Photosensitizing antihypertensive drug use and risk of cutaneous squamous cell carcinoma

• Published in: British journal of dermatology (1951) Vol. 179; no. 5; pp. 1088 - 1094
• Main Authors: Su, K.A., Habel, L.A., Achacoso, N.S., Friedman, G.D., Asgari, M.M.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-11-2018
• Subjects: Aged; Antihypertensive Agents - adverse effects; Antihypertensives; California - epidemiology; Carcinoma, Squamous Cell - epidemiology; Carcinoma, Squamous Cell - etiology; Drug Prescriptions - statistics & numerical data; Drug therapy; Female; Follow-Up Studies; Humans; Hypertension; Hypertension - drug therapy; Keratosis; Male; Middle Aged; Photosensitization; Photosensitizing Agents - adverse effects; Skin; Skin cancer; Skin Neoplasms - epidemiology; Skin Neoplasms - etiology; Smoking; Squamous cell carcinoma; Sunlight - adverse effects; White People; California
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.16713

Summary
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.
What's already known about this topic?
Certain antihypertensive drugs (ADs) are photosensitizing, heightening reactivity of the skin to sunlight.
Photosensitizing ADs may act as carcinogens by triggering phototoxic reactions, which cause acute DNA damage, or photoallergic reactions, which produce chronic inflammation.
Photosensitizing ADs have been associated with lip cancer, but whether they impact risk of cutaneous squamous cell carcinoma (cSCC) is unclear.
What does this study add?
This large cohort study of members of a managed care population with hypertension examined the association between AD use and cSCC risk.
This study suggests that use of photosensitizing ADs is associated with a 17% higher risk of cSCC compared with nonuse of ADs.
These results suggest that patients taking photosensitizing ADs may benefit from education on safe sun practices and closer screening for cSCC.
Linked Comment: Schmidt. Br J Dermatol 2018; 179:1027–1028.
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