Introduction to laser treatment of actinic keratoses

Actinic Keratoses or AK is a form of non-melanoma skin cancer (NMSC). At present the chances of AK becoming malignant ranges from 5% to 20%. There is no way to predict which AK will become malignant. Treatment of AK has been successful with traditional therapies, such as, cryosurgery, topical cytotoxic agents and surgical excision. Recently, laser and PDT have met with equal success.

To date, no large-scale studies have been done to assess the role of ablative laser therapy. However, anecdotal studies have been conducted to examine the role of CO2 and erbium: YAG laser in skin resurfacing, in the prophylaxis and treatment of multiple facial AK. These studies reported successful prophylaxis against NMSCs after CO2 laser resurfacing. In another study, thirty five patients with actinic involvement were given full face laser resurfacing. At one year of follow up, only five patients developed AK or basal cell carcinoma (BCC).

Photodynamic therapy (PDT)

The combination therapy of a photosensitizer and light, used in certain skin diseases and called photochemo therapy, is very old dating back to ancient Egypt, Greece and India. The modern photodynamic therapy (PDT) is a take from this ancient therapy, with the difference that the action here is an oxygen dependent photosensitive reaction. Later, for improved treatment, laser substituted ordinary light. PDT, therefore, comprises mainly, three components; light, photosensitizer and oxygen.

Traditionally, large complex lasers were used for PDT. But now a wide range of coherent and non-coherent light sources are available. These include dye lasers pumped by argon or metal vapor lasers and frequency doubled Nd: YAG lasers.

Topical photosensitizers, such as, 5-ALA and the methyl ester of ALA, mALA, have been developed for treating skin cancers, replacing systemic photosensitizers without the significant photo toxicity. The most common side effects of 5-ALA and mALA are temporary irritation and edema, during and immediately after treatment. Scarring and dyschromia may also occur. One drawback of these topical photosensitizers is their limited depth of penetration, though extra penetration depths are yet to be established.

Topical photosensitizers and their combination with lasers have allowed PDT to be used in cutaneous diseases. PDT is now a treatment option for actinic keratoses (AK) and is rapidly becoming an established option for treating non-hyperkeratonic AKs. Traditionally, blue light of 430nm and red light of 630nm have been used. The treatment effects of pulse dye laser, at wave lengths of 580nm, 595nm and 600nm, and incoherent light sources of wave lengths 580nm to 740nm, on human keratinocytes treated with the topical photosensitizer ALA was compared. It was found that PDL at 585nm and incoherent light sources produced the maximum cytotoxic effects. It was inferred that PDL may be as effective as continuous light at 28 days after treatment.

The safety and efficacy of 595nm PDL in AK treatment, was evaluated on 41 patients, 3 hours and 14 to 18 hours after the incubation of 20% 5-ALA sensitizer. On the average, lesion clearance per patient was 90%, which compared favorably with lesion clearance by other treatments. In addition, treatment time was less, discomfort was minimal and the post operative erythema cured in five to six days. Importantly, it was the first study to show that short incubation period was as effective as a long one.

At present, several research groups are engaged in evaluating differences between various light sources and ALA-PDT in the treatment of AK. In one study, treatment of AK by ALA-PDT was compared with the treatment by 5-fluorouracil, in order to assess the efficacy and tolerance of these two therapies. The subjects in the study were 17 patients with dorsa of the hands. At six months follow up, no statistically significant difference was noted in the extent of clearance of the lesions by these two treatments.

In another prospective randomized study, the results of AK treatment by cryotherapy with two passes were compared to red light- PDT using methyl ALA as photosensitizer. It was found that patients treated with cryotherapy gave, by and large, a marginally better response. However, the cosmetic appearance and patient satisfaction was significantly higher in PDT patients. The inference drawn was that a repeat PDT would improve on the results.

Investigation was also conducted on ALA-PDT treatment of AK using a large field incoherent light. 78% of the lesions remained clear at one year. The side effects included pain, superficial ulceration, infection and dyschromia.

A type of PDT is photodynamic rejuvenation where the distinguishing feature is the use of intense pulse laser (IPL). In one study, two treatments of ALA-IPL gave 87% clearance in three months. Other studies reported fewer clearances. So far, this treatment has given variable results.