Over the past several years, the use of 20% 5-aminolevulinic acid (ALA) in photodynamic therapy (PDT) has grown tremendously with many clinicians utilizing this therapy for a variety of clinical conditions.
ALA-PDT: What Conditions Are Being Treated?
ALA-PDT is being used to treat many clinical entities as we reach the end of 2007. These include AKs and the signs of photodamage, i.e., photorejuvenation. ALA-PDT has also become a therapeutic option for those suffering from moderate to severe inflammatory acne vulgaris. Those suffering from sebaceous gland hyperplasia (SGH) are also benefiting from PDT, and it has found a niche in patients suffering from hidradenitis suppurativa (HS). These topics have been reviewed thoroughly in the medical literature. Highlights will be included in this article.
What Has Been Approved and a Look at the Original Studies
The available drug for use in PDT in the United States is known as Levulan Kerastick from DUSA Pharmaceuticals in Wilmington, MA. A second form of the drug, the methyl ester of 20% 5-ALA, which will be known as Metvixia, is from Galderma. This drug received FDA clearance for treating AKs, and when available, it will be recommended for use with red light.
Clinical studies in Europe with methyl ALA have demonstrated its efficacy in treating AKs and basal cell carcinomas (BCCs) with a 3-hour occluded drug incubation followed by exposure to a red light source. At the time of this writing, Metvixia is not available in the U.S. market, but will be available at some point in the near future.
In 2007, Levulan Kerastick is still the only ALA product currently available, and the remainder of this article will focus on this drug. Levulan Kerastick is used with the original blue light source, known as the Blu-U from DUSA Pharmaceuticals. The Kerastick preparation has been previously described, and reviews of its use in dermatology have been published in our literature.1-4
Treating AKs
Other clinical manuscripts have documented its efficacy in treating nonhyperkeratotic AKs of the face and scalp and have also demonstrated that short-contact, full-face treatments with ALA have shown efficacy in treating AKs and signs of photodamage. Also, a variety of lasers and light sources have activated ALA, as has also been previously described, based on the absorption spectrum of protoporphyrin IX (PpIX), the active form of the prodrug, ALA. The action absorption spectrum of PpIX is shown in Figure 1.
In summary, the Phase II pivotal clinical trial involved 39 individuals who had their individual AKs treated with the long 14- to 18-hour drug incubation and then received 16 minutes and 40 seconds of blue light therapy. After 8 weeks, 66% of the treated AKs had responded; and if a second treatment was performed, 85% of the AKs showed complete clearance. A “PDT effect,” downtime with healing, was observed following the therapy.5
From the success of the Phase II clinical trial, a larger Phase III clinical trial was performed. In this trial, 243 patients were treated in a similar fashion as described above. By week 12, 70% of the treated AKs responded, which increased to 88% at 24 weeks after a second treatment. Again, a PDT effect was seen in the majority of patients. A secondary endpoint in this study was that 94% of the individuals in the study rated their cosmetic appearance as good to excellent as a result of their treatments.6
From these clinical trials, Levulan received FDA approval. Further work included studies on the pulsed dye laser (PDL) by Alexiades-Armenakas et al, and showed that the PDL also worked well in clearing AKs7 and actinic cheilitis lesions.8 Shorter drug incubations were utilized in these trials, with patients showing similar efficacies at 3 hours as with the longer 14- to 18-hour drug incubation times.
Treating Photodamage
This author published a manuscript on the use of ALA on photoaging in 2002 — again with long drug incubations but demonstrating a photorejuvenation effect in those treated, showing benefits for the contiguous lesions that were treated.9 Two very important clinical papers appearing in the literature followed. The first by Touma et al10 showed that short-contact, full-face drug incubation for 1 hour was as efficacious in reducing the signs of photodamage as was the 14- to 18-hour drug incubation period. Their study utilized a blue light source.
Then Rodriquez et al11 described the use of an intense pulsed light source (IPL) in treating AKs and photorejuvenation. In this study, two IPL treatments with a shorter drug incubation time cleared all of the AKs and resulted in an 87% improvement in the signs of photoaging.
Several other important clinical trials soon appeared, making short-contact, full-face Levulan treatments the standard of care for the treatment of AKs and photorejuvenation.12-14 This was confirmed further by the publication of five clinical trials, which utilized a split-faced approach — either utilizing an IPL or PDL on one half of the face and ALA and the PDL or IPL on the other one half of the face. All of these trials showed further the benefits of ALA in treating AKs and photodamaged skin.15-19
In particular, Dover et al18 showed an improvement in the global score for photoaging (80% versus 50%), mottled hyperpigmentation (95% versus 65%), and improvement in fine lines (55% versus 20%).
Gold et al19 showed improvement in AKs (78% versus 53.6%), crow’s feet (55% versus 28.5%), tactile skin roughness (55% versus 29.5%), mottled hyperpigmentation (60.3% versus 37.2%), and improvement in erythema (84.6% versus 53.8%).
These trials were all conducted in the short-contact, full-face mode, and as a result, there were no appreciable PDT effects seen in any of these trials. This confirmed the fact that ALA-PDT is useful for the treatment of AKs and for photorejuvenation. It also showed that this therapy provided improvement in these parameters at a faster rate than with conventional laser and light source therapy alone. A clinical example of the use of ALA in the treatment of AKs and photorejuvenation is shown in Figure 2.
Treating Acne Vulgaris
ALA-PDT is also used off-label for the treatment of moderate to severe inflammatory acne vulgaris. Several open-labeled clinical trials have shown the effectiveness of utilizing short-contact, full-face ALA and a variety of lasers and light sources in treating this disorder.
Hongcharu et al20 and Itoh et al21,22 were the first to evaluate the use of ALA in inflammatory acne vulgaris. Goldman23 was the first to describe the use of short-contact (1 hour), full-face ALA-PDT utilizing either a blue light source or an IPL in treating inflammatory acne vulgaris and sebaceous gland hyperplasia. A relative clearing of the acne lesions was described, and no PDT effect was seen following the therapy.
Gold24 reported his experience with 10 patients and a 30-minute drug incubation with the blue light source. A 60% improvement in this patient group was seen as compared to 43% with light alone. Once again, PDT effects were not seen.
Goldman et al25 reported their experience with 22 patients and showed that there was more of a response in treating inflammatory acne vulgaris with ALA and a blue light than blue light alone. Gold et al26 reported a 72% improvement in 12 individuals utilizing short-contact ALA and an IPL.
Taub27 reported success with both blue light or an IPL as well, with no PDT effects seen.
Alexiades-Armenakas28 showed complete clearance utilizing a PDL in three sessions in her acne vulgaris clinical trial and a 45-minute ALA drug incubation.
Miller and Van Camp29 showed that the KTP laser yielded successful acne vulgaris treatments with ALA as well.
Two split-face acne vulgaris trials have been performed. Santos et al30 and Rojanamatin et al31 utilized short-contact ALA on one half of the face and followed this with full-face IPL therapies. In both of these clinical trials, the ALA-IPL side outperformed the IPL side, confirming that ALA-PDT was useful for moderate to severe inflammatory acne vulgaris. On a personal note, we and others have observed that when clearing occurs in these individuals, there appears to be an opportunity for the acne to remain clear for quite some time. Several patients have been clear for upward of 2 years, and a recent case by Nestor32 documented clearance for 5 years. An example of a patient treated with ALA for inflammatory acne vulgaris is shown in Figure 3.
Large U.S. Clinical Trial Underway to Study Acne Vulgaris
At the time of this writing, a large multi-center clinical trial was underway in the United States to further evaluate ALA-PDT in the treatment of moderate to severe inflammatory acne vulgaris. It is a placebo-controlled clinical trial with multiple arms to help us further define what role ALA-PDT will have in the future for acne therapy in the United States.
It is hoped that if the results confirm those from the previous clinical trials, a label extension might be given for ALA and insurance company approval of this therapy may be forthcoming.
Two Other Conditions Faring Well from ALA-PDT Treatment
Two other entities are worth noting in this review. ALA-PDT has been successfully described as a useful therapeutic modality for the treatment of sebaceous gland hyperplasia with PDL, IPLs, and blue light. Drug incubation times from the clinical trials vary, but most now favor a 1-hour drug incubation time with whichever light source is chosen.33-35
Hidradenitis suppurativa (HS), one of the more debilitating skin disorders dermatologists encounter and one that frustrates us on many occasions when developing an appropriate therapeutic plan, is the other condition worth noting. Several clinical trials have shown that blue light and ALA has improved HS and it should be considered as a therapy when encountering recalcitrant HS.36,37
How Well Are Dermatologists Embracing This Technology?
The state of ALA-PDT in 2007 is good and showing signs of continued growth in 2008 and beyond. The number of users of ALA-PDT continues to grow and when the numbers are examined closely, “medical” dermatologists are beginning to embrace this therapy as did the “cosmetic” and “surgical” dermatologists when Levulan was introduced. This makes sense, as more medical dermatologists are apt to treat acne vulgaris than some of their surgical counterparts and because they also have large AK practices. So, the use is increasing and it is expected to continue to increase in the foreseeable future.
A second drug, Metvixia, will arrive, hopefully in 2008. When a second drug becomes available, this will allow more users to begin utilizing PDT, which will be good for all of our patients.
Over the past several years, the use of 20% 5-aminolevulinic acid (ALA) in photodynamic therapy (PDT) has grown tremendously with many clinicians utilizing this therapy for a variety of clinical conditions.
ALA-PDT: What Conditions Are Being Treated?
ALA-PDT is being used to treat many clinical entities as we reach the end of 2007. These include AKs and the signs of photodamage, i.e., photorejuvenation. ALA-PDT has also become a therapeutic option for those suffering from moderate to severe inflammatory acne vulgaris. Those suffering from sebaceous gland hyperplasia (SGH) are also benefiting from PDT, and it has found a niche in patients suffering from hidradenitis suppurativa (HS). These topics have been reviewed thoroughly in the medical literature. Highlights will be included in this article.
What Has Been Approved and a Look at the Original Studies
The available drug for use in PDT in the United States is known as Levulan Kerastick from DUSA Pharmaceuticals in Wilmington, MA. A second form of the drug, the methyl ester of 20% 5-ALA, which will be known as Metvixia, is from Galderma. This drug received FDA clearance for treating AKs, and when available, it will be recommended for use with red light.
Clinical studies in Europe with methyl ALA have demonstrated its efficacy in treating AKs and basal cell carcinomas (BCCs) with a 3-hour occluded drug incubation followed by exposure to a red light source. At the time of this writing, Metvixia is not available in the U.S. market, but will be available at some point in the near future.
In 2007, Levulan Kerastick is still the only ALA product currently available, and the remainder of this article will focus on this drug. Levulan Kerastick is used with the original blue light source, known as the Blu-U from DUSA Pharmaceuticals. The Kerastick preparation has been previously described, and reviews of its use in dermatology have been published in our literature.1-4
Treating AKs
Other clinical manuscripts have documented its efficacy in treating nonhyperkeratotic AKs of the face and scalp and have also demonstrated that short-contact, full-face treatments with ALA have shown efficacy in treating AKs and signs of photodamage. Also, a variety of lasers and light sources have activated ALA, as has also been previously described, based on the absorption spectrum of protoporphyrin IX (PpIX), the active form of the prodrug, ALA. The action absorption spectrum of PpIX is shown in Figure 1.
In summary, the Phase II pivotal clinical trial involved 39 individuals who had their individual AKs treated with the long 14- to 18-hour drug incubation and then received 16 minutes and 40 seconds of blue light therapy. After 8 weeks, 66% of the treated AKs had responded; and if a second treatment was performed, 85% of the AKs showed complete clearance. A “PDT effect,” downtime with healing, was observed following the therapy.5
From the success of the Phase II clinical trial, a larger Phase III clinical trial was performed. In this trial, 243 patients were treated in a similar fashion as described above. By week 12, 70% of the treated AKs responded, which increased to 88% at 24 weeks after a second treatment. Again, a PDT effect was seen in the majority of patients. A secondary endpoint in this study was that 94% of the individuals in the study rated their cosmetic appearance as good to excellent as a result of their treatments.6
From these clinical trials, Levulan received FDA approval. Further work included studies on the pulsed dye laser (PDL) by Alexiades-Armenakas et al, and showed that the PDL also worked well in clearing AKs7 and actinic cheilitis lesions.8 Shorter drug incubations were utilized in these trials, with patients showing similar efficacies at 3 hours as with the longer 14- to 18-hour drug incubation times.
Treating Photodamage
This author published a manuscript on the use of ALA on photoaging in 2002 — again with long drug incubations but demonstrating a photorejuvenation effect in those treated, showing benefits for the contiguous lesions that were treated.9 Two very important clinical papers appearing in the literature followed. The first by Touma et al10 showed that short-contact, full-face drug incubation for 1 hour was as efficacious in reducing the signs of photodamage as was the 14- to 18-hour drug incubation period. Their study utilized a blue light source.
Then Rodriquez et al11 described the use of an intense pulsed light source (IPL) in treating AKs and photorejuvenation. In this study, two IPL treatments with a shorter drug incubation time cleared all of the AKs and resulted in an 87% improvement in the signs of photoaging.
Several other important clinical trials soon appeared, making short-contact, full-face Levulan treatments the standard of care for the treatment of AKs and photorejuvenation.12-14 This was confirmed further by the publication of five clinical trials, which utilized a split-faced approach — either utilizing an IPL or PDL on one half of the face and ALA and the PDL or IPL on the other one half of the face. All of these trials showed further the benefits of ALA in treating AKs and photodamaged skin.15-19
In particular, Dover et al18 showed an improvement in the global score for photoaging (80% versus 50%), mottled hyperpigmentation (95% versus 65%), and improvement in fine lines (55% versus 20%).
Gold et al19 showed improvement in AKs (78% versus 53.6%), crow’s feet (55% versus 28.5%), tactile skin roughness (55% versus 29.5%), mottled hyperpigmentation (60.3% versus 37.2%), and improvement in erythema (84.6% versus 53.8%).
These trials were all conducted in the short-contact, full-face mode, and as a result, there were no appreciable PDT effects seen in any of these trials. This confirmed the fact that ALA-PDT is useful for the treatment of AKs and for photorejuvenation. It also showed that this therapy provided improvement in these parameters at a faster rate than with conventional laser and light source therapy alone. A clinical example of the use of ALA in the treatment of AKs and photorejuvenation is shown in Figure 2.
Treating Acne Vulgaris
ALA-PDT is also used off-label for the treatment of moderate to severe inflammatory acne vulgaris. Several open-labeled clinical trials have shown the effectiveness of utilizing short-contact, full-face ALA and a variety of lasers and light sources in treating this disorder.
Hongcharu et al20 and Itoh et al21,22 were the first to evaluate the use of ALA in inflammatory acne vulgaris. Goldman23 was the first to describe the use of short-contact (1 hour), full-face ALA-PDT utilizing either a blue light source or an IPL in treating inflammatory acne vulgaris and sebaceous gland hyperplasia. A relative clearing of the acne lesions was described, and no PDT effect was seen following the therapy.
Gold24 reported his experience with 10 patients and a 30-minute drug incubation with the blue light source. A 60% improvement in this patient group was seen as compared to 43% with light alone. Once again, PDT effects were not seen.
Goldman et al25 reported their experience with 22 patients and showed that there was more of a response in treating inflammatory acne vulgaris with ALA and a blue light than blue light alone. Gold et al26 reported a 72% improvement in 12 individuals utilizing short-contact ALA and an IPL.
Taub27 reported success with both blue light or an IPL as well, with no PDT effects seen.
Alexiades-Armenakas28 showed complete clearance utilizing a PDL in three sessions in her acne vulgaris clinical trial and a 45-minute ALA drug incubation.
Miller and Van Camp29 showed that the KTP laser yielded successful acne vulgaris treatments with ALA as well.
Two split-face acne vulgaris trials have been performed. Santos et al30 and Rojanamatin et al31 utilized short-contact ALA on one half of the face and followed this with full-face IPL therapies. In both of these clinical trials, the ALA-IPL side outperformed the IPL side, confirming that ALA-PDT was useful for moderate to severe inflammatory acne vulgaris. On a personal note, we and others have observed that when clearing occurs in these individuals, there appears to be an opportunity for the acne to remain clear for quite some time. Several patients have been clear for upward of 2 years, and a recent case by Nestor32 documented clearance for 5 years. An example of a patient treated with ALA for inflammatory acne vulgaris is shown in Figure 3.
Large U.S. Clinical Trial Underway to Study Acne Vulgaris
At the time of this writing, a large multi-center clinical trial was underway in the United States to further evaluate ALA-PDT in the treatment of moderate to severe inflammatory acne vulgaris. It is a placebo-controlled clinical trial with multiple arms to help us further define what role ALA-PDT will have in the future for acne therapy in the United States.
It is hoped that if the results confirm those from the previous clinical trials, a label extension might be given for ALA and insurance company approval of this therapy may be forthcoming.
Two Other Conditions Faring Well from ALA-PDT Treatment
Two other entities are worth noting in this review. ALA-PDT has been successfully described as a useful therapeutic modality for the treatment of sebaceous gland hyperplasia with PDL, IPLs, and blue light. Drug incubation times from the clinical trials vary, but most now favor a 1-hour drug incubation time with whichever light source is chosen.33-35
Hidradenitis suppurativa (HS), one of the more debilitating skin disorders dermatologists encounter and one that frustrates us on many occasions when developing an appropriate therapeutic plan, is the other condition worth noting. Several clinical trials have shown that blue light and ALA has improved HS and it should be considered as a therapy when encountering recalcitrant HS.36,37
How Well Are Dermatologists Embracing This Technology?
The state of ALA-PDT in 2007 is good and showing signs of continued growth in 2008 and beyond. The number of users of ALA-PDT continues to grow and when the numbers are examined closely, “medical” dermatologists are beginning to embrace this therapy as did the “cosmetic” and “surgical” dermatologists when Levulan was introduced. This makes sense, as more medical dermatologists are apt to treat acne vulgaris than some of their surgical counterparts and because they also have large AK practices. So, the use is increasing and it is expected to continue to increase in the foreseeable future.
A second drug, Metvixia, will arrive, hopefully in 2008. When a second drug becomes available, this will allow more users to begin utilizing PDT, which will be good for all of our patients.
Over the past several years, the use of 20% 5-aminolevulinic acid (ALA) in photodynamic therapy (PDT) has grown tremendously with many clinicians utilizing this therapy for a variety of clinical conditions.
ALA-PDT: What Conditions Are Being Treated?
ALA-PDT is being used to treat many clinical entities as we reach the end of 2007. These include AKs and the signs of photodamage, i.e., photorejuvenation. ALA-PDT has also become a therapeutic option for those suffering from moderate to severe inflammatory acne vulgaris. Those suffering from sebaceous gland hyperplasia (SGH) are also benefiting from PDT, and it has found a niche in patients suffering from hidradenitis suppurativa (HS). These topics have been reviewed thoroughly in the medical literature. Highlights will be included in this article.
What Has Been Approved and a Look at the Original Studies
The available drug for use in PDT in the United States is known as Levulan Kerastick from DUSA Pharmaceuticals in Wilmington, MA. A second form of the drug, the methyl ester of 20% 5-ALA, which will be known as Metvixia, is from Galderma. This drug received FDA clearance for treating AKs, and when available, it will be recommended for use with red light.
Clinical studies in Europe with methyl ALA have demonstrated its efficacy in treating AKs and basal cell carcinomas (BCCs) with a 3-hour occluded drug incubation followed by exposure to a red light source. At the time of this writing, Metvixia is not available in the U.S. market, but will be available at some point in the near future.
In 2007, Levulan Kerastick is still the only ALA product currently available, and the remainder of this article will focus on this drug. Levulan Kerastick is used with the original blue light source, known as the Blu-U from DUSA Pharmaceuticals. The Kerastick preparation has been previously described, and reviews of its use in dermatology have been published in our literature.1-4
Treating AKs
Other clinical manuscripts have documented its efficacy in treating nonhyperkeratotic AKs of the face and scalp and have also demonstrated that short-contact, full-face treatments with ALA have shown efficacy in treating AKs and signs of photodamage. Also, a variety of lasers and light sources have activated ALA, as has also been previously described, based on the absorption spectrum of protoporphyrin IX (PpIX), the active form of the prodrug, ALA. The action absorption spectrum of PpIX is shown in Figure 1.
In summary, the Phase II pivotal clinical trial involved 39 individuals who had their individual AKs treated with the long 14- to 18-hour drug incubation and then received 16 minutes and 40 seconds of blue light therapy. After 8 weeks, 66% of the treated AKs had responded; and if a second treatment was performed, 85% of the AKs showed complete clearance. A “PDT effect,” downtime with healing, was observed following the therapy.5
From the success of the Phase II clinical trial, a larger Phase III clinical trial was performed. In this trial, 243 patients were treated in a similar fashion as described above. By week 12, 70% of the treated AKs responded, which increased to 88% at 24 weeks after a second treatment. Again, a PDT effect was seen in the majority of patients. A secondary endpoint in this study was that 94% of the individuals in the study rated their cosmetic appearance as good to excellent as a result of their treatments.6
From these clinical trials, Levulan received FDA approval. Further work included studies on the pulsed dye laser (PDL) by Alexiades-Armenakas et al, and showed that the PDL also worked well in clearing AKs7 and actinic cheilitis lesions.8 Shorter drug incubations were utilized in these trials, with patients showing similar efficacies at 3 hours as with the longer 14- to 18-hour drug incubation times.
Treating Photodamage
This author published a manuscript on the use of ALA on photoaging in 2002 — again with long drug incubations but demonstrating a photorejuvenation effect in those treated, showing benefits for the contiguous lesions that were treated.9 Two very important clinical papers appearing in the literature followed. The first by Touma et al10 showed that short-contact, full-face drug incubation for 1 hour was as efficacious in reducing the signs of photodamage as was the 14- to 18-hour drug incubation period. Their study utilized a blue light source.
Then Rodriquez et al11 described the use of an intense pulsed light source (IPL) in treating AKs and photorejuvenation. In this study, two IPL treatments with a shorter drug incubation time cleared all of the AKs and resulted in an 87% improvement in the signs of photoaging.
Several other important clinical trials soon appeared, making short-contact, full-face Levulan treatments the standard of care for the treatment of AKs and photorejuvenation.12-14 This was confirmed further by the publication of five clinical trials, which utilized a split-faced approach — either utilizing an IPL or PDL on one half of the face and ALA and the PDL or IPL on the other one half of the face. All of these trials showed further the benefits of ALA in treating AKs and photodamaged skin.15-19
In particular, Dover et al18 showed an improvement in the global score for photoaging (80% versus 50%), mottled hyperpigmentation (95% versus 65%), and improvement in fine lines (55% versus 20%).
Gold et al19 showed improvement in AKs (78% versus 53.6%), crow’s feet (55% versus 28.5%), tactile skin roughness (55% versus 29.5%), mottled hyperpigmentation (60.3% versus 37.2%), and improvement in erythema (84.6% versus 53.8%).
These trials were all conducted in the short-contact, full-face mode, and as a result, there were no appreciable PDT effects seen in any of these trials. This confirmed the fact that ALA-PDT is useful for the treatment of AKs and for photorejuvenation. It also showed that this therapy provided improvement in these parameters at a faster rate than with conventional laser and light source therapy alone. A clinical example of the use of ALA in the treatment of AKs and photorejuvenation is shown in Figure 2.
Treating Acne Vulgaris
ALA-PDT is also used off-label for the treatment of moderate to severe inflammatory acne vulgaris. Several open-labeled clinical trials have shown the effectiveness of utilizing short-contact, full-face ALA and a variety of lasers and light sources in treating this disorder.
Hongcharu et al20 and Itoh et al21,22 were the first to evaluate the use of ALA in inflammatory acne vulgaris. Goldman23 was the first to describe the use of short-contact (1 hour), full-face ALA-PDT utilizing either a blue light source or an IPL in treating inflammatory acne vulgaris and sebaceous gland hyperplasia. A relative clearing of the acne lesions was described, and no PDT effect was seen following the therapy.
Gold24 reported his experience with 10 patients and a 30-minute drug incubation with the blue light source. A 60% improvement in this patient group was seen as compared to 43% with light alone. Once again, PDT effects were not seen.
Goldman et al25 reported their experience with 22 patients and showed that there was more of a response in treating inflammatory acne vulgaris with ALA and a blue light than blue light alone. Gold et al26 reported a 72% improvement in 12 individuals utilizing short-contact ALA and an IPL.
Taub27 reported success with both blue light or an IPL as well, with no PDT effects seen.
Alexiades-Armenakas28 showed complete clearance utilizing a PDL in three sessions in her acne vulgaris clinical trial and a 45-minute ALA drug incubation.
Miller and Van Camp29 showed that the KTP laser yielded successful acne vulgaris treatments with ALA as well.
Two split-face acne vulgaris trials have been performed. Santos et al30 and Rojanamatin et al31 utilized short-contact ALA on one half of the face and followed this with full-face IPL therapies. In both of these clinical trials, the ALA-IPL side outperformed the IPL side, confirming that ALA-PDT was useful for moderate to severe inflammatory acne vulgaris. On a personal note, we and others have observed that when clearing occurs in these individuals, there appears to be an opportunity for the acne to remain clear for quite some time. Several patients have been clear for upward of 2 years, and a recent case by Nestor32 documented clearance for 5 years. An example of a patient treated with ALA for inflammatory acne vulgaris is shown in Figure 3.
Large U.S. Clinical Trial Underway to Study Acne Vulgaris
At the time of this writing, a large multi-center clinical trial was underway in the United States to further evaluate ALA-PDT in the treatment of moderate to severe inflammatory acne vulgaris. It is a placebo-controlled clinical trial with multiple arms to help us further define what role ALA-PDT will have in the future for acne therapy in the United States.
It is hoped that if the results confirm those from the previous clinical trials, a label extension might be given for ALA and insurance company approval of this therapy may be forthcoming.
Two Other Conditions Faring Well from ALA-PDT Treatment
Two other entities are worth noting in this review. ALA-PDT has been successfully described as a useful therapeutic modality for the treatment of sebaceous gland hyperplasia with PDL, IPLs, and blue light. Drug incubation times from the clinical trials vary, but most now favor a 1-hour drug incubation time with whichever light source is chosen.33-35
Hidradenitis suppurativa (HS), one of the more debilitating skin disorders dermatologists encounter and one that frustrates us on many occasions when developing an appropriate therapeutic plan, is the other condition worth noting. Several clinical trials have shown that blue light and ALA has improved HS and it should be considered as a therapy when encountering recalcitrant HS.36,37
How Well Are Dermatologists Embracing This Technology?
The state of ALA-PDT in 2007 is good and showing signs of continued growth in 2008 and beyond. The number of users of ALA-PDT continues to grow and when the numbers are examined closely, “medical” dermatologists are beginning to embrace this therapy as did the “cosmetic” and “surgical” dermatologists when Levulan was introduced. This makes sense, as more medical dermatologists are apt to treat acne vulgaris than some of their surgical counterparts and because they also have large AK practices. So, the use is increasing and it is expected to continue to increase in the foreseeable future.
A second drug, Metvixia, will arrive, hopefully in 2008. When a second drug becomes available, this will allow more users to begin utilizing PDT, which will be good for all of our patients.
