Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.     

Cytokines at different stratum corneum levels in normal and sodium lauryl sulphate-irritated skin

BACKGROUND/PURPOSE: Cytokines play an important role in inflammatory and repair processes occurring in the skin. The objectives of this study were to determine the amounts of cytokines and protein isolated by tape stripping in the different layers of the stratum corneum (SC), and to compare normal skin with skin exposed in vivo to the irritant sodium lauryl sulphate (SLS). METHODS: In eight volunteers, we determined the amount of total and soluble protein and also interleukin-1alpha (IL-1alpha) in pooled tape strips obtained from the upper, intermediate and lower parts of the SC. Three different types of tape were compared (Diamond , D-squame or Sentega tape). In a separate study, 20 volunteers were repeatedly exposed to 0.1% SLS over a 3-week period. The amounts of IL-1alpha, IL-1RA and IL-8 in strips obtained from the three different SC levels of SLS-exposed skin were compared with an unexposed site. RESULTS: For normal skin, the amounts of soluble protein and IL-1alpha were similar for the three tapes. Diamond tape showed the highest yield of total protein. The total protein yield per strip decreased to lower SC levels, whereas soluble protein and IL-1alpha normalized by soluble protein did not change across the SC. After SLS induced skin irritation, IL-1alpha decreased and IL-1RA and IL-8 increased at increasing depth into the SC. CONCLUSIONS: Tape stripping is a suitable method to determine SC cytokine concentrations in human skin. With this technique, it is possible to study changes in cytokine concentrations at different SC layers after skin irritation.     

Tandem repeated irritation in aged skin induces distinct barrier perturbation and cytokine profile in vivo

Background The barrier perturbation pattern and molecular markers of inflammation upon tandem repeated irritation in chronologically aged skin have not been previously studied. Objectives We aimed to investigate the barrier impairment kinetic and in vivo cytokine profile following sequential irritation with sodium lauryl sulfate (SLS) and undiluted toluene (Tol) in aged compared with young skin. Methods Four fields on the volar forearm of healthy aged and young volunteers (median age, respectively, 63·9 and 32·6 years) were sequentially exposed to 0·5% SLS and undiluted toluene in a controlled tandem repeated irritation test; an adjacent nontreated field served as control. The permeability barrier function was monitored by repeated measurements of transepidermal water loss (TEWL), capacitance and erythema every 24 h up to 96 h. The stratum corneum cytokines were harvested by sequential tape stripping and quantified by multiplex bead array and enzyme‐linked immunosorbent assay. Results Compared with young skin, aged skin was characterized by delayed and/or less pronounced alterations in the visual irritation score, TEWL, chromametry a*‐value and capacitance, assessed by the respective Δ‐values for each parameter and monitoring time point. In both groups, exposure to SLS/SLS, SLS/Tol and Tol/SLS resulted in decreased interleukin (IL)‐1α levels, whereas the application of Tol/Tol induced an increase in IL‐1α. Furthermore, decreased IL‐1 receptor antagonist (IL‐1RA) levels and a lower IL‐1RA/IL‐1α ratio were found following repeated exposure to the irritants. Conclusions Our results provide evidence for selective alterations in the cytokine profile and distinct barrier impairment kinetic following tandem repeated irritation with SLS and Tol in aged compared with young skin in vivo.     

Continuous topical administration of a petrolatum formulation by a novel disposable diaper. 2. Effect on skin condition

BACKGROUND: Diaper dermatitis is a common childhood affliction. Aiming to help reduce the prevalence of this problem, we have developed a novel diaper to deliver to the skin dermatological formulations intended to help protect the skin from overhydration and irritation. OBJECTIVE: To determine the clinical benefits of a novel disposable diaper designed to deliver a petrolatum-based formulation continuously to the skin during use. METHODS: Two independent, blinded, randomized clinical trials were conducted, involving an aggregate total of 391 children, 8-24 months of age. All comparisons were done versus a control diaper, identical to the test product except for the absence of the petrolatum formulation. The studies determined the effects of the novel diaper on skin erythema and diaper rash. RESULTS: Use of the formulation-treated diaper was associated with significant reductions in severity of erythema and diaper rash compared to the control product. CONCLUSIONS: The results demonstrated the clinical benefits associated with continuous topical administration of a petrolatum-based formulation by this novel diaper. We anticipate that this advance in diaper design will contribute significantly to further reduce the prevalence and severity of irritant contact dermatitis in the diaper area.     

A non-invasive tape absorption method for recovery of inflammatory mediators to differentiate normal from compromised scalp conditions

Background/aims: A simple non-invasive tape (Sebutape^TM) adsorption method was used to recover inflammatory proteins from normal and compromised human scalp (i.e. dandruff and seborrheic dermatitis) in order to assess the inflammatory and immunologic changes relevant to these clinical conditions. Methods: The scalps of subjects identified by a dermatologist as having either dandruff (n = 18), seborrheic dermatitis (n = 19) or normal scalp (n = 16) were visually graded to obtain total adherent scalp flaking scores (TASFS). Sebutape samples were then collected from both the high and low TASFS scalp sites using a one-minute tape application. To recover inflammatory molecules, tapes were extracted in buffered saline with sonication and the tape extracts analysed using commercial immunoassay methods for pro-inflammatory cytokines [i.e. interleukin-1α (IL-1α), IL-1β, IL-1 receptor antagonist (IL-1ra), IL-8 and tumor necrosis factor-α (TNF-α)] and the immunologic cytokines [i.e. IL-2, IL-4, IL-10, IL-12, IL-15 and interferon gamma (IFN-γ)]. Nitric oxide (NO) was also assayed on tape extracts using the Greiss reaction. To account for differences in protein loading on the tapes all cytokine and NO results were normalized using the total protein (TP) amounts recovered in tape extracts. Results: The IL-1α/TP levels recovered from dandruff and seborrheic scalps were significantly decreased (P = 0.03) compared to normal appearing scalp levels. The scalp levels of IL-1ra/TP and the ratio of IL-ra to IL-1α were significantly (P = 0.002) or directionally (P = 0.07) higher in seborrheic dermatitis scalps and dandruff scalps, respectively, compared to normal scalps. The IL-1ra and the IL-1ra/IL-1α ratio values correlated well with the TASFS. The TNF-α/TP levels recovered from dandruff scalps were significantly higher (P = 0.02) than levels recovered from seborrheic dermatitis and normal scalp subjects. IL-2/TP was significantly increased (P = 0.01) and IFN-γ and NO significantly decreased (P = 0.05) in the seborrheic dermatitis scalp samples compared to normal controls. Conclusion: The Sebutape method has proven useful for distinguishing normal from diseased scalp conditions. The cytokines recovered from the scalp tape samples showed distinct patterns that differentiated dandruff, seborrheic dermatitis and normal scalp populations. These methods may also prove useful for monitoring the clinical efficacy of therapeutic actives for treating dandruff and seborrhea.     

Differential cytokine expression in skin after single and repeated irritation by sodium lauryl sulphate

Abstract:  In vivo levels of cytokines and presence of neutrophils and eosinophils in skin irritation are not well known. Our objective was to get more insight in inflammatory mediators and markers involved in single and repeated skin irritation. We sampled epidermis-derived fluid using a novel technology that includes application of a negative pressure on the skin after creation of micropores in the stratum corneum by a laser. In nine volunteers, transdermal fluid was sampled after a single 4-h 10% sodium lauryl sulphate exposure and a repeated 3-week exposure (0.1% sodium lauryl sulphate). Twenty-seven cytokines were assessed by multiplex assay, and IL-1α, eosinophil cationic protein and myeloperoxidase by enzyme-linked immunosorbent assay. Levels of eosinophil cationic protein were increased after irritation and correlated with levels of myeloperoxidase. The levels of inflammatory mediators showed large interindividual differences in unexposed and exposed skin. Despite this variation, several mediators clearly showed increased levels: CC chemokine ligand (CCL)11, CXCL10 and vascular endothelial growth factor after both single and repeated exposure, IL-1α and basic fibroblast growth factor after single exposure and interleukin-1 receptor antagonist (IL-1RA) after repeated exposure. After repeated exposure, CCL5 and the ratio IL-1RA/IL-1α both increased compared with single exposure. We conclude that single and repeated irritation induces differential and concerted expression of various inflammatory mediators and markers.     

Faecal enzymes: in vivo human skin irritation

Digestive enzymes in faeces have been reported to posses skin irritation potential. The present study was designed to investigate the in vivo irritant potentials of faecal concentrations of proteolytic and lipolytic digestive enzymes in bile salt mixtures. In a 21-day cumulative irritation assay, clinical evaluation and noninvasive bioengineering techniques were used. 5 days occlusive exposure to phosphate buffer (pH = 8) caused no visual skin damage but reflectance spectroscopy demonstrated significant vasodilation ( p < 0.01) and increases in transepidermal water loss (TEWL) and skin pH were also observed ( p < 0.01). These increases were still present at days 12 and 19. Occlusive exposure to physiologic concentrations of faecal enzymes resulted in significant visual and objective scores at day 5, 12, and 19, with increased readings as a function of exposure time ( p < 0.01). The enzyme mixture containing lipase caused delayed onset of skin erythema and epidermal barrier disruption compared to elastase and chymotrypsin containing solutions. Prolonged occlusive exposure to digestive enzymes in faecal concentrations caused severe skin erythema and epidermal barrier disruption in a human model, suggesting a possible etiologic role of digestive enzymes in perianal, circumstomal or diaper dermatitis.     

Effects of UV irradiation with one minimal erythema dose on human afferent skin lymph in vivo

Ultraviolet (UV) irradiation of the skin induces complex local and systemic immunomodulatory reactions. The biological effects of UV irradiation on human skin derived afferent lymph however are unknown. The aim of this study was to examine the effects of a single combined UV-A and UV-B irradiation with 1 minimal erythema dose (MED) on human skin derived lymph in vivo. After cannulation of a superficial lymph vessel on the lower leg, lymph flow and cell output per hour were determined before and for 6 days after UV irradiation of the lymph draining skin area in 5 volunteers. Furthermore, expression of CDla, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells and cytokine levels (IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, TNF-α and IFN-γ) in the afferent lymph were analyzed by cytofluorometry and ELISA. After UV irradiation a small initial enhancement in the daily lymph flow per hour was noticed in correlation with the slight erythematous skin reaction. Following resolution of the skin reaction, a delayed increase in cell output in correlation with an additional peak in the lymph flow was found between the 4th and 6th day after UV irradiation. However, no changes in the expression of CDla, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells were detectable. Interestingly, in parallel to the increased lymph flow and cell output, only elevated IL-8 protein levels were reproducibly detected in the afferent lymph after UV irradiation. Furthermore, using immunohistochemistry positive staining for IL-8 was found on migrating mononuclear lymph cells. In conclusion, our data demonstrate that a single UV irradiation of the skin with 1 minimal erythema dose leads to a delayed enhancement of lymph flow, number of migrating lymph cells and cytokine levels of IL-8. Moreover, we provide evidence that migrating lymph cells, besides resident epidermal and dermal cells, may contribute to the detected levels of IL-8 in the afferent lymph.     

Effect of Diaper Cream and Wet Wipes on Skin Barrier Properties in Infants: A Prospective Randomized Controlled Trial

The effect of different diaper care procedures on skin barrier function in infants has been minimally investigated and may be assessed using objective methods. In a single‐center, prospective trial, 89 healthy 9‐month‐old infants (±8 wks) were randomly assigned to three diaper care regimens: group I used water‐moistened washcloths at diaper changes (n = 30), group II additionally applied diaper cream twice daily (n = 28), and group III used wet wipes and diaper cream twice daily (n = 31). Transepidermal water loss (TEWL), skin hydration (SCH), skin pH, interleukin 1α (IL‐1α) levels, and microbiologic colonization were measured in diapered skin (upper outer quadrant of the buttocks), nondiapered skin (upper leg), and if diaper dermatitis (DD) occurred, using the most affected skin area at day 1 and weeks 4 and 8. Skin condition was assessed utilizing a neonatal skin condition score and diaper rash grade. On diapered skin, SCH decreased in groups II and III, whereas TEWL values were reduced in group II only. Skin pH increased in groups II and III. In general, SCH, skin pH, and IL‐1α levels were higher in healthy diapered skin than in nondiapered skin. The incidence and course of DD was comparable in all groups. Areas with DD had greater TEWL and skin pH than unaffected skin areas. Infants who received diaper cream had lower SCH and TEWL and higher pH levels in the diapered area than on nondiapered skin. No correlation with the occurrence of DD was found.     

Erythema multiforme on exposed and non-exposed skin following polymorphic light eruption: a case report

We report a 35-year-old caucasian female with a history of polymorphic light eruption (PLE) who, after the outbreak of pruritic papules following the first sun exposure of the year, developed target lesions in two different bouts, the first on sun-exposed skin and the second on sun-protected sites. A diagnosis of erythema multiforme (EM) developing as a result of PLE was made. As far as we were able to search in the literature, EM occurring in two bouts has not been described previously. We discuss the differential diagnosis.     

Comedolytic effect and reduced skin irritation of a new formulation of all-trans retinoic acid-loaded solid lipid nanoparticles for topical treatment of acne

Novel drug delivery systems, such as solid lipid nanoparticles (SLN), have been proposed to reduce retinoic acid (RA)-induced skin irritation. However, one question still remains: could it be accomplished without reducing efficacy? To evaluate this question the comedolytic effects and epidermal thickening of RA-loaded SLN were compared to the conventional RA formulations (gel or cream), as well as the potential of these formulations to induce skin irritation. The comedolytic effects and epidermal thickening of these formulations, both containing RA at 0.01 or 0.05%, were investigated in a rhino mouse model, while the studies of RA-induced skin irritation were evaluated through rabbit skin irritation tests and in the rhino mouse model. RA-loaded SLN, as compared to the placebo, produced a comedolytic effect with a significant reduction of the utricle diameter, which proved to be similar to that observed for marketed gels or creams regardless of the RA concentration. RA formulations (SLN or marketed cream) also induced an epidermal proliferation leading to a thickened epidermis in treated animals. In both animals studied (rhino mice and rabbits), the RA-loaded SLN, when compared to conventional formulations, promoted a significant reduction in RA-induced skin irritation (erythema and scaling). Then, RA-loaded SLN represents an interesting alternative to reduce RA-induced skin irritation without reducing efficacy, and constitutes an innovative approach for the topical treatment of acne with RA.     

Culture and drug biotransformation capacity of adult human keratinocytes from post-mortem skin

Summary 'I'hc aim of this study was to analyse viability, growth, differentiation and drug metabolic capacity of cultured human keratinocytes obtained from post-mortem skin. Epidermal cells were prepared from 1-day post-mortem paired sun-exposed (outer) and sun-protected (inner) sites of the upper arm. of donors aged 47–80 years, The percentage of viable cells obtained from post-mortem skin was only slightly lower than that usually obtained for keratinocytes isolated from fresh skin, and no alterations of epidermal markers were noted. Keratinocytes isolated post-mortem from non-exposed skin had a higher viability (78 versus 73%). and a more active proliferation, while their attachment rate, keratin composition, lipid synthesis capacity and transglutaminase activity levels were similar to those of epidermal cells obtained from the sun-exposed skin. Keratinocytes Isolated from postmortem skin expressed various phase I and II activities at levels similar to those obtained with keratinocytes isolated from fresh skin while drug metabolizing enzyme activities were consistently higher in sun-exposed compared to sun-protected cells. The results support the conclusion that skin collected post-mortem can represent an alternative source of viable and functional epidermal cells, and that the functional changes that occur in adult keratinocytes habitually exposed to the sun, affect much more strongly the drug metabolism capacity than the expression of differentiation markers.     

Clinical effects of diaper types on the skin of normal infants and infants with atopic dermatitis

Cloth diapers, cellulose core diapers (conventional disposable diapers), and cellulose core diapers containing absorbent gelling material were examined for their effects on diaper rash and skin microbiology of normal infants and infants with atopic dermatitis in a 26-week double-blind clinical trial. Infants with atopic dermatitis wearing the diapers containing absorbent gelling material had significantly lower diaper rash grades than infants with atopic dermatitis wearing cloth diapers at five of eight grading visits. Infants with atopic dermatitis wearing conventional cellulose core diapers had statistically less rash at one of eight visits. There was no statistically significant difference between diaper types at three of the eight visits. At no time did the cloth group have less diaper rash than the conventional cellulose or absorbent gelling material disposable diaper group. A statistical correlation between the severity of general atopic dermatitis outside the diaper area and the diaper rash condition under the diaper occurred only in the atopic dermatitis group wearing cloth diapers. Isolation of microorganisms from the intact, uninvolved skin surface both inside and outside the diaper showed no biologically significant changes in the presence or numbers of selected skin organisms. Repeated isolation, at multiple grading visits of Staphylococcus aureus from uncompromised skin inside the diaper area was infrequent but correlated with the diagnosis of atopic dermatitis when observed.     

The use of a 3895 bp mitochondrial DNA deletion as a marker for sunlight exposure in human skin

Previous work has examined the use of mitochondrial DNA (mtDNA) damage as a biomarker of cumulative sun exposure in human skin. These studies have simply compared mtDNA damage between sun-protected and sun exposed skin. This approach is limited because non-melanoma skin cancer (NMSC) is predominantly formed on body sites which are 'usually' sun exposed as opposed to sites which are 'occasionally' sun exposed and as such they differ in their cumulative ultraviolet (UV) exposure. This study addresses this limitation by investigating the frequency of occurrence of a rarely reported 3895 bp mtDNA deletion in 104 age-matched human skin samples taken from different sun-exposed body sites. There was a significant increase in the deletion frequency with increasing UV exposure (p<0.0001). Furthermore there was a significantly greater deletion frequency in 'usually' sun exposed compared with 'occasionally' sun-exposed body sites in both the dermis (p=0.0018) and epidermis (p<0.0001). Investigation of the 3895 bp deletion in the same NMSC samples used in a previous study of the 4977 bp common deletion, showed a greater frequency of the 3895 bp deletion (8/10 vs 4/10, respectively). Additionally, we have linked the 3895 bp deletion with the UVR component of sunlight by inducing the deletion in vitro with repetitive sub-lethal doses of a UVA+UVB light source.     

Stratum corneum cytokines,structural proteins,and transepidermal water loss: effect of hand hygiene

Background/aims: There are few reports on the cytokine response to high frequency hand hygiene among health care workers (HCWs) in an occupational setting. We have observed significant skin barrier compromise consistent with chronic irritant contact dermatitis in HCWs. We hypothesized that repetitive hand hygiene would activate the epidermal inflammatory cascade and lead to changes in structural proteins and cytokines. Methods: Keratin 6, keratin 1, 10, 11, involucrin, IL1α, TNFα, IL8, IL1RA, and IL10 were analyzed from the SC using bead‐based arrays. Knuckle and dorsum samples were evaluated for HCWs (n=23) before and after repetitive hand hygiene and compared with those of age‐matched non‐wet workers (n=23) without hand skin irritation. Erythema, dryness, and barrier integrity were measured. Results: Transepidermal water loss (TEWL) was higher for HCWs but unchanged with exposure. IL1α and TNFα were highest in control volar forearm. IL1α, TNFα, and IL8 were significantly lower in HCWs than controls despite higher erythema, dryness, and TEWL. Decreases in keratin 1, 10, 11, increases in keratin 6, and reduction in IL1α, TNFα, and IL8 were seen after hand hygiene. Conclusion: This preliminary study showed significantly lower SC biomarker levels in HCW compared with controls and regional differences between the hand and forearm. Exposure to repetitive hand hygiene results in substantial chronic skin irritation without time for barrier recovery between work periods. The impact on SC structural proteins and cytokines has many commonalities with chronic inflammation, although mechanistic questions remain.     

Acute exposure of human skin to ultraviolet or infrared radiation or heat stimuli increases mast cell numbers and tryptase expression in human skin in vivo

Background  Mast cells are key effector cells in diverse immunological and pathological processes. It is still unclear why there are more mast cells at peripheral and sun-exposed skin sites than at sun-protected sites.
Objectives  To investigate changes in mast cell numbers associated with natural ageing and photoageing, and to observe the effects of ultraviolet (UV) and infrared (IR) radiation and heat on the prevalence of mast cells and tryptase expression in human skin in vivo .
Methods  Sun-exposed and sun-protected skin samples were taken from individuals in four different age groups. UV, IR or heat-treated buttock skin of young volunteers was also obtained. Mast cells were quantified by immunohistochemical staining of mast cell-specific tryptase and chymase. The expression of tryptase was determined by Western blotting.
Results  Both sun-exposed and sun-protected skin showed a gradual decrease in total mast cells (MC_Total) number with ageing. The number of mast cells in sun-exposed skin was significantly higher than that in sun-protected skin. After UV irradiation (2 minimal erythema doses), MC_Total and mast cells expressing tryptase and chymase were significantly increased at 24 and 48 h postirradiation. After IR irradiation (3 minimal heating doses) and heat treatment (43 °C for 90 min), MC_Total reached peak induction at 8 and 48 h after stimulation, respectively. Tryptase expression was also clearly upregulated by UV, IR and heat.
Conclusions  Our data demonstrate that mast cell numbers decreased with ageing in human skin. Also, mast cells may be activated and recruited by UV, IR and heat. These findings should further our understanding of the reason for the high prevalence of mast cells at peripheral sun-exposed skin sites.     

Investigating the release of inflammatory cytokines in a human model of incontinence-associated dermatitis

Incontinence-associated dermatitis (IAD) is a painful complication in elderly patients, leading to reduced quality of life. Despite recent attention, its underlying inflammatory mechanisms remain poorly understood. This study was designed to quantify the release of inflammatory cytokines in a human model of IAD. The left volar forearm of ten healthy volunteers was exposed to synthetic urine and synthetic faeces for 2 h, simulating the effects of urinary and faecal incontinence, respectively, and the subsequent cytokine response compared to that of an untreated control site. Inflammatory cytokines were collected using both the Sebutape® absorption method and dermal microdialysis and quantified using immunoassays. Results from the former demonstrated an upregulation in IL-1α, IL-1RA and TNF-α. Synthetic urine caused a higher median increase in IL-1α from baseline compared to synthetic faeces, whereas synthetic faeces were associated with significantly higher median TNF-α levels compared to synthetic urine (p = 0.01). An increase in IL-1α/IL-1RA ratio was also observed with significant differences evident following exposure to synthetic urine (p = 0.047). Additionally, microdialysis revealed a time-dependent increase in IL-1β and IL-8 following exposure of up to 120 min to synthetic urine and synthetic faeces, respectively. This study demonstrated the suitability of both sampling approaches to recover quantifiable cytokine levels in biofluids for the assessment of skin status following exposure to synthetic fluids associated with incontinence. Findings suggest some differences in the inflammatory mechanisms of IAD, depending on moisture source, and the potential of the cytokines, IL-1α and TNF-α, as responsive markers of early skin damage caused by incontinence.     

Relationship Between Skin Barrier Function in Early Neonates and Diaper Dermatitis During the First Month of Life: A Prospective Observational Study

Diaper dermatitis, a common skin problem in newborn infants, is characterized by poor functioning of the skin barrier. This study aimed to elucidate the relationship between skin barrier function in 4‐day‐old infants and the occurrence of diaper dermatitis during the first month of life. We recruited healthy Japanese infants born at 35 weeks of gestation or more. We measured indicators of skin barrier function, namely skin pH and transepidermal water loss, in 4‐day‐old infants on four places on the body. Individual characteristics were recorded from the infants' medical charts. The presence of diaper dermatitis was judged using the diaper rash and erythema scoring scale, which was based on daily recording of the infants' skin condition by their parents. The parents also filled out a questionnaire 1 month after birth regarding stool frequency and certain external factors. The association between diaper dermatitis and skin barrier function was assessed using multiple logistic regression analysis. The analysis included 88 infants. The incidence of diaper dermatitis was 25.0%. After adjusting for stool frequency for 1 month we noted that high pH on the inner arm skin in 4‐day‐old infants increased the risk of diaper dermatitis during the first month of life (adjusted odds ratio 3.35 [95% confidence interval = 1.12, 10.04]). Early neonatal skin pH may predict the risk of diaper dermatitis during the first month of life. Our results may be useful in devising strategies to prevent diaper dermatitis.     

Effect of skin barrier competence on SLS and water-induced IL-1alpha expression

For screening of a potential irritant it is essential that an early marker for irritation should be chosen which could be detected before the physiological signs of irritation occur. Interleukin 1 alpha (IL-1alpha) is widely accepted as such a marker in both in vivo and in vitro test systems. In this study, we have determined the mRNA levels of IL-1alpha in the epidermis after topical application of sodium dodecyl sulphate (SLS) in both a commercially available epidermal kit (EpiDerm) and in excised skin. Furthermore, we have determined the effect of water, the vehicle for SLS, on IL-1alpha mRNA levels. Topical application of water to excised skin increases IL-1alpha mRNA levels sixfold in the epidermis whereas topical application of water to EpiDerm cultures did not alter IL-1alpha mRNA levels. This is explained by the finding that EpiDerm cultures have a sub-optimal barrier function when compared with excised skin - topical application of SLS was clearly toxic at much lower concentrations in EpiDerm cultures (0.2% SLS) than in excised skin (5% SLS). Also caffeine penetration was 10-fold higher through EpiDerm cultures than through the excised skin. Therefore, incubation of control EpiDerm cultures at 100% humidity effectively mimics topical exposure to water. An additional increase in IL-1alpha mRNA levels observed between topical application of water and SLS is similar (about threefold) in both experimental systems. In conclusion, in vitro reconstructed epidermis models, such as EpiDerm, can be used as a predictive model for irritancy screening. However, great care should be taken when interpreting the results due to the fact that EpiDerm cultures do not have a competent barrier function and therefore lower irritant concentrations are required than in in vivo or ex vivo studies in order to induce cytotoxic effects. Furthermore, the irritant effects of the vehicle should not be neglected. Our results show clearly that the topical application of water to excised skin results in increased levels of IL-1alpha mRNA in the epidermis. This is a cytokine that is widely used as an early marker for skin irritation.