Acta Dermato-Venereologica 99-2CompleteContent | Page 32

242 SHORT COMMUNICATION Pulse–Daylight–Photodynamic Therapy in Combination with Corticosteroid and Brimonidine Tartrate for Multiple Actinic Keratoses: A Randomized Clinical Trial Stine Regin WIEGELL 1 , Urs Broby JOHANSEN 2 and Hans Christian WULF 1 Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, and 2 Clinic of Dermatology, Karlslunde, Denmark. E-mail: [email protected] 1 Accepted Sep 23, 2018, E-published Sep 24, 2018 The introduction of daylight-mediated photodynamic therapy (d-PDT) has resulted in pain-free field treatment of multiple actinic keratoses (AK) of the face and scalp (1). Erythema and crusting may be less pronounced after d-PDT compared with conventional PDT (c-PDT) using red light (2, 3). During PDT of multiple AK of the face and scalp, patients are affected by inflammation, which may cause absence from work or social activities. In a recent study we introduced the concept of pulse-PDT, in which methyl aminolevulinate (MAL) cream is applied for only 30 min under occlusion and then removed to ensure selective accumulation of the photosensitizer pro- toporphyrin IX (PpIX) in the mitochondria and cytosol of the diseased cells (4). The study showed that the use of pulse-PDT could reduce erythema after PDT of multiple AK on the face and scalp (4). The use of a super-potent corticosteroid before and just after pulse-PDT further reduced erythema. The objective of this randomized study was to eva- luate whether the combination of pulse-corticosteroid- daylight-PDT (PS-d-PDT) would result in less post-PDT erythema than d-PDT without affecting the efficacy of the treatment of multiple AK on the face and scalp. A further aim was to clarify whether the use of brimonidine tartrate (BT), a selective α 2 -adrenergic receptor agonist, could result in a further short-term reduction in PDT- induced erythema. MATERIALS AND METHODS Twenty-five male patients with a total of 823 AK were included in the study. AK on the face or scalp were marked in 2 symmetrical squared areas and randomized to d-PDT or PS-d-PDT, respectively. After lesion counting and mapping, a sunscreen (Actinica ® SPF 50+, Galderma, Uppsala, Sweden) was applied. Following lesion preparation with a curette, MAL cream (Metvix ® , Galderma) was applied to both treatment areas without occlusion. After 30 min, the MAL cream was removed in the area randomized to PS-d-PDT and super-potent glucocorticosteroid (Dermovat ® , GlaxoSmithKline, Broendby Denmark) was applied. The MAL was not removed from the d-PDT until after daylight exposure. Patients exposed themselves continuously to daylight for 2 h, after which they stayed indoors for the remainder of the day. Erythema was evaluated 24 h after PDT, at which time BT gel was applied in both treatment areas, and erythema was re-evaluated 30 min later. Erythema was measured using a skin reflectance meter (Optimize Scientific 558; Chromo-Light, Vedbaek, Denmark) (5) and evaluated visually by the investigator using a 4-point scale. Patients scored the pain using a numerical scale (0–10) in both areas every 30 min during daylight exposure. doi: 10.2340/00015555-3049 Acta Derm Venereol 2019; 99: 242–243 The study was approved by the ethics committee of Region Hovedstaden (H-4-2011-151). Statistical analyses were performed with GraphPad Prism ® (GraphPad Software Inc., USA). Wilcoxon matched-pairs signed rank test was used to compare paired data and for correlations Spearman R correlation was used. A p-value < 0.05 was considered significant. RESULTS No difference was found between the 2 treatment areas in baseline characteristics, such as lesion count and ery­ thema. Ninety percent of the lesions were grade I AK. One patient was excluded from the BT part of the study due to treatment with MAO-inhibitors. The visually evaluated erythema one day after treat- ment was less in areas treated with PS-d-PDT compared with d-PDT (p = 0.0032). Measured erythema was significantly increased the day after both treatments compared with baseline (p < 0.0001). Median erythema was significantly higher in the d-PDT areas than in the PS-d-PDT areas the day after treatment (p = 0.028) (Table I). The use of BT on the treated areas 1 day after treatment significantly reduced erythema (p < 0.0001) (Table I). BT removed PDT-induced erythema as no significant difference was found between erythema before PDT and after BT in either d-PDT or PS-d-PDT treated areas (p = 0.77 and p = 0.27, respectively). Both treatments were almost pain-free, with a median maximal pain score of 1 (p = 0.81). No significant difference in efficacy was found between the 2 treatment areas (p = 0.42) (Table I). At 3-month follow-up a mean of 1.4 new AK had developed in the d-PDT-treated areas, compared with 2.6 new AK in the PS-d-PDT-treated areas ( p =  0.012). Lesion response rate was not associated with increased erythema ( p =  0.51 and p =  0.78). Table I. Erythema and number of actinic keratosis before and after treatment in both areas d-PDT Median (IQR) Erythema Baseline 24 h after PDT 24 h after PDT and BT Actinic keratosis Baseline 3-month lesion response rate (%) PS-d-PDT Median (IQR) p- value 39.9 (35.2–43.9) 38.6 (33.1–41.9) 0.32 47.8 (41.1–51.0) 44.6 (41.0–48.3) 0.0028 42.4 (36.2–45.6) 37.8 (33.6–42.0) 0.015 15 (13–20) 14 (12–21) 0.59 75.8 (64.7–86.7) 80.0 (66.7–87.5) 0.42 PDT: photodynamic therapy; BT: brimonidine tartrate; d-PDT: daylight-PDT; PS- d-PDT: pulse-steroid-daylight-PDT; IQR: interquartile range. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.