Elsevier

Clinics in Dermatology

Volume 26, Issue 6, November–December 2008, Pages 608-613
Clinics in Dermatology

Photodynamic therapy in skin rejuvenation

https://doi.org/10.1016/j.clindermatol.2007.09.009Get rights and content

Abstract

Photodynamic therapy is a noninvasive technique used in the treatment of various skin disorders. This article will provide readers with an extensive review of the popular chosen topical photosensitizers, varied used light sources and lasers, and medical and cosmetic indications treated with photodynamic therapy.

Introduction

Photodynamic therapy (PDT) is a noninvasive technique used in the treatment of various skin disorders. It has been used for skin cancer, precancerous changes of the skin, and for cosmetic purposes in skin rejuvenation. Photodynamic therapy was first introduced in the early 1900s as an experimental treatment that consisted of oxygen, light, and a photosensitizing agent to cause tumor cell destruction. Systemic photosensitizing drugs were used because these agents accumulated selectively in tumor cells and therefore led to selective cell destruction. Photodynamic therapy was first used for the treatment of internal malignancies such as tumors of the bladder and esophagus, as well as some skin conditions. The drawback to these early treatments was the prolonged cutaneous photosensitivity of the used systemic agents. It was not until 1990, when Kennedy and colleagues introduced the use of 5-aminolevulinic acid (ALA), that PDT as we know of it today dramatically changed. 5-Aminolevulinic acid became a potent topical photosensitizing agent that could be used for photodynamic therapy without significant phototoxicity. The US Food and Drug Administration approved this agent in 1999 in combination with light for the treatment of actinic keratoses (AKs). Since then, photodynamic therapy has generated vast interest in terms of research and clinical application. In Europe, PDT is being used for AKs and basal cell carcinomas.

Photodynamic therapy photorejuvenation, as a named procedure for aesthetic and cosmetic laser surgeons, took hold when Bitter,1 in 2000, published the first clinical article on the topic of photorejuvenation. In Bitter's study, more than 90% of the patients studied had a greater than 75% improvement in rosacea symptoms (facial erythema and flushing), 84% had an improvement in their fine wrinkles, 78% had significant changes in their facial pigment, and 49% noted an improvement in their pore size. Each patient in this study received five full-face intense pulsed light treatments at a 1-month interval. This is still the standard of care performed today. Others also noted improvements in photodamage, that is, photorejuvenation with the IPLs, including several studies by Goldberg and Samady,2 Weiss et al,3 and Sadick.4 In the study by Goldberg, one third of the individuals (n = 30) noted substantial improvements with their IPL treatments, whereas one half of the subjects noted some improvement with the IPL. Weiss, in a retrospective analysis of his IPL-treated patients, found that, at 5 years, patients still maintained improvement in their skin texture (83%), telangiectasias (82%), and dyschromia (79%). Furthermore, in work reported by Sadick, more than 90% of treated patients had improvement in their wrinkle appearance. Other important investigations included clinical studies by Negishi et al5 showing the effectiveness of IPL photorejuvenation treatments in the Asian population and by Hernandez-Perez6 showing improvement in patients of Hispanic ethnicity.

IPL photorejuvenation has become a mainstay in the aesthetic and cosmetic arena; it improves both vascular and pigmented concerns and improves the collagen and elastic tissue changes associated with photodamaged skin. The procedure has become predictable and, in the right hands, with the proper training and guidance, is very safe and effective, with consistent results and minimum downtime. That these treatments result in minimum downtime for patients is very significant and is one of the main reasons for its popularity today. As a result, IPL use has increased tremendously over the past several years, with now almost every laser company producing an IPL to compliment their laser portfolio. IPLs on the market today are better than ever, with squared-off pulses and efficient cooling systems common in today's devices.

IPL photorejuvenation is safe, effective, predictable, and is a minimum downtime procedure. The success of IPL treatments has led to the obvious question. Is it possible to improve on the use of this procedure? A variety of clinical investigators have been pondering these questions for the past several years. Many believe this can be done through the use of PDT to enhance the photorejuvenation process.

Photodynamic therapy, in its simplest form, is a procedure that requires a photosensitizer, light, and oxygen. The most common photosensitizer available for use with PDT is 20% ALA. Once applied to the skin, ALA is transformed into protoporphyrin IX (PpIX), the active ingredient for a PDT reaction to occur. Previous work has shown that PpIX is absorbed into actinically damaged skin cells and into the pilosebaceous units of the skin. On exposure to a light source of a proper wavelength, singlet oxygen is formed, a PDT reaction will occur, causing destruction of the cells in which PpIX has accumulated. Research with ALA-PDT initially focused on its use on AKs and, in the United States, with blue light. Blue light was chosen because it coincides with the largest absorption band of PpIX, known as the Soret band. This wavelength is not the only wavelength that will activate ALA; and other lasers and light sources, as will be described below, also play key roles in the concept of “photodynamic photorejuvenation.”

Section snippets

Photosensitizing drugs

Currently, there are two topical agents that are widely used as photosensitizing drugs for PDT. These are ALA and methyl ALA. These agents stimulate the production of porphyrins, which act as powerful photosensitizers.

Light sources

Several light sources are available for PDT. Human tissue has the highest absorption for ALA in a spectral range of 600 to 800 nm. Numerous other wavelengths, however, have been successfully used. Nevertheless, it would appear that the ideal wavelength that matches the absorption spectra of photosensitizers is 630 nm. At a spectra of 630 to 700 nm, malignant tumor cells of basal cell carcinoma and squamous cell carcinoma have been demonstrated to have a higher intensity of PpIX fluorescence,

Lasers

Lasers have been used in PDT for the curative treatment of AKs, superficial basal cell carcinoma, Bowen disease, and even as palliative treatment of cutaneous metastases in some patients. Kaviani and colleagues13 used laser light in the PDT of different kinds of basal cell carcinoma and obtained excellent response rates except for the pigmented type.

Basal cell carcinoma

Photodynamic therapy has been shown to be highly effective for the treatment of superficial basal cell carcinoma.15, 16 A large number of clinical trials and observational studies using ALA-PDT have demonstrated its superior effect as treatment of superficial basal cell carcinoma, with lesser recurrence rates for the treatment of this form of basal cell carcinoma when compared with other forms of basal cell carcinoma. Studies on nodular basal cell carcinoma showed varying results, with response

Skin rejuvenation

In one of the most important studies evaluating ALA-PDT, and its role in photodynamic skin rejuvenation, Touma et al23 presented evidence that a 1-hour drug incubation time was as efficacious as a 14- to 18-hour drug incubation time in improving parameters of photodamage, that is, photorejuvenation. Patients noted improvements in facial skin sallowness, fine wrinkling, and mottled hyperpigmentation.

Another important clinical trial was that of Ruiz-Rodriquez et al24 who also looked at a shorter

My approach

There are no specific guidelines as to how PDT must be used for skin rejuvenation. A recent US consensus paper does outline steps that may be taken when using PDT.30

Informed consent requires that the treating physician review with the relevant risks and benefits of the procedure. A signed, written consent will verify that one has reviewed the necessary information and potential reasonable complications with a patient. In the United States, at the present time, ALA-PDT used for skin rejuvenation

Conclusions

Photodynamic therapy continues to flourish as one of the primary therapeutic modalities for certain skin conditions, offering advantages of excellent cosmetic outcome and outstanding results. New indications will continue to emerge as research and clinical trials continue to offer new techniques and concepts to improve the efficacy of this treatment option.

The future for ALA-PDT and MAL-PDT looks very exciting. Further clinical trials will continue to define protocols and parameters for the use

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