RESUMO
Immune checkpoint inhibitors (ICIs) have revolutionized treatment strategies in the field of oncology. Their favourable outcomes in terms of efficacy and side-effect profile can be thwarted by the development of immune-related adverse events (irAEs). Cutaneous irAEs are relatively common in patients undergoing immunotherapy and include common inflammatory dermatoses (e.g. eczematous, psoriasiform and lichenoid phenotypes), maculopapular eruptions, pruritus and immunobullous disorders. Most of these reactions can be managed without ICIs having to be stopped completely; however, there are some life-threatening toxicities that dermatologists and oncologists should be aware of. In this review, we focus on how to recognize the commonly associated cutaneous irAEs, touching upon rarer reactions and red flags; finally, we provide guidance on their management.
Assuntos
Exantema , Neoplasias , Dermatopatias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Dermatopatias/induzido quimicamente , Pele , Exantema/etiologia , Imunoterapia/efeitos adversosRESUMO
BACKGROUND: Checkpoint inhibitor (CPI) therapy has significantly improved overall survival in several cancers including metastatic melanoma (MM) and in the adjuvant setting. Cutaneous immune-related adverse events (irAEs) secondary to CPIs are commonly observed; however, autoimmune blistering disorders such as bullous pemphigoid (BP) are rare. OBJECTIVES: To review the prevalence, incidence risk, clinicopathological features and management of toxicity in bullous cutaneous irAEs associated with CPI therapy. METHODS: A multicentre, retrospective, observational study of CPI-associated bullous irAEs in adults with all cancers across four UK specialist centres between 2006 and 2019. RESULTS: In total, 7391 patients were identified. CPI-associated bullous irAEs including BP (n = 16) occurred in 0·3% (n = 22). The median age of onset was 76 years, and there was a male predominance. Most patients had cutaneous melanoma (73%, n = 16), of which 81% (13 of 16) were BRAF wildtype. Grade 1, 2, 3 and 4 skin toxicity occurred in 9%, 45%, 41% and 5%, respectively. The mucosae were involved in 27%, and 25% of confirmed cases of BP did not present with bullae. The median time to onset of bullous irAEs was 12 months, with a median total symptom duration of 6 months. Single PD-1/PD-L1 agents had a longer time to onset of symptoms than combination therapy (median 12 vs. 7 months, respectively). Overall, 91%, 64% and 9% of patients required one, two or three lines of treatment, respectively. Two cases occurred after completion of CPIs (1 and 3 months). Of the 20 cases that presented while on CPIs this was permanently discontinued in 55% (11 of 20) and temporarily held in 20% (four of 20). In the four held cases of CPI, bullous eruption reflared in 50%. CONCLUSIONS: CPI-associated bullous skin toxicity is a rare cutaneous irAE occurring in approximately 0·3% of cases over 13 years of treated patients in this series. Not all cases are diagnostic of BP, but management remains the same. There is a prolonged latency of onset compared with other cutaneous irAEs, with a median time of 12 months, and they can occur after cessation of therapy. Discontinuation of CPIs may be required. Recognizing bullous irAEs promptly and referral to dermatology are essential to optimize management and improve patient outcomes and tumour responses. What is already known about this topic? Checkpoint inhibitor (CPI)-associated bullous pemphigoid is a rare dermatological immune-related adverse event (irAE) that has been reported in small case series and reports. What does this study add? This is the largest multicentre, observational study conducted in the UK over the longest period of 13 years, which demonstrates an overall incidence of bullous cutaneous irAEs secondary to CPIs of 0·3%. Clinical presentation is variable, with one-quarter of patients with bullous pemphigoid presenting without bullae, and mucosal involvement was noted in 27%. Prolonged pruritus is frequently a prodromal symptom. The median time to diagnosis is 12 months and irAEs rarely present after cessation of treatment. Time to onset of symptoms is longer with a single CPI, but with a shorter duration of symptoms compared with combination CPI therapy. Most patients had cutaneous melanoma, of which 81% were BRAF wildtype.
Assuntos
Inibidores de Checkpoint Imunológico , Melanoma , Penfigoide Bolhoso , Neoplasias Cutâneas , Idoso , Feminino , Humanos , Masculino , Vesícula/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Melanoma/tratamento farmacológico , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/diagnóstico , Receptor de Morte Celular Programada 1 , Proteínas Proto-Oncogênicas B-raf , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Melanoma Maligno CutâneoRESUMO
This Athena case describes possible differential diagnoses in a patient with multiple blisters. Histopathology showed subepidermal clefting and superficial dermal inflammation, while immunohistochemistry showed linear deposition of IgG and C3 along the basement membrane zone.
Assuntos
Vesícula , Imunoglobulina G , Diagnóstico Diferencial , Humanos , Imuno-HistoquímicaRESUMO
PURPOSE: Treatment with Palbociclib, a cyclin-dependent kinase 4/6 inhibitor, has demonstrated significantly improved progression-free survival in patients with hormone receptor-positive, HER2-negative, advanced breast cancer, when used in combination with letrozole or fulvestrant endocrine therapies. However, limited information exists on its cutaneous adverse effects (AE). Hence, we conducted a retrospective cohort study to investigate the prevalence and management of cutaneous AE during palbociclib and endocrine therapy. METHOD: We included 324 adult patients with advanced breast cancer who received palbociclib between March 2016 and August 2020 within a tertiary comprehensive cancer centre. Patient demographics, details of previous and concurrent treatments, as well as treatment-related cutaneous AE were recorded from electronic records. RESULTS: The incidence of treatment-related cutaneous AE was 14.2% (46 from a total of 324 patients). The most frequent cutaneous reactions included maculopapular rash (41%), asteatosis (37%), pruritus and urticaria (20%), and bullous dermatitis reactions (9%). We identified two patients with treatment-induced subacute cutaneous lupus erythematosus, one case of bullous pemphigoid, and a single erythema multiforme. Patients received an average of 9 cycles of treatment, completing an average of 6 cycles before developing cutaneous AE, which persisted for a median of 43 days. Only 15% (n = 7) of affected patients required temporary suspension, and 4% (n = 2) required discontinuation. The majority were managed with potent topical steroids, with oral corticosteroids being required in 3 patients, and one patient required hydroxychloroquine. CONCLUSION: Our study describes both the spectrum of cutaneous AE of palbociclib and endocrine therapy, and approaches to management. Prompt management may limit the negative impact on patients, facilitating beneficial continuation of palbociclib and endocrine therapy.
Assuntos
Neoplasias da Mama , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina , Intervalo Livre de Doença , Feminino , Humanos , Piperazinas , Piridinas , Receptor ErbB-2 , Estudos RetrospectivosRESUMO
Lichenoid reactions are one of the many cutaneous immune-related adverse events seen with the use of immune checkpoint inhibitors, particularly anti-PD1 inhibitors. We present a rare care of severe lichen planopilaris secondary to pembrolizumab, with progression even after cessation of immunotherapy. It is important to recognise the significant long-term impact of these cutaneous adverse effects on patient's quality of life.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Imunoterapia/efeitos adversos , Líquen Plano/induzido quimicamente , Humanos , Líquen Plano/prevenção & controle , Melanoma/dietoterapiaAssuntos
Toxidermias , Inibidores de Checkpoint Imunológico , Combinação Trimetoprima e Sulfametoxazol , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Feminino , Toxidermias/etiologia , Toxidermias/epidemiologia , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Pessoa de Meia-Idade , Idoso , Incidência , Exantema/induzido quimicamente , Estudos Retrospectivos , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêuticoRESUMO
Cutaneous toxicities associated with BRAF inhibitor treatment in patients with metastatic melanoma have been well described. We present a rare association of granulomatous dermatitis in association with the BRAF inhibitor vemurafenib. Three patients with metastatic melanoma all presented with asymptomatic papular eruptions 8-21 months into vemurafenib therapy. Skin biopsies confirmed the diagnosis of granulomatous dermatitis. Other causes of granulomatous dermatitis including infectious agents and sarcoid were excluded. Treatment with potent topical and oral steroids improved the eruptions, but only after the cessation of vemurafenib did all 3 cases of granulomatous dermatitis completely resolve within 2 weeks. It is important to recognize that this association, unlike most other BRAF inhibitor-related skin toxicities, can occur many months after commencement of therapy and that vemurafenib treatment can be continued without clinically significant adverse effects.
Assuntos
Antineoplásicos/efeitos adversos , Toxidermias/etiologia , Granuloma/induzido quimicamente , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Pele/efeitos dos fármacos , Vemurafenib/toxicidade , Biópsia , Toxidermias/diagnóstico , Feminino , Granuloma/diagnóstico , Humanos , Melanoma/enzimologia , Melanoma/secundário , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/metabolismo , Pele/patologia , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Poromas are a group of benign growths of poroid differentiation derived from cells of the terminal sweat duct and connected to the epidermis, normally presenting as solitary papules, plaques or nodules. Rarely they can be eruptive in nature and as such are described as poromatosis. We report an unusual case of widespread poromatosis occurring in a woman with metastatic breast cancer who had recently completed chemo-radiotherapy.
Assuntos
Dermatologia/educação , Mentores , COVID-19/epidemiologia , Humanos , Pandemias , Reino Unido/epidemiologiaAssuntos
Schistosoma haematobium/isolamento & purificação , Esquistossomose/diagnóstico , Dermatopatias Parasitárias/diagnóstico , Pele/parasitologia , Adulto , Animais , Antiplatelmínticos/uso terapêutico , Biópsia , Feminino , Humanos , Schistosoma haematobium/efeitos dos fármacos , Esquistossomose/tratamento farmacológico , Esquistossomose/parasitologia , Esquistossomose/patologia , Pele/efeitos dos fármacos , Pele/patologia , Dermatopatias Parasitárias/tratamento farmacológico , Dermatopatias Parasitárias/parasitologia , Dermatopatias Parasitárias/patologia , Resultado do TratamentoAssuntos
Melanoma/secundário , Neoplasias Cutâneas/patologia , Adulto , Herpes Zoster/patologia , Humanos , Indóis/uso terapêutico , Masculino , Melanoma/diagnóstico por imagem , Melanoma/tratamento farmacológico , Neoplasias Meníngeas/secundário , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Prurido/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/uso terapêutico , Tomografia Computadorizada por Raios X , VemurafenibAssuntos
Antineoplásicos/efeitos adversos , Eritema/induzido quimicamente , Dermatoses da Mão/induzido quimicamente , Anticoagulantes/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Edema/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Tromboembolia Venosa/tratamento farmacológicoAssuntos
Antineoplásicos/efeitos adversos , Indóis/efeitos adversos , Melanoma/tratamento farmacológico , Paniculite/induzido quimicamente , Paniculite/diagnóstico , Mutação Puntual , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/efeitos adversos , Adulto , Antineoplásicos/administração & dosagem , Diagnóstico Diferencial , Eritema Nodoso/diagnóstico , Feminino , Ácido Glutâmico , Humanos , Indóis/administração & dosagem , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Sulfonamidas/administração & dosagem , Valina , VemurafenibRESUMO
Granulomatous slack skin disease (GSSD) is a rare condition characterized clinically by redundant skin folds, which show a predilection towards flexural areas, and histologically by a granulomatous T-cell infiltrate and loss of elastic fibres. The disease is often indolent, although rapid progression and transformation have been described. There is much debate as to whether this condition is a subset of mycosis fungoides or a separate disease entity in itself. We describe a case of GSSD with unique manifestations including granulomatous bone marrow involvement and hypercalcaemia. The patient has twice achieved a good response to pentostatin after failure of combination chemotherapy. This is the first report of the successful use of the purine analogue pentostatin in the management of GSSD.