Topical calcineurin inhibitors, topical glucocorticoids and cancer in children: A nationwide study

Abstract

Systemic immunosuppression is significantly associated with the development of non-melanoma skin cancer (NMSC) and lymphoma in adults (1). The introduction of topical calcineurin inhibitors (TCI) tacrolimus and pimecrolimus for treatment of atopic dermatitis (AD) led the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to issue a “black box warning” that the compounds could, in theory, be considered “cancerogenic” (2). This has led to a dramatic reduction in the prescription of these compounds and increased anxiety among patients, parents and doctors. However, many and large studies have not been able to confirm an increased risk of cancer in children using TCI (3-5). One study showed that the development of skin tumours was increased by application of 3% tacrolimus on guinea pig skin, together with either DMBA (7,12-dimethylbenz(alpha)anthracene) and/or TPA (12-O-tetradecanoylphorbol-13-acetate) painting, which are strong inducers of benign papillomas and, in a minor group (8.5%), squamous cell carcinoma (6). A study in mice using ultraviolet light induction of skin cancer could not show that 3 times weekly application of TCI augmented the occurrence of skin carcinomas (7). A database study has suggested that, among 953,064 persons using TCI, cutaneous T-cell lymphoma (CTCL) was increased (8). TCI were introduced in Denmark in 2002. Children who had been exposed to TCI or topical glucocorticoids (TGC) between 2002 and 2009 were evaluated for the incidence of melanoma, NMSC, lymphoma and leukaemia during the period 2004 to 2011 through the Danish Cancer Registry (DCR).