Actinic keratoses (AKs) are common lesions which are induced by chronic sunlight exposure [
A variety of treatment strategies are available for AKs; they have specific risks and benefits and include topical agents and surgical procedures [
To further improve the duration and long-term results of the treatment, we also evaluated an alternative dosing regimen including sequential photodynamic therapy (PDT) and imiquimod. PDT is noninvasive targeted treatment which uses visible light to activate a photosensitizing agent, resulting in the formation of cytotoxic reactive oxygen species. This procedure leads to diseased tissue destruction. The therapy is highly effective in the treatment of AKs [
Due to different mechanisms of action, better clinical long-term results with less toxicity are expected from applying the PDT and imiquimod 5% cream sequentially.
The aim of this investigation was to determine the efficacy, tolerability, safety, and cosmetic outcome of PDT with 5% imiquimod cream sequential treatment in patients with AKs and to give the background for the initiation of future studies in order to confirm the results and evaluate long-term therapeutic benefits.
Patients were eligible if they were at least 18 years old and had clinically typical visible AK lesions located anywhere on the head or hands. Hyperkeratotic or hypertrophic AK lesions were not excluded. Patients were excluded if they were organ transplant recipients or if they had any dermatological disease or condition in the treatment or surrounding area.
The lesions were gently abraded using a curette (Stiefel) so that the surface crust was removed. 5-aminolevulinic acid (ALA) was applied for 4 h, respectively, for AK. The cream was all the time occluded. In addition, regional anesthesia was applied for 30 min prior to irradiation. The Aktilite CL128 laser was used for irradiation in all patients.
Baseline screening was conducted before PDT. The lesions were measured and the exact location of AKs was documented with digital photography. Two weeks after the single session of PDT, patients started to apply imiquimod 5% cream to the treatment area once daily, three days per week. Imiquimod was left on the skin for at least eight hours before being washed off. Treatment continued for four weeks (course 1) followed by a clinical evaluation and decision about the further procedure. Patients without clinically visible AK lesions in the treatment area were considered to be completely clear and their treatment ended. Patients who had not cleared all of their AK lesions in the treatment area at the end of course 1 participated in a second four-week course of treatment. Patients were clinically evaluated at least six months after the end of the treatment—one patient withdrew from further treatment because of a lack of response to the treatment. All patients gave written informed consent to participate in this investigation.
Mr. JR is male patient, 64 years old with Fitzpatrick skin phototype II. He presented with numerous hyperkeratotic lesions on his scalp (Figure
Clinical followup, Case 1. (a) Status before PDT; several hyperkeratotic lesions, hardly visible, and palpable (b) two weeks after PDT, before imiquimod; (c) two weeks after imiquimod; (d) four weeks after imiquimod, end of first course; (e) four weeks after imiquimod, end of second course; (f) seven months after the end of treatment: no visible or palpable AKs and less hyperpigmentation.
Mr. HF is a male patient, 82 years old with Fitzpatrick skin phototype III. Numerous hyperkeratotic lesions were localized on his scalp. Two target lesions on his forehead were chosen for examination. The reaction to the PDT-treatment was pronounced (Figure
Clinical followup, Case 2. (a) Two weeks after PDT, before imiquimod; (b) two weeks after imiquimod; (c) end of first course; (d) two weeks after imiquimod, second course; (e) four weeks after imiquimod, end of second course; (f) eleven months after the end of treatment: even surface and no visible or palpable AKs.
Mrs. AD is a female patient, 42 years old with Fitzpatrick skin phototypes II-III. Numerous hyperkeratotic lesions were localized on her hands (Figure
Clinical followup, Case 3. (a) Before PDT; (b) two weeks after PDT; (c) two weeks after imiquimod; (d) four weeks after imiquimod, end of first course; (e) two weeks after imiquimod, second course; (f) four weeks after imiquimod, end of second session: less scaling of the skin, more homogenous surface, the skin texture appeared even better, and AKs still present.
The findings of this investigation demonstrate that the sequential application of PDT and imiquimod 5% cream is a well-tolerated method in the treatment of actinic keratoses with high efficacy and safety and with an excellent cosmetic outcome. Sequential application of PDT and imiquimod has not been widely evaluated in the literature. There are only two known published studies that have compared the sequential application of PDT and imiquimod 5% cream [
Shaffelburg designed a randomized, vehicle-controlled, split-face study to explore the safety and efficacy of photodynamic therapy followed by imiquimod [
Both studies showed good results in AK treatment. In the present investigation, two out of three patients showed in long-term followup a high benefit from this therapy modality with only one patient being a nonresponder. This could be explained by high UV-damage of the skin of the patient. The patient was very young being 42 years old, and she had reported skin problems for approximately five years. Various topical treatments (imiquimod and diclofenac in hyaluronic acid as monotherapy) were tried without any side effects nor any response in the past. This could be an explanation for the lack of the additional benefit from the combined therapy. In addition, the AKs were localized on the hands and the treatment of them seems to be more complicated. The present investigation showed that a single-session PDT and a period of eight weeks of imiquimod administration would be enough to obtain good clinical results. Nevertheless, this investigation analyzed only three cases and this was a big limitation. For confirmation of the results and evaluation of long-term therapeutic benefits, further studies are needed.
In conclusion, two patients with long-term followup showed no relapse of AKs. Sequential therapy consisting of PDT and imiquimod 5% cream seems to provide good results in the treatment of actinic keratoses.
Actinic keratosis
Basal cell carcinoma
Local side effects
Nonmelanoma skin cancer
Photodynamic therapy
Squamous cell carcinoma
Ultraviolet.
This paper is not under consideration for publication elsewhere. All the authors have agreed to its submission and have declared that there is no conflict of interests. There are no financial disclosures from any author to make. Informed consent was obtained from all the study subjects. This study was supported with a research Grant from MEDA Pharmaceuticals. One author has been a speaker for MEDA Pharmaceuticals.