5 clinical pearls for treating facial actinic keratoses

At the MauiDerm 2014 meeting, conference organizer George Martin, M.D., shared five clinical pearls for treating facial actinic keratosis (AK).

1. Phase 3 data on 0.5 percent 5-fluorouracil (5-FU) showed that one week of daily use of 0.5 percent 5-FU cleared nearly 75 percent of individual AKs. Try: 0.5 percent 5-FU QD x one week, wait one month, then follow with two to three weeks QD application to “clean up” remaining AKs. This regiment has gained widespread acceptance by patients and physicians as a more tolerable field therapy. The 5 percent 5-FU BID is equivalent to 0.5 percent 5-FU and can be used interchangeably.  

2. Ingenol mebutate 0.015 percent applied nightly x3 has been a remarkably effective therapy with great patient compliance. However, its Food and Drug Administration approval was for limited areas (25 cm²). As a full-face therapy, it appears very effective; however, controlled studies on “full-face” clearance/efficacy is lacking. Patients need to be counseled that they will experience a “chemical peel” effect with burning and stinging beginning four hours after application. This is due to its MOA, which includes a direct cytotoxic effect. Analgesia is generally required. Clinically, we have observed while treating full-face, a selectivity of ingenol mebutate for AKs with minimally affected areas between the AK lesions.

3. If you perform photodynamic therapy (PDT) in your practice and use one- to three-hour aminolevulinic acid (ALA) incubation periods, recent phase 2 studies from DUSA Pharmaceuticals show that one-, two- or three-hour incubation periods are roughly equally efficacious but require two treatments eight weeks apart for most patients to achieve > 70 percent individual lesion clearance. To maximize the efficacy of a one-hour incubation, consider pretreating with 5-FU for one week to the face or 10 days to the scalp, and then perform a one-hour ALA incubation.

This combination will eliminate the need for a second PDT. For those patients with refractory facial AKs, consider pretreating for seven days with 3.75 percent imiquimod followed by ALA PDT (one- to three-hour incubation). Excellent long-term results (18 months) have been observed when destructive techniques such as PDT are combined with immune modulators.

4. Can ALA PDT be painless? Try incubating for 15 minutes with ALA and then place the patient under the blue light for one hour. Preliminary results (G. Martin MD) demonstrate that ALA PDT as monotherapy or in combination with 5-FU or 3.75 percent imiquimod is, in fact, “painless.” Large-scale studies are warranted to determine efficacy.

5. The use of 3.75 percent imiquimod for diffuse facial AKs while effective, results in substantial downtime of nearly six weeks. Consider 3.75 percent imiquimod QD x7 days, two weeks’ rest, then Q weekly. There will be some initial unsightliness but chronic immune stimulation (> 1 year) appears to be helpful in limiting AK recurrences and may prove over time to inhibit the development of invasive squamous cell carcinoma.