The incidence of cutaneous squamous cell carcinoma in patients receiving voriconazole therapy for chronic pulmonary aspe
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The incidence of cutaneous squamous cell carcinoma in patients receiving voriconazole therapy for chronic pulmonary aspergillosis Chris Kosmidis 1,2
&
Anna Mackenzie 2 & Chris Harris 2 & Rola Hashad 1,3 & Fiona Lynch 2 & David W. Denning 1,2
Received: 28 February 2020 / Accepted: 20 July 2020 # The Author(s) 2020
Abstract Voriconazole has been associated with cutaneous squamous cell carcinoma (cSCC) in transplant patients but less is known about the risk in less severely immunosuppressed patients. Our aim was to estimate the incidence of cSCC after voriconazole exposure in patients with chronic pulmonary aspergillosis on a background of chronic lung disease. The notes of patients seen at a tertiary referral centre from 2009 to 2019 with chronic pulmonary aspergillosis were reviewed for the diagnosis of cSCC and voriconazole use documented. Among 1111 patients, 668 (60.1%) received voriconazole for longer than 28 days. Twelve patients received a diagnosis of cSCC; nine had used voriconazole. Mean duration of voriconazole use was 36.7 months. The crude incidence rate was 4.88 in 1000 person/years in those who had voriconazole and 2.79 in 1000 patient/years in those who did not receive voriconazole for longer than 28 days. On Cox regression, age (HR 1.09, 95% CI 1.02–1.16, p = 0.01) and male gender (HR 3.97, 95% CI 0.84–18.90, p = 0.082) were associated with cSCC. Voriconazole use was associated with a slightly increased risk, which was not significant (HR 1.35, 95% CI 0.35–5.20, p = 0.659). Voriconazole use beyond 28 days did not lead to a significantly increased risk of cSCC in a large cohort of patients with chronic pulmonary aspergillosis. Keywords Voriconazole . Squamous cell carcinoma . Skin cancer . Chronic pulmonary aspergillosis
Introduction The spectrum of disease caused by Aspergillus encompasses allergic, chronic, saprophytic and invasive disease, depending on the degree of host immunosuppression. Chronic pulmonary aspergillosis (CPA) affects immunocompetent or mildly immunosuppressed patients with chronic lung disease, such as COPD, bronchiectasis, prior pulmonary TB or sarcoidosis (Smith and Denning 2011). Voriconazole is one of the firstline agents in CPA and is often used long-term. Guidelines * Chris Kosmidis [email protected] 1
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
2
National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, 2nd Floor Education and Research Centre, Southmoor Road, Manchester M23 9LT, UK
3
Department of Medical Microbiology and immunology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
suggest at least six months of treatment; however, in practice it may be used for longer durations, often for years, as response may be delayed and relapses are common (Denning et al. 2016). Long-term voriconazole treatment is associ
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