Morphological and molecular characterization of actinic lentigos reveals alterations of the dermal extracellular matrix.

BACKGROUND: Actinic lentigos (AL) are benign hyperpigmented skin lesions associated with photoageing. Despite their high prevalence, biological mechanisms driving their formation remain unclear. OBJECTIVES: To provide new insights about the physiopathology of AL through a comprehensive description of their histological and molecular features. METHODS: Quantitative analysis of dermoscopic images was used to select AL containing elongated patterns, predicted to display a highly deformed dermal-epidermal junction (DEJ), on the back of the hands of 15 Caucasian women. Biopsies from lesional and adjacent nonlesional (NL) areas were processed for histological analysis or gene expression profiling. RESULTS: Histological staining confirmed a drastic deformation of the DEJ in AL, with deep epidermal invaginations into the dermis. Although the melanin content was significantly higher in AL compared with NL epidermis, the distribution of melanocytes along the DEJ was unchanged. Transcriptomic analysis revealed a signature of 529 genes differently expressed in AL vs. NL skin. Alteration of epidermal homeostasis was confirmed by the dysregulation of keratinocyte proliferation and differentiation markers. Surprisingly, canonical genes involved in melanogenesis were not significantly modulated in AL. A striking finding was the overexpression of a large group of genes involved in dermal extracellular matrix organization and remodelling. Dermal alterations were confirmed by immunolabellings on AL and NL sections. CONCLUSIONS: Drastic disorganization of the cutaneous structure in AL is accompanied by a specific molecular signature revealing alterations in both epidermal and dermal compartments. In particular, our results suggest that local modifications of the dermal extracellular matrix might contribute to hyperpigmentation in AL.

In vitro and in vivo studies with tetra-hydro-jasmonic acid (LR2412) reveal its potential to correct signs of skin ageing.

BACKGROUND: LR2412, a synthetic derivative of jasmonic acid, improved the reconstruction and homeostasis of our organotypic skin models. OBJECTIVES: The need for efficient 'anti-ageing' treatments, in particular for the management of photoaged skin, prompted us to investigate this new ingredient for its potential to correct signs of skin ageing in vitro and in vivo and to identify its mode of action. RESULTS: In vitro, penetration of LR2412 was evaluated using a Franz diffusion cell on excised human skin. Its exfoliating properties and interactions with the stratum corneum were studied using electron microscopy and X-ray diffraction. Experiments were performed on a human reconstructed skin model. In vivo, the effects of LR2412 on steroid-induced skin atrophy, a clinical skin ageing model, were assessed vs. vehicle. A patch test study evaluated its effect on deposition of fibrillin-rich microfibrils in the papillary dermis in clinically photoaged volunteers. A clinical study on the appearance of crow's feet wrinkles was conducted over 3 months of daily application. Penetration studies revealed that LR2412 reaches viable epidermis and superficial dermis, which are skin targets of anti-ageing actives. Within the upper layers of the stratum corneum LR2412 accelerates desquamation and improves the mechanical properties. At the dermal-epidermal junction of reconstructed skin, collagen IV, laminin-5 and fibrillin were stimulated. In vivo, LR2412 reversed steroid-induced atrophy. The patch test model confirms the deposition of fibrillin-rich microfibrils, then an in use clinical study revealed that it reduced facial wrinkles. CONCLUSIONS: The in vitro and in vivo data demonstrate that based on its multiple interactions within human skin, LR2412 has potential to partially correct the signs of ageing in intrinsically and photoaged skin.

Skin ageing: a comparison between Chinese and European populations. A pilot study.

BACKGROUND: Although limited data are available, it is commonly considered that Europeans and Asians have different skin ageing features. OBJECTIVES: The present studies have been carried out to evaluate the influence of age and sun-exposure on the main clinical signs of Asian skin ageing. METHODS: One hundred and sixty Chinese and 160 French age-matched women (age range: 20-60 years old) were clinically examined and scored by the same dermatologist. Facial wrinkles (crow's-feet, glabella and perioral wrinkles) and pigmented spots (on face and hands) were assessed in situ and standardized photographs of the face were taken. Lifelong sun-exposure was estimated from answers to a questionnaire. Comparisons were made between 10-year age groups. RESULTS: Results show that, for each facial skin area, wrinkle onset is delayed by about 10 years in Chinese women as compared to French women. Facial wrinkling rate over the years is linear in French women and not linear in Chinese women who appear to experience a fast ageing process between age 40 and 50. Pigmented spot intensity is a much more important ageing sign in Chinese women (severe for 30% of women over 40) than in French women (severe for less than 8% of women, irrespective of age). CONCLUSION: These first results underline that main skin ageing features (wrinkles, spots) progress differently in the Chinese and French women we have studied. They require to be confirmed on broad multicentre studies involving larger cohorts.

Reversal effects of topical retinoic acid on the skin of kidney transplant recipients under systemic corticotherapy.

The systemic long-term corticosteroid treatment administered to kidney graft recipients (KGR) within the framework of the required immunosuppressive therapy induces an atrophy of the skin, from the sixth month onwards. We studied the effect of topical all-trans retinoic acid (0.05%; Galderma Labs.) applied to the forearms of 27 KGR (14 men, 13 women) over a 6-month period. Twenty-four subjects completed the trial. The following results were obtained in the treated forearm versus the untreated forearm (excipient alone): clinically, an increase in skin thickness; by noninvasive techniques, an increase in skin thickness, skin elasticity, skin conductance, and TEWL, and a reduction in the size of the corneocytes. No change in stratum corneum lipid content was observed. A sex-related difference was noted in the response to treatment under our experimental conditions, the female patients responding better. A punch biopsy (4 mm) was performed on both forearms of four patients after the 6-month period. Histologic and ultrastructural examination revealed epidermal and dermal changes evoking increased cellular metabolism in the retinoic acid-treated forearms.

Characterization of the skin in vivo by high resolution magnetic resonance imaging: water behavior and age-related effects.

The age-related modifications of magnetic resonance imaging parameters in the skin have been studied in vivo. Modification of these parameters should provide important information about alterations in water structure and content in aged skin. Relaxation times, T1 and T2, and relative proton density, which corresponds to the mobile water proton fraction of tissues, have been measured on people under age 40 and over 70 on a sun-protected area. Results have confirmed in vivo skin layer differentiation through relaxation times performed in a previous study. Moreover, relative proton density quantification has shown that epidermal mobile water is at least twice as abundant as dermal mobile water. No significant age-related T1 and T2 modification could be established, basically because of a large dispersion of values. The main result concerns the upper part of dermis (about 200 microns in thickness) which contains significantly more mobile water protons in chronologic aged skin than in young adult skin. This increase has been related both to an increase of total water content in dermis with age and to an apparent decrease of collagen and proteoglycan content. Associated with alterations of their structure, this decrease reduces macromolecular-water interaction sites. This finding has to be compared with ultrasound evaluation of aged skin, which is characterized by modifications of the echogenicity, related to collagen bundles size and density, in the outer part of dermis, too. Both of the imaging techniques tend to consider the outer part of dermis as one of the privileged sites of skin aging.

Hair diameter diversity: a clinical sign reflecting the follicle miniaturization.

BACKGROUND: The degree of androgenetic alopecia is generally evaluated either by global clinical scales or time-consuming methods like phototrichogram or histological studies. We describe a new clinical and reliable scoring method based on hair diameter diversity. OBSERVATIONS: (1) The clinical macroscopic scoring we propose for hair density was significantly correlated with Hamilton classification and with histological hair density. (2) Diversity in hair diameter was the main and most accurate clinical parameter linked to follicle miniaturization. (C) The anagen-telogen ratio decreased in parallel with the decrease in clinical hair density score. CONCLUSIONS: Considering that hair follicle miniaturization is the key point during androgenic alopecia onset and development, diversity in hair diameter represents an important feature to consider as an accurate clinical sign reflecting hair follicle miniaturization. Moreover, diversity in hair diameter seems to be an easily accessible and reliable parameter that should be taken into consideration for further characterization of hair disorders. By itself, we believe that this clinical feature constitutes a new tool of substantial help for the diagnosis and management of androgenic alopecia.

Frey's syndrome analysis with biosensor. A preliminary study.

OBJECTIVE: Objective quantification of Frey's syndrome (gustatory sweating), following total parotidectomy. A biosensoring method of enzymatic electrodes enabling the detection of L-lactate on intact skin with the use of a skin extraction device and enzymatic electrodes is presented and analyzed. DESIGN: A criterion standard study. SETTING: This prospective trial was undertaken at our research laboratory (University of Paris [France]). Parotidectomy was performed in our department, which is a tertiary care center for parotid gland pathology. PATIENTS: Twenty-eight patients with gustatory sweating following total parotidectomy and nine control patients not operated on were asked to take part in this prospective study. MAIN OUTCOME AND MEASURES: Gustatory sweating was assessed in all patients using a clinical scale, the Minor starch iodine test, and the L-lactate biosensoring method. RESULTS: Instrumentation and assay procedure for the L-lactate biosensoring method are detailed. Statistical analysis of data was performed using the Kruskal-Wallis H Test and the Mann-Whitney U Test. Results demonstrate that this method enables objective measurement of the L-lactate on skin without the need for chemical reagents, continuous nondestructive analysis in real time, and physiological dynamic monitoring of the L-lactate rate of production after stimulus. Data achieved strongly suggested that the aberrant regeneration theory is the main clue to Frey's syndrome pathogenesis. CONCLUSION: This safe, reliable, noninvasive, objective, and highly sensitive method provides an investigative tool for clinicians as well as physiologists involved with patients presenting gustatory sweating following parotid gland surgery.

Oily skin: specific features in Chinese women.

BACKGROUND/PURPOSE: Inconsistent data are available on the various types of skin, their prevalence and characterization, particularly regarding Asian skins. This observation prompted to conduct a large study in China to assess the prevalence of oily skin and identify the specific factors related to that type of skin. METHODS: The multicentre trial involved 1787 Chinese women in Shenyang, Harbin, Beijing, Chengdu and Suzhou, between 18 and 65 years of age. Data on history of acne, the presence of environmental factors and a detailed self-evaluation of the skin were collected using a standardized questionnaire. A clinical evaluation of facial skin oiliness was carried-out by a dermatologist at each centre. Sebum secretion was measured on the forehead using Sebumeter SM810. Statistical analysis (multiple correspondence analysis) of typology was conducted based on self-evaluation data. RESULTS: According to self-evaluation data, oily skin prevalence in the overall Chinese population of the study was 25.6%. Self-evaluation results were quite consistent with sebum measurements and with clinical assessment by dermatologist. Parameters associated with oily skin were (i) shiny skin and a past history of acne, (ii) irregular menstruation, and (iii) highly reactive or sensitive skin. Moreover, a clear and significant link was noted between oily skin and the ingestion of spicy or sweet food. Lastly, sebum levels were found to be twice as high in Beijing as in the other cities and were correlated to higher oily skin prevalence. CONCLUSION: The study demonstrated the capacity of women for proper self-evaluation of their skin type. It also suggests a potential link between nutritional factors such as spicy and/or sweet diets and oily skin as well as between sensitive and oily skin in this population.

Extension-induced changes in the microrelief of the human volar forearm: variations with age.

The skin microrelief can be assessed in vivo using a noninvasive method based on the image analysis of negative replicas, shadowed by oblique illumination. This technique was used to study changes in the surface furrows of the human volar forearm, related to the degree of extension, in volunteers of three age groups. Results confirmed that the skin in elderly subjects can be characterized by the lack of one of the two perpendicular furrow orientations observed in the young. During extension of the arm, the response of the microrelief in young subjects was clearly different from that in the elderly. Young skin buffered strain through a progressive shift in line density and furrow depth from one orientation to the other, whereas in the elderly, a progressive rotation of the single furrow orientation occurred. These differences would appear to be related to changes in the architecture and physical properties of the dermis. Microrelief, in the elderly subjects, showed a mean line density of 24/cm, regardless of the degree of extension. This constancy may reflect the ultimate stage in the chronological aging of the skin and may be characteristic of a loosened and relaxed dermis.

[Treatment of actinic aging with topical vitamin A acid in different concentrations]. / Traitement du vieillissement actinique par la vitamine A acide topique à différentes concentrations.

Vitamin A acid has been used for 20 years in the local treatment of acne. In 1986, Kligman published a description of the efficacy of this molecule against skin ageing. In 1987, we began a study which is still in progress. It is intended to confirm the beneficial effects already observed in photosenescence and to demonstrate them by non-invasive methods and by standardized photographs. This study was randomized and carried out under double blind. Each patient acted as her own control. The concentration administered was 0.025 per cent for 6 months and then 0.05 per cent. The patient was followed up every month for 6 months and then every 4 months. The results demonstrated a reduction in the number and depth of the wrinkles and a regression of the pigmented spots. Safety was excellent and all the patients were highly satisfied with the treatment.

In vivo epidermal thickness measurement: ultrasound vs. confocal imaging.

BACKGROUND/PURPOSE: In this study, in vivo skin imaging methods, ultrasound (US) and confocal microscopy (CM) were compared with regards to their accuracy in measuring the epidermal thickness. In addition an attempt was made to clarify the biological significance of the second echo-rich line observed on US skin images, i.e. whether it represents the dermal-epidermal junction or the papillar-reticular dermis limit. METHODS: US images were obtained with an in-house device (22 MHz probe) and the CM images with the VivaScope 1000 (Lucid Inc., Rochester, NY, USA). Skin from the dorsal forearm, the back of hand and the palm skin of 11 subjects (25-40 years) were examined. Repeatability of the procedure and reproducibility of the results were evaluated on repeated measurements taken at 1-month interval. RESULTS: Both techniques are correlated. When a CM measurement is performed from the stratum corneum (SC) surface to the bottom of the papillae, results obtained with US and CM are very similar. Thus, the second echo-rich line on US skin imaging is likely to reflect a virtual line joining the bottom of the papillae. CM is limited to the measurement of a relative thin epidermis, due to the signal-to-noise ratio, which decreases with depth. US technique offers a better repeatability and reproducibility, particularly for SC measurement. This is mainly due to the small size of the investigated field of view in CM. CONCLUSIONS: This study confirms the accuracy of US and the feasibility of CM imaging techniques for in vivo epidermal thickness measurement. Echography probably measures a maximal epidermal thickness since it encompasses the bottom of the papillae.

Clinical morphology of sodium lauryl sulfate (SLS) and nonanoic acid (NAA) irritant patch test reactions at 48 h and 96 h in 152 subjects.

In this study of 152 women, comparison of patch test responses between 2 irritants over 96 h at 2 symmetrical anatomical sites is studied. 2 irritants, each at 4 different concentrations (nonanoic acid (NAA) 80%, 40%, 20%, 10%; sodium lauryl sulfate (SLS) 3%, 2%, 1% and 0.5%) and using propan-1ol and 'water for injection' as the respective controls, were placed as 15 microl aliquots, soaked onto filter paper discs in Finn Chambers, on the volunteer's left and right lower back. The patches were removed at 47, and read at 48 and 96 h. Irritant reactions were evaluated for erythema and surface changes by degree and area affected. Statistical analysis of the results showed that erythema decreased with time for all concentrations of NAA, and at higher concentrations for SLS. Surface changes increased with time for SLS and at higher concentrations of NAA. There was no statistically significant difference comparing left and right sides. Traditionally in patch testing, reactions which fade after 48 h have been regarded as irritant rather than allergic. This study refutes that assumption. Data from our left to right comparisons, made in the same individuals at the same time, show that irritant reactions may be more reproducible than previously appreciated.

Noninvasive measurement of the effect of lifetime exposure to the sun on the aged skin.

The cumulative and comparative effects of chronological and actinic changes to the skin were studied in an elderly population. Two adjacent sites with different degrees of exposure to the sun were examined to distinguish the contribution of each factor, by means of noninvasive measurements. The following parameters were measured on the skin of the low neck (an exposed site), as well as on the adjacent clothes-protected skin of 30 elderly women: electrical conductance, color, microrelief, biomechanical properties and the thickness of both the full skin and the subepidermal nonechogenic band (SENEB), using ultrasound measurements. Persistent exposure to the sun accentuated most of the age-induced modifications. The following changes were significantly more marked in exposed skin: SENEB thickening, full-skin thinning, loss of extensibility and elasticity, and color heterogeneity. The cumulative effects of sun exposure and chronological aging lead to atrophy in elderly people. These results suggest that, if there is an autoprotective skin reaction, such as thickening in young adults, it is eliminated in old people.