Long-term remission of recurrent herpes labialis following topical imiquimod application on distant healthy skin: a clinical and immunological study

Background: Given the limitations of current antiviral therapies, safer and more effective approaches to the management of recurrent herpes labialis (RHL) are needed. Methods: A patient with a 23-year history of RHL and 14 healthy individuals were studied. The patient applied imiquimod to distant healthy skin for 3 weeks. Peripheral blood (PB) samples were collected from the patient during treatment and 21 months after its discontinuation; samples were collected from the controls once. The distribution of lymphocyte populations in PB were analysed by flow cytometry and PB cytokine levels were measured using cytometric bead arrays. Results: The patient showed long-term remission of the disorder subsequent to a 3-week imiquimod application to distant healthy skin. Imiquimod treatment induced the activation and proliferation of T-helper and cytotoxic T-cells, B-cells and T-regulatory cells. In addition, there was a very strong transient increase of T-helper 1 cells (resulting in interferon-gamma secretion) and type 1 (pro-inflammatory) polarization of the immune response accompanied by a sustainable interferon-alpha production. At follow-up 21 months after treatment cessation, with the patient remaining relapse-free, the patient had control levels of all cytokines, increased levels of activated cytotoxic T-cells, continuous production of new T-helper cells and B-cells and near-to-normal levels of T-regulatory cells. Conclusions: Our results indicate that topical application of imiquimod to healthy skin is capable of causing systemic immunomodulation. This treatment might represent a new and effective alternative to established therapeutic and prophylactic regimens for RHL.