RESUMO
Checkpoint inhibitor (CPI) therapy has significantly improved overall survival for metastatic melanoma, and is now approved for use in the adjuvant setting. Modulating the immune system is recognized to cause cutaneous immune-related adverse events (irAEs). We conducted a retrospective observational cohort study of adult patients with melanoma at our tertiary referral centre, who received CPI therapy from 2006 to March 2018. This is the single largest study of cutaneous irAEs occurring on CPI therapy in patients with melanoma to date and encompasses 12 years. The results showed that cutaneous toxicity occurs in 24% of patients but is generally manageable, with < 5% patients discontinuing treatment.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Inibidores de Checkpoint Imunológico/toxicidade , Melanoma/tratamento farmacológico , Dermatopatias/induzido quimicamente , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Estudos Retrospectivos , Dermatopatias/patologia , Suspensão de Tratamento/tendências , Adulto JovemRESUMO
Invasive dermatophyte infection, with extension beyond the dermis, in immunocompetent hosts is exceptionally rare. Dermatophytes are keratinophilic and are usually confined to the stratum corneum, hair and nails. Susceptibility to dermatophyte infections is incompletely understood, but inherited mutations in key signalling pathways of the innate immune system have been identified. We report the first case of an invasive dermatophyte infection associated with abrupt onset of a prurigo-induced pseudoperforation and a loss-of-function mutation in signal transducer and activator of transcription 3 (STAT3).
Assuntos
Dermatomicoses/diagnóstico , Infecções Fúngicas Invasivas/diagnóstico , Prurigo/diagnóstico , Fator de Transcrição STAT3/genética , Trichophyton/isolamento & purificação , Antifúngicos/uso terapêutico , Biópsia , Análise Mutacional de DNA , Dermatomicoses/tratamento farmacológico , Dermatomicoses/imunologia , Dermatomicoses/microbiologia , Glucocorticoides/uso terapêutico , Virilha/diagnóstico por imagem , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/imunologia , Infecções Fúngicas Invasivas/microbiologia , Mutação com Perda de Função , Masculino , Pessoa de Meia-Idade , Prurigo/tratamento farmacológico , Prurigo/genética , Prurigo/imunologia , Fator de Transcrição STAT3/imunologia , Fator de Transcrição STAT3/metabolismo , Pele/microbiologia , Pele/patologia , Células Th17/imunologia , Células Th17/metabolismo , Tomografia Computadorizada por Raios XAssuntos
Vacina BNT162/efeitos adversos , Toxidermias/diagnóstico , Toxidermias/etiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Ipilimumab/efeitos adversos , Nivolumabe/efeitos adversos , Antibacterianos/efeitos adversos , COVID-19/prevenção & controle , Feminino , Humanos , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Combinação Trimetoprima e Sulfametoxazol/efeitos adversosAssuntos
Vesícula/etiologia , Ficus/efeitos adversos , Dermatoses do Pé/etiologia , Hipopigmentação/etiologia , Transtornos de Fotossensibilidade/diagnóstico , Transtornos de Fotossensibilidade/patologia , Creme para a Pele/efeitos adversos , Idoso , Biópsia , Técnica Direta de Fluorescência para Anticorpo , Dermatoses do Pé/patologia , Humanos , Masculino , Luz Solar/efeitos adversosRESUMO
We report three cases of skin toxicity associated with oral mitogen-activated protein kinase kinase (MEK) inhibitor treatment for metastatic malignant melanoma (MM). All three patients developed oedema, and a single patient experienced eyelash trichomegaly. This is the first known report of eyelash trichomegaly secondary to MEK inhibitor use. We also discuss possible mechanisms for MEK inhibitor-associated oedema development. This series supports the role of the dermatologist in the screening and management of patients in the rapidly developing oncology setting, as new targeted agents can give rise to marked skin toxicity.
Assuntos
Acrilonitrila/análogos & derivados , Compostos de Anilina/efeitos adversos , Edema/induzido quimicamente , Melanoma/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Dermatopatias/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Acrilonitrila/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Neoplasias Cutâneas/secundárioRESUMO
BACKGROUND: Vemurafenib significantly improved overall survival compared with dacarbazine in patients with metastatic or unresectable BRAF V600E-positive melanoma in the BRIM-3 trial. However, vemurafenib was associated with a number of skin-related adverse events (AEs). OBJECTIVES: To investigate the incidence and management of vemurafenib-associated skin AEs. METHODS: This retrospective, observational study included adult patients with stage IIIC or IV melanoma who received vemurafenib between March 2010 and August 2013. Patients received oral vemurafenib 960 mg twice daily, with dose interruptions and reductions allowed for AE management. RESULTS: In total 107 patients were treated with vemurafenib during the study period. The most frequent clinically important skin-related AEs were rash (64%), squamoproliferative growths (41%), photosensitivity (40%) and squamous cell carcinoma (SCC) or keratoacanthoma (KA; 20%). Rare cases of granulomatous dermatitis and cutaneous T-cell lymphoma were also found. Rash was manageable with corticosteroids and dose modifications; squamoproliferative growths and SCCs/KAs were treated with cryotherapy and surgical excision, respectively. Patients were counselled regarding phototoxicity. The uncontrolled nature and retrospective design of the study, and the small patient numbers are limitations. CONCLUSIONS: Vemurafenib appears to have a predictable and manageable AE profile. Proactive management can limit the impact of AEs on patients, allowing treatment to continue despite toxicities.
Assuntos
Toxidermias/etiologia , Indóis/efeitos adversos , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/efeitos adversos , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/induzido quimicamente , Toxidermias/patologia , Toxidermias/terapia , Exantema/genética , Feminino , Humanos , Indóis/administração & dosagem , Ceratoacantoma/induzido quimicamente , Linfoma Cutâneo de Células T/induzido quimicamente , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Mutação/genética , Transtornos de Fotossensibilidade/induzido quimicamente , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Neoplasias Cutâneas/genética , Sulfonamidas/administração & dosagem , Vemurafenib , Adulto JovemAssuntos
Melanoma/sangue , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/sangue , Deficiência de Vitamina D/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Estudos Retrospectivos , Índice de Gravidade de Doença , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Adulto JovemAssuntos
Dapsona/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatoses Faciais/tratamento farmacológico , Granuloma/tratamento farmacológico , Administração Cutânea , Adulto , Anti-Infecciosos/uso terapêutico , Dermatoses Faciais/patologia , Géis , Glucocorticoides/uso terapêutico , Granuloma/patologia , Humanos , Isotretinoína/uso terapêutico , Limeciclina/uso terapêutico , Masculino , Prednisolona/uso terapêutico , Falha de TratamentoRESUMO
Morphoea is a localized inflammatory disorder of the dermis and subcutaneous fat and radiotherapy is a rarely reported cause (estimated incidence of 2 per 1000). Morphoea is commonly mistaken for an inflammatory recurrence of breast cancer, resulting in unnecessary investigations and treatment. We report the case of a 40-year-old woman who developed radiation-induced morphoea of the breast 7 months following adjuvant radiotherapy. She was treated with topical and systemic steroids as well as psoralen plus ultraviolet (UV)A before proceeding to UVA1 phototherapy. We also review the literature and discuss other management options.
Assuntos
Lesões por Radiação/radioterapia , Radioterapia Adjuvante/efeitos adversos , Esclerodermia Localizada/radioterapia , Terapia Ultravioleta/métodos , Adulto , Neoplasias da Mama/radioterapia , Feminino , Humanos , Esclerodermia Localizada/etiologia , Resultado do TratamentoRESUMO
The incidence of melanoma has increased rapidly over the past 30 years, and the disease is now the sixth most common cancer among men and women in the U.K. Many patients are diagnosed with or develop metastatic disease, and survival is substantially reduced in these patients. Mutations in the BRAF gene have been identified as key drivers of melanoma cells and are found in around 50% of cutaneous melanomas. Vemurafenib (Zelboraf(®) ; Roche Molecular Systems Inc., Pleasanton, CA, U.S.A.) is the first licensed inhibitor of mutated BRAF, and offers a new first-line option for patients with unresectable or metastatic melanoma who harbour BRAF mutations. Vemurafenib was developed in conjunction with a companion diagnostic, the cobas(®) 4800 BRAF V600 Mutation Test. The purpose of this paper is to make evidence-based recommendations to facilitate the implementation of BRAF mutation testing and targeted therapy in patients with metastatic melanoma in the U.K. The recommendations are the result of a meeting of an expert panel and have been reviewed by melanoma specialists and representatives of the National Cancer Research Network Clinical Study Group on behalf of the wider melanoma community. This article is intended to be a starting point for practical advice and recommendations, which will no doubt be updated as we gain further experience in personalizing therapy for patients with melanoma.
Assuntos
Antineoplásicos/uso terapêutico , Indóis/uso terapêutico , Melanoma/tratamento farmacológico , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/uso terapêutico , Algoritmos , Odontologia Baseada em Evidências , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Melanoma/genética , Terapia de Alvo Molecular/métodos , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/genética , VemurafenibAssuntos
Neoplasias da Mama/complicações , Síndromes Paraneoplásicas/patologia , Pênfigo/patologia , Plaquinas/imunologia , Adenocarcinoma , Autoanticorpos/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Desmogleína 1/imunologia , Desmogleína 3/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/metabolismo , Plaquinas/metabolismo , Resultado do TratamentoAssuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/uso terapêutico , Toxidermias/tratamento farmacológico , Erupções Liquenoides/tratamento farmacológico , Tretinoína/uso terapêutico , Idoso , Alitretinoína , Toxidermias/etiologia , Humanos , Erupções Liquenoides/induzido quimicamente , Masculino , Doenças da Unha/induzido quimicamente , Doenças da Unha/tratamento farmacológico , Nivolumabe , Receptor de Morte Celular Programada 1/antagonistas & inibidoresRESUMO
Until recently, no effective treatment was available for patients with metastatic malignant melanoma, and median overall survival was little more than 6 months with the current standard of care, dacarbazine. In 2012, the first specific BRAF mutation inhibitor, vemurafenib, was licensed for the monotherapy of adults with BRAF V600 mutation-positive unresectable or metastatic melanoma. Like other targeted therapies, vemurafenib is associated with a predictable pattern of adverse events, including skin toxicities. We review the most common cutaneous adverse events associated with vemurafenib, based on data from clinical trials, and our own experiences of treating patients in trials and clinical practice. Overall, these toxicities are not preventable, but they rarely necessitate permanent treatment discontinuation and are generally manageable with dose modification and supportive care. We provide a treatment algorithm offering guidance on the most appropriate approach to managing the main skin toxicities to help clinicians unfamiliar with this novel agent to become confident in using vemurafenib effectively in the management of patients with metastatic melanoma.
Assuntos
Toxidermias/etiologia , Indóis/efeitos adversos , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/efeitos adversos , Ensaios Clínicos como Assunto , Toxidermias/diagnóstico , Toxidermias/prevenção & controle , Humanos , VemurafenibAssuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/induzido quimicamente , Fluoruracila/administração & dosagem , Indóis/efeitos adversos , Neoplasias Cutâneas/induzido quimicamente , Sulfonamidas/efeitos adversos , Administração Cutânea , Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Feminino , Virilha , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , VemurafenibRESUMO
We present a patient with an unusual enterocutaneous syndrome. Long-term, low-dose acitretin treatment has stabilized the development of gastrointestinal lesions while synchronously reducing cutaneous morbidity.
Assuntos
Acitretina/administração & dosagem , Pólipos Adenomatosos/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Polipose Intestinal/tratamento farmacológico , Ceratolíticos/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Pólipos Adenomatosos/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Feminino , Genes Neoplásicos/genética , Humanos , Polipose Intestinal/diagnóstico , Fígado/enzimologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/diagnóstico , Síndrome , Resultado do TratamentoRESUMO
CONTEXT: It is well recognized that the presence of a foreskin predisposes to penile carcinoma and sexually transmitted infections. We have investigated the relationship between the presence or absence of the foreskin and penile dermatoses. OBJECTIVE: To determine whether there is an association between circumcision and penile dermatoses. DESIGN: A retrospective case control study of patients attending the department of dermatology with genital skin conditions. SUBJECTS: The study population consisted of 357 male patients referred for diagnosis and management of genital skin disease. The control population consisted of 305 male patients without genital skin disease attending the general dermatology clinics over a 4-month period. MAIN OUTCOME MEASURES: The relationship between circumcision and the presence or absence of skin disease involving the penis was investigated. The rate of circumcision in the general male dermatology population was determined. RESULTS: The most common diagnoses were psoriasis (n = 94), penile infections (n = 58), lichen sclerosus (n = 52), lichen planus (n = 39), seborrheic dermatitis (n = 29), and Zoon balanitis (n = 27). Less common diagnoses included squamous cell carcinoma (n = 4), bowenoid papulosis (n = 3), and Bowen disease (n = 3). The age-adjusted odds ratio for all penile skin diseases associated with presence of the foreskin was 3.24 (95% confidence interval, 2.26-4.64). All patients with Zoon balanitis, bowenoid papulosis, and nonspecific balanoposthitis were uncircumcised. Lichen sclerosus was diagnosed in only 1 circumcised patient. Most patients with psoriasis, lichen planus, and seborrheic eczema (72%, 69%, and 72%, respectively) were uncircumcised at presentation. The majority of men with penile infections (84%) were uncircumcised. CONCLUSIONS: Most cases of inflammatory dermatoses were diagnosed in uncircumcised men, suggesting that circumcision protects against inflammatory dermatoses. The presence of the foreskin may promote inflammation by a köebnerization phenomenon, or the presence of infectious agents, as yet unidentified, may induce inflammation. The data suggest that circumcision prevents or protects against common infective penile dermatoses.