Detection and clearance of subclinical actinic keratosis (AK) with imiquimod (5%) treatment

Abstract

Background: Actinic keratosis is a crucial element in the multistage process of carcinogenesis leading to invasive squamous cell carcinoma (SCC). AK usually develops on sun-damaged skin and frequently involves an extensive area, identified as an ultraviolet-induced “field of cancerization.” This area is characterized by the coexistence of early “subclinical” AK lesions and cumulates in multifocal SCC. Most ablative procedures do not target all lesions in a dysplastic area but focus on clearly visible lesions. Yet, untreated subclinical lesions might explain the high recurrence rate of AK after treatment. Thus, simultaneous treatment of clinical and subclinical AK lesions may mitigate disease recurrence. Recent case studies have demonstrated that imiquimod cream (5%) is a safe and effective treatment for AK. We examined the potential efficacy of topical imiquimod (5%) in treating clinical and subclinical AK lesions.Methods: A randomized, double-blind study was conducted in patients with biopsy-proven AK (3–10 lesions/patient). Patients applied imiquimod cream (5%) or vehicle 3 times/week for up to 12 weeks. A rest period of up to 3 weeks, followed by resumption at a decreased application frequency (1–2 times/week), was permitted to manage adverse events. The number, size, and appearance of AK lesions were evaluated during each clinic visit. Complete or partial clearance was verified by histologic analysis.Results: Thirty-six patients (treatment group = 25, vehicle-control group = 11) completed the 12-week study. After 2–3 weeks of imiquimod (5%) treatment, AK lesion counts were elevated over baseline as subclinical lesions became clinically visible. The treatment area was characterized by mild erythema, and subclinical lesions appeared red and inflamed. On histologic examination, these lesions displayed signs of early AK. With the detection of subclinical lesions, the total number of AK lesions during treatment increased by ∼300%. At the end of the 12-week study, complete clearance of clinical and subclinical AK lesions was observed in 21 of 25 (84%) patients, and an additional 2 of 25 (8%) patients exhibited partial clearance. The control group had no reductions in the number or size of AK lesions.Conclusions: Imiquimod cream (5%) was effective in clearing baseline AK lesions and early subclinical AK lesions. These findings suggest imiquimod therapy may lead to a lower recurrence rate relative to therapies that only treat visible lesions. Background: Actinic keratosis is a crucial element in the multistage process of carcinogenesis leading to invasive squamous cell carcinoma (SCC). AK usually develops on sun-damaged skin and frequently involves an extensive area, identified as an ultraviolet-induced “field of cancerization.” This area is characterized by the coexistence of early “subclinical” AK lesions and cumulates in multifocal SCC. Most ablative procedures do not target all lesions in a dysplastic area but focus on clearly visible lesions. Yet, untreated subclinical lesions might explain the high recurrence rate of AK after treatment. Thus, simultaneous treatment of clinical and subclinical AK lesions may mitigate disease recurrence. Recent case studies have demonstrated that imiquimod cream (5%) is a safe and effective treatment for AK. We examined the potential efficacy of topical imiquimod (5%) in treating clinical and subclinical AK lesions. Methods: A randomized, double-blind study was conducted in patients with biopsy-proven AK (3–10 lesions/patient). Patients applied imiquimod cream (5%) or vehicle 3 times/week for up to 12 weeks. A rest period of up to 3 weeks, followed by resumption at a decreased application frequency (1–2 times/week), was permitted to manage adverse events. The number, size, and appearance of AK lesions were evaluated during each clinic visit. Complete or partial clearance was verified by histologic analysis. Results: Thirty-six patients (treatment group = 25, vehicle-control group = 11) completed the 12-week study. After 2–3 weeks of imiquimod (5%) treatment, AK lesion counts were elevated over baseline as subclinical lesions became clinically visible. The treatment area was characterized by mild erythema, and subclinical lesions appeared red and inflamed. On histologic examination, these lesions displayed signs of early AK. With the detection of subclinical lesions, the total number of AK lesions during treatment increased by ∼300%. At the end of the 12-week study, complete clearance of clinical and subclinical AK lesions was observed in 21 of 25 (84%) patients, and an additional 2 of 25 (8%) patients exhibited partial clearance. The control group had no reductions in the number or size of AK lesions. Conclusions: Imiquimod cream (5%) was effective in clearing baseline AK lesions and early subclinical AK lesions. These findings suggest imiquimod therapy may lead to a lower recurrence rate relative to therapies that only treat visible lesions.