Lasers: Destroying actinic keratoses

Key Points

In the United States, destruction of actinic keratoses (AKs) is the single most commonly performed dermatologic procedure in the outpatient setting.

With a reported progression rate to invasive squamous cell carcinoma of anywhere from 1 to 100 per 1,000, and no manner of differentiating those AKs most prone to progression, it is important to treat these lesions. Yet the question exists: With so many other therapeutic options, do lasers and light sources have a role in this treatment armamentarium?

AKs, senile keratoses, solar keratoses, pre-cancers, whatever the nomenclature, the incidence is high, and the problem is persistent. Traditional modalities, such as cryotherapy, are effective, but difficult to use when treating large numbers of AKs. Resultant dyspigmentation and scarring are also of concern when these destructive methods are used in cosmetically significant areas such as the face.

Ablative lasers, theoretically, would be the laser of choice for AKs, due to their destructive nature. Research does show that both the traditional CO₂ and the Er:YAG lasers are effective at reducing AK lesions. Cure rates have been quoted at anywhere between 50 percent to 100 percent for either ablative device. In one of the only prospective, randomized trials, Er:YAG resurfacing was shown to be more effective at preventing recurrences when compared to topical 5-FU.

However, side effects and downtime far exceed those seen with standard therapies for AKs.

Plasma resurfacing (Rhytec) was introduced to the U.S. market in 2005. Though not a laser device, plasma resurfacing uses nitrogen plasma energy to resurface the skin. Nitrogen plasma is not mediated by chromophore absorption, and, hence, has a difference mechanism of action than laser or light energy. It is approved for treatment of benign lesions, including AKs.

No data is published on the response rates of AKs with plasma resurfacing.

The fraxel Re:store laser (Reliant) was approved last year for the treatment of AKs. In one study, the average reduction in number of AK lesions was 74 percent. Biopsies showed histologic improvement in keratinocyte atypia.

Nonablative fractional devices have excellent safety profiles, and, hence, do have an advantage over traditional ablative resurfacing. The use of nonablative fractional resurfacing for AKs should be performed using high-density settings in order to achieve effective cure rates. In addition, several treatments are needed for ideal response rates.

Photodynamic therapy (PDT) using 20 percent 5-aminolevulinic acid (ALA) activated by blue light-emitting diodes (LEDs) was approved for treatment of non-hyperkeratotic AKs of the face and scalp in 1997. The methyl ester was approved in 2004, but is not commercially available in the United States.

ALA (Levulan, Dusa Pharmaceuticals)/PDT is an easy-to-use modality for selective treatment of both localized and broad areas of AKs. Initial approval was for 14- to 18-hour incubation. The newer one- to three-hour regimens have shown similar efficacy, while reducing discomfort and eliminating the time constraints.

Currently used one- to three-hour incubations have shown to have cure rates equivalent to those seen with longer incubation times - somewhere around 80 percent to 91 percent with a single treatment. Prior to treatment, the skin is prepared with alcohol or acetone to remove the sebum and allow for better penetration of the ALA. The ALA is applied as a liquid to the affected areas only, or to the entire face in cases of extensive photodamage.

The liquid dries quickly and is left in place to incubate for an average of one to three hours. ALA is absorbed into the skin, where it is converted to protoporphyrin IX (PpIX), a photosensitizer. PpIX is selectively accumulated in precancerous cells resulting in a 10 times higher concentration of PpIX in abnormal cells when compared to the normal surrounding tissues. Activation with a light source results in a cytotoxic reaction, destroying the abnormal cells. This phototoxic reaction in precancerous cells occurs while sparing the surrounding tissues, resulting in a selectivity not achievable with most methods of destruction.

Post-treatment, the patient must practice strict sun avoidance for a 24- to 48-hour period in order to avoid reactivation of the protoporphyrin IX. This can be accomplished using a high-SPF physical sunblock and limiting outdoor activities and/or intense light exposure. Social downtime can be anywhere from zero to seven days, depending on the amount of actinic damage.

Comparisons of 5-FU and short incubation ALA/PDT showed that ALA/PDT was at least as effective at clearing AKs, and was better-tolerated than 5-FU (J Drugs Derm 2003).

ALA is approved by the Food and Drug Administration (FDA) for activation with blue LED, yet activation with other sources can also yield good results.

The use of IPL, long pulsed-dye laser and red light have all been shown to effectively activate PpIX. Direct comparisons of these devices to the blue LED are not available.

With the newer short incubation times, ease of use, low rate of complications, and favorable cosmetic outcomes, PDT becomes my top 'laser and light source' treatment for AKs of the face and scalp.

Dr. Kaufman is assistant professor of clinical dermatology at the University of Miami Miller School of Medicine and director of lasers for the University of Miami Cosmetic Group.The Cosmetic Group is involved in research and development of lasers and light devices as well as other aesthetic procedures, such as fillers and toxins.