RESUMO: A terapêutica dirigida e a imunoterapia melhoraram significativamente o prognóstico dos doentes com melanoma avançado. Por outro lado, a expansão destes fármacos levou ao aumento do espetro de efeitos adversos cutâneos. Embora a maioria das reações seja de baixo grau, muitas causam morbilidade considerável, com forte impacto na qualidade de vida dos doentes. O diagnóstico precoce e a intervenção atempada poderão evitar a descontinuação dos tratamentos oncológicos. Neste artigo, revemos os efeitos adversos cutâneos das pequenas moléculas e anticorpos monoclonais usados no tratamento do melanoma, assim como a sua fisiopatologia e abordagem terapêutica.

ABSTRACT: Targeted therapy and immunotherapy have markedly improved prognosis of advanced melanoma patients. With expanded use of these drugs, a range of cutaneous adverse events has emerged. Although the vast majority of adverse events are low-grade, they many cause significant morbidity and can affect patients' quality of life. Early diagnosis and prompt intervention may prevent unnecessary discontinuation of life-saving anticancer therapies. In this article, we review the cutaneous adverse events of small molecules and monoclonal antibodies used for the therapy of melanoma and discuss their pathophysiology and recommendations for prevention and management of these adverse events.

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.

Introdução: As transaminases não são enzimas específicas do hepatócito e são várias as condições que se associam ao seu aumento. A Distrofia Muscular de Duchenne (DMD) é uma doença de transmissão autossómica recessiva ligada ao cromossoma X que se caracteriza por fraqueza muscular progressiva. Descrição do caso: Apresentamos o caso de um menino de 6 anos referenciado à consulta de pediatria para investigação de elevação persistente do valor das transaminases. Sem história familiar de doença hepática ou neuromuscular. Dos antecedentes pessoais a salientar, marcha autónoma aos 15 meses, tendência para marcha em pontas, dificuldade em subir escadas e correr e cansaço fácil em relação aos pares. À observação destacava-se hipertrofia gemelar e abdominal, ligeira hiperlordose lombar, diminuição da força muscular proximal dos membros inferiores e manobra de Gowers positiva. Perante a história clínica, exame objetivo e exames complementares já realizados, foi colocada a hipótese de distrofia muscular e doseada também a enzima creatina quinase (CK) cujo valor estava muito aumentado. A biópsia muscular evidenciou a ausência de distrofina e a sequenciação do gene desta proteina identificou a mutação c.3103C>T (p.Gln1035X) confirmando o diagnóstico de DMD. Comentário: Nem sempre o aumento das transaminases é sinónimo de doença hepática. Perante a elevação mantida destas enzimas, a exclusão de hepatopatia é obrigatória. No entanto, este achado laboratorial também pode surgir na doença muscular. Destacamos o doseamento da CK como avaliação mandatória, evitando a investigação exaustiva centrada na patologia hepática. Os autores pretendem alertar para o diagnóstico diferencial de doença neuromuscular através de um caso em que a anamnese, a clínica e o perfil analítico são sugestivos.

Introduction: Transaminases are non-specific markers of hepatocyte function. There are several conditions associated with elevated transa-minases such as Duchenne muscular dystrophy (DMD), an X-linked recessive disorder characterized by progressive muscle weakness. Case Report: We report the case of a 6 year-old boy referred to the pediatric department for evaluation of raised transaminases. He had no family history of liver or neuromuscular disease. From his past history we noted independent gait at 15 months, toe-walking, difficulty climbing stairs and running, and fatigue in comparison to his peers. On clinical examination there was calf and abdominal hypertrophy, slight lumbar lordosis, proximal lower limb weakness and a positive Gowers’ sign. Given the clinical history, physical examination and la-boratory findings, the diagnosis of muscular dystrophy was suspected. Serum creatine kinase was found to be elevated. A muscle biopsy was performed and revealed absence of dystrophin. DMD gene sequencing identified the mutation c.3103C > T (p.Gln1035X) which confirmed the diagnosis of DMD. Comment: The finding of raised transaminases is not always diagnostic of liver disease. With prolonged elevation of those enzymes, liver disease must be excluded but this laboratory finding may also appear in muscle disease. CK levels should also be measured to avoid exhaustive testing for liver disease. The authors advise clinicians to consider neuromuscular diseases in the differential diagnosis of cases presenting a with suggestive clinical and laboratory findings.

Apesar de infrequente, a alopecia pode ser causada por tumores cutâneos benignos. Os neurofibromas são neoplasias benignas comuns com origem na baínha externa dos nervos. O neurofibroma difuso é uma variante rara de neurofibroma que ocorre tipicamente na cabeça e pescoço de crianças e adultos jovens. Histologicamente caracteriza-se por um tumor infiltrativo, composto por células fusiformes, localizado na derme e tecido celular subcutâneo. Apesar de rara, a transformação maligna já foi descrita. A associação dos neurofibromas difusos e neurofibromatose tipo 1 ainda não está determinada dado que alguns autores contestam a baixa incidência habitualmente referida. Descrevemos o caso de um homem de 42 anos com um neurofibroma difuso do couro cabeludo com aprasentacao de placas de alopecia.

Although infrequent, alopecia can be caused by benign cutaneous tumours. Neurofibromas are common benign tumors that originate in the peripheral nerve sheath. Diffuse neurofibroma is a rare variant of neurofibroma that is thought to occur mainly in the head and neck of children and young adults. Histology generally shows an infiltrative tumor, composed of spindle cells in the dermis and subcutaneous tissue. Despite being rare, malignant transformation has been reported. The association between diffuse neurofibromas and neurofibromatosis type 1 still remains to be determined since some authors question the low incidence usually described. We report the case of a 42-year-old man who had a diffuse neurofibroma on the scalp presenting as alopecic plaques.