Field Treatment of Actinic Keratosis on the Scalp

C. Bower


The British Journal of Dermatology. 2017;176(6):1425-1426. 

The management of actinic keratosis (AK) requires the consideration of multiple different factors. Estimates of the premalignant potential for AKs vary greatly, with international guidelines varying in their recommendations as to whether all lesions require treatment.[1] This issue of the BJD includes an interesting paper by Weiss et al.[2] on a novel topical therapy used over entire scalps of balding men with AKs.

While AKs can occur in isolation, they often present over a wide area, particularly on the scalp of bald men. This can present therapeutic challenges when using destructive therapies such as cryotherapy and curettage and cautery, as these treatments are better used for isolated lesions.

When selecting appropriate topical treatments, consideration has to be given to efficacy, tolerability and adherence. The licensed topical treatments for AKs all have fairly similar clearance data from clinical trials, with few direct comparison studies published, and no data on the relationship between different AK treatments and decreased rates of squamous cell carcinoma (SCC).[3] A meta-analysis evaluation[4] of AK therapies based on complete clearance rates ranked topical treatments from highest efficacy to lowest efficacy as follows: 5-fluorouracil (5-FU) 5%; 5-FU 0·5%; photodynamic therapy (PDT) with aminolaevulinic acid; imiquimod; ingenol mebutate and methyl aminolaevulinate PDT (equal ranking); diclofenac with hyaluronic acid; cryotherapy.

The intensity of localized skin reactions varies between topical treatments. Ingenol mebutate can cause a fairly intense local reaction, but this is offset by the advantage of a simple short treatment regimen and excellent adherence data.[5] Solaraze (topical diclofenac) causes little in the way of local reactions, but is limited by the need for patients to continue with use twice daily for a full 3 months to achieve maximum clinical efficacy. Combined nonadherence and nonpersistence is reported to be as high as 88% with topical treatments.[6]

Topical therapeutic options are limited by the area that the treatment can cover, and by licensing restrictions. Ingenol mebutate, 5% imiquimod (Aldara) and 5-FU 0·5% + salicylic acid 10% (Actikerall) can be applied to an area of only 25 cm2. The average bald scalp has up to 250 cm2 of exposed skin. In order to treat extensive AK on the scalp, it would be necessary therefore to treat sequentially with these treatments, increasing the duration of treatment and overall cost. AK tends to be a chronic recurring problem, and patients are likely to require multiple treatment episodes over a lifetime. Options for long-term management could be either more self-care (not supported with single-treatment aliquot dispensing), or treatment of more extensive areas to potentially reduce the rate at which future AKs/SCCs develop.

In the study by Weiss et al.,[2] a novel formulation of ingenol disoxate has been investigated for treating AK over areas of between 25 cm2 and 250 cm2 on the balding scalp of men. Doses of 0·037% and 0·05% were effective and superior to vehicle as field treatments for AK, with reported mean percentage reduction after approximately 2 months being higher with ingenol disoxate (72·7–78·5%) compared with data for ingenol mebutate (50·1–55%) on the balding scalp. The treatment was well tolerated, with higher treatment satisfaction compared with vehicle despite a lower score on side-effects. Adherence was > 98%.

The perfect AK treatment would combine ability to treat all lesions at the same time, good clearance, acceptable local reactions, good cosmetic outcome and a high level of adherence and persistence. Data from the Weiss et al. study[2] show promise in meeting many of these criteria. Further studies would be welcome, particularly with evaluation over 6 or 12 months, and ideally more head-to-head comparisons of treatment strategies for AK.[7] An additional challenge is to prove that any treatment actually reduces the risk of development of future SCCs.