplicaciones de este método son múltiples y el modo de realización sencillo.

Some substances exhibit characteristics of fluorescence, which can easily be captured with adapted digital photograph systems. Topical application of phorphirin derivates, such as aminolaevunilic acid (ALA) and methylaminolaevulinic acid (MAL), causes a typical red fluorescence in some tumoral and inflammatory lesions, and help diagnosis. This is called photodynamic diagnosis or fluorescence diagnosis. Other substances, such as tatraciclines, have also been used in photodynamic diagnosis with good results. The applications of this method are multiple, and simple to apply.