Photodynamic therapy - PDT
Levulan® (ALA) or methyl aminolevulinate (MAL) + red and/or blue light
For about a decade now, dermatologists have begun providing in-office light therapy to their patients in a 2-step procedure which helps traditional light therapy work better by helping to shrink or destroy sebaceous (oil) glands, albeit with more side effects. Photodynamic therapy is normally administered 3-5 times at 2-4 week intervals and is often reserved for moderate to severe acne because of the seriousness of the procedure and the downtime involved.
How is it performed?
First, a photosensitizing agent, most commonly either a 5-20% solution of Levulan® (5-aminolevulinic acid - ALA) or a 20% solution of methyl aminolevulinate (MAL) is applied and allowed to incubate on the skin under an occlusive dressing for up to 3 hours. This 3-hour incubation time allows the photosensitizing agent to be absorbed into the skin and into the sebaceous glands. Next, red or blue light is shone on the skin, normally for 15-20 minutes. This light activates the photosensitizing agent, which kills acne bacteria and helps shrink oil glands. More recently, practitioners have begun using lasers and pulsed dye light as sources of light in PDT procedures as well.
What type of light is best?
This is a critical topic when it comes to acne and something that may account for the limited or entire lack of success some people experience with PDT. Red or blue LED light are most commonly used for PDT. Red light, because of its longer wavelength, penetrates deeper into the skin than blue light. According to a 2014 review article in the journal Clinical Cosmetic and Investigational Dermatology, "Although blue light allows sufficient tissue penetration for the treatment of thin actinic keratosis (small, rough, raised areas found on areas of your skin), red light penetrates deeper and is more effective for the treatment of thicker lesions and deeper targets such as the sebaceous gland...The literature has focused primarily on MAL-PDT followed by red light because targeting of the sebaceous glands is optimized with this regimen."1 If your dermatologist wants to use only blue light for PDT, you may want to ask why this is the case.
A new LED device that uses a combination of red and green light has recently been introduced. Although evidence for the efficacy of this device is limited, one study reported that it reduced acne by 89% and did not produce any severe side effects.2 More studies will be required to adequately estimate the results of this new green light device.
More recently, practitioners have begun using lasers instead of LED light as sources of light in PDT procedures. The main difference between lasers and LED light devices is that lasers shine light on a smaller, more focused area of the skin, and emit stronger light to that area compared to LED devices. The advantage of using lasers is that they may require a shorter incubation time with the photosensitizer.3
Practitioners have also begun using intense pulsed light (IPL) for PDT therapy. IPL uses high-powered light sources that flash light onto the skin. Unlike lasers and LED light devices, which shine light of a specific color, IPL shines broad-spectrum light that includes wavelengths of 500 to 1200 nm.4 IPL combined with the photosensitizer ALA seems to result in a moderate reduction (55-65%) in acne, although studies that evaluated the effectiveness of IPL have a small sample size and more studies are needed in order to reach a conclusive result.5-7
Which photosensitizing agent is best?
This is also an important topic and one that may partially account for the frustration of people who do not achieve the results they desire with PDT. With acne in particular, methyl aminolevulinate (MAL) may be a better choice as photosensitizing agent since it may have a higher affinity for fatty environments like sebaceous glands and the sebum (skin oil) therein. MAL may also achieve deeper skin penetration than ALA.
The length of time that the physician allows the chosen photosensitizer to incubate is also important to the success of PDT. Some evidence is showing that a full 3-hour (180 minute) incubation time may be best.1 Due to crowdedness inside doctors’ offices and the desire for patient turnover, this incubation time can be cut short, potentially sacrificing results. However, if lasers or intense pulsed light are used in combination with ALA, incubation time of only 45 minutes is sufficient.3 Be sure to carefully ask your doctor about incubation time.
Recently, researchers have been testing a new photosensitizer with anti-inflammatory properties called indole-3-acetic acid (IAA), which has been shown to have fewer side effects than ALA or MAL, including far less pain during the procedure. However, it also produces less damage to the sebaceous glands, which may result in lower efficacy. Two studies, both of which used a small sample size, reported that IAA treatment results in a more modest reduction in acne (about 30% reduction) than ALA treatment.8-9 However, IAA does not produce any negative side effects and may therefore be a good option for those who experience severe pain or swelling with ALA or MAL treatment. IAA has not been approved for use in the United States yet, but may become available in the future.
In contrast to at-home light devices without photosensitizing agents, patients undergoing photodynamic therapy in a dermatologist's office can expect to experience pain during treatment, sometimes severe. Side effects of PDT include redness, swelling, itching, and peeling and/or crusting for a week or so, as well as occasional hyperpigmentation (skin darkening) that can last for a month after the procedure and is more common in people of darker skin types. Most people prefer not to leave the house for several days after the procedure. Patients may also experience a flare of acne that is transient in nature and should subside. Because the skin is highly photosensitized, it is also imperative that patients stay completely out of the sun and even avoid bright indoor light for 2 days after treatment.
Side effects vary depending upon the type of photosensitizer used, with MAL tending to produce the most severe pain during treatment and potentially a higher chance of hyperpigmentation. Researchers are currently performing studies on lower concentrations of photosensitizers to gauge whether this will provide the same results with fewer side effects.4 As mentioned, researchers are also looking into other photosensitizers that produce less pain, fewer side effects, and require shorter incubation times, such as Indole-3-acetic acid (IAA) with green light.9 Unlike ALA and MAL, IAA reduces the amount of sebum without causing destruction of sebaceous glands, which accounts for fewer side effects experienced with IAA compared to ALA or MAL treatment, but may also produce shorter-term results.12 Also, sebaceous glands produce oil that lubricates and protects the skin, so killing sebaceous glands outright may not be prudent.
Regardless of which source of light is used, most patients report feeling mild to moderate pain and swelling and peeling of the skin after photodynamic therapy.13 These side effects are temporary and usually go away 1-2 weeks after treatment.
Long term side effects: Photodynamic therapy is still a relatively new treatment and studies have not evaluated potential long-term side effects. PDT therapy works by shrinking oil glands. It shrinks them from what we can see from studies for at least 3 months and perhaps much longer or even permanently. This can be a double-edged sword. On the positive side, it can reduce acne since people with acne tend to have larger sebaceous glands (skin oil glands) glands that produce more total oil than people without acne. But on the negative side, sebum occupies several roles in human skin, and it is unknown what the long-term consequences would be from permanently impairing sebum output. Sebum has antibacterial properties, regulates immune response in the skin, helps the skin retain moisture, and distributes antioxidants, hormones, and pheromones over the skin. Scientists also wonder if there are undiscovered actions of sebum, for instance contributing to the graceful ageing of the skin later in life.
The following chart shows all of the studies performed thus far on PDT.
|Treatment||Number of studies||Number of participants||% Reduction in acne||Side effects|
|ALA + Red LED||711,14-18||8, 10,10 30, 75, 78, 297||50-95%||Mild to moderate pain and swelling|
|ALA + Red LED + Green LED||12||46||89%||No severe side effects reported. No information on mild to moderate side effects given.|
|ALA + Blue LED||119||18||44%||Swelling and peeling|
|ALA + IPL||45-7,20||12, 13, 19, 41||55-75%||Moderate pain and swelling|
|ALA + PDL Laser||221-22||19, 44||100%, 30%||Minor swelling and peeling|
|MAL + Red LED||323-25||36, 44, 153||37-68%||Mild to severe pain and swelling|
|MAL + PDL Laser||126||15||53%||Moderate to severe pain|
|IAA + Green LED||28-9||22, 25||29-33%||None|
Results from studies point toward an average reduction in inflammatory acne of about 60% after 3 treatments.14,18,23,27-34 The best results are experienced by people with more severe forms of acne.2,11,19,35 When results are experienced, they tend to be semi-permanent. Researchers normally perform follow-up from studies for a maximum of 3 months, so it is hard to tell how long results last, but some dermatologists report 1- or even 2-year reduction in symptoms.
A large systematic review published in 2016 reviewed all available clinical studies that evaluated the use of photodynamic therapy. The reviewers concluded that PDT is effective, and is effective even for more severe cases of acne, and works on body acne as well.13
[A] Majority of studies reviewed... showed the effectiveness of PDT in treating mild to severe acne vulgaris on face…There are also studies that have successfully demonstrated the effectiveness of PDT on acne lesions on the back and at different sites."13
However, it is important to keep in mind that while a few of the studies included large numbers of patients, most of these studies included only a small number of people and some relied on patient reports of the severity of their acne and their own satisfaction with the treatment, which is not an objective method of quantifying the results. In addition, there was a large variability in the treatments administered in each study, with researchers using different doses of photosensitizing agents (between 5 and 20% of ALA), duration of laser treatments, and treatment frequencies.13 More studies on a larger population with a controlled regimen of treatment are needed to reach conclusive results on the effectiveness of photodynamic therapy on acne.
Reviews on Acne.org are mixed, but keep in mind that the type of photosensitizer, incubation time, and light source used tends to vary depending on the procedure the reviewer has undergone. If you and your physician decide that photodynamic therapy is a good option for you, please leave your review once you are finished, or better yet, start a gallery of your progress and allow us to follow along.
Each treatment costs on average about $400 and is normally not covered by insurance. To inquire about treatment, contact your dermatologist.
The bottom line
At this time, PDT looks like a promising treatment, however we do not yet know how long the effects last, nor the long-term side effects. There are many topical treatments which can keep acne at bay which do not potentially permanently alter the skin. See a list of various acne treatments here.
- Wan, M. T. & Lin, J. Y. Current evidence and applications of photodynamic therapy in dermatology. Clin Cosmet Investig Dermatol 7, 145–163 (2014).
- Dong, Y. et al. A new LED device used for photodynamic therapy in treatment of moderate to severe acne vulgaris. Photodiagnosis Photodyn Ther 13, 188–195 (2016).
- Jih, M. H. & Kimyai-Asadi, A. Laser treatment of acne vulgaris. Semin Plast Surg 21, 167–174 (2007).
- Bisaccia, E., Lugo, A., Johnson, B. & Scarborough, D. Intense pulsed light systems. (2006).
- Santos, M. A., Belo, V. G. & Santos, G. Effectiveness of photodynamic therapy with topical 5-aminolevulinic acid and intense pulsed light versus intense pulsed light alone in the treatment of acne vulgaris: comparative study. Dermatol Surg 31, 910–915 (2005).
- Yeung, C. K., Shek, S. Y., Yu, C. S., Kono, T. & Chan, H. H. Liposome-encapsulated 0.5% 5-aminolevulinic acid with intense pulsed light for the treatment of inflammatory facial acne: a pilot study. Dermatol Surg 37, 450–459 (2011).
- Gold, M. H., Biron, J. A., Boring, M., Bridges, T. M. & Bradshaw, V. L. Treatment of moderate to severe inflammatory acne vulgaris: photodynamic therapy with 5-aminolevulinic acid and a novel advanced fluorescence technology pulsed light source. J Drugs Dermatol 6, 319–322 (2007).
- Kwon, S. H. et al. A new therapeutic option for facial seborrhoeic dermatitis: indole-3-acetic acid photodynamic therapy. J Eur Acad Dermatol Venereol 28, 94–99 (2014).
- Huh, S. Y., Na, J. I., Huh, C. H. & Park, K. C. The effect of photodynamic therapy using indole-3-acetic Acid and green light on acne vulgaris. Ann Dermatol 24, 56–60 (2012).
- Asayama-Kosaka, S., Akilov, O. E. & Kawana, S. Photodynamic Therapy with 5% delta-Aminolevulinic Acid is Safe and Effective Treatment of Acne Vulgaris in Japanese Patients. Laser Ther 23, 115–120 (2014).
- Ma, L. et al. Low-dose topical 5-aminolevulinic acid photodynamic therapy in the treatment of different severity of acne vulgaris. Photodiagnosis Photodyn Ther 10, 583–590 (2013).
- Na, J. I. et al. Indole-3-acetic acid: a potential new photosensitizer for photodynamic therapy of acne vulgaris. Lasers Surg Med 43, 200–205 (2011).
- Keyal, U., Bhatta, A. K. & Wang, X. L. Photodynamic therapy for the treatment of different severity of acne: A systematic review. Photodiagnosis Photodyn Ther 14, 191–199 (2016).
- Pollock, B. et al. Topical aminolaevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action. Br J Dermatol 151, 616–622 (2004).
- Wang, H. W. et al. Prospective study of topical 5-aminolevulinic acid photodynamic therapy for the treatment of moderate to severe acne vulgaris in Chinese patients. J Cutan Med Surg 16, 324–333 (2012).
- Yang, G. L. et al. Short-term clinical effects of photodynamic therapy with topical 5-aminolevulinic acid for facial acne conglobata: an open, prospective, parallel-arm trial. Photodermatol Photoimmunol Photomed 29, 233–238 (2013).
- Fabbrocini, G. et al. The effect of aminolevulinic acid photodynamic therapy on microcomedones and macrocomedones. Dermatology 219, 322–328 (2009).
- Hong, S. B. & Lee, M. H. Topical aminolevulinic acid-photodynamic therapy for the treatment of acne vulgaris. Photodermatol Photoimmunol Photomed 21, 322–325 (2005).
- Taub, A. F. Photodynamic therapy for the treatment of acne: a pilot study. J Drugs Dermatol 3, S10–14 (2004).
- Mei, X., Shi, W. & Piao, Y. Effectiveness of photodynamic therapy with topical 5-aminolevulinic acid and intense pulsed light in Chinese acne vulgaris patients. Photodermatol Photoimmunol Photomed 29, 90–96 (2013).
- Orringer, J. S. et al. Photodynamic therapy for acne vulgaris: a randomized, controlled, split-face clinical trial of topical aminolevulinic acid and pulsed dye laser therapy. J Cosmet Dermatol 9, 28–34 (2010).
- Alexiades-Armenakas, M. Long-pulsed dye laser-mediated photodynamic therapy combined with topical therapy for mild to severe comedonal, inflammatory, or cystic acne. J Drugs Dermatol 5, 45–55 (2006).
- Wiegell, S. R. & Wulf, H. C. Photodynamic therapy of acne vulgaris using 5-aminolevulinic acid versus methyl aminolevulinate. J Am Acad Dermatol 54, 647–651 (2006).
- Bissonnette, R., Maari, C., Nigen, S., Provost, N. & Bolduc, C. Photodynamic therapy with methylaminolevulinate 80 mg/g without occlusion improves acne vulgaris. J Drugs Dermatol 9, 1347–1352 (2010).
- Pariser, D. M. et al. Photodynamic therapy with methyl aminolaevulinate 80 mg g(-1) for severe facial acne vulgaris: a randomized vehicle-controlled study. Br J Dermatol 174, 770–777 (2016).
- Haedersdal, M., Togsverd-Bo, K. & Wulf, H. C. Evidence-based review of lasers, light sources and photodynamic therapy in the treatment of acne vulgaris. J Eur Acad Dermatol Venereol 22, 267–278 (2008).
- Hong, J. S., Jung, J. Y., Yoon, J. Y. & Suh, D. H. Acne treatment by methyl aminolevulinate photodynamic therapy with red light vs. intense pulsed light. Int J Dermatol 52, 614–619 (2013).
- Hongcharu, W. et al. Topical ALA-photodynamic therapy for the treatment of acne vulgaris. J Invest Dermatol 115, 183–192 (2000).
- Wiegell, S. R. & Wulf, H. C. Photodynamic therapy of acne vulgaris using methyl aminolaevulinate: a blinded, randomized, controlled trial. Br J Dermatol 154, 969–976 (2006).
- Akaraphanth, R., Kanjanawanitchkul, W. & Gritiyarangsan, P. Efficacy of ALA-PDT vs blue light in the treatment of acne. Photodermatol Photoimmunol Photomed 23, 186–190 (2007).
- Goldman, M. P. & Boyce, S. M. A single-center study of aminolevulinic acid and 417 NM photodynamic therapy in the treatment of moderate to severe acne vulgaris. J Drugs Dermatol 2, 393–396 (2003).
- Horfelt, C., Funk, J., Frohm-Nilsson, M., Wiegleb Edstrom, D. & Wennberg, A. M. Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne vulgaris: results of a randomized, controlled study. Br J Dermatol 155, 608–613 (2006).
- Pinto, C., Schafer, F., Orellana, J. J., Gonzalez, S. & Hasson, A. Efficacy of red light alone and methyl-aminolaevulinate-photodynamic therapy for the treatment of mild and moderate facial acne. Indian J Dermatol Venereol Leprol 79, 77–82 (2013).
- Shaaban, D., Abdel-Samad, Z. & El-Khalawany, M. Photodynamic therapy with intralesional 5-aminolevulinic acid and intense pulsed light versus intense pulsed light alone in the treatment of acne vulgaris: a comparative study. Dermatol Ther 25, 86–91 (2012).
- Gold, M. H. et al. The use of a novel intense pulsed light and heat source and ALA-PDT in the treatment of moderate to severe inflammatory acne vulgaris. J Drugs Dermatol 3, S15–19 (2004).