frequent in patients treated with ALA than vehicle.15
Late-Onset Adverse Events
PDT has been associated with hyperpigmentation and scarring in rare cases; however, the most concerning potential AE is development of NMSC, also a rare event.17 Because patients with AK are already predisposed to NMSC, it is difficult to associate PDT with NMSC pathogenesis. However, PDT could potentially mediate development of NMSC via generation of ROS or immunosuppressive effects.17 Therefore, careful assessment of NMSC rates in patients receiving PDT treatment is warranted (Table 2).
In the upper extremity trial by Berman et al, 16 skin carcinomas were diagnosed; 9 SCCs were diagnosed in 7 patients receiving ALA-PDT (all with a prior history of SCC), and 3 SCCs were diagnosed in patients receiving vehicle-PDT.1 Three BCCs were diagnosed in patients who received vehicle-PDT.1 In the trial by Jiang et al, new SCC developed in 2 patients who received ALA and one who received vehicle; all had a previous history of SCC.15 In the study of high-risk patients conducted by Piacquadio et al, there were a total of 27 NMSCs reported during follow-up; the rate was significantly lower in patients who received ALAPDT 3 times compared with patients who received vehicle.21
Patient Education for ALA-PDT
Patient education related to the use of ALA-PDT for the treatment of AK should begin with a discussion of the risks and benefits of treating AK. Patients with AK should be educated that they have evidence of sun damage and are at risk for development of NMSC. Regardless of treatment decisions, education should include information about signs and symptoms that require further evaluation, including bleeding or painful lesions, and lesions that grow or begin to protrude.3 Risks and benefits of available treatment options should also be discussed.
Several barriers hinder use of field therapy with ALA-PDT, including the time needed to explain the treatment regimen, properly apply the treatment, address the immediate pain and inflammation, and ensure that patients adhere to requirements associated with the regimen.4 Benefits of ALA-PDT include that it is more convenient and less invasive than surgery, is not associated with long-term side effects, and results in little to no scarring. Additionally, it avoids potential adherence issues that may arise with treatments applied exclusively by the patient.
If treatment with ALA-PDT is selected, it is important to educate patients about the regimen. ALA treatment must be applied prior to PDT treatment; the specific incubation time depends on the location. Patients should be advised that if they are unable to return for the PDT treatment during the appropriate period after applying the solution, they should avoid exposure of the photosensitized lesions to sunlight for at least 40 hours. Patients should also be advised to avoid medications that enhance the phototoxic reaction to PDT, such as St. John’s wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides and tetracyclines.18
It is imperative that clinicians provide patients with comprehensive education regarding proper home care following ALA-PDT treatment. Patients must remain indoors and avoid all direct sunlight (even sitting by a window) for 36 hours. If patients must go outside, appropriate protective apparel such as a widebrimmed hat, long-sleeved shirt, and gloves may be used to protect the skin from sunlight and other bright light; sunscreen will not be effective.18 Patients should wash the treated area twice daily with a gentle cleanser and apply moisturizer 4 times daily. If the treated area is painful, patients may use nonprescription analgesics (ie, acetaminophen or ibuprofen) and apply ice packs for 5–10 minutes every few hours. Patients should be advised to expect redness and for the skin to feel dry and tight. Makeup may be used if desired once any crusting has healed. When patients go outdoors after the first 36 hours, they should use broad spectrum sunscreen that provides a physical barrier such as zinc oxide or titanium dioxide.16
Late-Onset Adverse Events
PDT has been associated with hyperpigmentation and scarring in rare cases; however, the most concerning potential AE is development of NMSC, also a rare event.17 Because patients with AK are already predisposed to NMSC, it is difficult to associate PDT with NMSC pathogenesis. However, PDT could potentially mediate development of NMSC via generation of ROS or immunosuppressive effects.17 Therefore, careful assessment of NMSC rates in patients receiving PDT treatment is warranted (Table 2).
In the upper extremity trial by Berman et al, 16 skin carcinomas were diagnosed; 9 SCCs were diagnosed in 7 patients receiving ALA-PDT (all with a prior history of SCC), and 3 SCCs were diagnosed in patients receiving vehicle-PDT.1 Three BCCs were diagnosed in patients who received vehicle-PDT.1 In the trial by Jiang et al, new SCC developed in 2 patients who received ALA and one who received vehicle; all had a previous history of SCC.15 In the study of high-risk patients conducted by Piacquadio et al, there were a total of 27 NMSCs reported during follow-up; the rate was significantly lower in patients who received ALAPDT 3 times compared with patients who received vehicle.21
Patient Education for ALA-PDT
Patient education related to the use of ALA-PDT for the treatment of AK should begin with a discussion of the risks and benefits of treating AK. Patients with AK should be educated that they have evidence of sun damage and are at risk for development of NMSC. Regardless of treatment decisions, education should include information about signs and symptoms that require further evaluation, including bleeding or painful lesions, and lesions that grow or begin to protrude.3 Risks and benefits of available treatment options should also be discussed.
Several barriers hinder use of field therapy with ALA-PDT, including the time needed to explain the treatment regimen, properly apply the treatment, address the immediate pain and inflammation, and ensure that patients adhere to requirements associated with the regimen.4 Benefits of ALA-PDT include that it is more convenient and less invasive than surgery, is not associated with long-term side effects, and results in little to no scarring. Additionally, it avoids potential adherence issues that may arise with treatments applied exclusively by the patient.
If treatment with ALA-PDT is selected, it is important to educate patients about the regimen. ALA treatment must be applied prior to PDT treatment; the specific incubation time depends on the location. Patients should be advised that if they are unable to return for the PDT treatment during the appropriate period after applying the solution, they should avoid exposure of the photosensitized lesions to sunlight for at least 40 hours. Patients should also be advised to avoid medications that enhance the phototoxic reaction to PDT, such as St. John’s wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides and tetracyclines.18
It is imperative that clinicians provide patients with comprehensive education regarding proper home care following ALA-PDT treatment. Patients must remain indoors and avoid all direct sunlight (even sitting by a window) for 36 hours. If patients must go outside, appropriate protective apparel such as a widebrimmed hat, long-sleeved shirt, and gloves may be used to protect the skin from sunlight and other bright light; sunscreen will not be effective.18 Patients should wash the treated area twice daily with a gentle cleanser and apply moisturizer 4 times daily. If the treated area is painful, patients may use nonprescription analgesics (ie, acetaminophen or ibuprofen) and apply ice packs for 5–10 minutes every few hours. Patients should be advised to expect redness and for the skin to feel dry and tight. Makeup may be used if desired once any crusting has healed. When patients go outdoors after the first 36 hours, they should use broad spectrum sunscreen that provides a physical barrier such as zinc oxide or titanium dioxide.16
CONCLUSION
ALA-PDT is effective and well tolerated for the treatment of
AK located on the face, scalp, and upper extremities. Clinical
trials have found dramatically improved rates of AK clearance
following treatment with ALA-PDT compared with PDT applied
with vehicle alone. Field therapy for AK with a treatment such as
ALA-PDT is supported for patients with multiple AKs and may
reduce the risk for future occurrence of NMSC. Patients treated
with ALA-PDT require thorough education to ensure that they
adhere to all treatment recommendations and are prepared
to manage local reactions. Additionally, regardless of whether
patients receive treatment with ALA-PDT, all patients with AK
should be educated regarding signs and symptoms that may
indicate progression to NMSC and require further evaluation.
DISCLOSURES
JG is a consultant, advisor, and/or speaker for AbbVie, Inc.;
Beiersdorf; Celgene Corporation; Dermira; Eli Lilly and
Company; Encore Dermatology, Inc.; Foamix Pharmaceuticals
Ltd; LEO Pharma; Mayne Pharma; Novartis Pharmaceuticals;
Ortho Dermatologics, Inc.; Primus Pharmaceuticals; PruGen
Pharmaceuticals; Regeneron Pharmaceuticals, Inc.; Sanofi-
Genzyme; Sun Pharmaceutical Industries, Inc.; and UCB S.A. SF
is a consultant, advisor, and/or speaker for AbbVie, Inc.; Eli Lilly
and Company; Novartis, and UCB.
ACKNOWLEDGMENT
Medical writing and editorial support was provided by Judith M.
Phillips, DVM, PhD, CMPP, of AlphaBioCom, LLC, and funded by
Sun Pharmaceutical Industries, Inc.
