Non-surgical treatments for hidradenitis suppurativa: A systematic review.

INTRODUCTION: The management of hidradenitis suppurativa is multidisciplinary, involving general measures, medical treatment and surgery. Non-surgical treatments, often first-line procedures, mainly concern forms of low-to-moderate severity or, conversely, very severe forms in non-operable patients or those refusing surgery. While many treatments have been attempted, few randomized controlled trials have been conducted, so the choice of treatments is most often based on the personal experience of the clinicians. The objective of this systematic review is to propose a synthetic analysis of the currently available non-surgical procedures. METHODS: This systematic review of the literature was conducted in accordance with the PRISMA criteria. We searched for articles in the Medline®, PubMed Central, Embase and Cochrane databases published between January 2005 and September 2015. RESULTS: Sixty-four articles were included. They generally had a low level of evidence; indeed, the majority of them were retrospective observational studies. They involved biotherapy (44%), dynamic phototherapy (16%), antibiotics (11%), Laser (8%), retinoids (6%) and immunosuppressive therapies, anti-inflammatory drugs, zinc, metformin, gammaglobulins and fumarates. CONCLUSIONS: None of the non-surgical treatments can treat all stages of the disease and offer long-term remission. Antibiotics and biotherapy seem to have real effectiveness but their effect remains suspensive and the disease is almost certain to reappear once they are stopped. As regards antibiotics, no association has shown their superiority in a study with a high level of evidence. And while some biotherapies seem quite effective, due to their side effects they should be reserved for moderate-to-severe, resistant or inoperable forms of the disease. Randomized controlled studies are needed before valid conclusions can be drawn. In the resistant or disabling forms, it is consequently advisable to orientate to the greatest possible extent towards radical surgery, which is the only treatment allowing hope for cure.

[Hyaluronic acid: structure, metabolism and implication in cicatrisation]. / Acide hyaluronique : structure, métabolisme et implication dans la cicatrisation.

Hyaluronan (HA) is a key component of the extra-cellular matrix and is involved in several mechanisms of the wound healing process. It is highly hygroscopic and is involved in the visco-elasticity of the skin. The properties of this molecule depend on its molecular weight. Native high molecular weight HA has structural properties whereas HA degradation products (oligomers) stimulate endothelial cell proliferation and migration. HA oligomers modulate inflammatory processes and promote neo-angiogenesis during the different steps of wound healing. HA mediates its biological effects through binding interactions with specific cell-associated receptors (CD44 and RHAMM). The tridimensional structure of HA is variable and acts as a framework for cell adhesion and migration. Thanks to its different physico-chemical properties, hylaluronic acid is very useful in the biomedical field.

[Lipids and skin inflammation: role of phospholipases A2]. / Lipides et inflammation cutanée: place des phospholipases A2.

Phospholipases A2 (PLA2) are enzymes that catalyse the hydrolysis of glycerophospholipids at the sn-2 position, generating free fatty acids and lysophospholipids. At present, PLA2 family consists of 12 groups. PLA2 are involved in many pathophysiological processes such as barrier function, eicosanoid production, and inflammation. They are implicated in inflammatory diseases of the skin: psoriasis, eczema, atopy. The presence of PLA2 activity has been demonstrated several years ago, however the precise localization of all these PLA2 in the epidermis and its appendages has to be determined. Further studies have shown that these enzymes are expressed in various layers of epidermis. This differential localization suggests different roles for each PLA2 in skin physiology and during inflammation.

Radiation-induced skin fibrosis after treatment of breast cancer: profilometric analysis.

BACKGROUND/AIM: Treatment of breast cancer involves an association of conservative surgery and radiotherapy. This implies various cutaneous complications, well known for their clinical and histological aspects. Little data are available concerning modifications of the cutaneous microrelief after radiotherapy. We have done a profilometric analysis of the skin of breast cancer patients treated with surgery and radiotherapy. The results obtained on the irradiated breast have been compared with the ones of the controlateral normal breast. METHODS: Twenty women, 43-55 year old were enrolled in the study 6-16 months after the end of a treatment associating conservative surgery and radiotherapy for breast cancer. Imprints using a silicone rubber material were performed over symmetrical areas of the treated breast and the controlateral one. All measures were performed over the upper-medial quadrant of each breast. The imprints are then blindly analysed using an image analyser. The following parameters were measured: RA (average roughness of the skin), RZ (average of the furrows depth), RS (residual length), Rn (number of furrows) and AR (space between the furrows). RESULTS: The comparison of the imprints shows important modifications of the microrelief after irradiation. We observe a slight increase of the skin roughness (RA: 26, 39 +/- 2, 58 versus 21, 84 +/- 1, 59), a significantly increase of the furrows depth (RZ: 121, 66 +/- 10, 46 versus 101, 26 +/- 6, 99) along with an increase of the residual length (RS: 580, 60 +/- 60, 60 versus 450, 46 +/- 48, 43). The number of furrows has not significantly decreased but the space between the furrows has increased on the irradiated breast. CONCLUSION: This study shows a breakdown effect of irradiation on the skin in correlation with the fibrosis inducing by ionising radiation. The imprints modifications are clearly different from those usually observed in the ageing process. Our results can be a basis for studying the effects of treatments on cutaneous complications linked to the radiation-induced fibrosis.

[Implication of VEGF, steroid hormones and neuropeptides in hair follicle cell responses]. / Rôles du VEGF, des hormones stéroïdes et des neuropeptides dans les réponses cellulaires des follicules pilaires.

Human hair follicles progress independently through the anagen, catagen, telogen and latency phases that correspond to growth arrest and hair shedding before initiation of a new anagen phase. Hair follicles are self-renewing and contain reservoirs of multi-potent stem cells. Identification of the messenger molecules and pathways operating in the growth and cycling of hair follicles, have provided substantial data. However, only a limited number of these signals is well understood. The specific response of hair follicle cells to these signals is correlated with the expression of their corresponding receptors. What regulates these responses? In this review, we will focus on the hair cycle and its control mechanisms. We will provide some elements in answer to these questions and present some of the markers of hair follicle cells, and hormonal and vascular growth factors, which may regulate respectively hair follicle cell metabolism and cycle, and the neuropeptide impact on hair follicle response and hair growth. The results of our study show the modifications in various expression patterns of receptors in dermal papilla cells, and demonstrate the cross-interaction between these different components. In conclusion, we present an accumulation of evidence suggesting that the regulation of hair growth requires a combination of hormonal, vascular and neuropeptide approaches that will provide further insight in defining new treatments for hair loss.

Environmental pollutants and skin cancer.

We are increasingly exposed to environmental pollution. Pollutants can be inhaled, ingested or come into contact with the skin depending on the form in which they occur. On metabolization, activation, or accumulation, pollutants can become extremely toxic for the vital organs and this is often related to a strong genotoxic effect. Since the skin acts as a barrier between the organism and the environment, it is frequently directly exposed to pollution. It is very often degraded by polluting agents and acts as an inlet toward other tissues. Numerous studies in man recognize and demonstrate the carcinogenic power of certain pollutants in the digestive and respiratory tracts. The "pollutants" that react most specifically with the skin are: ultraviolet radiation, polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene), volatile organic compounds (e.g., benzene), heavy metals, and ozone. Ultraviolet radiation, a "physical" pollutant, has been described as being the factor responsible for most skin cancers in man. The genotoxicity of UV light is well documented (type of lesion or mutation, etc.) and its carcinogenic effect is clearly demonstrated in vivo in man. A few epidemiological studies describe the carcinogenicity of certain pollutants such as arsenic or lead on the skin. However, most of the evidence for the role of pollutants in skin cancers comes from in vivo animal studies or from in vitro studies (e.g., PAHs). In this report, different studies are presented to illustrate the research strategies developed to investigate the mechanism of action of "chemical" pollutants and their potential role in human skin pathology. All the study models and the associated techniques of investigation are tools for a better understanding and thus more efficient prevention of the deleterious effects caused by the environment.

Nonablative remodeling: clinical, histologic, ultrasound imaging, and profilometric evaluation of a 1540 nm Er:glass laser.

BACKGROUND: Nonablative remodeling has been recently proposed as an alternative to CO2 and Er:YAG resurfacing. OBJECTIVE: To evaluate the efficacy and safety of a 1540 nm Er:glass laser with contact cooling in nonablative skin remodeling, focused on perioral and periorbital rhytides. METHODS: Sixty patients (mean age 47 years), Fitzpatrick skin types I-IV were treated four times over 6-week intervals. Patients were evaluated using digital photographs, histology, ultrasound imaging, and profilometry with silicone imprints in order to quantitate the degree of clinical improvement. RESULTS: All subjects reported subjective improvement in the quality and visual aspect of their skin. This was confirmed by a 40.2% reduction of anisotropy (P <.001) 6 weeks after the fourth treatment. Ultrasound imaging demonstrated a 17% increase of dermis thickness (P <.005). Biopsy specimens showed evidence of new collagen formation. CONCLUSION: This study has clearly demonstrated that irradiation with 1540 nm Er:glass laser can lead to new collagen formation, dermis thickening, reduction of anisotropy of the skin, and clinical improvements. The lack of adverse effects confirmed that this 1540 nm laser emitting in a pulsed mode coupled with an efficient cooling system is safe.

Use of thigh pressure cuffs to modulate simulated microgravity-induced changes in the skin measured with high-resolution B-scan ultrasound.

OBJECTIVE: The aim of the present study was to evaluate the fluid shift in a simulated microgravity experiment and to test the use of thigh cuffs to help alleviate the problem. METHODS: The change in skin thickness was assessed by a 20 MHz B-scan ultrasound device. This was performed on eight volunteers who underwent two successive 7-day periods of -6 degrees anti-orthostatic bed-rest, with or without the daytime use of thigh cuffs. The thigh cuffs were used to counteract the development of facial oedema. RESULTS: In the control group (without thigh cuffs), the results showed a steady increase in skin thickness of the combined dermis and hypodermis of the forehead and a reduction of the thickness of this tissue on the tibia. For the countermeasure group, although thigh cuffs were only employed during the daytime - being removed at night - their use reduced the amplitude and kinetics of the fluid shift, resulting in greater beneficial effects at the end of the day than early in the morning. CONCLUSION: These results of objective measurements of skin made using a non-invasive high frequency ultrasonography method confirm reports by cosmonauts of a reduction in facial oedema and a more 'comfortable' adaptation to microgravity by the use of thigh cuffs during space flight. This system is potentially promising for investigating fluid shifts in the skin and may prove useful in the evaluation of some oedematous skin diseases, as well as their therapy.

Immunomodulation induced by Avène spring water on Th1- and Th2-dependent cytokine production in healthy subjects and atopic dermatitis patients.

Avène spring water (ASW) is commonly used in France for treating atopic dermatitis and psoriasis. Previous works demonstrated modulation of cell membrane fluidity by ASW. The aims of the present study were (a) to investigate a possible in vitro effect of ASW on Th1- and Th2-dependent cytokine production using peripheral blood mononuclear cells from healthy individuals and (b) to investigate both the in vitro effect of ASW on AD patients' cells and the in vivo cellular and clinical modifications induced by a 3-week Avène Medical Spa water cure (AMSWC). The effect of ASW was tested on lymphocyte cultures, which were stimulated in vitro by various mitogens and a superantigen of staphylococcal origin. The lymphocyte proliferation and the production of the cytokines IL-2, IL-4 and IFN-gamma were tested. The results showed that ASW-containing medium enhanced the lymphoproliferative response to some mitogens. IL-2 and IFN-gamma production were also increased in stimulated culture supernatants. Conversely, ASW-containing medium induced a decrease in IL-4 production by normal peripheral blood lymphocytes. Furthermore, AMSWC was able to amend the clinical features as well as the immunological Th2 profile of atopic dermatitis.

Aplicación de una técnica colorimétrica para la evaluación del efecto de preparados de base tensiactiva sobre el estrato córneo / Application of a colorimetric technique for the evaluation of the action of tensiactive based formulations on the stratum corneum

Se propone una técnica basada en una unción con piranina, colorante fluorescente, para explorar y cuantificar alteraciones infraclínicas del estrato cómeo causadas por la aplicación previa y repetida de tensiactivos habitualmente utilizados en formulación de preparados dermatológicos y cosméticos de higiene. La intensidad de la fluorescencia, detectada mediante un programa de análisis de imágenes, es más elevada cuando la eficacia de la barrera hidrolipidica se reduce por la acción de los tensiactivos aplicados. El protocolo estudiado puede resultar de utilidad para la realización de screenings en la fase de preformulación de este tipo de productos (AU)

Skin topography measurement by interference fringe projection: a technical validation.

BACKGROUND/AIMS: The quantitative analysis of skin topography is frequently used in cosmetology to evaluate the efficacy of hydrating or anti-wrinkle creams (micro-topography studies) or creams for slimming or to alleviate stretch marks (macro-topography studies). Numerous methods involving the three-dimensional (3-D) reconstruction of the topography from silicone replicas have been developed. Some of the main techniques applied include optical profilometry based on the reflection of oblique lighting or on transparency, and profilometry by laser focusing or triangulation. METHODS: We chose to test the Dermatop system developed by Eotech Co., which is based on interference fringe projection profilometry associated with the Toposurf surface processing software. Owing to the system's principle of operation, we first ran three experiments to evaluate the influence of ambient lighting on the 3-D reconstruction and the surface roughness parameters, the influence of the calibration device built into the acquisition system and the influence of calibration in terms of ambient lighting correction. We then evaluated the accuracy, the repeatability and the reproducibility of the measurements provided by the system from known metal topographic standards and skin replicas. RESULTS: It was seen that external lighting can cause variations in the calculation of parameters SPa, SPt and SPtm which can reach error levels of about 5% if the operator does not almost systematically calibrate the apparatus between each measurement. These three experiments enabled us to standardise the protocol for the acquisition of 3-D information, in order to minimise the lighting problems and yet respect the requirements for routine studies. The correlation coefficient between the theoretical values and the mean of experimental values was 0.9955 for parameter SPa and 0.9983 for parameter SPtm. Repeatability presented variations of under 4%, irrespective of the parameters, and reproducibility of under 6%. CONCLUSIONS: The technique provides very satisfactory results from the point of view of accuracy, repeatability and reproducibility. It is an excellent compromise between cost, accuracy and the time required.

The discovery of Gramicidin S: the intellectual transformation of G.F. Gause from biologist to researcher of antibiotics and on its meaning for the fate of Russian genetics.

The discovery of Gramicidin S is considered to be the outcome of the intellectual transformation of Russian biologist G.F. Gause from simply a biologist to a researcher of antibiotics. Different historical conditions of this change as well as the development of experimental biology itself at this time are analysed in detail. The meaning of Gause's occupation of a new 'niche' in soviet science for the fate of Russian post-war genetics is defined as well.

Skin ageing: changes of physical properties of human skin in vivo.

We have investigated in vivo the change with age of various parameters that describe the physical properties of skin. The parameters were derived from pressure/displacement curves obtained by applying reduced pressure to a small area of skin and measuring the resulting displacement by 20 MHz scan echography. By fitting the pressure/displacement curves to a theoretical model, the following skin parameters were obtained: E, Young's modulus or stiffness (in Pascals); sigma(0), the initial stress (in Pascals); and the unrestored energy ratio (UER), an index related to cutaneous non-elasticity. These parameters, which are used in mechanics to define the intrinsic physical characteristics of materials, were measured for the first time on volar forearm skin of 206 male and female subjects, aged between 6 months and 90 years. The results showed that skin thickness increases until maturity and decreases for women over 50-60 years old, Young's modulus E increases linearly with age, and ageing is divided into two phases for natural stress, sigma(0) and the non-elasticity index UER. Natural stress sigma(0) increases until maturity and then rapidly decreases. The non-elasticity index decreases until puberty and steadily increases after puberty. This new procedure provides a simple quantitative assessment of the physical properties of the skin, revealing that the skin becomes thinner, stiffer, less tense and elastic with ageing.

Studies on epidermis reconstructed with and without melanocytes: melanocytes prevent sunburn cell formation but not appearance of DNA damaged cells in fair-skinned caucasians.

To assess the photoprotective role of melanocytes in the epidermis, we studied the effects of ultraviolet B on an epidermis reconstructed with and without melanocytes. To address more specifically the role of melanin in fair-skinned individuals, experiments were done with cells obtained from human skin of low phototypes (II-III). To study the effect of constitutive melanin and possibly that of newly synthesized melanin precursors, a single dose of ultraviolet B (0.10 or 0.15 J per cm2, corresponding to a 4-5 minimal erythema dose in vivo) was administered to reconstructs and the effects were monitored over the first 24 h. When reconstructs with and without melanocytes were compared, no difference was found for DNA damage/repair assessed with antibodies to cyclobutane pyrimidine dimers and 6-4 photoproducts. More necrotic/apoptotic cells, however, were noted 24 h following ultraviolet B irradiation in reconstructs lacking melanocytes. Twenty-four hours following ultraviolet B irradiation the number of necrotic/apoptotic cells and the number of cyclobutane pyrimidine dimer positive cells was coarsely concentration-dependent. The number of cyclobutane pyrimidine dimer positive cells, however, was independent of the type of reconstruct used (with/without melanocytes). In conclusion, low phototype melanocytes seem to protect epidermal basal cells against ultraviolet B-induced apoptosis/necrosis and may preserve the overall integrity of the epidermis after ultraviolet B irradiation. On the contrary, such melanocytes do not seem to have a protective role against DNA damage and may not prevent cancer.

Identification of pancreatic type I secreted phospholipase A2 in human epidermis and its determination by tape stripping.

Phospholipases A2 (PLA2) catalyse the release of fatty acids from the sn-2 position of phospholipids and have been suggested to play a key part in permeability barrier homeostasis. Using a sensitive and versatile fluorometric method, significant PLA2 activity has been detected in both human skin homogenates and tape strippings of stratum corneum. Based on various properties (resistance to heat and sulphuric acid treatment, neutral optimal pH, absolute requirement for millimolar calcium concentrations, inhibition by dithiothreitol and p-bromophenacyl bromide, and resistance to a trifluoromethyl ketone derivative of arachidonic acid, AACOCF3, a specific inhibitor of cytosolic PLA2), this enzyme was characterized as a secretory PLA2 (sPLA2). Immunohistochemistry revealed strong labelling of type I pancreatic sPLA2 at the stratum corneum-stratum granulosum junction, type II sPLA2 being undetectable. An increase in PLA2 activity in tape-stripped material from the deepest level of the stratum corneum was correlated with partial morphological disappearance of type I sPLA2 immunolabelling. Our data thus provide the first convincing evidence that pancreatic sPLA2 is significantly expressed in human epidermis, where it might participate in the accumulation of free fatty acids contributing to the permeability barrier. In addition, our method for determining PLA2 activity in easily available tape strippings should allow further clinical studies aimed to explore possible PLA2 abnormalities in various dermatoses.

Microrelief of the skin using a light transmission method.

The recently developed Skin Visiometer, based on light transmission through blue-coloured silicone replicas, was used to study skin microrelief. Calibrated metal plates displaying lines with depths between 6 and 361 microns, were used to determine the accuracy, sensitivity and reproducibility of the technique as well as the parameters of importance during measurement. The precision of the measurements was particularly good between 10 microns and 361 microns. The sensitivity of the method was between 10 and 20 microns. Replicas of volar forearm skin were taken from four groups (n = 15) of male and female volunteers in the age ranges 20 to 30 years and 55 to 65 years. In addition to the instrumental roughness parameters (Rz, Rt, Rm and Ra), the surface of the furrows, the number of primary and secondary lines and the number of intersections were determined. For both sexes, significantly lower values were observed for Rz, Rm and Rt in the younger age group than in the older age group. In addition, the numbers of primary and secondary lines and the number of intersections were higher, pointing to a more structured microrelief in younger forearm skin. Diurnal rhythm, the relative humidity of the measuring room and the position of the forearm were found to be significant factors, while room temperature and precleansing of the skin with mild products were not. Following the application of a hydrating cream (twice daily for 14 days) to the forearm skin of the older female age group, the Rz, Rt, Rm and Ra decreased, while the other parameters measured, except for the surface taken in by the lines, increased, indicating that the microrelief was modified towards the typical pattern observed in young skin.

Evaluation of cutaneous modifications in seventy-seven growth hormone-deficient children.

Cutaneous parameters such as dermal thickness, stiffness, elasticity, skin surface lipid and hydration were evaluated using noninvasive methods in 77 growth hormone-deficient (GHD) children before replacement therapy and in 70 non-GHD children. We showed that in GHD children, dermis was thinner (0.70 +/- 0.10 vs. 0.80 +/- 0.10 mm, p < 0.0001 for prepubertal children and 0.81 +/- 0.10 vs. 0.94 +/- 0.11 mm, p < 0.0001 for pubertal children), stiffer (178.5 +/- 57.3 vs. 113.09 +/- 37 kPa, p < 0.0001 for prepubertal children and 172.5 +/- 61.7 vs. 117.3 +/- 42.5 kPa for pubertal children, p < 0.001) and less elastic (0.44 +/- 0.09 vs. 0.39 +/- 0.06 (nonelasticity index), p < 0.01 for prepubertal children and 0.39 +/- 0.05 vs. 0.33 +/- 0.04, p < 0.001 for pubertal children) compared to controls. Fourteen GHD children were re-evaluated after 1 year of GH treatment: dermal thickness and skin stiffness were significantly improved (p < 0.001 and p < 0.05 respectively) while elasticity was not modified. During the same period, 11 controls did not show any significant cutaneous modification. IGF-1 values, but not IGFBP-3 values, correlated positively with dermal thickness in GHD children, before and after 1 year of GH treatment. To conclude, GHD children exhibited specific cutaneous modifications. In a subset of GHD children, we showed that these modifications were influenced by GH treatment. More extensive studies are needed to see if these changes correlated with other GH effects.

Seasonal variability in the biophysical properties of stratum corneum from different anatomical sites.

BACKGROUND/PURPOSE: A 10-month-long study on a panel of 24 young female subjects was carried out to determine whether various biophysical aspects of the stratum corneum (SC) varied with season. METHODS: Three different anatomical sites (calf, inner forearm and crow's foot wrinkle area of the face) were assessed in February, April, July and December of the same year. The assessments made were skin surface hydration using an electrical capacitance technique, transepidermal water loss by evaporimetry, number of corneocytes released using a turbine stimulation method, and skin surface topography using optical profilometry. RESULTS: The results showed significant anatomical differences: with the crow's foot site > forearm > calf, for skin surface hydration and corneocyte numbers; and the crow's foot site > forearm and calf, with no difference between the latter two sites, for TEWL measurements. With these techniques, seasonal differences were observed mainly in the calf, to a lesser extent in the forearm, but not in the crow's foot area. These mainly involved increases in these three parameters in July, as opposed to the other time-points. Parameters of skin surface topography however, showed no consistent seasonal pattern, but markedly higher values were observed for the forearm in comparison to the calf and crow's foot sites, which were similar. From meteorological data obtained, the average daily maximum temperature and hours of sunshine increased to peak values in July, as did the absolute humidity derived from relative humidity data. CONCLUSION: We conclude that the results are most likely to represent changes in the SC due to climatic factors, with the calf and forearm sites being most affected in comparison to the face (crow's foot wrinkle area), which seems unaffected. The reasons for this latter site remaining unchanged may be due to its greater UV exposure, sebum content, and that the use of facial cosmetics was allowed.

Characterisation of gravity-induced facial skin oedema using biophysical measurement techniques.

BACKGROUND/AIMS: In humans, the microgravity environment can be expected to induce swelling of facial tissues and shrinking of the tissues in the lower limbs, together with a loss in body weight. To evaluate fluid shifts in skin, the head-down bed-rest model was used. The aim of the present study was to evaluate the appearance of facial oedema in subjects undergoing anti-orthostatic bed-rest at an angle of -10 degrees. METHODS: The forehead of each of four subjects was measured before and after 1, 10 and 24 h in this head-down tilt position. At these time points, interstitial fluid migration and facial oedema were assessed using a high resolution B-scan ultrasound and a device for measuring the skin's mechanical properties. RESULTS: The results obtained showed a progressive increase in dermal thickness and initial stress, and a reduction in stiffness and elasticity of the skin during the study period. CONCLUSIONS: This preliminary study has demonstrated the feasibility of the method in measuring fluid displacement and retention in the skin. Furthermore, it highlights the influence of fluids on the mechanical behaviour of the skin. These techniques could be used for studying the redistribution of liquid masses during periods spent in space.