A single-center study of aminolevulinic acid and 417 nm photodynamic therapy in the treatment of moderate to severe acne vulgaris

Journal of Drugs in Dermatology, August, 2003 by Mitchel P Goldman, Sarah M Boyce

Abstract

This article describes a single-center trial involving twenty-two patients with acne vulgaris. Blu-U light was used in all patients, while half were pre-treated with aminolevulinic acid. Preliminary results show promise for this treatment in mild to moderate inflammatory acne vulgaris.

Background

The use of light in the treatment of acne dates back to the 1940s. Historically, different types of ultraviolet lights have been used to destroy follicular bacteria and speed resolution of acne lesions. With the advent of antibiotics and keratolytic agents, light treatment fell into disuse. In the past few years, however, the treatment of acne with light-based sources has been rejuvenated. No longer are carcinogenic UVB and UVA light sources utilized; newer forms of light delivery systems are beyond the UVA range in a "safer" spectrum.

Modern light therapy for acne was recently discussed in an article by Hirsch in the September 2002 issue of Cosmetic Dermatology (1). The pathogenesis of acne is multifactorial, involving the activation of various cytokines by an overproduction of Propionibacterium acnes in response to genetic factors as well as excessive sebum production. Dr. Hirsch detailed the ability of visible light to destroy P. acnes through activation of porphyrins (2-7).

Selective destruction of sebaceous glands has also been attempted. Before the advent of topical 5-aminolevulinic acid (ALA), a trial of intraperitoneal injection of ALA into mice was performed. This study demonstrated relatively selective photodamage to sebaceous glands after activation from a 100-watt tungsten lamp (8).

Other photosensitizing agents have also been studied to selectively destroy pilosebaceous units. Topical indocyanine green (IG) was used with an 810 nm diode laser to selectively damage enlarged sebaceous glands in patients with acne (9). This wavelength was ideal to penetrate to a 1 mm depth, a typical depth for sebaceous glands. Preliminary results from a "limited number of patients" demonstrated that the procedure was safe and effective. The only obvious drawback to this technique is the relative expense of the 810 diode laser necessary to activate IG.

With the advent of topical ALA, studies were performed with red light (550-700 nm) in the treatment of acne producing clearance that lasted 20 weeks. Severe damage to sebaceous glands was noted histologically, which was the probable mechanism of action for therapeutic efficacy. Significant associated side effects consisting of excessive light damage dampened enthusiasm for this therapy (10).

Itoh et al. (11) demonstrated clearing of acne after low dose, single treatment ALA/PDT. However, crust formation, erythema, and pigmentation lasting up to 4 weeks limited the acceptability of this treatment.

We present data from twenty-two patients treated with either Blu-U (417 nm) alone or after pre-treatment with Levulan (topical 5-aminolevulinic acid).

Materials and Methods. Twenty-two patients with mild to moderate acne vulgaris were enrolled in our study. Each patient was given a standard proprietary 2% salicylic acid cleanser (Cool Clenz[TM], York-Goldman Enterprises Inc., La Jolla, CA) and a one-week washout phase. Patients were excluded for pregnancy, active medical conditions that would interfere with participation in the study, severe comedonal acne, mental incompetence, a history of keloids, or treatment in the previous year with collagen, BOTOX[TM], chemical peels, dermabrasion, or laser resurfacing.

The patients were divided into two groups. Group 1 consisted of twelve patients who were treated for 6 minutes with Blu-U light once a week for two weeks, then evaluated two weeks later. Group 2 consisted of ten patients who were treated with topical ALA, allowed to sit for 15 minutes, and then treated for 6 minutes with Blu-U light. The patients in Group 2 were treated twice with the treatments two weeks apart, then evaluated two weeks later.

Evaluations consisted of lesion counts (papules, pustules, and comedones), a global severity evaluation by the investigator (Using a scale from 0-3 for severity (Fig. 1) and a scale from 0-4 for improvement (Fig. 2)), and standard photographs (Figs. 4 & 5).

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Results

Overall, patients in both groups improved (Fig. 3). In Group 1, there was a 25% improvement in severity of acne, compared with a 32% improvement in Group 2. Lesion counts from baseline to final also displayed improvement in both groups. Group 1 patients saw a 40% decrease in papules, a 65% decrease in pustules, and a 62% decrease in comedones. Group 2 patients saw a 68% decrease in papules, 61% decrease in pustules, and a 62% decrease in comedones.

[FIGURE 3 OMITTED]

No serious adverse events occurred. One patient experienced severe erythema and some crusting after post-treatment sun exposure.

Discussion

Light provides treatment both for active lesions as well as for other sebaceous glands that have not yet created acne lesions. Patients treated in this trial had mild to moderate acne. Preliminary results appear promising with most patients showing relative clearing of their acne after 2-4 weekly treatments. Treatment sessions were totally pain-free. Most patients also noticed a decrease in background erythema as well as an improvement in the roughness of their skin and tightening of the pores. Long-term results are unknown at this time. The only notable adverse effect was a generalized "sunburn-like" reaction if the patient spent time in the sunlight after treatment without using sunscreen. When patients wore a sunscreen with SPF of 45 or greater, there were no adverse events.