RESUMEN
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.
Asunto(s)
Exantema , Neoplasias , Enfermedades de la Piel , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/tratamiento farmacológico , Enfermedades de la Piel/inducido químicamente , Piel , Exantema/etiología , Inmunoterapia/efectos adversosRESUMEN
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.
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Inhibidores de Puntos de Control Inmunológico , Melanoma , Penfigoide Ampolloso , Neoplasias Cutáneas , Anciano , Femenino , Humanos , Masculino , Vesícula/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Melanoma/tratamiento farmacológico , Penfigoide Ampolloso/inducido químicamente , Penfigoide Ampolloso/diagnóstico , Receptor de Muerte Celular Programada 1 , Proteínas Proto-Oncogénicas B-raf , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Melanoma Cutáneo MalignoRESUMEN
The current monkeypox epidemic is a major public health concern as the global outbreak continues to grow. We present a case report to highlight the salient points for dermatologists. Human monkeypox is a zoonosis caused by monkeypox virus, belonging to the Orthopoxvirus genus and is a close relative of the variola virus. Pleomorphic skin lesions appear ranging from macules, papules, vesicles, pustules, some of which may appear umbilicated before crusting over. Dermatologists play a key role in early recognition of new cases, aiding diagnoses leading to prevention of disease spread through identification and isolation, contact tracing and education.
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Epidemias , Mpox , Virus de la Viruela , Humanos , Mpox/diagnóstico , Mpox/epidemiología , Dermatólogos , Monkeypox virusRESUMEN
The use of artificial intelligence as a medical device (AIaMD) in healthcare systems is increasing rapidly. In dermatology, this has been accelerated in response to increasing skin cancer referral rates, workforce shortages and backlog generated by the COVID-19 pandemic. Evidence regarding patient perspectives of AIaMD is currently lacking in the literature. Patient acceptability is fundamental if this novel technology is to be effectively integrated into care pathways and patients must be confident that it is implemented safely, legally, and ethically. A prospective, single-center, single-arm, masked, non-inferiority, adaptive, group sequential design trial, recruited patients referred to a teledermatology cancer pathway. AIaMD assessment of dermoscopic images were compared with clinical or histological diagnosis, to assess performance (NCT04123678). Participants completed an online questionnaire to evaluate their views regarding use of AIaMD in the skin cancer pathway. Two hundred and sixty eight responses were received between February 2020 and August 2021. The majority of respondents were female (57.5%), ranged in age between 18 and 93 years old, Fitzpatrick type I-II skin (81.3%) and all 6 skin types were represented. Overall, there was a positive sentiment regarding potential use of AIaMD in skin cancer pathways. The majority of respondents felt confident in computers being used to help doctors diagnose and formulate management plans (median = 70; interquartile range (IQR) = 50-95) and as a support tool for general practitioners when assessing skin lesions (median = 85; IQR = 65-100). Respondents were comfortable having their photographs taken with a mobile phone device (median = 95; IQR = 70-100), which is similar to other studies assessing patient acceptability of teledermatology services. To the best of our knowledge, this is the first comprehensive study evaluating patient perspectives of AIaMD in skin cancer pathways in the UK. Patient involvement is essential for the development and implementation of new technologies. Continued end-user feedback will allow refinement of services to ensure patient acceptability. This study demonstrates patient acceptability of the use of AIaMD in both primary and secondary care settings.
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BACKGROUND: An evaluation of outcome reporting is required to develop a core outcome set. OBJECTIVES: To assess primary outcomes and outcome measure reporting in pre-eclampsia trials. SEARCH STRATEGY: Five online databases were searched from inception to January 2016 using terms including "preeclampsia" and "randomized controlled trial". SELECTION CRITERIA: Randomized controlled trials evaluating treatments for pre-eclampsia published in any language were included. DATA COLLECTION AND ANALYSIS: Primary outcomes and data on outcome measure reporting were systematically extracted and categorized. MAIN RESULTS: Overall, 79 randomized trials including data from 31 615 women were included. Of those, 38 (48%) reported 35 different primary outcomes; 28 were maternal outcomes and seven were fetal/neonatal outcomes. Three randomized trials reported composite outcomes, incorporating between six and nine outcome components. The method of definition or measurement was infrequently or poorly reported. Even when outcomes were consistent across trials, different methods of definition or measurement were frequently described. CONCLUSIONS: In randomized trials evaluating interventions for pre-eclampsia, critical information related to the primary outcome, including definition and measurement, is regularly omitted. Developing a core outcome set for pre-eclampsia trials would help to inform primary outcome selection and outcome measure reporting.