Michèle Verschoore

New insights in photoaging, UVA induced damage and skin types

UVA radiation is the most prevalent component of solar UV radiation; it deeply penetrates into the skin and induces profound alterations of the dermal connective tissue. In recent years, the detrimental effects of UVA radiation were more precisely demonstrated at cellular and molecular levels, using adequate methods to identify biological targets of UVA radiation and the resulting cascade impairment of cell functions and tissue degradation. In particular gene expression studies recently revealed that UVA radiation induces modulation of several genes confirming the high sensitivity of dermal fibroblasts to UVA radiation. The major visible damaging effects of UVA radiation only appear after years of exposure: it has been clearly evidenced that they are responsible for more or less early signs of photoageing and photocarcinogenesis. UVA radiation appears to play a key role in pigmented changes occurring with age, the major sign of skin photoaging in Asians. Skin susceptibility to photoaging alterations also depends on constitutive pigmentation. The skin sensitivity to UV light has been demonstrated to be linked to skin color type.

Skin tolerance of adapalene 0.1% gel in combination with other topical antiacne treatments

BACKGROUND Adapalene (Differin gel) is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. OBJECTIVE We assessed, in healthy volunteers, the skin irritancy potential of three combinations, each including adapalene 0.1% gel and one topical marketed antiacne product. METHODS Twenty-five healthy volunteers were enrolled in a 21-day cumulative irritancy study performed in a double-blind, randomized, controlled, intraindividual design. Five days a week, the three materials (benzoyl peroxide, clindamycin phosphate, and erythromycin) were applied in a nonocclusive manner either alone or in combination with adapalene gel on seven cutaneous sites on the upper back. Adapalene was applied in the evening whereas the three other materials were applied in the morning. Irritation was evaluated and scored daily except on weekends. RESULTS All materials were well-tolerated when tested alone. The combinations of adapalene 0.1% gel and either benzoyl peroxide, clindamycin phosphate, or erythromycin were also well-tolerated. The mean cumulative irritancy indices indicated that all three combinations were nonirritating. CONCLUSION Under the conditions of the study, all tested treatments alone or in combination appeared nonirritating.

Adapalene 0.1% gel has low skin-irritation potential ☆ ☆☆ ★

Abstract Background: Adapalene is a new naphthoic acid derivative with potent retinoid and antiinflammatory properties, developed for the topical treatment of acne vulgaris. Objective: We compare the cutaneous safety of adapalene in different gel vehicles with tretinoin 0.025% gel. Methods: A total of 42 healthy human subjects were enrolled in two randomized, double-blind, controlled, intraindividual studies. In the first study (study A), adapalene aqueous 0.03% and 0.1% gels were evaluated for their 21-day cumulative irritation potential compared with vehicle alone, patch alone, and tretinoin 0.025% gel under occlusion. In the second study (study B), adapalene aqueous (0.03% and 0.1%) gels and adapalene alcoholic (0.03% and 0.1%) gels were evaluated for their 5-day cumulative irritation potential compared with their respective vehicles and tretinoin 0.025% gel. Transepidermal water loss (TEWL) was measured daily at each visit. Results: In study A, adapalene had a slight irritation potential that was in the same range as the gel vehicle and the patch alone, whereas tretinoin 0.025% gel was a severe irritant. In study B, no irritation was seen with either adapalene aqueous gels or adapalene gel vehicles or patch alone. The adapalene alcoholic gels were slightly irritating, and tretinoin gel produced intense irritation reactions in the majority of subjects. TEWL increased fourfold at the tretinoin site but remained unchanged at all adapalene sites. Conclusion: Adapalene 0.1% gel was significantly less irritating than tretinoin 0.025% gel. (J Am Acad Dermatol 1997;36:S104-9.)

Adapalene 0.1% gel is better tolerated than tretinoin 0.025% gel in acne patients

BACKGROUND Adapalene is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. OBJECTIVE We describe the results of a combined safety analysis of two multicenter trials conducted in the U.S. and Europe in which adapalene 0.1% gel was compared with tretinoin 0.025% gel in the treatment of mild to moderate acne vulgaris. METHODS A total of 591 acne patients were enrolled in these investigator-masked, randomized, controlled, parallel group studies. In the two studies, each patient was randomly assigned to receive topical adapalene 0.1% gel or tretinoin 0.025% gel once daily at bedtime, for 12 weeks. In addition to assessments of efficacy and facial skin tolerance, data on adverse events were recorded at each visit or at any other time the patient reported problems. We extracted data concerning adverse reactions (i.e., adverse events judged to be related to the study treatment) from both studies and combined the results to obtain a global comparison of safety of the two products. RESULTS A total of 15 of 296 patients (5.1%) reported 19 adverse reactions in the adapalene-treated groups, compared with 27 of 295 patients (9.1%) reporting 39 adverse reactions in the tretinoin-treated groups (p < 0.05). The number of patients discontinuing the study because of adverse events was approximately twice as low with adapalene (1.3% compared with 2.4%). Most adverse reactions for both products were related to skin irritation. No systemic adverse reactions were reported. CONCLUSION The results of these two multicenter clinical studies indicate that adapalene gel is better tolerated than tretinoin gel.

Nail toxicities induced by systemic anticancer treatments

Patients treated with systemic anticancer drugs often show changes to their nails, which are usually well tolerated and disappear on cessation of treatment. However, some nail toxicities can cause pain and functional impairment and thus substantially affect a patients quality of life, especially if they are given taxanes or EGFR inhibitors. These nail toxicities can affect both the nail plate and bed, and might present as melanonychia, leukonychia, onycholysis, onychomadesis, Beaus lines, or onychorrhexis, as frequently noted with conventional chemotherapies. Additionally, the periungual area (perionychium) of the nail might be affected by paronychia or pyogenic granuloma, especially in patients treated with drugs targeting EGFR or MEK. We review the nail changes induced by conventional chemotherapies and those associated with the use of targeted anticancer drugs and discuss preventive or curative options.

Circadian Variations in the Number of Actively Secreting Sebaceous Follicles and Androgen Circadian Rhythms

Sebum excretion has been shown to demonstrate a circadian rhythm using a gravimetric method (cigarette paper). With the newly introduced method of Sebutape, we confirmed this periodicity and showed that the elevation in sebum excretion is correlated with an increase in the number of secreting follicles. We found, furthermore, that the number of secreting follicles on the forehead showed a distinct and statistically significant circadian rhythmicity, in contrast to those of the chest, which remained almost constant. The quantification in plasma levels of cortisol, melatonin, delta-4-androstenedione, dehydroepiandrosterone sulphate, and free testosterone showed no correlation with sebum excretion at either site. These observations suggest that local factors are involved in control of sebum secretion.

The use of hydroxy acids on the skin: characteristics of C8-lipohydroxy acid.

The hydroxy acids are widely used in skin creams because of their exfoliating and rejuvenating effect on photoaged skin. As a member of this family, the salicylic acid derivative known in the literature as 2‐hydroxy‐5‐octanoyl benzoic acid or β‐lipohydroxy acid has also been proposed as an exfoliant and as a treatment of photoaged skin and acne. This article reviews the effects of the hydroxy acids and compares them to those of the salicylic acid derivative. We propose the name C8‐lipohydroxy acid (C8‐LHA) for this derivative to differentiate it from other related compounds. The lipophilic nature of C8‐LHA and its relatively slow penetration in the skin afford it an exfoliating effect that is efficient at low concentrations. It appears to have antimicrobial, anti‐inflammatory, and anticomedogenic properties, which make it effective against acne. Its antifungal and exfoliating properties are also likely to prove useful in combating dandruff.

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.

Determination of Melanin and Haemoglobin in the Skin of Idiopathic Cutaneous Hyperchromia of the Orbital Region (ICHOR): A Study of Indian Patients

Background: Idiopathic cutaneous hyperchromia at the orbital region (ICHOR) is a cutaneous hyperchromia characterised by bilateral darkening of the eyelid and orbital skin that contrasts with the adjoining facial skin. ICHOR is frequent in dark skin. It interferes with the face appearance which often causes difficulties in societal acceptance and may impact quality of life. Objective: The aim of this investigation was to study the epidemiology, clinical features and risk factors associated with ICHOR in Indian patients and also to study the distribution of melanin and haemoglobin in ICHOR patients. This study also assessed the relevance of SIAscopy technique (spectrophotometric intracutaneous analysis (SIA)), a new objective non-invasive method to measure melanin and haemoglobin concentration in vivo. Materials and Methods: Thirty-three patients diagnosed with ICHOR at the All India Institute of Medical Sciences, New Dehli, India, were included in the study. Epidemiological data were collected through a self-administrated questionnaire. Standard photographs were taken from each patient and SIAscopy measurements were done on dark circles and normal skin. Results: Surprisingly our study showed no significant correlation between ICHOR prevalence and family history, atopic and contact dermatitis, contemporaneous melasma and hormonal factors. The study confirms that sun exposure is a risk factor of dark circles aggravation. Indeed patients tend to reduce sun exposure after the onset of dark circles. SIAscopy analysis reveals significant differences in the concentration of total melanin, of dermal melanin and of haemoglobin between ICHOR skin and normal skin of the same patient. Conclusion: This study confirms that melanin deposits and blood stasis in dark circles may play a role in ICHOR pathogenesis and cause the darkening of skin under eyes. SIAscopy provides objective diagnostic information about ICHOR.

Proteomic analysis identifies new biomarkers for postmenopausal and dry skin

Abstract:  A proteomic analysis of stratum corneum (SC) samples of normal healthy skin revealed the presence of more than 70 proteins by 2D electrophoresis. The majority of these proteins to our knowledge have not yet been described in normal SC. We analysed by Western blot the levels of 25 proteins in the SC taken from postmenopausal and dry skin compared with young and normal skin, respectively. In postmenopausal skin, there was a significantly increased amount of heat shock protein 27, plakoglobin and desmoglein 1, whereas transglutaminase 3, apolipoprotein D and acid ceramidase levels were significantly reduced compared with the SC of young skin. We confirmed corneodesmosin as a marker of dry skin. In addition, we showed for the first time that the levels of both phosphatidylethanolamine‐binding protein 1 and annexin A2 were significantly increased in the SC of dry skin compared with the SC of normal skin. These results suggest that a proteomic analysis of the SC obtained using a non‐invasive varnish stripping method is an attractive alternative to invasive methods to better characterize changes in the physiology of ageing and dry skin.