Photodynamic Therapy - PDT
Levulan® (ALA) or Methyl Aminolevulinate (MAL) + Red and/or Blue Light
The Essential Information
What it is: Photodynamic therapy is a serious 2-step procedure performed in a doctor's office that helps shrink oil glands and clear acne. Studies show an average of 60% reduction in acne, and results appear to last for months afterward, and perhaps long term. Because it is so painful, comes with side effects, and can permanently change the skin, it is normally reserved for more severe cases of acne.
What it costs: When all is said and done, it normally costs between $1200-$2000.
What it entails: These two steps are performed for a total of about 3-5 times, at 2-4 week intervals:
- A product called a photosensitizer is applied to the skin, which makes the skin more sensitive to light.
- Powerful medical lamps with red and/or blue light is shone on the skin for about 15-20 minutes. Alternately, some doctors are now using lasers or a type of light called pulsed dye light (PDT).
Side effects: Most people who undergo photodynamic therapy claim that it is very painful. It also comes with far more severe side effects than traditional light therapy, including redness, swelling, itching, and peeling and/or crusting for a week or so after the procedure, as well as the potential--especially in darker-skinned people--for hyperpigmentation (skin darkening) that can last for a month. Most people choose not to leave the house for several days after the procedure.
Caution: Because photodynamic therapy impairs oil glands, and may shrink them long term, it is a serious procedure that should be entered into very carefully. Anything that potentially permanently alters the body should be met with caution. For instance, could shrinking oil glands permanently cause the skin to age faster? We do not yet know the long-term effects of photodynamic therapy.
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. Research suggests that red light, because of its longer wavelength, penetrates deeper into the skin than blue light and can work better for thicker lesions.1
Expand to read details of research
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.1Due 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.3Be 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.4,10-12 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.9Unlike 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.12Also, 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.13These 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 aging of the skin later in life.
The following chart shows all of the studies performed thus far on PDT.
Results from studies point toward an average reduction in inflammatory acne of about 60% after 3 treatments.14,18,23,27-34The best results are experienced by people with more severe forms of acne.2,11,19,35When 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
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.13More 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 are 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). https://www.ncbi.nlm.nih.gov/pubmed/24899818
- 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). https://www.ncbi.nlm.nih.gov/pubmed/26116283
- Jih, M. H. & Kimyai-Asadi, A. Laser treatment of acne vulgaris. Semin. Plast. Surg. 21, 167 - 174 (2007). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884837/
- Bisaccia, E., Lugo, A., Johnson, B. & Scarborough, D. Intense pulsed light systems. (2006). https://en.wikipedia.org/wiki/Intense_pulsed_light
- 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). https://www.ncbi.nlm.nih.gov/pubmed/16042935
- 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). https://www.ncbi.nlm.nih.gov/pubmed/21414073
- 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). https://www.ncbi.nlm.nih.gov/pubmed/17373194
- 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). https://www.ncbi.nlm.nih.gov/pubmed/17373194
- 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). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283851/
- 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). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112280/
- 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). https://www.ncbi.nlm.nih.gov/pubmed/24284115
- 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). https://www.ncbi.nlm.nih.gov/pubmed/21412803
- 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). https://www.ncbi.nlm.nih.gov/pubmed/27090488
- 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). https://www.ncbi.nlm.nih.gov/pubmed/15377348
- 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). https://www.ncbi.nlm.nih.gov/pubmed/25772520
- 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). https://www.ncbi.nlm.nih.gov/pubmed/24001378
- Fabbrocini, G. et al. The effect of aminolevulinic acid photodynamic therapy on microcomedones and macrocomedones. Dermatology 219, 322 - 328 (2009). https://www.ncbi.nlm.nih.gov/pubmed/19851060
- Hong, S. B. & Lee, M. H. Topical aminolevulinic acid-photodynamic therapy for the treatment of acne vulgaris. Photodermatol. Photoimmunol. Photomed. 21, 322 - 325 (2005). https://www.ncbi.nlm.nih.gov/pubmed/16313244
- Taub, A. F. Photodynamic therapy for the treatment of acne: a pilot study. J. Drugs Dermatol. 3, S10 - 14 (2004). https://www.ncbi.nlm.nih.gov/pubmed/15624736
- 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). https://www.ncbi.nlm.nih.gov/pubmed/23458393
- 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). https://www.ncbi.nlm.nih.gov/pubmed/20367670
- 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). https://www.ncbi.nlm.nih.gov/pubmed/16468292
- 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). https://www.ncbi.nlm.nih.gov/pubmed/16546587
- 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). http://europepmc.org/article/med/21061756
- 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). https://www.ncbi.nlm.nih.gov/pubmed/26663215
- 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). https://www.ncbi.nlm.nih.gov/pubmed/18221341
- 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). https://www.ncbi.nlm.nih.gov/pubmed/23046014
- Hongcharu, W. et al. Topical ALA-photodynamic therapy for the treatment of acne vulgaris. J. Invest. Dermatol. 115, 183 - 192 (2000). https://www.ncbi.nlm.nih.gov/pubmed/10951234
- 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). https://www.ncbi.nlm.nih.gov/pubmed/16634903
- 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). https://www.ncbi.nlm.nih.gov/pubmed/17803597
- 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). https://www.ncbi.nlm.nih.gov/pubmed/12884461
- 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). https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0781.2007.00290.x
- 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). https://www.ncbi.nlm.nih.gov/pubmed/23254733
- 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). https://www.ncbi.nlm.nih.gov/pubmed/22591502
- 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). https://www.ncbi.nlm.nih.gov/pubmed/15624737