Atopic Dermatitis and Cancer Risk

AD cancer

As inflammatory skin diseases, psoriasis and atopic dermatitis (AD) share many similarities. For example, both are characterized by a state of persistent immune activation with histologic and immunologic overlap and have been associated with increased morbidity, other comorbid diseases, negative impact on quality of life, and a significant economic burden.1-6 In addition, both diseases share similarities with respect to their treatment landscape, with evolution from treatments based primarily on chance observations to the development of treatments based on defined therapeutic mechanisms or targeted approaches. While these newer treatment approaches have better efficacy and/or safety profiles compared with traditional treatment options, such as immunosuppressive therapies or UV therapies, these are not without risk and many harbor warnings with regard to a potential increase in the risk of malignancy or infection.7  

It is important to understand that patients with psoriasis and AD may be at a higher risk for malignancy due to (1) exposure to a state of chronic, persistent, immune activation, which in it of itself can increase the risk for malignancy; (2) exposure to multiple, systemic, immunosuppressive therapies and UV therapies throughout their lifetime thus potentially increasing the risk for malignancy; and (3) an increase in known cancer-related risk factors such as smoking, increased alcohol consumption, and higher rates of obesity.8-12 As new systemic treatment options become available for the treatment of AD, it is important for physicians to understand what the underlying risk for malignancy is as this can have an impact on treatment selection. This article explores the literature on the overall risk of malignancy in AD and the risk associated with use of common topical and immunosuppressive medications, as well as newer therapeutic options.

Overall Risk of Cancer

Prior studies have shown inconsistent results with respect to the background risk of AD. In a study by Arana and colleagues approximately a 50% increased risk of any cancer was observed in patients with AD compared to controls (standardized incidence ratio [SIR]=1.49; 95% CI, 1.39-1.61).13 However, a study in the Taiwanese population showed no overall increased risk among patients with AD (SIR=0.97; 95% CI, 0.87-1.09).14 With respect to cancer specific risk, Legendre and colleagues found an increased risk for any lymphoma among patients with AD compared with controls (SIR=1.43; 95% CI, 1.12-1.81).15 Hwang and colleagues found a nonstatistically significant increased risk for melanoma (SIR=2.35; 95% CI, 0.26-8.47); however, other studies have shown opposite results.14,16 It is important to note that comparisons between these studies are limited due to inconsistencies in study design, populations studied, and the inability to disentangle the effect of disease severity from treatment effect on cancer risk thus limiting our ability to draw any meaningful conclusions. 

Risk Associated With Topical Therapies

In the risk of cancer associated with topical or systemic treatments in patients with AD, there is still considerable debate. For example, topical calcineurin inhibitors (TCIs), such as pimecrolimus cream and tacrolimus ointment, are considered to be effective nonsteroidal treatment options for patients with AD and have been approved for use in both adults and children. However, in 2006, the FDA determined that a theoretical risk for lymphoma and skin cancer existed with use of these medications based on a limited number of studies and despite any strong evidence to support an increased cancer risk.17,18 Furthermore, additional studies have shown no increased risk of cancer with use of TCIs. A prospective, longitudinal cohort study with more than 10 years of follow-up found no increased risk of malignancy among users of pimecrolimus in a real-world setting (SIR=1.2; 95% CI, 0.5-2.8).19 In addition, a comprehensive systematic review found no evidence that tacrolimus 0.03% or 0.1% resulted in an overall increase risk of malignancy in either children or adults.20 

As topical nonsteroidal treatment options are currently limited for patients with AD and because TCIs offer a safe and effective treatment option, careful discussion must be done with patients when prescribing these medications to eliminate or limit any fears which may preclude the use of these medications. Strategies to accomplish this, which have been previously discussed by others, include: (1) discussing the theoretical drug-related risks vs well-established risks of a chronic disease such as AD; (2) preparing patients to receive conflicting information from pharmacists or other health care professionals who may not be as well versed in prescribing TCIs; (3) emphasizing the benefits of a nonsteroidal option (ie, decrease risk of skin atrophy); and (4) discussing daily or maintenance approach as more favorable with use of TCIs vs topical corticosteroid use.21,22 

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