Acta Dermato-Venereologica Issue No. 97-5 97-5CompleteContent | Page 23

646 SHORT COMMUNICATION Monitoring Ingenol Mebutate Gel Treatment of Actinic Keratoses by Reflectance Confocal Microscopy José Luis LÓPEZ ESTEBARANZ, Ana PAMPIN FRANCO, Reyes GAMO VILLEGAS and Uxua FLORISTÁN Dermatology Service, Hospital Universitario Fundación Alcorcón, ES-28922 Madrid, Spain. E-mail: [email protected] Accepted Jan 12, 2017; Epub ahead of print Jan 17, 2017 Actinic keratoses (AK) commonly occur in elderly patients as a result of chronic exposure to ultraviolet radiation (1). While isolated AK lesions are usually treated with liquid nitrogen cryosurgery, subclinical lesions occurring in photo-damaged areas are treated by photodynamic therapy and topical agents (imiquimod, 5-fluoruracil, diclofenac, and ingenol mebutate) (2). The advantages of these treatments are that they are non- invasive, self-administered and effective against both clinical and subclinical lesions, but most of them require a long course of treatment and are associated with a high frequency of local skin reactions (LSRs). The most re- cently approved agent, ingenol mebutate (IM), needs to be applied for only 2 or 3 days, it has a shorter duration of LSRs, and improved adherence (3–5). Dermoscopy and reflectance confocal microscopy (RCM) are a help in diagnosis of AK and subsequent monitoring of treatments (6–8). A correlation between these techniques and histopathological examination has been demonstrated (6, 9). RCM offers the possibility of detecting morphological changes in clinical and sub- clinical AK at the treated area (10) and has been used to follow AK in response to different topical treatments (11). Two recent studies reported successful monitoring of morphological changes in AKs treated with IM using a dermoscopy, optical coherence tomography and RCM (7, 12). The aim of this case series report was to evaluate the response to IM gel in AK treatment on the face or scalp using RCM and clinical assessment. METHODS A total of 17 patients were enrolled in a prospective study of case series. All patients were over 50 years of age, with a clinical diagnosis of AK on the head and face, and indication for ingenol mebutate (IM) treatment. The study was approved by the local ethics committee and written informed consent was obtained from each participant before evaluation. All patients were treated with IM 0.015% gel (Picato ® , LEO Pharma, Ballerup, Denmark) applied once daily for 3 consecu- tive days in the affected area, covering both clinical AK and the area surrounding the lesions (field of cancerization), and area of approximately 25 cm 2 . AK in the target area were examined clinically to evaluate the treatment response at baseline and at the 8 th week follow-up visit, while RCM imaging was performed before treatment and at weeks 4 and 8. Images were obtained using a digital camera (Canon PowerShot G12, Canon USA Inc., New York, USA). Lesions were rated as complete response (CR; complete disap- pearance of the lesions in the treatment area), partial response (PR; reduction of ≥ 50% in the number of clinically visible AK) or non-response. doi: 10.2340/00015555-2607 Acta Derm Venereol 2017; 97: 646–648 RCM images of the areas selected at baseline were captured with a commercially available hand-held device (VivaScope 1500; Lucid-Tech, Inc., Henrietta, NY, USA). RCM images 6 × 6 mm were obtained horizontally from the lesion using the VivaBlock function modality. Vertical mapping using the VivaStack was performed at intervals of 5 μm up to a depth of 200 μm, begin- ning with the stratum corneum (SC ) through the entire epidermis and into the superficial dermis. Based on previous AK diagnostic criteria, the study areas were evaluated for the presence or absence of the following RCM features of AK: hyperkeratosis, parakera- tosis, disruption of the SC (irregular cornea), overall architectural disruption (atypical honeycomb pattern, architectural disarray, and irregular epidermal pattern), blood vessel dilatation, inflammatory infiltrate, and solar elastosis. RESULTS Of the 17 patients initially recruited into the study, 15 had follow-up data until week 4, and 12 patients finalized the study with evaluation at week 8. Demographic and clinical characteristics of patients, including AK clinical severity (Olsen grade) and RCM parameters at baseline are summarized in Table SI 1 . The therapeutic outcome at week 8 was evaluated clinically as CR in 7/12 (58%) patients and PR in 4/12 patients (33%). Only one patient was classified as a non-responder. To detect morphological changes following topical applications of IM, RCM evaluations of AK were per- formed at baseline and at weeks 4 and 8 after treatment. Disarranged epidermal pattern was identified in all pa- tients before initiation of treatment. Disruption of SC and hyperkeratosis were seen in 14/15 patients. A decreasing frequency of these abnormal features and parakeratosis was observed at week 4, especially in the number of patients with hyperkeratosis and disruption of the SC (identified in only 3 patients, respectively). Overall, these https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-2607 1 Table I. Reflectance confocal microscopy (RCM) findings before treatment, and 4 and 8 weeks after treatment Feature on RCM Before treatment (n=15) n (%) 4 weeks after treatment (n=15) n (%) 8 weeks after treatment (n=12) n (%) Hyperkeratosis Parakeratosis Disruption of the stratum corneum Disarranged epidermal pattern Solar elastosis Inflammatory infiltrate Blood vessel dilatation 14 (93) 9 (60) 14 (93) 15 (100) 12 (80) 11 (73) 9 (60) 3 (20) 1 (7) 3 (20) 7 (47) 12 (80) 11 (73) 9 (60) 1 1 2 5 8 6 7 (8) (8) (17) (42) (67) (50) (58) This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica.