Imiquimod Induces Sustained Remission of Actinic Damage: A Case Report Spanning One Decade of Observation

Our patient had a history of a recurrent BCC and was previously treated with imiquimod. He showed no inflammatory response to field therapy with 5-FU within the perimeter of prior immunomodulatory therapy. Although no frank scaling or crusting papules consistent with AK were observed in the previously treated area prior to 5-FU therapy, subclinical field damage in that area was expected because 10 years of additional sun exposure had accumulated since imiquimod therapy was completed. Several conclusions can be drawn from this observation. Primarily, no new clinically significant actinic lesions occurred on the previously treated skin. This observation is consistent with 12-month follow-up data on AKs treated with either 5-FU, imiquimod, or cryosurgery that identified imiquimod as having the lowest recurrence rate.⁸ Thus, a photoprotective effect may be ascribed to imiquimod therapy that extends beyond its drug effects on atypical keratinocytes. It has been one author’s personal experience (M.Q.) that patients treated with 5-FU experience recurrence of AKs within 3 to 5 years versus 10 years of remission with imiquimod. In our patient, imiquimod therapy seemed to reset the patient’s skin at the location of the prior BCC and surrounding field cancerization.

Studies with long-term follow-up are needed to investigate the need for re-treatment with imiquimod or 5-FU. The longevity of imiquimod treatment may be of importance beyond the treatment of AKs or NMSCs. For instance, during the treatment of lentigo maligna with imiquimod, Metcalf et al¹⁸ found a significant reduction in solar elastosis (P=.0036), normalization of epidermal thickness (P=.0073), and increased papillary dermal fibroplasia in pre- and posttreatment biopsies (P<.0001), which have been described as antiaging effects in the laypress. Some of these mechanisms appear to be implicated in the observations noted in our patient. The 10-year period between the 2 courses of therapy in our patient suggests that imiquimod may cause sustained healing of skin that was previously classified both clinically and microscopically as UV damaged.

Conclusion

Both topical immunomodulators such as imiquimod and topical chemotherapeutic agents such as 5-FU have a role in the field treatment of AK and the focal treatment of superficial BCC and SCC. As multiple topical immunomodulators continue to be evaluated, long-term studies assessing the need for re-treatment as well as the degree of sustained remission of sun damage will be necessary. We expect that their individual roles will continue to become more precisely defined and distinct in the coming years.