In patients with actinic keratosis (AK) treated with imiquimod cream, localized reactions in the treated area may be the precursor of influenza-like side-effect symptoms, according to study findings published in the Journal of the American Academy of Dermatology International.

For as long as topical imiquimod has been prescribed for actinic keratosis, external genital warts, and superficial basal cell carcinoma, some patients have complained of influenza-like symptoms. Researchers sought to examine the association between these side-effect symptoms and the elevation of serum cytokine levels, accounting for patient age, and amount of specific body area being treated.

To accomplish this, they conducted a single-center, open-label, investigator-initiated trial ( Identifier: NCT24435875) that included 22 patients (mean 62.8±8.99 years of age; 31.8% women) with 5 to 20 actinic keratosis  (AK), stratified into 2 age groups and 2 treatment areas.  In all, 12 patients were between 30 and 59 years of age and 10 patients were between 60 and 89 years of age. The area of treatment for 11 patients was the entire face or balding scalp whereas 11 patients were treated on their chest or upper extremities.

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All patients were treated with imiquimod 3.75% cream for 2 14-day cycles and all but 1 patient experienced partially resolved or total clearance of AK. There were 13 patients with localized skin reactions above the study average, of whom 7 also experienced influenza-like symptoms above the study average. Of these 7 patients, 5 were treated on the face or scalp and 2 on the trunk/arm; 4 of these 7 patients were in the younger age group and none of the 7 were among the patients in the older group treated on the trunk/arm.

Among all patients with localized skin reactions preceding systemic influenza symptoms, side-effects developed within 7 to 11 days of being treated. Researchers reported that “Levels of circulating cytokines had no predictive value.”

Study limitations included the small sample size and small number of cytokines investigated.

Researchers concluded that “The onset of local skin reactions may serve as a predictor for the potential onset of systemic symptoms that mimic those of influenza and could be used as a talking point for patients, though further research is needed.”

Disclosure: A study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Trial or study (research) supported by industry: Ortho Dermatologics.


Bhatia N. Local skin reactions and the onset of influenza-like signs and symptoms induced by imiquimod. JAAD Int. Published online March 30, 2022. doi:10.1016/j.jdin.2022.01.010

This article originally appeared on Dermatology Advisor