Evaluation of efficacy of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multicenter study

Disturbances of skin barrier function occur in several skin diseases, e.g., atopic dermatitis (AD), irritant/allergic contact dermatitis (ICD, ACD). Skin barrier damage triggers the production of cytokines that stimulate lipogenesis which may also cause inflammatory processes. The aim of this study was to evaluate the efficacy of a topical skin lipid mixture in the treatment of ICD, ACD and AD. 580 consecutive patients suffering from ICD, ACD or AD were treated with a skin lipid mixture containing ceramide-3 and patented nanoparticles. Patients received the lipid mixture alone or in combination with topical corticosteroids until clearance or for 8 weeks. Both treatment groups statistically improved all parameters considered at week 4 and 8 as compared to baseline. Between the 2 treatment groups, there was a statistically significant difference in favour of combined therapy for (ICD, ACD, AD, respectively): erythema, pruritus and overall disease severity; erythema and pruritus; erythema, pruritus, fissuring and overall disease severity. No statistically significant difference was found for (ICD, ACD, AD, respectively): dryness, scaling and fissuring; scaling, fissuring and overall disease severity; dryness and scaling. Between the 2 ACD treatment groups, there was a statistically significant difference in favour of the skin lipid mixture for dryness. In conclusion, the study shows that balanced lipid mixtures are effective in improving barrier properties and the clinical condition of the skin in contact dermatitis.     

Epithelial barrier function and atopic diathesis in rosacea and perioral dermatitis

BACKGROUND: Rosacea and perioral dermatitis (PD) are common dermatoses, the aetiology and pathogenesis of which remain speculative. Objectives To investigate skin barrier function and features of atopy in both diseases. METHODS: We studied 75 patients with rosacea and 75 with PD. Transepidermal water loss (TEWL) was measured in three regions of the face (lateral chin, perinasal cheek, side of the nose) and the patients were assessed for atopy by clinical criteria, prick tests and specific IgE against a mixture of aeroallergens (CAP SX1). The control group consisted of 125 individuals with no history of rosacea, PD or active atopic disease. RESULTS: In patients with PD, TEWL was significantly increased (P < 0.001) at all measurement points in comparison with the rosacea and control groups. Significantly (P < 0.001) higher values were also found regarding history and clinical signs of an atopic diathesis, prick test reactivity and specific IgE against aeroallergens. CONCLUSIONS: PD is characterized by a skin barrier disorder of facial skin. It differs from rosacea in that it involves a significantly increased TEWL and features of an atopic diathesis. However, it remains disputed as to whether PD is an individual skin disease or a subtype of rosacea in atopic patients.     

Skin occlusion and irritant and allergic contact dermatitis: an overview

Occlusion, widely used to enhance percutaneous absorption of drugs, also increases penetration of other chemicals and antigens, and hence may exacerbate irritant and allergic contact dermatitis. This overview summarizes the adverse effects of occlusion.     

Effects of site and menstrual cycle on barrier function and stratum corneum water-holding capacity

Background/aims: Areas of the skin with similar anatomical structure may have different functional behaviour. In vivo barrier function and stratum corneum water-holding capacity during the menstrual cycle on two sites of the volar forearm (upper and lower) and on the anterior aspect of the thigh were evaluated using the plastic occlusion stress test (POST).
Methods: 13 healthy women (age 31 ± 4) with regular menses entered the study. POST was performed by applying a plastic chamber (1.8 cm diameter) on the skin for 24 h. After removal the skin surface water loss (SSWL) was measured using an evaporimeter (EP1-Servomed, Sweden) every 5 min for 30 min. Measurements were taken on the 10th and 25th day of the menstrual cycle. Statistical analysis was performed using one-factor A nova for repeated measures. Free and bound water compartments of evaporation were also analysed.
Results: Higher hydration and SSWL were detectable on the 25th day of the cycle. However, no significant influence of menstrual cycle was found. Significant differences between the upper and lower volar foream were detected ( P < 0.001).
Conclusion: The differences observed were mainly related to the evaporation of bound water, confirming a different barrier function at the sites investigated; therefore, it must be taken into account that adjacent skin sites with equal structure may have different functional behaviour.     

Additive impairment of the barrier function by mechanical irritation, occlusion and sodium lauryl sulphate in vivo

BACKGROUND: The interaction between potential irritants in the workplace might be important because workers are not usually exposed to a single irritant, but to multiple potentially harmful substances. Physical irritant contact dermatitis caused by friction or mechanical abrasion is a common occupational dermatosis. Prolonged water exposure by occlusion is also common in the workplace. Several studies have revealed the negative effect of the common anionic detergent sodium lauryl sulphate (SLS) on permeability barrier function. OBJECTIVES: To study the additive impairment of permeability barrier function by mechanical irritation combined with 0.5% SLS or prolonged water exposure by occlusion, as models of mild irritation. METHODS: The volar forearms of 20 healthy volunteers were exposed to mechanical irritation and occlusion with water or 0.5% SLS for four consecutive days in a combined tandem repeated irritation test (TRIT). Permeability barrier function was measured with a Tewameter TM 210. Irritation was assessed with a Chromameter CR 300 and a visual score. RESULTS: Barrier disruption in our model was rated as follows: occlusion with SLS and mechanical irritation > occlusion with SLS > occlusion with water and mechanical irritation > mechanical irritation and occlusion with water > occlusion with a glove and mechanical irritation > mechanical irritation > occlusion with water. Barrier disruption caused by occlusion or mechanical irritation was enhanced by the tandem application. The choice of irritant under occlusion, time of occlusion and order of tandem application all affected the degree of barrier disruption. Evaporimetry was able to detect early stages in the development of an irritant reaction before it became visible. Chromametry was not able to detect this early response. CONCLUSIONS: Physical irritants (friction, abrasive grains, occlusion) and detergents such as SLS represent a significant irritation risk and should be minimized, especially when acting together, as shown in our TRIT model.     

Skin irritant reactivity following experimental cumulative irritant contact dermatitis

Despite the frequency of irritant contact dermatitis, very little is known about the duration of barrier function impairment following cumulative irritant contact dermatitis. We studied post-irritation irritant reactivity by assessing the response to SLS irritation in previously irritated sites. Cumulative irritant contact dermatitis was induced on the forearms of 15 volunteers aged 18 to 50 years by repeated occluded application of 0.5% SLS I h per day over 3 weeks. 3, 6 and 9 weeks later, previously irritated and unirritated control sites were challenged with 2% SLS under occlusion for 23 h. Irritation was assessed by visual scoring, transepidermal water loss (TEWL) as an indicator of epidermal barrier function, and capacitance as a parameter of epidermal water content. While no difference in irritant reactivity between pre-irritated and unirritated sites was observed 3 weeks following irritant contact dermatitis, there was a significant hyporeactivity of previously irritated skin as expressed by clinical scores, TEWL and capacitance at 6 and 9 weeks. Our results indicate that epidermal barrier function remains altered even 9 weeks after cumulative irritant contact dermatitis. With regard to patch testing, post-irritation hyporeactivity might be a cause of false-negative tests on previously irritated sites.     

Assessment of anti-inflammatory activity of Poria cocos in sodium lauryl sulphate-induced irritant contact dermatitis

OBJECTIVE: In the present study, we evaluated the anti-inflammatory activity of Poria cocos (PoCo) on experimentally induced irritant contact dermatitis (ICD) in a repeated sodium lauryl sulphate (SLS) irritation model. METHODS: The anti-irritative effect of PoCo was evaluated with a visual score and quantified by non-invasive bioengineering methods, namely chromametry and transepidermal water loss. Three concentrations of PoCo in base cream DAC (amphiphilic emollient; German pharmacopoeia) were tested in a 4-day repetitive irritation test using SLS. RESULTS: A statistically significant anti-inflammatory activity was observed for PoCo by all three methods when applied in parallel to the induction period of ICD. Application of PoCo after induction of ICD once a day for 5 days, starting just at the end of 4 days, was without any effect. CONCLUSION: An anti-inflammatory efficacy of PoCo on the elicitation phase of the ICD induced by repeated SLS test could be observed and quantified by three independent, non-invasive biophysical assessment parameters. This effect can be explained by its influence on pro-inflammatory enzymes, namely phospholipase A2.     

Repair of acetone- and sodium lauryl sulphate-damaged human skin barrier function using topically applied emulsions containing barrier lipids

BACKGROUND: It is generally acknowledged that well-formulated moisturizing skin care products can restore disturbed barrier function that can be assessed by transepidermal water loss (TEWL) measurements. When ceramides and/or other barrier lipids are incorporated, it is, however, not always clearly demonstrated which ingredients of the formulation exert the beneficial effects. OBJECTIVES: In this study the effects of topically applied ceramide-containing mixtures on the barrier repair of sodium lauryl sulphate (SLS)- and acetone-induced skin damage have been studied in human volunteers. TEWL and stratum corneum hydration measurements were carried out. The emulsions applied contained either a mixture of two types of ceramides, CerIII and CerIIIB (emulsion 1) or a complete mixture of ceramides III, IIIB and VI together with phytosphingosine, cholesterol and the free fatty acid linoleic acid (emulsion 2). RESULTS: After SLS damage, it was observed that barrier recovery was significantly accelerated by topical application (14 days, 2 x/d) of emulsion 2 compared with the results obtained with emulsion 1. Corneometrical results were not relevant due to the occurrence of scaly fissured skin, failing to provide a good skin/probe contact. Although no effect on TEWL could be observed, the improvement of skin hydration after acetone treatment and a single application of the emulsions, was significantly more positive for emulsion 2 than for emulsion 1. CONCLUSIONS: The investigative methods used in this study show that ceramides combined with other skin lipids can improve barrier repair after damage.     

Is atopic dermatitis a predisposing factor for experimental acute irritant contact dermatitis?

Proclivity to acute irritant contact dermatitis has been reviewed by comparing the response in patients with atopic dermatitis to controls. Although several controlled studies demonstrate such a proclivity, others do not, suggesting that the mechanisms involved are complex.     

Occlusion vs. skin barrier function

Background/aims: Skin occlusion may increase percutaneous absorption of applied chemicals, with some exceptions. It also obstructs the normal ventilation of the skin surface and increases stratum corneum hydration and hence compromises skin barrier function.
Methods/results: This review focuses the effects of occlusion on skin barrier function, in particularly, as defined with objective skin bioengineering technology.
Conclusions: The effects of occlusion on skin barrier function have been defined with various techniques. Optimal hydrocolloid materials can absorb excess water and reduce the unfavourable effects of occlusion.     

Expression of the C-C chemokine MIP-3 alpha/CCL20 in human epidermis with impaired permeability barrier function

External assault to the skin is followed by an epidermal response including synthesis of DNA, lipids, cytokines and migration of antigen presenting cells. MIP-3 alpha (CCL20, LARC, Exodus-1, Scya20) is a recently described C-C chemokine, predominantly expressed in extralymphoid tissue, which is known to direct migration of dendritic cell precursors and memory lymphocytes to sites of antigen invasion. We assessed the expression of MIP-3 alpha in human skin using semi-quantitative polymerase chain reaction. In vivo, MIP-3 alpha mRNA was constitutively expressed at low levels in untreated human epidermis. After acute disruption of the epidermal permeability barrier MIP-3 alpha mRNA was upregulated in the epidermal fraction, whereas dermal MIP-3 alpha mRNA levels remained unchanged. In vitro, MIP-3 alpha was increased in cultured keratinocytes treated with IL-1 alpha and TNF-alpha and was present in immature and mature dendritic cells, THP-1 monocytic cells and activated T cells. Finally, skin biopsies from patients with psoriasis, contact dermatitis and mycosis fungoides showed abundant expression. In biopsies from atopic dermatitis and graft vs. host disease a weak signal was present, whereas no expression was found in scleroderma and toxic epidermal necrolysis. We conclude that regulation of MIP-3 alpha mRNA is part of the epidermal response to external assault. Its upregulation may represent a danger signal for increased immunosurveillance in barrier disrupted skin and inflammatory skin conditions with impaired barrier function to counteract potential antigen invasion.     

面部糖皮质激素依赖性皮炎患者经皮水分丢失和皮肤含水量分析

目的 分析面部糖皮质激素依赖性皮炎患者的皮肤屏障功能。方法 将面部分为额部、鼻尖、下颌、双面颊、双侧口角的皮损区及左耳后无皮损区共8个点，分别测量95例面部糖皮质激素依赖性皮炎患者及25例健康对照者的经皮水分丢失（TEWL）和皮肤含水量。结果 与健康组相比，面部糖皮质激素依赖性皮炎组下颌、双侧口角、双面颊TEWL值均显著升高（t值分别为4.90，2.60，2.57，2.54，3.77，P < 0.01）；双侧口角、右面颊及额部的皮肤含水量均显著降低（t值分别为3.27，3.81，2.02，2.78，P < 0.05）。在8个测量点中，面部糖皮质激素依赖性皮炎组与健康组TEWL值均为下颌及双侧口角 > 双面颊及额部 > 耳后无皮损区；皮肤含水量降低均为下颌及双侧口角 > 双面颊及额部 > 耳后无皮损区。结论 面部糖皮质激素依赖性皮炎患者下颌、双侧口角、双面颊区域皮肤屏障功能受损，口周区域TEWL值较高，而面颊皮肤水分含量较少。     

Acute irritant contact dermatitis: recovery time in man

Our understanding of the details of the recovery time of acute irritant contact dermatitis (ICD) is limited. We examined skin reactivity to a model surfactant, sodium lauryl sulfate (SLS). on previous acute ICD and normal sites over time with visual grading and noninvasive instruments. Acute ICD was induced on the upper arms of 18 volunteers (aged 30 to 51 years) by occluded application of 1% SLS for 24 h. Previous ICD and normal sites were provoked by occluded application of 2% or 7.5% SLS 30 min daily 4 consecutive days. Skin reactivity was assessed daily by visual erythema scoring (VES), transepidermal water loss (TEWL), skin color reflectance (SCR) and electrical capacitance (EC). Skin function of previous ICD sites assessed, by VES, TEWL. SCR, and EC did not normalize until 2 weeks later: all parameters of previous ICD returned to normal after 3 weeks. While skin reactivity to 2% und 7.5% SLS showed no differences between previous ICD and normal sites at 4 weeks, differences of irritant reactivity especially 7,5% SLS between previous ICD and normal sites were significant at 3 weeks post-provocation. Our results demonstrate that irritation evaluated with irritant provocation was long-lasting, even though skin functional parameters assessed by various bioengineering instruments returned to normal. Complete recovery of skin function including irritability after acute ICD induced by 1% SLS was achieved approximately 4 weeks later. The date were generated with a model surfactant: it remains to be determined whether similar responses will be noted with chemicals of different physicochemical properties.     

Disruption of barrier function in dermatophytosis and pityriasis versicolor

Dermatophytes have the ability to form molecular attachments to keratin and use it as a source of nutrients, colonizing keratinized tissues, including the stratum corneum of the skin. Malassezia species also affect the stratum corneum of the skin. Therefore, dermatophytosis and pityriasis versicolor of the skin are thought to be important factors of profound changes in skin barrier structure and function. We aimed to describe the changes in transepidermal water loss (TEWL), stratum corneum hydration, and skin pH in the lesions of the dermatophytosis and pityriasis versicolor. Thirty-six patients with dermatophytosis (14 with tinea cruris, 13 with tinea corporis and nine with tinea pedis or tinea manus) and 11 patients with pityriasis versicolor were included in this study. TEWL, stratum corneum conductance and skin pH were determined by biophysical methods to examine whether our patients exhibited changes in barrier function. Dermatophytosis and pityriasis versicolor except tinea pedis and tinea manus showed highly significant increase in TEWL compared with adjacent infection-free skin. Hydration was significantly reduced in lesional skin compared with adjacent infection-free skin. From this study, infections with dermatophytes and Malassezia species on the body can alter biophysical properties of the skin, especially the function of stratum corneum as a barrier to water loss. On the contrary, infections with dermatophytes on the palms and soles little affect the barrier function of the skin.     

Baseline transepidermal water loss in patients with acute and healed irritant contact dermatitis

To examine the skin harrier function of patients with acute and healed irritant contact dermatitis ( n = 80) baseline transepidermal water loss (TEWL) was quantitatively measured using an evaporimeter. Healthy subjects served as controls ( n = 40). Test areas were the forearm and the thigh. A significant increase in TCVV'L was observed in the patients with acute and with healed irritant contact dermatitis (ICD) as compared LO healthy volunteers ( P ≤ 0.01). TEWL values in both test areas were com parable and markedly correlated ( p ≤ 0.01). with each other in every group. Thus, it is possible that basal TEWL depends more on the intrinsic skin barrier function of the subjects rather than the 2 anatomical regions examined. TEWL at the forearm with acme ICD was significantly higher ( P ≤ 0.01). than that of the group with healed ICD, but not for TCWL at the thigh suggesting that ICD may aggravate the barrier function of the adjacent involved skin. It is assumed, that increased basal TEWL in patients with ICD may relied a constitutional deviation of epidermal barrier function. This event seems to be comparable with the well-known symptom of atopic individuals. Using a detailed atopic scoring system in such a study may clarify the question of whether a proportion of patients with hand ICD may indeed be atopic individuals.     

Study of cumulative irritant contact dermatitis in man utilizing open application on subclinically irritated skin

We evaluated the effect of subclinical irritation on the cutaneous reaction elicited by cumulative short-term (30-min) application of sodium lauryl sulphate (SLS), by measuring transepidermal water loss (TEWL) and assigning visual scores. 11 healthy adult volunteers, free of skin disease and with no history of atopic dermatitis, were treated with SLS solution (1%, 2%, 5%, 7.5%). On a Monday, we applied 80 μl of 1% SLS solution and deionized water (control), using large aluminum chambers with filter paper discs, for 30 min. We measured TEWL values 2x before and after patch application of control and 1% SLS solution, and then applied 80 μl of SLS solution (2%. 5%. 7.5%) using filter paper discs. From Tuesday to Friday, we applied 80 μl of each solution, using filter paper discs, and measured TEWL before and after open application of test solutions. Compared with each corresponding group, TEWL values of SLS patch groups (S-2.0, S-5.0, S-7.5) were higher than, those of water patch groups (W-2.0, W-5.0, W-7.5), respectively. TEWL values of each groups increased stepwise and the final (hour 97) TEWL values were higher than those of baseline (hour 0) TEWL. The mean visual scores of the vehicle control were lower than those of other test groups, but there were no statistically significant differences in visual scores between each test group. These findings suggested that impaired skin barrier function, elicited by subclinical irritation from short-duration contact with some irritants, might augment the cumulative irritant contact dermatitis caused by repeated open exposure to other surfactants. Relatively short-term and minimal exposure, not in great excess of many daily surfactant exposures, produced cumulative irritation. TEWL measurements were more discriminating than visual grading.     

Stratum corneum hydration and flexibility are useful parameters to indicate clinical severity of congenital ichthyosis

To determine any correlation between the stratum corneum barrier function and the phenotypic severity of congenital ichthyosis, we studied stratum corneum hydration, flexibility, thickness and transepidermal water loss (TEWL) in patients with congenital ichthyosis. Seven patients with congenital ichthyosis aged 2-46 years and age-matched controls were included in the present study. We divided seven patients into two groups; patients with non-bullous type (non-bullous congenital ichthyosiform erythroderma patients) and patients with the bullous type of congenital ichthyosis (bullous congenital ichthyosiform erythroderma and ichthyosis bullosa of Siemens). Stratum corneum hydration, thickness and flexibility were measured using a Corneometer ASA-M2. The stratum corneum thickness was also examined using a skin biopsy technique. TEWL was measured using Evaporimeter AS-TW1. The clinical severity of ichthyosis phenotype was evaluated using a visual analogue scale (VAS). Stratum corneum hydration and flexibility were significantly reduced in both congenital ichthyosis patient groups. Stratum corneum thickness was significantly increased in both groups. In the patient group with non-bullous congenital ichthyosis, significant negative correlations were confirmed between the VAS score and stratum corneum hydration and between the VAS score and flexibility. A significant, positive correlation was also observed between the VAS score and stratum corneum thickness. There was a positive correlation between the VAS score and TEWL on both the extensor and flexor sides of the forearm and back. We conclude that stratum corneum hydration, flexibility and thickness measured by the corneometer, and TEWL on the arm may be a useful indicator of the severity of ichthyosis phenotype.