Journal of Clinical and Aesthetic Dermatology

Psoriasis and Cutaneous Supplement 2016

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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Page 22 of 35

U pdates on Psoriasis and Cutaneous Oncology: Proceedings from the 2016 MauiDerm Meeting [ S E P T E M B E R 2 0 1 6 • V O L U M E 9 • N U M B E R 9 ] S U P P L E M E N T T O T H E J O U R N A L O F C L I N I C A L A N D A E S T H E T I C D E R M AT O L O G Y S 1 9 compliance is a major challenge in all of clinical practice, it can be particularly difficult for field AK therapy when patients are required to undergo prolonged "downtime." Furthermore, field AK therapy requires a great deal of patient education, reassurance, and motivation, and many busy clinics simply cannot handle this aspect of field AK therapy well. The paradigm shift in field AK therapy is that treatments that typically required weeks (diclofenac, imiquimod, even 5-fluorouracil) are being replaced by treatments that can be conducted in days or weeks, such as ingenol mebutate (IM) 0.15% and PDT-ALA. These newer options not only do not compromise efficacy, they may enhance it (Table 8). After field AK treatment, the AK burden can further be reduced by treating the patient once per quarter with liquid nitrogen, possibly doing more field therapy, adding a topical tretinoin, and patient education, especially regarding the consistent use of sunscreen. Imiquimod 3.75% is an effective topical treatment for AK field therapy, but it can result in prolonged irritation and downtime. A novel protocol for its use requires the patient to apply 3.75% imiquimod daily for seven days, then take a two-week "vacation" with no use of the agent, followed by an application of imiquimod 3.75% once a week. The concept behind continuous once weekly use of 3.75% imiquimod after one week of daily therapy is that because AKs are a chronic disease with recurrences after field therapy, chronic treatment should be required beyond what is traditionally recommended. Preliminary investigator-initiated "proof of concept" studies (George Martin, MD) have shown dramatic AK clearances beyond two years. Patients should be educated about the advantages (less irritation, less "downtime," convenience, ongoing AK targeted therapy) and drawbacks (must continue weekly applications indefinitely) to this course. PDT is a well-established treatment for field AK and is carried out with ALA or MAL, which is no longer marketed in the United States, but used extensively in the European Union. In the United States, the approved light sources are red light (MAL) or blue light (ALA). FDA-approved treatment protocols require a multi-hour incubation period (for example, 14 hours) followed by light exposure. Results of PDT-ALA on head/scalp and torso/extremities demonstrate good and durable results after one or two treatments (Figures 3A and 3B). Using fluorokinetic analysis, it is possible to predict maximum accumulation during PDT-ALA using fluorescence detection (Figures 4A and 4B). While PDT is an effective field AK treatment, it is associated with pain that can be treatment limiting. A "kinder, gentler" version of PDT was proposed in which patients were incubated with MAL and exposed to daylight for 1.5 or 2.5 hours. 129 The protocol in this study required MAL to be applied topically to the skin (affected areas on face and/or scalp) by the patient; this was left in place for 30 minutes. After that, the TABLE 8. A short summary of topical treatment strategies for field AK therapy TREATMENT DOSAGE TOTAL CLEARANCE MEDIAN CLEARANCE ONE-YEAR CLEARANCE COMMENTS 5-FU BID x 2–6 wk 47.5–84% 75–88% 33–40% Painful Poor appearance Diclofenac BID x 90 d 12–48% 83% 14–30% Reduces inflammation L ong course Imiquimod 5% 2x/wk for 16 wk 20–45.1% 83.3% 40–73% Compliance issues Poor appearance Flu-like symptoms Imiquimod 3.75% 6 wk cycle Rx 35.6% 81.5% 40.5% Poor cosmetic appearance IM 0.015% Daily x 3 (face/scalp) 50% 85% 46.1% Shortest course IM 0.05% Daily x 2 (torso/ extremities) 27.8% 69.1% 44% Effective on chest, other areas less so PDT-ALA RX x 1 to 2 70–90% ≥80% ≥50% Painful BID=twice a day; d=day; FU=fluorouracil; IM=ingenol mebutate; Rx=prescription; wk=week; x=times

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