Topical application of imiquimod and associated fever in children

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To the Editor: A 5-year-old child with molluscum contagiosum on the axillary fossae, the left elbow, the left popliteal fossa, and the right thigh was treated with imiquimiod 5% cream 3 times weekly. At each application the mother used 12.5 mg on these surfaces. Two days after the first application, the child developed a temperature of 40°C (rectal) accompanied by severe headaches; temperature decreased to normal 5 days after the first application. During these 5 days, the mother stopped the treatment. When the fever disappeared, imiquimod was applied again to the same areas. Less than 24 hours after the second treatment, the child became febrile again at 39°C, and then the fever disappeared in 1 day. Thereafter the mother applied imiquimod for a third time and the next day a 24-hour fever of 39°C appeared again. Lastly, during the fourth and last imiquimod application, once again in less than 24 hours, a febrile state of 39.5°C developed (Fig 1).

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• Fig 1. 

  Correlation between imiquimod applications (arrows) and fever. Fever appeared 2 days after first cream application. Treatment was stopped during 5 days. During second, third, and fourth imiquimod applications, feverish state developed in 24 hours.

Although it is currently known that the systemic intake of imiquimod can provoke influenza-like symptoms, asthenia, and headaches,¹ observation of such side effects during cutaneous application is sparse. Only Hengge et al² report a case of fever between 39.1°C and 40°C in a patient treated with topical imiquimod among 53 patients using this cream for common warts and molluscum contagiosum. In our case, the correlation between fever and imiquimod treatment is particularly striking. We believe, therefore, that one has to be careful when using this substance for the treatment of the young patient.

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References 

1. Witt PL, Ritch PS, Reding D, McAuliffe TL, Westrick L, Grossberg SE, et al.  Phase I trial of an oral immunomodulator and interferon inducer in cancer patients. Cancer Res. 1993;53:5176–5180
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2. Hengge UR, Esser S, Schultewolter T, Behrendt C, Meyer T, Stockfleth E, et al.  Self-administered topical 5% imiquimod for the treatment of common warts and molluscum contagiosum. Br J Dermatol. 2000;143:1026–1031
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