Photosensitizing Antihypertensive Drug Use and Risk of Cutaneous Squamous Cell Carcinoma

K.A. Su; L.A. Habel; N.S. Achacoso; G.D. Friedman; M.M. Asgari

Disclosures

The British Journal of Dermatology. 2018;179(5):1088-1094. 

In This Article

Abstract and Introduction

Abstract

Background: Many antihypertensive drugs (ADs) are photosensitizing, heightening reactivity of the skin to sunlight. Photosensitizing ADs have been associated with lip cancer, but whether they impact the risk of cutaneous squamous cell carcinoma (cSCC) is unknown.

Objectives: To examine the association between AD use and cSCC risk among a cohort of non–Hispanic white individuals with hypertension enrolled in a comprehensive integrated healthcare delivery system in northern California (n = 28 357).

Methods: Electronic pharmacy data were used to determine exposure to ADs, which were classified as photosensitizing, nonphotosensitizing or unknown, based on published literature. We identified patients who developed a cSCC during follow–up (n = 3010). We used Cox modelling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Covariates included age, sex, smoking, comorbidities, history of cSCC and actinic keratosis, survey year, healthcare utilization, length of health plan membership and history of photosensitizing AD use.

Results: Compared with nonuse of ADs, risk of cSCC was increased with ever having used photosensitizing ADs (aHR = 1·17, 95% CI 1·07–1·28) and ever having used ADs of unknown photosensitizing potential (aHR = 1·11, 95% CI 1·02–1·20), whereas no association was seen with ever having used nonphotosensitizing ADs (aHR = 0·99; 95% CI 0·91–1·07). Additionally, there was a modest increased risk with an increased number of prescriptions for photosensitizing ADs (aHR = 1·12, 95% CI 1·02–1·24; aHR = 1·19, 95% CI 1·06–1·34; aHR = 1·41, 95% CI 1·20–1·67 for one to seven, eight to 15 and ≥ 16 fills, respectively).

Conclusions: These findings provide moderate support for an increased cSCC risk among individuals treated with photosensitizing ADs.

Introduction

Many commonly used medications, including certain antihypertensive drugs (ADs), are photosensitizing, heightening reactivity of the skin to sunlight.[1–7] The photosensitizing properties of these medications are related to their distinct chemical structures that allow for the absorption of ultraviolet radiation (UVR).[7–10] In the presence of UVR, photosensitizing medications may act as carcinogens by triggering phototoxic reactions, which cause acute DNA damage, and photoallergic reactions, which produce chronic inflammation.[8] Phototoxic reactions, which occur shortly after medication administration, result from radiation–induced production of reactive oxygen species.[8] Photoallergic reactions, which occur after a latent period of days to months, result from the radiation–induced formation of antigens that elicit a delayed T–cell–mediated hypersensitivity reaction.[8] The ensuing chronic inflammation may promote cutaneous carcinogenesis.[11] Given the association between UVR, DNA damage, chronic inflammation and development of cutaneous squamous cell carcinoma (cSCC), photosensitizing medications may increase cSCC risk.[12] A common malignancy with a rapidly rising incidence, cSCC is associated with substantial morbidity and cost.[13]

Epidemiological data on the association between photosensitizing drug use and cSCC risk remain limited. Photosensitizing ADs have been associated with lip cancers, the majority of which are mucosal squamous cell carcinomas (SCCs).[14,15] However, whether photosensitizing AD use affects cSCC risk is unclear. Previous observational studies have produced conflicting results,[16–24] and limitations have included small sample sizes,[22] reliance on self–reported medication history,[23] confounding by indication, incomplete capture of cases[19,20,24] and lack of pathological verification.[19,20,22,24] In this study, we examined the association between AD use and cSCC risk among 28 357 non–Hispanic white (NHW) patients with hypertension in a closed healthcare system in northern California with integrated electronic pharmacy records and pathologically verified cSCC cases.

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