Journal of Clinical and Aesthetic Dermatology

OCT 2017

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

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33 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY October 2017 • Volume 10 • Number 10 O R I G I N A L R E S E A R C H treatment. Of the three treatment-resistant lesions present at the end of the original study, two were also present on Day 0 of the extension study. On noninvasive imaging, both lesions contained elements of seborrheic keratosis, benign lesions that feature areas of thickened and well-defined architectural plateaus on OCT (Figure 5, yellow arrows). Reports in the literature describe seborrheic keratosis displaying a classic appearance on OCT of a markedly thickened epithelium, which might contain hypodense structures corresponding to horn pseudocysts on histopathology. 16 More importantly, researchers have observed a reduction in treatment response to ingenol mebutate 0.05% gel among seborrheic keratotic lesions. 17 The advantage of using OCT to diagnose such AKs that contain mixed morphology is the ability to detect subtle architectural changes that would otherwise be indistinguishable with the naked eye and even with dermoscopy. Recognition of these atypical AKs might facilitate more optimal therapy that is tailored to the patient, improve treatment response, and reduce the risk of recurrence. One limitation of the extension study was that almost half of the patients in the original study could not be enrolled. These patients were excluded because they had received another treatment for AK during the intervening year, were unavailable, or were otherwise unable to participate. The relatively small cohort size was another limitation, as was the homogeneity of the patients with respect to race and gender. Furthermore, the study was performed at a single center. Finally, although it was assumed for purposes of the extension phase that the untreated lesions at Day 60 of the original study were the same ones that persisted for one year, the possibility that these lesions cleared spontaneously in the interim and were replaced with recurrent or new lesions cannot be excluded. CONCLUSION OCT has been shown to be an effective diagnostic tool for the clinician for detecting the presence of AKs, as well as early actinic damage due to the chronic effects of field cancerization. OCT as a noninvasive imaging technology permits this diagnosis while avoiding a biopsy, based on the high diagnostic correlation between OCT and histopathology that we demonstrated in our original study. A significant number of clinical and subclinical lesions that cleared in the original study following treatment with ingenol mebutate gel 0.015% remained clear one year later, while most of the untreated lesions, both clinical and subclinical, were still present. The majority of these formerly untreated lesions did clear, however, after appropriate treatment with ingenol mebutate gel 0.015% in the extension study. These results suggest that ingenol mebutate 0.015% remains an effective agent as a field therapy for both AK and subclinical actinic damage, and that it can provide reliable, long-term clearance. OCT can be particularly helpful to clinicians for detecting early precancerous lesions and distinguishing AKs that contain specific morphologic elements that render them difficult to treat. This allows clinicians to fully tailor the ideal therapy for their patients as a component of comprehensive prevention of skin cancer. REFERENCES 1. Schmitt JV, Miot HA. Actinic keratosis: a clinical and epidemiological revision. An Bras Dermatol. 2012;87(3):425–434. 2. Feldman SR, Fleischer AB Jr. Progression of actinic keratosis to squamous cell carcinoma revisited: clinical and treatment implications. Cutis. 2011;87(4):201–207. 3. Vatve M, Ortonne JP, Birch-Machin MA, Gupta G. Management of field change in actinic keratosis. Br J Dermatol. 2007;157(Suppl 2):21–24. 4. Markowitz O, Schwartz M, Feldman E, et al. Defining field cancerization of the skin using noninvasive optical coherence tomography imaging to detect and monitor actinic keratosis in ingenol mebutate 0.015%-treated patients. J Clin Aesthet Dermatol. 2016;9(5):18–25. 5. Jorizzo JL, Markowitz O, Lebwohl MG, et al. A randomized, double-blinded, placebo-controlled, multicenter, efficacy and safety study of 3.75% imiquimod cream following cryosurgery for the treatment of actinic keratosis. J Drugs Dermatol. 2010;9(9):1101–1108. 6. Berman B, Cohen DE, Amini S. What is the role of field-directed therapy in the treatment of actinic keratosis? Part 1: overview and investigational topical agents. Cutis. 2012;89(5):241–250. 7. Filosa A, Filosa G. Actinic keratosis and squamous cell carcinoma: clinical and pathological features. G Ital Dermatol Venereol. 2015;150(4):379–384. 8. Schwartz M, Siegel DM, Markowitz O. Commentary on the diagnostic utility of non-invasive imaging devices for field cancerization. Exp Dermatol. 2016;25(11):855–856. 9. Scope A, Marchetti MA. An evolving approach to the detection of melanoma and other skin cancers using in vivo reflectance confocal microscopy. JAMA Dermatol. 2016;152(10):1085–1087. 10. Gambichler T, Pljakic A, Schmitz L. Recent advances in clinical application of optical coherence tomography of human skin. Clin Cosmet Invest Dermatol. 2015;8:345–354. 11. Mamalis A, Ho D, Jagdeo J. Optical coherence tomography imaging of normal, chronologically aged, photoaged and photodamaged skin: a systematic review. Dermatol Surg. 2015;41(9):993–1005. 12. Schmitz L, Reinhold U, Bierhoff E, Dirschka T. Optical coherence tomography: its role in daily dermatology practice. JDDG. 2013;11(6):499–507. 13. Ondo AL, Padilla RS, Miedler JD, et al. Treatment- refractory actinic keratoses successfully treated using simultaneous combination topical 5-fluorouracil cream and imiquimod cream: a case-control study. Dermatol Surg. 2012;38(9):1469–1476. 14. Lebwohl M, Shumack S, Stein Gold L, et al. Long- term follow-up study of ingenol mebutate gel for the treatment of actinic keratoses. JAMA Dermatol. 2013;149(6):666–670. 15. Garbe C, Bassett-Seguin N, Poulin Y, et al. Efficacy and safety of follow-up field treatment of actinic keratosis with ingenol mebutate 0.015% gel: a randomized, controlled 12-month study. Br J Dermatol. 2016;174(3):481–482. 16. Forsea AM, Carstea EM, Ghervase L, et al. Clinical application of optical coherence tomography for the imaging of non-melanocytic cutaneous tumors: a pilot multi-modal study. J Med Life. 2010;3(4):381–389. 17. Rosen R, Freeman M, Zibert JR, et al. Ingenol mebutate 0.05% gel reduces cancer cells in squamous cell carcinoma in situ and shows marginal effect in seborrheic keratosis. JDDG. 2013;11(Suppl 7):Abstract FC-003. JCAD

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