Cutaneous Adverse Events of Anti-PD-1 Therapy and BRAF Inhibitors.

OPINION STATEMENT: The treatment of advanced melanoma has undergone a dramatic transformation over the last decade with the advent of targeted and immunomodulatory therapies. This transition from cytotoxic chemotherapy has yielded improvements in both survival and quality of life; yet despite their therapeutic advantages, these treatments have been associated with a diverse range of cutaneous adverse events (AEs). These range from relatively benign eczematous conditions to more severe inflammatory and bullous disorders, and can include induction of second malignancies. AEs can result in serious morbidity and risk of mortality if not recognised and managed early. As a consequence of their novelty, and rapid uptake, these agents have been subject to intense scrutiny and there is a general understanding that cutaneous AEs should be anticipated in treatment plans. Dermatologists should be integrated into management teams to assist in the development of treatment protocols for anticipated common AEs and to provide expert management of more severe, rare or unusual AEs. Our experience has shown a reduction in treatment interruptions, more rapid recognition of unusual AEs and improved management pathways for patients suffering cutaneous AEs.

A randomised controlled trial of consumption of dark chocolate in pregnancy to reduce pre-eclampsia: Difficulties in recruitment, allocation and adherence.

In 2013-2014 we undertook a randomised controlled trial (RCT) to determine whether the daily ingestion of dark chocolate during pregnancy could reduce the incidence of pre-eclampsia in primigravidae. However, after two years we had not succeeded in recruiting more than 3.5% of the number of participants required to answer the research question, and the trial was halted. We also reviewed the literature on this topic and found it to be limited. We report here our findings and discuss the difficulties facing researchers in this area.

Acquired lipodystrophy associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors have become the mainstay of treatment for metastatic melanoma. This article presents a new case of acquired generalised lipodystrophy (AGL) during anti-programmed cell death-1 (anti-PD-1) therapy and a systematic review of the literature with an aim to further understand the pathogenesis. A comprehensive search was conducted using PubMed, Embase, MEDLINE and Cochrane Central databases. We identified four cases of lipodystrophy associated with anti-PD-1 immunotherapy, including our own. Of these, three were associated with nivolumab, and one with pembrolizumab. Body composition changes occurred at a median of 7 months after anti-PD-1 initiation. All cases reported AGL, with subcutaneous fat loss affecting majority of the body. There were three reported cases of insulin resistance associated with AGL. AGL should be a recognised adverse event associated with anti-PD-1 therapy.