Hydrogel barrier/repair creams and contact dermatitis.

BACKGROUND: Barrier creams are important to protect the skin in occupations with chemical exposure. The value of hydrogels in barrier creams has never been studied. OBJECTIVE: The purpose of this study was to evaluate the current technology in barrier cream formulation and explore the utility of hygrogels in skin protection. METHODS: A total of 80 men, women, and children between the ages of newborn to 80 years >were studied with the following dermatologic conditions: household hand dermatitis (21), occupational hand dermatitis (18), latex glove irritant contact dermatitis (9), diaper dermatitis (5), cutaneous wounds (17), and allergic contact dermatitis (ACD) (10). In this study, the investigators used a split body approach, in a double-blind randomized fashion, where one body site was treated with a traditional petrolatum-based cream while the other body site was treated with a hydrogel-based barrier/repair cream. Both subject and investigator assessments were recorded by questionnaire. RESULTS: The hydrogel barrier/repair cream showed better skin improvement than the petrolatum-based cream in both subject assessment (62%, P =.0048) and investigator assessment (75%, P =.0000003). CONCLUSION: Hydrogel barrier/repair creams might represent a new, effective approach to skin protection.     

Abnormal epidermal barrier in the pathogenesis of contact dermatitis

A crucial role of the epidermal permeability barrier is obvious in contact dermatitis. An intact skin barrier prevents the penetration of harmful substances into the skin. Irritants and allergens that stay on the skin surface and come into contact with the stratum corneum only do not harm the skin. After disruption of the skin barrier, however, irritants may penetrate into the living epidermal layers, injure the keratinocyte membrane, and release cytokines, which leads to inflammation and to irritant contact dermatitis. The skin barrier is often disrupted by chronic exposure to water plus detergents, solvents, or other irritants. A disrupted barrier in irritant contact dermatitis also allows for the penetration of allergens. Allergens may come into contact with Langerhans and T cells, induce immunological reactions, and cause inflammation, which results in allergic contact dermatitis. Treatments in contact dermatitis should restore the skin barrier to prevent relapse of the disease. Topical corticosteroids, most often used in treating contact dermatitis, reduce immunological reactions and inflammation but do not lead to a complete barrier repair. Skin barrier repair is more complete after treatment with calcineurin inhibitors and bland lipid-based emollient; therefore, these preparations should be preferred for long-term treatment of contact dermatitis.     

Barrier recovery and influence of irritant stimuli in skin treated with a moisturizing cream

Moisturizers are used daily by many people to alleviate symptoms of clinically and subjectively dry skin. Recent studies suggest that certain ingredients in creams may accelerate the recovery of a disrupted barrier and decrease the skin susceptibility to irritant stimuli. In the present single-blind study, a moisturizing cream was tested for its influence both on barrier recovery in surfuctant-damaged skin and on the susceptibility of normal skin to exposure to the irritant sodium lauryl sulphate (SLS). Parameters measured were transepidermal water loss (TEWL) and skin corneometer values, indicating degree of hydration. Treatment of surfactant-damaged skin with the test cream for 14 days promoted barrier recovery, as observed as a decrease in TEWL. Skin corneometer values also normalized more rapidly during the treatment. In normal skin, use or the test cream significantly reduced TFWL after 14 days of treatment, and irritant reactions to SLS were, significantly decreased. Skin corneometer values increased after only 1 application and remained elevated after 14 days. In conclusion, the accelerated rate of recovery of surfactant-damaged skin and the lower degree of SLS-induced irritation in normal skin treated with the test cream may be of clinical relevance in attempts to reduce contact dermatitis due to irritant stimuli.     

The role of CD44 in cutaneous inflammation

Abstract:  CD44 is a transmembrane glycoprotein expressed in various tissues including the skin. Previous studies indicated that CD44 is required for epidermal permeability barrier homeostasis and keratinocyte differentiation. Yet, while some studies have demonstrated that CD44 is critical for the development of inflammation, others have shown that CD44 is not essential for the development of cutaneous inflammation. In this study, we evaluated the changes in epidermal CD44 expression in a variety of skin inflammatory models and determined whether CD44 is required for the development of cutaneous inflammation. Inflammatory responses were compared in CD44 KO versus wild-type mice in acute models of irritant and allergic contact dermatitis, as well as in a subacute allergic contact dermatitis induced by repeated hapten treatment. Inflammatory responses were assessed by measuring ear thickness and epidermal hyperplasia in haematoxylin & eosin-stained sections. Our results demonstrate that: (i) epidermal CD44 expression increases in both acute and subacute cutaneous inflammatory models; and (ii) acute disruption of the epidermal permeability barrier function increases epidermal CD44 expression. Whereas inflammatory responses did not differ between CD44 KO and wild-type mice in acute models of irritant and allergic contact dermatitis, both inflammatory responses and epidermal hyperplasia increased in CD44 KO mice following repeated hapten challenges. These results show first, that permeability barrier disruption and inflammation stimulate epidermal CD44 expression, and second, that CD44 modulates epidermal proliferation and inflammatory responses in a subacute murine allergic contact dermatitis model.     

Beneficial effects of a skin tolerance-tested moisturizing cream on the barrier function in experimentally-elicited irritant and allergic contact dermatitis

In experimentally-induced irritant (ICD) and allergic (ACD) contact dermatitis, an oil-in-water (o/w) cream was applied to investigate its effects on a disturbed barrier function compared to untreated physiological barrier repair. Transepidermal water loss (TEWL) measurements were performed. Before the start of the experiments, the skin tolerance of the cream was examined, revealing the non-irritating characteristics of the ingredients and the absence of any contact allergic patch test reaction. In the ICD study, sodium lauryl sulfate (SLS) patches were applied to the forearms of young female volunteers. Consequently, it was observed that repeated cream application (14 days, 2x/day) significantly improved the TEWL of SLS-damaged skin, leading to a complete recovery on day 15. In the ACD study, disruption of skin barrier function was obtained by a nickel-mediated contact allergy patch (CAP) test. The cream was then applied 2x/day for 4 consecutive days. Assessment of TEWL clearly showed that recovery of the disrupted skin significantly improved after cream application in comparison to untreated barrier repair.     

Contact dermatitis

Contact dermatitis is a common skin disease caused by contact with irritants or allergens. Irritant contact dermatitis is a result of nonspecific irritant factors, which cause activation of mainly innate immunity, resulting in skin inflammation. Contact hypersensitivity, which manifests itself as allergic contact dermatitis, is result of adaptive immune response, where sensitization to hapten-carrier complexes leads to T-cell-mediated contact allergy. Subsequent contact with the hapten results in skin inflammation. This review concentrates on the role of cutaneous receptors in contact dermatitis and highlights potential targets for treatment interventions.     

The tandem repeated irritation test: a new method to assess prevention of irritant combination damage to the skin

The effect of a protective cream was tested in a new tandem repeated irritation test with tandem application of 0.5% sodium lauryl sulphate (SLS) and undiluted toluene. The irritants were applied twice daily for 30 min to the ventral forearms of 20 volunteers. Irritant cutaneous reactions were quantified by a visual score, transepidermal water loss, chromametry and skin capacitance. Concurrent application of SLS/toluene induced stronger reactions than those caused by twice daily application of each irritant on its own. A protective effect of the protective cream was obtained against all treatment combinations and was significant for SLS/SLS (p < or = 0.01) and SLS/ toluene (p < or = 0.05). Our results indicate that the tandem repetitive irritation test has great potential in the evaluation of skin care products to prevent irritant contact dermatitis.     

Skin problems associated with multifunctional acrylic monomers in ultraviolet curing inks

Fifteen cases of contact dermatitis and three of irritant contact conjunctivitis due to multifunctional acrylic monomers in printing inks are described. Seven with dermatitis were sensitized to pentaerythritol triacrylate but evidenced no cross-reactivity to methyl methacrylate. The other eight cases of dermatitis were irritant. Pentaerythritol triacrylate has been shown experimentally to be a cutaneous sensitizer for guinea-pigs and man. Multi-functional acrylates should be handled with minimal skin contact, to avoid cutaneous problems.     

Effect of glove occlusion on the skin barrier

Wet work tasks are the most common exposures leading to occupational irritant contact dermatitis. Use of liquid‐proof gloves is recommended when performing wet work, however, gloves may also contribute to impairment of the skin barrier and development of irritant contact dermatitis. The aim of this study is to review the literature on the effects of glove occlusion on skin barrier function. The PubMed database was searched up to 1 February 2015 for articles on the association between glove occlusion and skin barrier function, including human studies only and in English. Only experimental studies including assessment of the skin barrier function were included in the data analysis. Thirteen articles were identified, 8 with focus on occlusion alone, 7 with focus on occlusion in combination with irritant exposure (some overlapping), and 2 field studies. In conclusion, data from the literature showed that the negative effect of occlusion in itself is limited, and that only extensive and long‐term occlusion will cause barrier impairment. However, studies investigating combined effect of occlusion and exposure to soaps/detergents indicate that occlusion significantly enhances the skin barrier damage caused by detergents/soaps in a dose‐response fashion.     

Effect of a topical corticosteroid, a retinoid and a vitamin D3 derivative on sodium dodecyl sulphate induced skin irritation

Exposure of the skin to sodium dodecyl sulfate (SDS) leads to disruption of barrier and skin irritation. We used repetitive short exposure to a low molarity SDS solution as an in vivo model to mimic the development of irritant contact dermatitis. In this model, we studied clinical (erythema), functional (transepidermal water loss(TEWL)) and cell biological changes, 24 healthy volunteers were patch tested with SDS (0.2%) for 4 h a the day for 5 consecutive days. After removal of the patches, the exposed sites were treated 1 × daily either with a topical corticosteroid (triamcinolon acetoide cream 0.05%). a retinoid (tretinoin cream 0.025%). or a vitamin D₃ derivative (calcipotriol ointment 50 microgram/g). Irritant reactions were assessed by erythema scoring and measurement of barrier function with TEWL up to 14 days after the first challenge. Skin biopsies were taken for cell biological changes at day 4. Vehicle-treated sites served as controls. Repetitive exposure of human skin to SDS resulted in a gradual increase in erythema scoring and TEWL associated with the upregulation of proliferative cells as measured by the expression of Ki-67-antigen and of differentiation markers, visualized by increased expression of involucrin and epidermal-fatty-acid binding protein (E-FABP). Skin irritation as assessed by erythema scoring and TEWL was not significantly suppressed by triamcinolone cream. However, a significant reduction of the number of cycling keratinocytes and a decrease in involucrin positive cell layers was observed in this group. Neither treatment with calcipotriol ointment nor with tretinoin cream induced improvement of skin irritation as judged by visual scoring and TEWL. In contrast to steroid treatment no significant elf eel of calcipotriol ointment or tretinoin cream treatment was observed with regard to the number of cycling cells and differentiation markers. Further studies are needed to assess whether treatment with topical corticosteroids is an effective modality in skin irritation and irritant contact dermatitis.     

Dry skin, barrier function, and irritant contact dermatitis in the elderly

Dry skin is characterized by a decreased lipid content and a delayed reconstitution of the epidermal barrier after skin irritation. These are problems of high relevance in the aged population, especially in the development of irritant contact dermatitis. Asteatotic and perineal irritant dermatitis are the most important subtypes of irritant contact dermatitis in the elderly. This contribution presents a compressed survey on these subtypes and elucidates their relation to an impaired barrier function. Typical irritants affecting aged individuals are explained and compared with irritants that seem to be more significant in younger people. Results of biophysical investigations, such as measurement of transepidermal water loss, are discussed regarding their age-dependence. Transepidermal water loss decreases with age, which was formerly interpreted as an indication of a decreased sensitivity. Today, we know that reconstitution of the epidermal barrier after irritation is delayed once it has been impaired. Reasons are decreased activities of enzymes involved in lipid synthesis and processing, a changed cytokine profile, a reduced acidification of aged skin, and alterations in the function of epidermal stem cells. Owing to these new insights, a reevaluation of the sensitivity of aged skin has to be initiated, especially with regard to occupational dermatology.     

Sequential application of cold and sodium lauryl sulphate decreases irritation and barrier disruption in vivo in humans

BACKGROUND: Irritant contact dermatitis (ICD) is one of the most frequent types of occupational dermatitis. Different factors are involved in the development of contact dermatitis. In the food-processing industry, the combined exposure to different irritants may be involved in the development of ICD. Few data have been published regarding the irritant potential of sodium lauryl sulphate (SLS) in combination with cold. OBJECTIVES: The present study was intended to analyse whether cold exposure and low skin temperature influence the development of ICD. METHODS: Twenty (part I) and 12 (part II) healthy volunteers were exposed twice daily for 4 days to SLS alone, different low temperatures alone (4 degrees C six times for 90 s with an interval of 20 s or 15 degrees C for 10 min) or a combination of cold and SLS (19.6 microL SLS 1% cm(-2), part I; or 52.6 microL SLS 0.5% cm(-2), part II) using the tandem repetitive irritation test. Irritant cutaneous reactions were measured by noninvasive biophysical methods with transepidermal water loss as a parameter for permeability barrier function and skin colour reflectance together with visual scoring as parameters for inflammatory reactions. RESULTS: Cold alone caused no significant skin reaction compared with untreated control. Exposure to SLS alone and SLS together with cold (independent of the applied temperature of 4 or 15 degrees C) twice daily induced a clear irritant reaction and barrier disturbance. Reactions did not differ whether SLS was applied before or after cold. Furthermore, 'tandem application' of cold and SLS diminished the barrier disruption and irritant reaction compared with SLS alone. CONCLUSIONS: We conclude that the application of cold may have a protective effect on the development of ICD, at least in our short-term model.     

The effect of irritant dermatitis on cutaneous bioavailability of a metronidazole formulation, investigated by microdialysis and dermatopharmacokinetic method

Background:  Determination of drug penetration in diseased skin represents a challenge.
Objective:  To compare dermal microdialysis and tape-strip sampling of drug penetration in normal skin and skin with irritant dermatitis.
Methods:  The two methodologies were employed simultaneously in 16 healthy volunteers. Samples were collected in a study of the penetration of a metronidazole cream formulation (Flagyl^® 1%) applied to forearm skin in both areas with irritant dermatitis and normal skin. Barrier perturbation and the depth of microdialysis probes were quantified by non-invasive bioengineering methods.
Results:  Microdialysis showed a significant threefold increase in metronidazole penetration in skin with irritant dermatitis compared with unmodified skin. Conversely, the concentration of metronidazole in tape-strip samples was significantly decreased in irritant dermatitis.
Conclusion:  The selection of sampling methodology should be based on the skin layer of interest as well as the integrity of the skin barrier. Whenever the dermal tissue is the target for topical treatment, microdialysis sampling should be the method of choice.     

Severe irritant reaction following sequential waxing and use of a chemical depilatory cream in an adolescent

A 15-year-old girl presented with leg wounds that were sustained after waxing and subsequent chemical depilation. History revealed prior usage of chemical depilatories without irritation. Given this finding, we suspect that waxing disrupted the epidermal barrier and, therefore, rendered the patient more susceptible to severe irritant contact dermatitis upon depilation. While there are reported cases of irritant contact dermatitis and chemical burns secondary to waxing or depilatory cream use in adults, a literature review found no reported cases of chemical burns in a pediatric patient or adult consequent to using these methods in tandem.     

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.     

Sodium lauryl sulphate penetration in an in vitro model using human skin

Because of their ability to impair the skin barrier function, detergents constitute a major risk factor for the development of irritant contact dermatitis. Sodium lauryl sulphate (SLS) is a commonly used detergent for experimental studies within the area of irritant contact dermatitis. In the present study, penetration of S³⁵-labelled SLS was studied in an in vitro model using human cadaver skin. The investigations showed that SLS is capable of permeating the skin barrier when applied under occlusion. SLS could be detected in the dermis and the amount of SLS found here was shown to depend on the dose of SLS applied on the skin. Penetration of SLS continued after removal of the SLS applied as a patch test on the skin surface. Considerable inter-individual variation in the penetration of SLS was demonstrated between different donors.     

Purpura after application of EMLA cream in two children

The eutectic mixture of local anesthetic cream, a 1 : 1 mixture of prilocaine and lidocaine, 2.5% each, is frequently used in pediatric and dermatologic practice to obtain local anesthesia. Side effects include transient skin blanching, erythema, urticaria, allergic contact dermatitis, irritant contact dermatitis, hyperpigmentation, and purpura. We report two children with a purpuric reaction after application of this mixture cream. Purpura after application of this anesthetic cream is a rare nonallergic reaction and only 17 occurrences have been reported, to our knowledge, in the literature. Patch tests could not be performed in our two patients because of lack of parental consent but we suggest that the purpuric reactions were most probably of toxic origin. The pathogenesis of purpura after application of eutectic mixture of local anesthetics cream, which resolves within 2 weeks without dermatologic sequelae and without any specific therapy, is complex. The lesions are probably caused by the direct effect of the cream components on the vessels but many other factors, such as atopic dermatitis, prematurity, subjective predisposition to purpura, trauma, and thrombocytopenia may play important pathogenetic roles.     

Fruit acids do not enhance sodium lauryl sulphate-induced cumulative irritant contact dermatitis in vivo

Combined exposure to different irritants in the workplace may lead to irritant contact dermatitis, which is the main type of occupational dermatitis among bakers and confectioners. Following previous work on "tandem irritation", a panel of healthy volunteers was exposed twice daily for 4 days to the organic fruit acids: citric, malic, and lactic acid, either alone or in tandem application with 0.5% sodium lauryl sulphate (SLS) in a repetitive irritation test. Irritant cutaneous reactions were quantified by visual scoring and non-invasive measurement of transepidermal water loss and skin colour reflectance. Twice daily application of either citric or malic acid alone did not induce a significant irritant reaction. Combined exposure to one of the fruit acids and SLS caused marked barrier disturbance, but the latter irritant effect was smaller than that obtained by combined exposure to SLS and water. Thus, combined exposure to the above-mentioned fruit acids and SLS did not enhance cumulative skin irritation.     

Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm)

Patients with atopic skin show a defective barrier function both in rough and in clinically normal skin, with an increasing risk of developing contact dermatitis. Moisturizing creams are often used in the treatment of dry skin. The purpose of this study was to investigate the influence of treatment with a urea-containing moisturizer on the barrier properties of atopic skin. Fifteen patients with atopic dermatitis treated one of their forearms twice daily for 20 days with a moisturizing cream. Skin capacitance and transepidermal water loss (TEWL) were measured at the start of the study and after 10 and 20 days. On day 21 the skin was exposed to sodium lauryl sulphate (SLS) and on day 22 the irritant reaction was measured non-invasively. Skin capacitance was significantly increased by the treatment, indicating increased skin hydration. The water barrier function, as reflected by TEWL values, tended to improve (P = 0.07), and the skin susceptibility to SLS was significantly reduced, as measured by TEWL and superficial skin blood flow (P < 0.05). Thus, it seems that certain moisturizers could improve skin barrier function in atopics and reduce skin susceptibility to irritants. The mechanism and the clinical relevance need further investigation.     

Reduced levels of glutathione S-transferases in patch test reactions to dithranol and sodium lauryl sulphate as demonstrated by quantitative immunocytochemistry: evidence for oxidative stress in acute irritant contact dermatitis

There is increasing evidence that oxidative stress plays a role in the pathogenesis of acute irritant contact dermatitis. As part of on-going studies into the effect of irritant chemicals on the anti-oxidant enzyme systems in the skin, we have examined the changing levels of two classes of glutathione S-transferase in patch test reactions to dithranol and sodium lauryl sulphate, using quantitative immunocytochemistry. Although no changes were evident after 6 hrs, significant reductions in the density of staining for glutathione S-transferase alpha were seen with both irritants after 48 hrs and 96 hrs. Glutathione S-transferase pi levels were reduced to a lesser degree, reaching significance for dithranol at the 96 hrs time point only, and for sodium lauryl sulphate at 48 hrs only. The results support the hypothesis that oxidative stress plays a role in chemically-induced inflammation, not only in the case of irritants such as dithranol which are known to directly generate reactive oxygen species, but also with chemicals not generally associated with free radical generation.