Efficacy of different photoprotection strategies in preventing actinic keratosis new lesions after photodynamic therapy. The ATHENA study: a two-center, randomized, prospective, assessor-blinded pragmatic trial.

Background: Treatment of actinic keratosis (AK) and field cancerization with photodynamic therapy (PDT) is an effective therapeutic approach with a significant reduction in the number of AK lesions (-75% or more) associated with a significant cosmetic improvement of the photodamaged skin. Recently, also, the daylight PDT (DL-PDT) has proven to be as effective as the conventional PDT (C-PDT), but with a better tolerability. After C-PDT and DL-PDT it is advised to use photoprotection strategies to improve the clinical evolution and prevent the appearance of new AK lesions that usually appear 3-6 months after the last phototherapy session. However, there are no robust clinical data regarding the type of photoprotection to be used (SPF level, duration of treatment, etc.) after successful PDT.Study aim: The present study (ATHENA trial) evaluated the efficacy and tolerability of a topical product based on 0.8% piroxicam and 50+ solar filters (ACTX), applied twice a day as sequential therapy after C-PDT or DL-PDT on the evolution of AK lesions number compared to the use of very high photoprotection products commonly used in this clinical setting (SPF50+ or SPF100+ associated with photolyase) (Standard Sunscreens: SS group). Subjects and methods: This was a multicenter, randomized, two-arm, prospective controlled, assessor-masked outcome evaluation, parallel group (1:1), pragmatic study of 6 months duration in patients with multiple AK lesions suitable for photodynamic therapy. The objectives of the study were the evaluation of the evolution of the number of AK lesions during the period of treatment/application of the study products, and the Investigator global clinical assessment score (IGA score; 4: marked improvement, 3: good, 2: moderate; 1 no improvement; 0: worsening) 2, 3, and 6 months after the last PDT session. A total of 68 subjects (50 men, 18 women; mean age 70 years), 34 assigned to treatment with ACTX and 34 to treatment with SS (17 treated with a SPF50+ and 17 with a photolyase-containing SPF100+ products), were enrolled in the study.Results: The number of AK lesions present before C-PDT/DL-PDT was 11.8 ± 5.8 in the ACTX group and 12.4 ± 6.9 in the SS group. In both groups, there was a progressive reduction of AK lesions observed at baseline (-86% and -87% after 2 months and -88% and -83% at month 3 in ACTX and in the SS group, respectively). At month 6, AK mean lesion number was 1.8 ± 1.6 in the ACTX and 3.2 ± 2.3 in the SS group; this difference was statistically significant (p = 0.03). The IGA score at the end of the study was 3.2 in the ACTX and 2.7 in the SS group (p = 0.05). The percentage of subjects with an IGA score of 4/3 (very good or good) was 81% in the ACTX and 55% in the SS group (p = 0.06).Conclusion: In subjects with AK treated with C-PDT or DL-PDT, a "medicalized" photoprotection treatment is associated with a favorable clinical outcome with progressive reduction of lesions. In contrast to a very high photoprotection (SPF50+ or SPF100+/photolyase), the use of piroxicam 0.8%/SPF 50+ is associated with a significantly greater improvement in clinical evolution of AK lesions.

Toxoplasma gondii infection in raptors from Italy: Seroepidemiology and risk factors analysis.

Toxoplasma gondii is a zoonotic parasite infecting a wide range of intermediate hosts, including birds. Nevertheless, scant information on the spread of infection in wild bird populations is available to date. With the aim of updating information on T. gondii infection in birds of prey and possible risk factors associated with the infection, a serosurvey was planned on both wild and captive raptors. An overall of 93 raptors from Northern Italy were tested for the presence of anti-T. gondii antibodies with a commercial modified agglutination test (MAT). A T. gondii prevalence of 10.7% was recorded; the highest seroprevalence was observed within the Family Strigidae (12.5%). Only wild animals tested positive; any statistical difference among species, taxonomic family, age, origin, use, migratory behavior and diet composition was not highlighted. Toxoplasmosis in birds of prey, sentinel species for the environmental spread of T. gondii, should always be considered within sanitary programs devoted to avian species protection.

Efficacy of a film-forming medical device containing sunscreen (50+) and piroxicam 0.8% in actinic keratosis and field cancerization: a multicenter, assessor-blinded, 3 month trial.

INTRODUCTION: Sunscreen protection in subjects with actinic keratosis (AK) is highly recommended to prevent clinical evolution of this in situ skin cancer condition. Use of topical anti-cyclooxygenase drugs such as diclofenac and piroxicam reduces the number of lesions and improves the cancerization field. A film-forming medical device in a cream formulation containing organic and inorganic sun-filters (50+ SPF) and piroxicam 0.8% (ACTX) has shown in a pilot, single-center, open trial to reduce AK lesions improving the cancerization field. AIM: We evaluated in a multicenter, assessor-blinded, 3 month trial the efficacy of ACTX in AK. METHODS: A total of 70 subjects with at least three AK lesions on the scalp or face were enrolled after written informed consent. Primary outcomes of the study were the clinical evolution of number of AK lesions on a target zone area and the evolution of dermoscopy features of the target lesion, assessing erythema, scaling, pigmentation, and follicular plug, using a 5 point score (from 0 to 4; maximum score: 16). Lesion count and dermoscopy score were evaluated in a blind fashion assessing digital color high definition coded images. A secondary outcome was the Investigator Global Score (IGS) of clinical evolution of the target area using a 7 point scale from -2 (significantly worse) to +4 (completely cured). IGS was evaluated in an open fashion. Subjects were instructed to apply the cream twice daily on the target area, using one finger-tip unit for the treatment of a 35 cm2 area. RESULTS: All but one subject (40 men and 30 women, mean age 73 years) concluded the study period. At baseline the mean (±SD) number of AK lesions in the target area were 7.0 (5.9) with a median value of 5 and the dermoscopy score of the target lesion was 7.0 (2.3) with a median value of 7.0. ACTX treatment reduced AK lesions to 3.2 (2.9), (p = .0001; Wilcoxon Test), representing a 55% relative reduction. Dermoscopy score was reduced to 3.3 (2.6) (p = .0001) (a reduction of 53%). The IGS after ACTX treatment was +1.9 (1.1), with a median of 2.0. A total of 86% of subjects showed a clinical improvement of IGS (≥1) with a very significant/complete clearance (score +3 or +4) in 42% subjects. No change or a worsening of AK lesions was observed in 14% of the subjects. The product was well tolerated. No serious adverse events were reported during the duration of the trial. CONCLUSION: In this multicenter, assessor-blinded trial, the use of a film-forming medical device with sun protection and anti-inflammatory actions was effective in reducing AK lesions and improving the dermoscopy aspect of the target lesion in 86% of treated subjects. A head-to-head trial evaluating the efficacy of this medical device in comparison with diclofenac is warranted to establish whether this therapeutic approach could offer additional advantages in term of AK lesion reduction compared to an established topical treatment. (Trial ID: ISRCTN72020277).

Comparative Effects of Sunscreens Alone vs Sunscreens Plus DNA Repair Enzymes in Patients With Actinic Keratosis: Clinical and Molecular Findings from a 6-Month, Randomized, Clinical Study.

Recent experimental irradiation studies have shown that the addition of DNA repair enzymes (photolyase and endonuclease) to traditional sunscreens may reduce ultraviolet radiation (UVR)-induced molecular damage to the skin to a greater extent than sunscreens alone. In this 6-month, randomized, clinical study, we sought to compare the clinical and molecular effects of sunscreens plus DNA repair enzymes vs. those of traditional sunscreens alone in patients with actinic keratosis (AK). A total of 28 AK patients were randomized to topically apply sunscreens plus DNA repair enzymes (enzyme group; n = 14) or sunscreens alone (sunscreen group; n = 14) for 6 months. The main outcome measures included 1) hyperkeratosis, 2) field cancerization (as measured by fluorescence diagnostics using methylaminolaevulinate), and 3) levels of cyclobutane pyrimidine dimers (CPDs) in skin biopsies. Both regimens produced a significant reduction of hyperkeratosis at 6 months, with no difference between the two groups. Field cancerization was significantly reduced by both regimens, but the decrease observed in the enzyme group was significantly more pronounced than in the sunscreen group (P < 0.001). At 6 months, CPDs decreased by 61% in the enzyme group and by 35% in the sunscreen group compared with baseline values (P < 0.001). These findings indicate that, despite a similar effect on hyperkeratosis, the addition of DNA repair enzymes to sunscreens was more effective in reducing field cancerization and CPDs than sunscreens alone. Taken together, our findings indicate that sunscreens plus DNA repair enzymes may be superior to traditional sunscreens alone in reducing field cancerization and UVR-associated molecular signatures (CPDs) in AK patients, potentially preventing malignant transformation into invasive squamous cell carcinoma in a more efficient manner.

The density of melanocytic nevi correlates with constitutional variables and history of sunburns: a prevalence study among Italian schoolchildren.

In several studies from northern Europe, north America and Australia, melanocytic nevi are correlated with pigmentary traits and with intense sun exposure in a way similar to malignant melanoma. However, it is unclear if these data can be extrapolated to populations in other geographic locations and with different prevalent phenotypes. Our study was conducted among schoolchildren aged 13-14 years in 16 Italian cities. The parents of 3,127 children of a total of 3,160 (99%) consented to our study. A structured questionnaire was used to collect information about sun exposure and lifetime history of sunburns. Children were also examined by trained dermatologists to assess pigmentary traits and to make a count of melanocytic nevi. The median nevus density was higher among boys than girls. Areas that are usually chronically exposed to the sun exhibited a higher density of nevi compared to intermittently and rarely exposed areas. A higher density of nevi was found in children with lighter skin, blond hair and blue eyes. Red-haired children had a remarkably lower nevus density compared to the other color categories. The density of nevi increased with an increased number of reported episodes of sunburns. The results concerning nevi >/=6 mm in diameter paralleled those obtained for the total nevus density. However, at variance with total nevus density, a significant relation was also observed between larger nevi and freckling. Our study confirms that, in Italian schoolchildren, there is a relation between pigmentary traits, history of sunburns and the density of melanocytic nevi. Melanocytic nevi and malignant melanoma share a similar risk factor profile.