Photodynamic Therapy Effectively Treats Actinic Keratoses Without Pre-Illumination Incubation Time
March 2017 | Volume 16 | Issue 3 | Case Reports | 275 | Copyright © March 2017
Jessica Gandy BS, Brian Labadie BS, Dina Bierman Farshidi MD, and Christopher Zachary MBBS FRCP
Department of Dermatology, University of California, Irvine, CA
BACKGROUND: Actinic keratoses (AKs) are dysplastic lesions of the epidermis that have the potential to progress to non-melanoma skin cancers (NMSC). Traditional photodynamic therapy (PDT) requires a pre-illumination incubation time, which adds to overall in-office time and has been linked to pain. Our group has found a novel protocol to effectively treat AKs with PDT that eliminates the pre-illumination incubation period and uses 2 back-to-back cycles of 16 minute 40 seconds.
METHODS: The patient was prepped with soapy water and isopropyl alcohol, and thick AKs were descaled with a curette. Next, 5-aminolevulinic acid (ALA) was applied to the treatment areas and the patient was immediately placed under the blue light for 33 minutes and 20 seconds (two cycles of 16m/40s).
RESULTS: During therapy, the patient reported no pain. At one week, treated areas revealed a good reaction. The procedure was repeated at one month to treat residual AKs. At a 4-month follow-up, the patientâ€™s face and scalp showed near clearance of any AKs.
CONCLUSION: During PDT, the photosensitizer aminolevulinic acid (ALA), or in Europe methyl aminolevulinate (MAL), is utilized as a synthetic precursor that preferentially accumulates in dysplastic cells. The precursor then converts to PpIX via the heme pathway and causes apoptosis of the cells when excited, most commonly by either blue-violet (400-430 nm) or red (630-635 nm) light. Shorter incubation times are associated with reduced pain because less PpIX will have accumulated in the treated tissue by the start of the exposure to the light. The doubling of the light exposure time allows comparable levels of the photosensitizing molecule to accumulate and be activated so as to produce an equivalent reaction. The associated reduction in pain along with a more convenient treatment schedule makes this PDT protocol more tolerable and convenient to some patients.
J Drugs Dermatol. 2017;16(3):275-278.
Actinic keratoses (AKs) are dysplastic premalignant lesions of the epidermis that often occur in Fitzpatrick I-III skin-type patients who have been chronically exposed to sunlight. If left untreated, AKs can progress to skin cancer.1 It has been shown that the risk of progression to primary squamous cell carcinoma (SCC) is 0.6 percent by 1 year and 2.57 percent by year 4.2 Moreover, it is accepted that up to 65 percent of all SCCs were at one time diagnosed as AKs.2 Appropriately, early treatment and eradication of AKs is important to prevent progression to invasive disease.Treatment options for AKs vary depending on the extent of disease. Liquid nitrogen destruction is an excellent treatment for local disease, while more extensive disease requires field therapy with either photodynamic therapy (PDT), topical chemotherapy, or laser treatment.3-13 When compared to topical chemotherapy, PDT is arguably better tolerated and offers patients less down time and pain. PDT has been approved for the treatment of mild to moderate AKs of the face and scalp, and uses a topical photosensitizer, either methyl aminolevulinate (MAL), or its ester, aminiolevulinic acid HCL (ALA), that is activated by blue or red light. Current standard of care involves the application of a photosensitizer, a pre-illumination incubation time of 1-3 hours, and exposure to blue-violet light (400-430 nm) for 16 minutes and 40 seconds or to red light (630-635 nm).14,15 The photosensitizer is taken up by all cells but is particularly metabolized in pre-malignant cells via the heme biosynthesis pathway to protoporphyrin IX (PpIX) due to a relative decrease activity of ferochelatase within dysplastic cells.15,23,24 Following blue-violet or red light exposure to these areas in the presence of oxygen, cytotoxic free radicals form and eradicate the dysplastic cells with minimal damage to surrounding tissue.15,21,22,25,26To date, patient enthusiasm for PDT has been limited due to the lengthy in-office procedure protocols and associated pain.15-17 Pain is thought to be directly proportional to the length of pre-illumination incubation time as more photosensitizer is allowed to accumulate prior to the light exposure. Recent groups have sought to decrease incubation times to shorten office visits and reduce associated pain, while maintaining comparable treatment outcomes.18-21 The shortest effective incubation time studied to date has been 1 hour by Pariser and colleagues.21 In their study they demonstrated that shortening the incubation