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.

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.

Vascular endothelial growth factor is an autocrine growth factor for hair dermal papilla cells.

The transition of the late anagen to the catagen phase is concomitant with the disappearance of perifollicular capillaries, and therefore cyclical hair growth might depend on the ability of the dermal papilla to synthesize and release soluble growth and differentiation factors toward pre-existing capillaries. We characterized an angiogenic growth factor in the conditioned medium of dermal papilla cells indistinguishable from vascular endothelial growth factor as judged by biochemical and immunologic criteria. In addition, these cells bind vascular endothelial, growth factor on two binding sites and proliferate or migrate in the presence of this growth factor. Moreover, neutralizing antibodies inhibit these biologic effects, confirming that vascular endothelial growth factor might contribute to hair growth either by acting directly on papilla cells or by stimulating the local vascularization.

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.

Inhibitory effects of bFGF, VEGF and minoxidil on collagen synthesis by cultured hair dermal papilla cells.

Dermal papilla cells of rat vibrissa follicles cultivated in monolayers and in three-dimensional collagen gels show a different morphology in these culture systems. Dermal papilla cells cultured in lattices tend to express morphological features resembling those seen in vivo. Quantification of total collagen by incorporation of 3H-proline in monolayer cultures and in collagen lattices show that the amount of collagen found in dermal papilla cells is higher than that secreted. Moreover, collagen synthesis measured in lattices is reduced to about 50% of that found in monolayer cultures. The influence of growth factors on collagen synthesis by hair dermal papilla cells was investigated. We studied the effects of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and minoxidil on collagen synthesis in monolayers and in lattices. VEGF, bFGF and minoxidil significantly decreased the total amount of collagen. In monolayer cultures, there was approximately a 30% inhibition of collagen production with 5 ng/ml bFGF, 0.1 ng/ml VEGF and 100 ng/ml minoxidil. However, in the lattices this inhibition was reduced to about half. These results suggest that both culture substrate and growth factors influence collagen production by rat hair dermal papilla cells.

An in vivo method for measuring the mechanical properties of the skin using ultrasound.

In this study, we report a new and original device called the "echorheometer," comprising a suction system with an ultrasound scanner (A-mode, TM-mode and B-mode) that enables the simultaneous visualization and measurement of the deformation of skin structures in vivo. With the scanner described here, high resolution is obtained using a strongly focused, wide-band 20-MHz center frequency transducer, with an axial resolution of 0.07 mm. This device can determine, noninvasively, not only those skin structures that are involved in the deformation, but also their morphological variation and their extent of involvement with the degree of stress applied. Using this device, the behavior of the dermis and subcutaneous fat, while under suction, was investigated on the volar forearm of 10 volunteers. The results showed that the resistance to the applied vertical stress is essentially due to the dermis rather than the subcutaneous fat, and that there is a certain amount of infiltration of fluid into the tissues under suction. In addition, it was shown that the dermal response to an applied suction is initially due to its own natural tension and that, with increasing deformation, the intrinsic dermal elasticity has a greater contribution to the resistance of stress. With this information, we hope to develop a mechanical model to define appropriate mechanical parameters for skin. This will allow the evaluation of changes in the dermis and also enable therapeutic intervention to be assessed. Furthermore, it could also be applied to studies of skin ageing and the assessment of cosmetic product efficacy (emolliency, hydratation, etc.).

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.

In vivo model of the mechanical properties of the human skin under suction.

BACKGROUND/AIMS: A new method for the in vivo characterization of the mechanical properties of skin has been developed. This comprises a suction chamber and an ultrasound device to measure both the vertical displacement of the skin's surface, and the skin's thickness. METHODS: A mathematical model of the mechanical behaviour of a taught elastic membrane is used to obtain a set of parameters intrinsic to the skin, such as Young's modulus (E) and the initial stress (sigma0), which reflect the stiffness and the natural tension of the skin, respectively. We also calculated an index of non-elasticity of the skin (unrestored energy ratio, UER), which takes into account the volume of tissue mobilized. It determines a ratio between the energy input to the skin and the energy it dissipates. These parameters were evaluated from the volar forearm of 10 normal male volunteers. RESULTS: The results were: 129+/-88 kPa for E, 13.5+/-5 kPa for sigma0, and 0.42+/-0.04 for UER; with reproducibilities of 9.5%, 12.4% and 6.4%, respectively. CONCLUSIONS: This new suction device was found useful for the study of the behaviour of the skin, and the device may be used for the evaluation of certain skin diseases and their therapy.

Image analysis of scaly skin using Dsquame(R) samplers: technical and physiological validation.

An image analysis-based technique for evaluating skin scaliness using Dsquame(R) instant testers is presented, with four surface texture parameters characterizing this condition. Studies on the variability of the technique were carried out to determine the influence of instrumental and physiological factors. Parameters of texture, optical density, number and surface area of squames are calculated from images of obliquely lit Dsquame(R) samples. Repeated measurements were done on artificial and real samples to determine instrumental and sample variability, respectively. In addition, the technique was used in a volunteer study to assess anatomical differences and seasonal variation. For five consecutive measurement days, the artificial samples remained stable, with coefficients of variation for repeatability and reproducibility of less than 8% for all parameters. During the same period, the real samples showed decreases mainly in those parameters of texture and optical density. In the volunteer study, the calf showed significantly higher values (more scaly) in December than July, with no seasonal change in forearm or crow's foot area sites. Assessments of Dsquame(R) instant tester samples using image analysis-derived parameters provides information on the quantity and quality of skin scaliness or flakiness. As such, it is a useful tool for studying desquamation. The technique presented is repeatable and reproducible; however, samples need to be analysed the same day to avoid deterioration problems. Anatomical differences have been demonstrated, with, in addition, the calf showing marked winter/summer changes in comparison to the face and forearm.

Sex- and site-dependent variations in the thickness and mechanical properties of human skin in vivo.

A new method for the in vivo characterization of the physical properties of skin is presented. This comprises an ultrasound device to measure the vertical displacement of the surface of the skin, as well as its thickness and that of the hypodermis under suction. In combination with this, a mathematical model is used to calculate the following skin parameters: Young's modulus, the initial stress and an index of non-elasticity. These parameters were evaluated from the volar forearm and the forehead of 30 male and 30 females, of similar ages (28 +/- 6-years-old). The sensitivity of the testing procedure, allowing the characterization of the mechanical parameters of the skin, easily differentiated these two sites, and in some cases, differences between women and men were demonstrated. The main results showed for both sexes that the thickness (P = 0.0001), Young's modulus (P = 0.0001), and the index of non-elasticity (P = 0.0001) were greater for the forehead than for the ventral forearm, but that the initial stress was lower (P = 0.0001). The results show that the skin is thicker, stiffer and less tense and elastic on the forehead than on the ventral forearm, suggesting structural differences between these two sites (collagen fibre network, elastic fibres, epidermis, stratum corneum, microvascularization, actinic damage, presence of sebaceous glands, etc.). It is hoped that this device will be useful for the evaluation of certain skin disorders (scleroderma, Ehlers-Danlos syndrome, cutis laxa, oedema, etc.) and their therapy, as well as being a useful tool in skin ageing and cosmetic product assessment.

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.

[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.

Cell stress and implications of the heat-shock response in skin.

Heat-shock proteins (HSPs), or so-called 'stress proteins' may play an important role in cutaneous pathophysiology. HSPs are a group of highly conserved molecules that are expressed by all cells when subjected to heat or other forms of physical or chemical stress. The physiological roles of stress proteins are varied and are important in stress and nonstress conditions. They bind to other cellular proteins and participate in protein folding pathways during stress and also during the synthesis of new polypeptides. HSPs are also essential for thermotolerance and for prevention and repair of damage caused in DNA after ultraviolet exposure. Although HSPs are expressed in the skin in both epidermis and dermis, HSPs may influence many other cellular processes in the inflammatory and immune skin response. Many authors have speculated on a link between HSPs and human skin disease characterized by inflammation and proliferation.