Clinical trials in dermatology. The phase I trials]

Application of the new topical product on the diseased skin should be preceded by its safety evaluation on the healthy skin in human volunteers. We propose here guidelines for the evaluation of the irritation, sensitization, phototoxicity and photoallergy potentials for topical products. The methods for evaluation of percutaneous absorption are also discussed. The studies presented here are not the object of any regulations. Therefore, we propose here an approach for the safety evaluation of topical products in human volunteers.     

A comparison of the efficacy and tolerability of adapalene 0·1% gel versus tretinoin 0·025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials

The purpose of this meta-analysis was to determine if adapalene 0·1% gel (Differin®) provided superior efficacy and better tolerability than tretinoin 0·025% gel in the treatment of acne vulgaris. All comparative studies, both published and unpublished, from the United States and Europe, that fulfilled rigorous protocol criteria (multicentre, randomized, investigator-blind) were used. Five comparative studies met these criteria. In total, the meta-analysis evaluated 900 patients (450 treated with adapalene 0·1% gel, 450 treated with tretinoin 0·025% gel) with mild-to-moderate acne from the combined clinical trials. To avoid study bias, the meta-analysis used an intention-to-treat analysis. Statistical methodology for the meta-analysis included analysis of covariance, analysis of variance and Cochran–Mantel–Haenszel test. All statistical tests were two-sided, with the 0·05 probability level used to establish statistical significance, and 95% confidence intervals used to assess equivalence. Adapalene demonstrated equivalent efficacy to tretinoin in terms of reducing total lesion count. Adapalene demonstrated more rapid efficacy, as evidenced by a significant difference in the reduction of inflammatory and total lesions at week 1. Adapalene also demonstrated considerably greater local tolerability at all evaluation periods. The findings from this meta-analysis suggest that adapalene 0·1% gel constitutes a pharmacologic advance over such classic retinoids as tretinoin for the treatment of acne vulgaris.     

Cutaneous solar ultraviolet exposure and clinical aspects of photodamage

Solar ultraviolet (UV) radiation reaching the earth is a combination of UVB (290-320 nm) and UVA (320-400 nm) wavelengths. Since UVA is less energetic than UVB, UVB has long been thought to be the factor responsible for the damaging effects of solar radiation. But with modern tools such as in vitro models, it has been proven that UVA plays a major role. The objective of this review is to show how skin may be exposed to UV light and to highlight the clinical aspects of UV-induced skin damages with the respective contribution of UVB or UVA. Even if UVA is less energetic than UVB, it is more abundant and penetrates deeper into the skin, reaching as far as the dermis. Various factors also influence skin exposure to UV light: the latitude, season, and time of the day. Acute as well as chronic sun exposure induces short- and long-term clinical damages. Erythema and pigmentation are immediate responses of normal human skin exposed to UV radiation. The long-term effects are photoaging and photocarcinogenesis. In particular, UVA appears to play a major role in the deterioration of dermal structure leading to the photoaged appearance of the skin.     

Photoprotection and vitamin D status

Vitamin D is produced by the skin in response to ultraviolet radiation (UVR) from sunlight. A lack of vitamin D, known as vitamin D deficiency, can cause bones to become soft and weak, which can lead to bone deformities. Whilst UVR exposure is a main source of vitamin D, it is also a primary cause of skin cancer, leading to debates on how to get the balance between ideal (sufficient) vitamin D levels and sun protection. This review aimed to offer practical recommendations on the impact of sunscreen use on vitamin D status. An international panel of thirteen experts in endocrinology, dermatology, photobiology, epidemiology and biological anthropology reviewed the literature relating to vitamin D levels and sunscreen use prior to a one day meeting in June 2017. They examined the current methods for assessing and determining vitamin D sufficiency, current public health recommendations, the impact of sun exposure on vitamin D and the effects of sunscreen use. There is no international agreement on the ideal vitamin D levels, with recommendations varying greatly. A blood level of ≥ 50 nmol/L 25(OH)D was the most widely held target level during this review. It was concluded that daily use of broad-spectrum sunscreen (offering both UVA and UVB protection) will not affect vitamin D production in healthy people. However, people with photosensitive disorders are an exception to this and would therefore benefit from vitamin D screening as well as supplementation.