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Monitoring treatment response in patients affected by actinic keratosis: Dermoscopic assessment and metalloproteinases evaluation after piroxicam 0.8% and sunfilter cream

Piroxicam (PXM), an enolic benzothiazine, inhibits the synthesis of cyclooxygenase-1 and -2, downregulates the production of prostaglandins and thromboxane, prevents polyamines production and suppresses metalloproteinases (MMPs) activities, the most prominent tumorigenesis-proteinases family (Campione et al., 2015; Jetter, Chandan, Wang, & Tsoukas, 2018). We recently studied the effects of long-term or short-term PXM treatment on actinic keratoses (AKs) and field of cancerization in immunocompetent subjects and organ transplant recipients (Babino et al., 2016; Campione, Diluvio, Paternò, & Chimenti, 2010; Garofalo et al., 2017). In this open-label trial, we described dermoscopic assessment of AK patients and evaluated the expression of MMP-1 and -2 at baseline and after treatment with PXM. Typical dermoscopic features seems to be associated with nonpigmented AKs: white-to-yellow surface scales, pink-to-red pseudonetwork, targetoid-like appearance, and rosette sign. Dermoscopic pattern of pigmented AKs are: multiple slate-gray-to-dark brown dots and globules, annular granular structures, uniform pigmented background and superficial, brown, broken-up pseudo-network (Fargnoli, Kostaki, Piccioni, Micantonio, & Peris, 2012; Zalaudek, & Argenziano, 2015). MMPs play a critical role in several processes including angiogenesis, cell proliferation, tumor invasion and metastasis (Polette, Nawrocki-Raby, Gilles, Clavel, & Birembaut, 2004). Greater MMP-2 expression was observed in high grade AKs (de Oliveira Poswar et al., 2015). Thirteen Caucasian patients affected by 30 AKs were enrolled (eight men and five women; age range: 61–78 years), after ethics committee approval. AKs were located on face, arms, dorsum of the hands, bald scalp, and upper back the upper limbs. PXM 0.8% and 50+ sun filters were applied twice daily for a period of 12 weeks. The clinical monitoring was performed by AKESA score at baseline, at intermediate visit and after 12-weeks-treatment (Campione et al., 2015). Dermoscopic images were obtained using a dermoscope (DermLite 3Gen LLC, Dana Point California) at 10-fold magnification and collected using DermLite foto equipment at 20to 50-fold magnification. A punch-biopsy was performed before and after therapy for morphological (Hematoxylin & Eosin staining [H&E]) and immunohistochemical evaluations. Immunoevaluation was based on the mean number of immunostaining cells per high power field, using an arbitrary score 0–3. Statistical analysis was developed using test for qualitative variables, and Student's t-test and ANOVA for continuous variables. Differences were considered statistically significant for value of p < .05 (SPSS, version 12.0 Chicago, IL). After treatment, there was a highly significant clinical improvement in lesions based on the decrease of AKESA score (data not shown). The baseline dermoscopic features were red pseudo-network (90%), white/yellow areas and keratotic follicular openings (73.3%), strawberry pattern (63.3%), white-to-yellow scales (63.3%), telangiectasia (53.3%), annular granular structures and yellow dots surrounded by white rim (33.3%), gray pseudo-network (20%), rosette sign and glomerular vessels (16.6%). After treatment, white-to-yellow scales (13.3%), red pseudo-network (33.3%), strawberry pattern (16.6%), teleangiectasia (23.3%), annular granular structures (6.6%), white/yellow areas (16.6%), keratotic follicular openings (16.6%), yellow dots surrounded by white rim (3.3%), and rosette sign (0%) decreased. In two patient, gray pseudo-network and glomerular vessels, were unchanged (6.6%) (Figure 1). H&E staining confirmed typical morphological features of AK (hyperplasia, spongiosis, dermal elastosis) and restoration of normal skin architecture after PXM treatment. Also immunoevaluation of MMP-1 and MMP-2 showed a reduction of staining in treated-skin compared with baseline (Figure 2; p < .05). In most patients, a progressive reduction of AK dermoscopic criteria (rosette sign, annular granular structures, strawberry pattern, white/yellow areas, keratotic follicular openings, teleangectasia, glomerular vessels, gray pseudo-network, yellow dots surrounded by white rim) until their disappearance was observed after treatment. Red pseudo-network, white/yellow areas, and yellow scales still remaining in a few patients. Histological and immunoevaluation confirmed restoration of normal skin architecture and reduced levels of MMPs expression after treatment, confirming the role of this proteinases family in skin cancer. We report the dermoscopic assessment histological and immunoevaluation of AKs in patients treated by this novel non-ablative agent, confirming PMX as a promising therapy also from the dermoscopic and histological point of view. Received: 12 August 2018 Revised: 27 September 2018 Accepted: 6 October 2018 DOI: 10.1111/dth.12772