Assessment of sinecatechins 10% ointment used as proactive sequential therapy in recurrence rate of genital warts lesions after cryotherapy. The PACT-II Trial (postablation immunomodulator treatment of condylomata with sinecatechins): a prospective assessor-blinded, multicenter, pilot trial.

BACKGROUND: Cryotherapy is commonly used as ablative treatment of external genital warts (EGW). However, after cryotherapy recurrence of lesions affects on average 45% (42-70%) of subjects in the 6 months after the treatment. Sinecatechins 10% are an effective topical treatment of EGW. A low recurrence rate (<6%) was observed in pivotal phase 3 trials conducted with this product. Topical sinecatechins have demonstrated to significantly reduce the recurrence rate of EGW in subjects treated with laser therapy (The PACT-I trial). So far, no prospective data are available regarding the efficacy of sinecathechins as immunomodulator sequential therapy after cryotherapy in EGW subjects. The purpose of this study was to assess the rate of recurrence lesions after the use of topical sinecatechins 10%, as sequential proactive immunomodulation treatment after cryotherapy in subjects with EGW (The PACT-II Trial: the postablation immunomodulator treatment of condylomata with sinecatechins trial) (Trial Registration number: ISRCTN44037479). METHODS: In a prospective, assessor-blinded, multicenter trial a total of 55 subjects with a diagnosis of multiple EGW (36 men and 19 women, mean age 47±10 years) and a mean lesion number of 9±7, after their informed consent, were enrolled in the study. All subjects were treated with cryotherapy (an average of 2 sessions). After the ablative treatment, all subjects were instructed to apply sinecatechin 10% ointment 3 times daily for 4 consecutive months. The primary study endpoint was the evaluation (assessor-blinded) of recurrent lesions after 6 months (2 month of follow-up after the conclusion of topical treatment). The secondary study endpoints were the appearance of new EGW lesions (lesions affecting area not treated by cryotherapy) and the local tolerability. RESULTS: At baseline, the mean number of EGW lesions were 9±7. After cryotherapy, the mean lesions number were reduced to 1.6±1.8. At month 4, EGW mean lesion number were 0.2±0.4 (P=0.0001 vs. after cryotherapy). At month 6, recurrence of lesions was detected in 10 subjects (18%; 95% CI: 9-30%) with an average of 1.4 lesions. Of these recurrent lesions, 6 occurred in completely healed lesions site after cryotherapy and 8 in partially healed ones. New lesions (outside the cryotherapy treated area) were observed in 10 subjects. The product was very well tolerated. No serious side effects were reported. Three subjects reported moderate skin irritation on the application site. CONCLUSIONS: The PACT-II Trial has shown that the recurrence rate of EGW lesions after successful cryotherapy using sinecatechins as immunomodulator sequential therapy is lower in comparison with the percentage documented in the literature without sequential therapy (20 vs. 45%). These results are in line with already published data evaluating the role of sinecatechins after laser therapy (PACT-I trial). Future comparative, double-blind controlled trials assessing the efficacy of different proactive strategies are warranted.

Assessment of clinical efficacy of lidocaine/tetracaine 7%/7% peel cream in fractional microablative laser procedure-associated pain for facial skin aging treatment. A randomized, controlled, single-blind trial.

BACKGROUND: Lidocaine/tetracaine 7%/7% peel cream (L/T-pC) is very effective in reducing pain in several dermatological procedures, such as hair or tattoo laser removal or conventional photodynamic therapy associated pain. Fractional laser resurfacing (FLR) is an effective treatment strategy for facial skin aging. The main drawback of FLR is the procedure-associated pain. So far, no controlled data are available regarding the efficacy of L/T-pC in reducing pain during a full-facial microablative FLR session in subjects with facial skin aging. AIM: To assess the clinical efficacy of L/T-pC in reducing pain during microablative FLR treatment in subjects with facial skin aging. We conducted a prospective, randomized, parallel-group, controlled, single-blind trial, performed in out-patients attending to a Laser Clinic for facial skin aging treatment. SUBJECTS AND METHODS: A total of 30 subjects (4 men, 26 women; mean age 42 ± 10 years; range 28-57) with mild to moderate facial skin aging (Glogau score ≥2), suitable for FLR treatment, were enrolled after their written informed consent. Participants were randomized to L/T-pC application (45 min before the laser treatment with the removal of the cream just before the starting of laser session) (n = 20) or to control (emollient cream; n = 10). FLR was performing using a fractional microablative CO2 laser (Smartxide DOT 2 Deka) using a pulse power of 18 W (range 15-20) and pulse duration of 1.5 msec. The primary endpoint was the comparison of the mean visual analogue score (VAS) values between the two groups using a 10-cm scale (0 = no pain; 10: the most severe pain). The VAS score was measured just after the FLR session. Effective anesthesia (percentage of subjects with a VAS score ≤3) and the assessment of local tolerability and safety of the peel cream were the secondary trial endpoints. RESULTS: All the enrolled subjects concluded the trial. In the L/T-pC group, the VAS mean score was 3.0 ± 1.2. In the control group, the VAS mean score was 8.6 ± 0.5, representing a 65% reduction of the VAS score in the active treated group vs. controls. The difference between the two groups was statistically significant (p = 0.0001; Mann-Whitney test) with an absolute difference of -5 ± 0.4 cm; 95%CI of the difference: from -4.6 to -6.4 cm). Adequate anesthesia (VAS score≤3) was reported in 80% of subjects in the active group vs. 0% in the control arm. The cream was very well tolerated. One subject in the active group manifested moderate/severe edema in the cream application area, subsiding in 6 h. No other side effects were reported. CONCLUSION: The application of L/T pC 7%/7% peel cream before a fractional laser resurfacing session significantly reduced the procedure-associated pain with good tolerability and safety profile.

Inter-observer evaluation of erythema-directed photography for the assessment of erythema and telangiectasias in rosacea.

BACKGROUND: Persistent centrofacial erythema associated with telangiectasias is one of the most common phenotypes of rosacea in clinical practice, and the assessment of each component is crucial as each of them may require a different approach. The aim of this study was to evaluate the inter-observer reliability of standard photography vs erythema-directed photography for the assessment of erythema and telangiectasias in rosacea. MATERIALS AND METHODS: One hundred full-face images of 50 rosacea patients (50 standard photographs and 50 erythema-directed digital photographs) were evaluated by 8 independent experienced dermatologists using a 5-item score for erythema and telangiectasias, respectively. Inter-rater reliability, by comparing erythema and telangiectasias scores and calculating the percentage of agreement between evaluators, was assessed and the strength of agreement using the Cohen's Kappa values (95% CI) was calculated. RESULTS: Poor and fair strength of agreement for erythema and telangiectasias using standard photography vs moderate and good strength of agreement using erythema-directed digital photography was found. CONCLUSION: Erythema-directed digital photography may provide a better strength of agreement and higher reliability among independent observers compared to standard photography in the assessment of erythema and telangiectasias in rosacea, thus suggesting new horizons for digital appraisal of skin diseases.

Efficacy of sinecatechins 10% as proactive sequential therapy of external genital warts after laser CO2 ablative therapy: The PACT study (post-ablation immunomodulator treatment of condylomata with sinecatechins): a randomized, masked outcome assessment, multicenter trial.

External genital warts (EGW) are the most common viral sexually transmitted infection. Ablative treatments like cryotherapy, curettage, and CO2 laser therapies offer rapid onset of effect, fast clearance, and reduction of virus load. However, these procedures are associated with high recurrence rates (RRs) ranging from 20% to 77% in the short and medium terms and do not provide sustained clearance. After laser therapy removal of EGW, an RR up to 77% has been reported. Topical sinecatechins (TS) 10% is a patient-applied regimen for the treatment of EGW with a low RR (<6.5%) at three months after completion of the therapy in the pivotal trials conducted so far. Sinecatechins can be considered a suitable proactive sequential therapy (PST) after ablative strategies to obtain a low RR. So far, no prospective data are available regarding the efficacy of sinecatechins 10% as PST. We evaluated the efficacy and tolerability of TS 10% ointment applied twice daily in subjects with "difficult to treat" EGW after CO2 laser ablative treatment in a prospective controlled trial. A total of 87 subjects (76 men and 11 women; mean age 42 years) were enrolled in this three-month masked outcome assessment parallel group trial with imbalanced randomization allocation (2:1). One week after a successful CO2 laser treatment, 60 subjects were randomized to TS 10% treatment and 27 subjects to no treatment (control group: ConTRol (CTR); no sequential therapy). All patients had a history of an average of 4.5 previous ablative treatments in the last 12 months due to recurrent EGW. Mean (standard deviation) baseline number of treated lesions was 6.5 (2.7). One subject in the TS arm dropped out due to burning sensation after the application of the product. Therefore, 86 subjects completed the study. After three months, in the TS group, three subjects presented new EGW lesions (RR: 5%) on treated sites. In the CTR group, eight subjects presented new EGW lesions (RR: 29%) on treated sites (p = 0.0024; odds ratio: 0.16; 95% confidence interval: 0.04-0.68). In the TS group, 34 subjects (56%) reported mild to moderate erythema or burning sensation at the application site. In this prospective multicenter trial, the use of TS 10% as PST after ablative treatment with CO2 laser was associated with a lower recurrence rate of new EGW lesions in the short term in comparison with the control group. Comparative larger trials are warranted to evaluate the role of this approach as PST (Trial Registration Number: ISRCTN44037479).

A two-center, assessor-blinded, prospective trial evaluating the efficacy of a novel hypertonic draining cream for cellulite reduction: A Clinical and instrumental (Antera 3D CS) assessment.

INTRODUCTION: Gynoid lipodystrophy, also known as cellulite, is a very common skin alteration representing mainly a cosmetic problem rather than a real disease. An effective treatment of cellulite has not been well established. The initial phase of cellulite is characterized by subdermal tissue edema with interstitial fluids retention. A new hypertonic topical product with draining action (HTC) containing NaCl 13%, escine, caffeine, and beta-sitosterol has been recently developed. A 28-day double-blind placebo-controlled study has shown that this cream is able to reduce thigh circumference and the thickness of adipose tissue. No data so far are available regarding an objective evaluation of skin appearance for a longer application period. STUDY AIM: To evaluate the clinical efficacy of 2-month HCT treatment with clinical and instrumental assessments. SUBJECTS AND METHODS: In a prospective, 2-center, assessor-blinded trial 20 women (mean age 34 years) with cellulite of Grade I-III in severity were enrolled after their informed consent. HTC was applied once daily for 60 days. Primary outcomes of the trial were the evolution of thigh circumference measurements (assessed at baseline, after 1 and 2 months) and the computer-analysis of skin profilometry (ie, skin volumes) of a prespecified target area evaluated by means of Antera 3D CS digitalized images (assessed at baseline and at the end of the trial). Secondary outcome was the orange peel severity score (from 0 to 5) before and after pitch test. RESULTS: All subjects concluded the study period. Thigh circumference was reduced by -0.88 (right)/-1.2 cm (left) and by -1.8(right)/-2.1 (left) cm, after 30 and 60 days of treatment, respectively (P = .001, Wilcoxon test vs baseline). Antera 3D profilometry of the target zone showed a significant reduction in skin depression expressed in mm3 of -56% (from 59.7 to 26.73 mm3 ) after HTC application. Orange peel (no pitch test) mean (SD) score was 2.3 (1) at baseline, 2.0 (1) and 1.8 (0.8) after 1 and 2 months (P = .0031), respectively. After-pitch orange peel score was significantly reduced after treatment (from 3.3 to 2.2). CONCLUSION: Once daily application of HTC for 2 months has confirmed its efficacy in the improvement of objective and subjective assessments of cellulite parameters.(Trial Number registration: ISRCTN15111614).