Photodynamic therapy (PDT) using 20% 5-aminolevulinic acid (ALA) (Levulan Kerastick, DUSA Pharmaceuticals, Inc.) received FDA clearance in 1999 for the treatment of non-hypertrophic actinic keratoses (AKs) of the face and scalp. While this formulation remains the only one available in the United States, methyl aminolevulinate (Metvix, Galderma Laboratories and PhotoCure, AS) has now been FDA approved, but has not yet been released in the United States.
The mechanism of action of PDT in the treatment of cutaneous conditions appears to be a cytotoxic effect through the production of singlet oxygen. In the process, ALA first diffuses through the stratum corneum and penetrates into the epidermis and the dermis. The cells then convert ALA into protoporphyrin IX (PpIX). Finally, light source irradiation of PpIX generates singlet oxygen leading to cell death.
Treatment of Our Patient
The patient first underwent a chemical peel of the entire scalp using 35% trichloracetic acid (TCA) 2 weeks prior to PDT. Immediately prior to the topical application of ALA, fractional resurfacing using a 2940-nm erbium:YAG laser (ProFractional, Sciton Inc.) was performed to enhance cutaneous penetration (Figure 1). Next, ALA was applied to the entire scalp and allowed to incubate for 1 hour. This was followed by irradiation of the treated area with blue light-emitting diode (LED) device (BLU-U, DUSA Pharmaceuticals, Inc.) for 16 minutes and 40 seconds.
At a follow-up visit, the number of AKs had decreased significantly (Figure 2); however, the patient will likely require additional treatment sessions because of the extensive nature of his condition.
Technique
Prior to the application of ALA, the skin is typically prepped using a vigorous alcohol or acetone scrub. To further enhance cutaneous penetration of ALA, the patient can undergo microdermabrasion on the day of the procedure. Additionally, a 30% to 35% TCA peel may be performed 2 to 3 weeks prior to PDT for patients who have extensive actinic keratoses of the scalp.
After a report by Ruiz-Rodriguez et al, we recently added fractional laser resurfacing immediately prior to PDT for patients with extensive actinic damage.
Following ALA application, the treatment area may be occluded with a plastic wrap to further enhance penetration. Incubation times vary, with the original FDA approval indicating a 14- to 18-hour skin contact time. Since then, however, much shorter incubation periods, usually 30 minutes to 3 hours, have been shown to result in similar efficacy and are most commonly utilized.
Various laser and light sources have been used for activating ALA. Also, a range of treatment durations, device settings, and total passes have been employed in PDT.
The FDA approved a blue light source at 420 nm — the BLU-U LED device — for the activation of the Levulan Kerastick. In the original studies, treatment duration was set at 16 minutes and 40 seconds (1,000 seconds). In the last decade, however, additional light sources and lasers have been extensively studied for the purpose of ALA activation. There have been several reports on the use of pulsed dye laser (PDL) for facial and scalp AKs as well as for actinic cheilitis. Multiple studies have also demonstrated the utility of intense pulse light (IPL) in the treatment of facial AKs, as well as in photorejuvenation of the skin. Red LED devices are also sometimes used because of deeper penetration of the longer wavelengths into the skin.
Because the procedure may be uncomfortable or even painful during the activation phase, various techniques have been developed to counter this effect. These include pre-treatment with acetaminophen or other pain medications, rest periods, or cooling devices, such as Cryo5 (Zimmer MedizinSysteme GmbH) or a simple room fan, utilized during the treatment.
Most experts agree that greater post-treatment erythema and desquamation lead to better clinical improvement with PDT. Furthermore, edema, burning, and stinging are expected. However, additional uncontrolled ALA activation by the patient should be avoided. To this extent, we instruct patients verbally and with written handouts to completely avoid sunlight for at least 48 hours following the procedure.
While the current FDA-approved indication for PDT remains the treatment of AKs, a large spectrum of clinical conditions has been reported to respond to this therapeutic modality. Off-label uses of PDT include photorejuvenation, treatment of inflammatory acne, benign sebaceous hyperplasia, hidradenitis suppurativa, lichen sclerosus et atrophicus, and superficial non-melanoma skin cancers (NMSC). In addition, initial reports seem to indicate that PDT may convey some degree of chemoprevention in patients with a significant predisposition to NMSC, such as those with basal cell nevus syndrome or organ transplant recipients.
Points to Remember
In order to increase cutaneous penetration of ALA, pre-treatment techniques, such as a vigorous scrub, microdermabrasion, chemical peel, or fractional ablative resurfacing, may be utilized. A short ALA contact time appears to be as effective as the overnight incubation. Post-treatment sun avoidance is critical to prevent further ALA activation and subsequent severe sunburn.
Dr. Cohen is the Director of AboutSkin Dermatology and DermSurgery in Colorado. His practice focuses on Mohs surgery and cosmetic dermatology. He is Past President of the Colorado Dermatologic Society, and the Past Chair of the ASDS Patient Education Committee. He is also on the volunteer faculty as an Assistant Clinical Professor at the University of Colorado Department of Dermatology.
Dr. Berlin is in private practice at the Skin Laser and Surgery Specialists of New York and New Jersey in New York, NY. He is also Clinical Assistant Professor of Dermatology at the New Jersey Medical School in Newark, NJ. Dr. Berlin’s practice focuses on Mohs and laser surgery as well as cosmetic dermatology.
Photodynamic therapy (PDT) using 20% 5-aminolevulinic acid (ALA) (Levulan Kerastick, DUSA Pharmaceuticals, Inc.) received FDA clearance in 1999 for the treatment of non-hypertrophic actinic keratoses (AKs) of the face and scalp. While this formulation remains the only one available in the United States, methyl aminolevulinate (Metvix, Galderma Laboratories and PhotoCure, AS) has now been FDA approved, but has not yet been released in the United States.
The mechanism of action of PDT in the treatment of cutaneous conditions appears to be a cytotoxic effect through the production of singlet oxygen. In the process, ALA first diffuses through the stratum corneum and penetrates into the epidermis and the dermis. The cells then convert ALA into protoporphyrin IX (PpIX). Finally, light source irradiation of PpIX generates singlet oxygen leading to cell death.
Treatment of Our Patient
The patient first underwent a chemical peel of the entire scalp using 35% trichloracetic acid (TCA) 2 weeks prior to PDT. Immediately prior to the topical application of ALA, fractional resurfacing using a 2940-nm erbium:YAG laser (ProFractional, Sciton Inc.) was performed to enhance cutaneous penetration (Figure 1). Next, ALA was applied to the entire scalp and allowed to incubate for 1 hour. This was followed by irradiation of the treated area with blue light-emitting diode (LED) device (BLU-U, DUSA Pharmaceuticals, Inc.) for 16 minutes and 40 seconds.
At a follow-up visit, the number of AKs had decreased significantly (Figure 2); however, the patient will likely require additional treatment sessions because of the extensive nature of his condition.
Technique
Prior to the application of ALA, the skin is typically prepped using a vigorous alcohol or acetone scrub. To further enhance cutaneous penetration of ALA, the patient can undergo microdermabrasion on the day of the procedure. Additionally, a 30% to 35% TCA peel may be performed 2 to 3 weeks prior to PDT for patients who have extensive actinic keratoses of the scalp.
After a report by Ruiz-Rodriguez et al, we recently added fractional laser resurfacing immediately prior to PDT for patients with extensive actinic damage.
Following ALA application, the treatment area may be occluded with a plastic wrap to further enhance penetration. Incubation times vary, with the original FDA approval indicating a 14- to 18-hour skin contact time. Since then, however, much shorter incubation periods, usually 30 minutes to 3 hours, have been shown to result in similar efficacy and are most commonly utilized.
Various laser and light sources have been used for activating ALA. Also, a range of treatment durations, device settings, and total passes have been employed in PDT.
The FDA approved a blue light source at 420 nm — the BLU-U LED device — for the activation of the Levulan Kerastick. In the original studies, treatment duration was set at 16 minutes and 40 seconds (1,000 seconds). In the last decade, however, additional light sources and lasers have been extensively studied for the purpose of ALA activation. There have been several reports on the use of pulsed dye laser (PDL) for facial and scalp AKs as well as for actinic cheilitis. Multiple studies have also demonstrated the utility of intense pulse light (IPL) in the treatment of facial AKs, as well as in photorejuvenation of the skin. Red LED devices are also sometimes used because of deeper penetration of the longer wavelengths into the skin.
Because the procedure may be uncomfortable or even painful during the activation phase, various techniques have been developed to counter this effect. These include pre-treatment with acetaminophen or other pain medications, rest periods, or cooling devices, such as Cryo5 (Zimmer MedizinSysteme GmbH) or a simple room fan, utilized during the treatment.
Most experts agree that greater post-treatment erythema and desquamation lead to better clinical improvement with PDT. Furthermore, edema, burning, and stinging are expected. However, additional uncontrolled ALA activation by the patient should be avoided. To this extent, we instruct patients verbally and with written handouts to completely avoid sunlight for at least 48 hours following the procedure.
While the current FDA-approved indication for PDT remains the treatment of AKs, a large spectrum of clinical conditions has been reported to respond to this therapeutic modality. Off-label uses of PDT include photorejuvenation, treatment of inflammatory acne, benign sebaceous hyperplasia, hidradenitis suppurativa, lichen sclerosus et atrophicus, and superficial non-melanoma skin cancers (NMSC). In addition, initial reports seem to indicate that PDT may convey some degree of chemoprevention in patients with a significant predisposition to NMSC, such as those with basal cell nevus syndrome or organ transplant recipients.
Points to Remember
In order to increase cutaneous penetration of ALA, pre-treatment techniques, such as a vigorous scrub, microdermabrasion, chemical peel, or fractional ablative resurfacing, may be utilized. A short ALA contact time appears to be as effective as the overnight incubation. Post-treatment sun avoidance is critical to prevent further ALA activation and subsequent severe sunburn.
Dr. Cohen is the Director of AboutSkin Dermatology and DermSurgery in Colorado. His practice focuses on Mohs surgery and cosmetic dermatology. He is Past President of the Colorado Dermatologic Society, and the Past Chair of the ASDS Patient Education Committee. He is also on the volunteer faculty as an Assistant Clinical Professor at the University of Colorado Department of Dermatology.
Dr. Berlin is in private practice at the Skin Laser and Surgery Specialists of New York and New Jersey in New York, NY. He is also Clinical Assistant Professor of Dermatology at the New Jersey Medical School in Newark, NJ. Dr. Berlin’s practice focuses on Mohs and laser surgery as well as cosmetic dermatology.
Photodynamic therapy (PDT) using 20% 5-aminolevulinic acid (ALA) (Levulan Kerastick, DUSA Pharmaceuticals, Inc.) received FDA clearance in 1999 for the treatment of non-hypertrophic actinic keratoses (AKs) of the face and scalp. While this formulation remains the only one available in the United States, methyl aminolevulinate (Metvix, Galderma Laboratories and PhotoCure, AS) has now been FDA approved, but has not yet been released in the United States.
The mechanism of action of PDT in the treatment of cutaneous conditions appears to be a cytotoxic effect through the production of singlet oxygen. In the process, ALA first diffuses through the stratum corneum and penetrates into the epidermis and the dermis. The cells then convert ALA into protoporphyrin IX (PpIX). Finally, light source irradiation of PpIX generates singlet oxygen leading to cell death.
Treatment of Our Patient
The patient first underwent a chemical peel of the entire scalp using 35% trichloracetic acid (TCA) 2 weeks prior to PDT. Immediately prior to the topical application of ALA, fractional resurfacing using a 2940-nm erbium:YAG laser (ProFractional, Sciton Inc.) was performed to enhance cutaneous penetration (Figure 1). Next, ALA was applied to the entire scalp and allowed to incubate for 1 hour. This was followed by irradiation of the treated area with blue light-emitting diode (LED) device (BLU-U, DUSA Pharmaceuticals, Inc.) for 16 minutes and 40 seconds.
At a follow-up visit, the number of AKs had decreased significantly (Figure 2); however, the patient will likely require additional treatment sessions because of the extensive nature of his condition.
Technique
Prior to the application of ALA, the skin is typically prepped using a vigorous alcohol or acetone scrub. To further enhance cutaneous penetration of ALA, the patient can undergo microdermabrasion on the day of the procedure. Additionally, a 30% to 35% TCA peel may be performed 2 to 3 weeks prior to PDT for patients who have extensive actinic keratoses of the scalp.
After a report by Ruiz-Rodriguez et al, we recently added fractional laser resurfacing immediately prior to PDT for patients with extensive actinic damage.
Following ALA application, the treatment area may be occluded with a plastic wrap to further enhance penetration. Incubation times vary, with the original FDA approval indicating a 14- to 18-hour skin contact time. Since then, however, much shorter incubation periods, usually 30 minutes to 3 hours, have been shown to result in similar efficacy and are most commonly utilized.
Various laser and light sources have been used for activating ALA. Also, a range of treatment durations, device settings, and total passes have been employed in PDT.
The FDA approved a blue light source at 420 nm — the BLU-U LED device — for the activation of the Levulan Kerastick. In the original studies, treatment duration was set at 16 minutes and 40 seconds (1,000 seconds). In the last decade, however, additional light sources and lasers have been extensively studied for the purpose of ALA activation. There have been several reports on the use of pulsed dye laser (PDL) for facial and scalp AKs as well as for actinic cheilitis. Multiple studies have also demonstrated the utility of intense pulse light (IPL) in the treatment of facial AKs, as well as in photorejuvenation of the skin. Red LED devices are also sometimes used because of deeper penetration of the longer wavelengths into the skin.
Because the procedure may be uncomfortable or even painful during the activation phase, various techniques have been developed to counter this effect. These include pre-treatment with acetaminophen or other pain medications, rest periods, or cooling devices, such as Cryo5 (Zimmer MedizinSysteme GmbH) or a simple room fan, utilized during the treatment.
Most experts agree that greater post-treatment erythema and desquamation lead to better clinical improvement with PDT. Furthermore, edema, burning, and stinging are expected. However, additional uncontrolled ALA activation by the patient should be avoided. To this extent, we instruct patients verbally and with written handouts to completely avoid sunlight for at least 48 hours following the procedure.
While the current FDA-approved indication for PDT remains the treatment of AKs, a large spectrum of clinical conditions has been reported to respond to this therapeutic modality. Off-label uses of PDT include photorejuvenation, treatment of inflammatory acne, benign sebaceous hyperplasia, hidradenitis suppurativa, lichen sclerosus et atrophicus, and superficial non-melanoma skin cancers (NMSC). In addition, initial reports seem to indicate that PDT may convey some degree of chemoprevention in patients with a significant predisposition to NMSC, such as those with basal cell nevus syndrome or organ transplant recipients.
Points to Remember
In order to increase cutaneous penetration of ALA, pre-treatment techniques, such as a vigorous scrub, microdermabrasion, chemical peel, or fractional ablative resurfacing, may be utilized. A short ALA contact time appears to be as effective as the overnight incubation. Post-treatment sun avoidance is critical to prevent further ALA activation and subsequent severe sunburn.
Dr. Cohen is the Director of AboutSkin Dermatology and DermSurgery in Colorado. His practice focuses on Mohs surgery and cosmetic dermatology. He is Past President of the Colorado Dermatologic Society, and the Past Chair of the ASDS Patient Education Committee. He is also on the volunteer faculty as an Assistant Clinical Professor at the University of Colorado Department of Dermatology.
Dr. Berlin is in private practice at the Skin Laser and Surgery Specialists of New York and New Jersey in New York, NY. He is also Clinical Assistant Professor of Dermatology at the New Jersey Medical School in Newark, NJ. Dr. Berlin’s practice focuses on Mohs and laser surgery as well as cosmetic dermatology.
