Acantholytic pityriasis rubra pilaris associated with topical use of imiquimod 5%: case report and literature review

Abstract Topical use of immune response modifiers, such as imiquimod, has increased in dermatology. Although its topical use is well tolerated, it may be associated with exacerbations of generalized cutaneous inflammatory diseases, possibly through the systemic circulation of pro-inflammatory cytokines. This report describes a case of development of pityriasis rubra pilaris, a rare erythematous-papulosquamous dermatosis, in a woman aged 60 years during treatment with imiquimod 5% cream for actinic keratosis. It evolved with erythrodermic conditions and palmoplantar keratoderma, presenting progressive clinical resolution after the introduction of methotrexate. The authors emphasize the importance of recognizing possible systemic reactions associated with the topical use of imiquimod.

Treatment of actinic keratoses and cancerization field of the face and scalp with 0 015% ingenol mebutate gel in Brazilian individuals: safety, tolerability and patients' perspectives

Abstract: Background: Actinic keratosis (AK) represents a risk of progression to squamous cell carcinoma. Ingenol mebutate gel is a novel therapeutic option for field-directed treatment. Objectives: To evaluate the safety, tolerability and patients' perspectives, related to the therapeutic success of managing AKs on the face and scalp with ingenol mebutate gel in Brazilian individuals. Methods: This was an observational, retrospective and descriptive study of 68 areas of actinic keratosis on the face and scalp treated with Ingenol mebutate gel involving a total of 37 patients. The drug was applied for three consecutive days on an area of of 25 cm2 and documentation was performed on baseline and days 4, 8, 15, 60 and 180. On day 4, the composite local skin reaction score was calculated. At the end, a questionnaire was applied to evaluate patients' perspectives about the treatment. Results: Adherence was 100%, no serious adverse events were recorded and the mean composite local skin reaction score (standard deviation) was 8.61±4.22. The treatment was considered optimum by 75.68% of the patients. Study limitations: Calculation of composite local skin reaction score performed only on the fourth day. Conclusions: Treatment with ingenol mebutate gel was considered safe and tolerable in Brazilian subjects. Patients had a maximum adherence rate and a great improvement in self-esteem. The results of this research reproduce the findings of the literature.

Queilitis actínica: Reporte de tres casos y revisión de literatura / Actinic Cheilitis: Report of Three Cases and Review of Literature

RESUMEN La queilitis actínica (QA) es un desorden potencialmente maligno del labio inducido por la exposición crónica a la luz ultravioleta, que afecta principalmente al bermellón del labio inferior de personas adultas y de piel clara. Si no es tratada en forma oportuna puede transformarse en un carcinoma de células escamosas del labio. Histológicamente la QA presenta una serie de alteraciones a nivel epitelial que van desde hiperplasia a displasia; en el tejido conectivo se presentan distintos grados de elastosis actínica acompañada por infiltrado inflamatorio. El objetivo de este trabajo es presentar tres casos de pacientes con QA y analizar sus características clínicas e histopatológicas.

ABSTRACT Actinic cheilitis (AC) is a potentially malignant lip disorder induced by chronic exposure to ultraviolet light, which mainly affects the vermilion of the lower lip of adults and fair skin. If it is not treated in a timely manner it can become a squamous cell carcinoma of the lip. Histologically, AC presents a series of alterations at the epithelial level ranging from hyperplasia to dysplasia; Connective tissue presents different degrees of actinic elastosis accompanied by inflammatory infiltrate. The objective of this work is to present three cases of patients with AC and analyze their clinical and histopathological characteristics.

Ingenol mebutate in the treatment of actinic keratoses: clearance rate and adverse effects

Abstract: Background: Actinic keratoses are benign intraepithelial skin neoplasms that develop in photoexposed areas and can progress to invasive carcinoma. They are seen frequently in dermatological practice, occurring in 5.1% of consultations. Ingenol mebutate (IM) was recently approved in Brazil as a topical therapy for field cancerization in actinic keratosis. Objective: To evaluate the clearance rate and adverse events in the treatment of actinic keratoses with ingenol mebutate. Methods: A longitudinal, prospective, non-randomized, interventional, open, single-center study was conducted. Patients with actinic keratoses applied ingenol mebutate on a 25cm2 area of the face and/or scalp for three consecutive days (0.015%) or on the forearm for two days (0.05%). Results: 27 patients completed the protocol, of whom 13 on the face and/or scalp and 14 on the forearm. Complete clearance occurred in 53.8% in the first group and 42.8% in the second. Partial response was observed in 15.4% and 35.7%, respectively. The most common side effects were erythema, edema, desquamation, pruritus, and local erosion. Study limitations: The study had a small sample and was not randomized, double-blind, placebo-controlled, or vehicle-controlled. Conclusion: Ingenol mebutate is well-tolerated for the treatment of actinic keratosis, with good patient adherence thanks to the short treatment period.

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.

Oral acetylsalicylic acid and prevalence of actinic keratosis / Ácido acetilsalicílico oral e prevalência de queratoses actínicas

Objective: To investigate the influence of a regular oral use of acetylsalicylic acid in the prevalence of actinic keratosis. Methods: A case-control study with dermatologic outpatients above 50 years of age assessed between 2009 and 2011. Cases were defined as those who had been under regular use of oral acetylsalicylic acid for more than six consecutive months. The assessment focused on: age, sex, skin-type, tobacco smoking, use of medication, occurrence of individual or family skin cancer, and sunscreen and sun exposure habits. Actinic keratoses were counted in the medial region of the face and upper limbs. Counts were adjusted by co-variables based on a generalized linear model. Results: A total of 74 cases and 216 controls were assessed. The median time of acetylsalicylic acid use was 36 months. Cases differed from controls as to the highest age, highest prevalence of use of angiotensin-converting enzyme inhibitors and fewer keratosis on the face and on the upper limbs (p<0.05). The multivariate model showed that the use of acetylsalicylic acid was associated to lower counts of face actinic keratosis and upper-limb erythematous actinic keratosis (p<0.05), regardless of other risk factors. Conclusion: The regular use of oral acetylsalicylic acid for more than six months was associated to a lower prevalence of actinic keratosis, especially facial and erythematous ones. .

Objetivo: Queratoses actínicas são proliferações atípicas de queratinócitos com potencial para se transformarem em carcinoma invasivo. Estudos clínicos e laboratoriais têm observado um efeito preventivo de anti-inflamatórios não hormonais no desenvolvimento de diversas neoplasias. Neste estudo, investigamos a influência do uso regular do ácido acetilsalicílico na prevalência de queratoses actínicas. Métodos: Estudo caso-controle com pacientes dermatológicos acima de 50 anos de idade, avaliados entre 2009 e 2011. Os casos foram definidos como aqueles que estavam sob uso regular de ácido acetilsalicílico por via oral por mais de seis meses consecutivos. Avaliou-se idade, sexo, fototipo, tabagismo, uso de medicamentos, ocorrência de câncer de pele no indivíduo ou na família, hábitos de proteção e exposição solar. As queratoses actínicas foram contadas nos membros superiores e região medial da face. As contagens foram ajustadas pelas covariáveis em um modelo linear generalizado. Resultados: Um total de 74 casos e 216 controles foi avaliado. O tempo médio de uso de ácido acetilsalicílico foi de 36 meses. Casos diferiam dos controles quanto a idade mais elevada, maior prevalência de uso de inibidores da enzima conversora da angiotensina e menos queratoses na face e membros superiores (p <0,05). O modelo multivariado mostrou que o uso do ácido acetilsalicílico esteve associado a contagens mais baixas de queratoses actínicas na face de queratoses não hipertróficas nos membros superiores (p <0,05). Conclusão: O uso regular do ácido acetilsalicílico por via oral por mais de seis meses esteve associado a uma menor prevalência de queratose actínica, especialmente faciais e eritematosas. .

Comparative study of actinic keratosis treatment with 3% diclofenac sodium and 5% 5-fluorouracil / Estudo comparativo do tratamento de ceratoses actinicas com diclofenaco sodico 3% e 5-fluorouracil 5%

BACKGROUND: Actinic keratosis is a frequent lesion which occurs in sunlight exposed areas. Diclofenac sodium and 5-Fluorouracil are effective, non-invasive and easy-to-apply topical treatment options. OBJECTIVES: To assess and compare the effectiveness of 3% diclofenac sodium associated with 2.5% hyaluronic acid and of 5% 5-Fluorouracil for the treatment of actinic keratosis, as well as the patient's degree of satisfaction and tolerability. METHODS: 28 patients with a clinical diagnosis of actinic keratosis were randomized to receive diclofenac sodium or 5-Fluorouracil and were clinically assessed before and after treatment as well as 8 weeks after the end of treatment. Modified versions of the Investigator and Patient Global Improvement Scores were used. RESULTS: The average number of lesions in the diclofenac sodium group before and after treatment was 13.6 and 6.6 (p<0,001), respectively, while it was 17.4 and 3.15 (p<0.001) in the 5-Fluorouracil group. There was a significant reduction in the number of lesions in the 5-Fluorouracil group in relation to the diclofenac sodium group (p<0.001). To the non-blinded physician, there was a higher satisfactory therapeutic response in the 5-Fluorouracil group (p<0.001); to the blinded physician, there was a higher satisfactory response in this same group, although not statistically significant (p=0.09). There was a high degree of satisfaction in both groups (73% in the diclofenac sodium group and 77% in the 5-Fluorouracil group; p=0.827). Regarding adverse effects, the diclofenac sodium group presented a higher degree of satisfaction (93.3% vs 38.4%; p=0.008). Erythema, edema, crusts and itching were significantly higher in the 5-Fluorouracil group. CONCLUSION: We concluded that 5-Fluorouracil was more effective; however, it showed lower tolerability than diclofenac sodium. .

FUNDAMENTOS: Ceratose actínica é uma lesão frequente que ocorre em áreas de exposição solar. Diclofenaco sódico e 5-Fluorouracil são opções de tratamento tópico efetivo, não invasivo e de fácil aplicação. OBJETIVOS: Avaliar e comparar a efetividade do diclofenaco sódico 3% associado ao ácido hialurônico 2,5% e do 5-fluorouracil 5% no tratamento de ceratose actínica, assim como a tolerabilidade e o grau de satisfação do paciente. MÉTODOS: 28 pacientes com diagnóstico clínico de ceratoses actínicas foram randomizados para receber diclofenaco sódico ou 5-fluorouracil e foram avaliados clinicamente antes, ao término e após 8 semanas do tratamento. Utilizou-se o Escore de Melhora Global do Investigador e do Paciente, ambos modificados. RESULTADOS: A média de lesões no grupo do diclofenaco sódico antes e depois do tratamento foi de 13,6 e 6,6 (p<0,001) e no grupo do 5-fluorouracil foi de 17,4 e 3,15 (p<0,001). Houve uma diminuição significativa no número de lesões no grupo do 5-fluorouracil em relação ao grupo do diclofenaco sódico (p<0,001). Para o médico não cegado houve uma resposta terapêutica satisfatoriamente maior no grupo do 5-fluorouracil (p<0,001); para o cegado, houve uma maior resposta nesse mesmo grupo, porém não significativa (p=0,09). Houve alta satisfação com o tratamento em ambos os grupos (73% no diclofenaco sódico e 77% no 5-fluorouracil; p=0,827). Já em relação aos efeitos adversos, o grupo do diclofenaco sódico apresentou taxa de satisfação maior (93,3% vs 38,4%; p=0,008). Eritema, edema, crostas e prurido foram significativamente maiores no tratamento com 5-fluorouracil. CONCLUSÕES: Concluímos que o 5-fluorouracil foi mais efetivo, ...

Retinoids for prevention and treatment of actinic keratosis / Retinoides para a prevencao e tratamento das queratoses actinicas

Actinic keratosis is a common cause of dermatological consultations and it presents a strong association with squamous cell carcinoma. Many substances are used for treatment and prevention, such as retinoids. Nevertheless, many studies on retinoids emphasize their application in treating and preventing non melanoma skin cancers. In this article, we reviewed studies about systemic and topical retinoids used with immunocompetent patients and organ transplant recipients with actinic keratosis, as primary or secondary outcomes. The majority of these papers pointed to a reduction in actinic keratosis count after treatment with retinoids. However, studies need to be better-defined in order to address the lack of a standardized dose, the absence of control groups, the low number of patients and short follow-up periods. Blind, randomized and controlled clinical trials with adequate sample sizes, specifically focused on actinic keratosis, are needed to clarify the real benefit of topical and/or oral retinoids. Comparison of efficacy and safety between oral and topical retinoids in the prevention and treatment of non-melanoma skin cancers and actinic keratosis is an essential pre requisite to establish new strategies to control these conditions. .

A queratose actínica é uma causa comum de consultas dermatológicas e apresenta forte associação com o carcinoma espinocelular. Muitas substâncias são utilizadas para seu tratamento e prevenção, assim como os retinoides. Entretanto, muitos estudos sobre retinoides salientam seu uso no tratamento e prevenção de cânceres de pele não melanoma. Neste artigo, nós revisamos estudos que avaliam o uso dos retinoides sistêmicos e tópicos para pacientes imunocompetentes e imunossuprimidos com queratoses actínicas, como desfechos primários e secundários. A maioria destes estudos mostra redução na contagem das queratoses actínicas após o tratamento com retinóides. Além disso, ajustes no delineamento dos estudos deveriam ser feitos quanto à falta de padronização da dose, ausência de grupos controle, número pequeno de pacientes e tempo curto de seguimento. Ensaios clínicos cegos, randomizados e controlados com tamanho amostral adequado tendo como alvo específico as queratoses actínicas são necessários para esclarecer o real benefício dos retinoides tópicos e/ou orais. A comparação da eficácia e segurança entre os retinoides orais e tópicos na prevenção e tratamento dos cânceres de pele não melanoma e queratoses actínicas é um pré-requisito essencial para o estabelecimento de novas estratégias para o controle destas condições.

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.