Decreased levels of sphingosine,a natural antimicrobial agent,may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus

The stratum corneum of the skin of patients with atopic dermatitis is highly susceptible to colonization by various bacteria, including Staphylococcus aureus. The defense system of the skin against bacterial invasion appears to be significantly disrupted in atopic dermatitis skin, but little is known about the defense mechanism(s) involved. As one sphingolipid metabolite, sphingosine is known to exert a potent antimicrobial effect on S. aureus at physiologic levels, and it may play a significant role in bacterial defense mechanisms of healthy normal skin. Because of the altered ceramide metabolism in atopic dermatitis, the possible alteration of sphingosine metabolism might be associated with the acquired vulnerability to colonization by S. aureus in patients with atopic dermatitis. In this study, we measured the levels of sphingosine in the upper stratum corneum from patients with atopic dermatitis, and then compared that with the colonization levels of bacteria in the same subjects. Levels of sphingosine were significantly downregulated in uninvolved and in involved stratum corneum of patients with atopic dermatitis compared with healthy controls. This decreased level of sphingosine was relevant to the increased numbers of bacteria including S. aureus present in the upper stratum corneum from the same subjects. This suggests the possibility that the increased colonization of bacteria found in patients with atopic dermatitis may result from a deficiency of sphingosine as a natural antimicrobial agent. As for the mechanism involved in the decreased production of sphingosine in atopic dermatitis, analysis of the activities of ceramidases, major sphingosine-producing enzymes, revealed that, whereas the activity of alkaline ceramidase did not differ between patients with atopic dermatitis and healthy controls, the activity of acid ceramidase was significantly reduced in patients with atopic dermatitis and this had obvious relevance to the increased colonization of bacteria in those subjects. Further, there was a close correlation between the level of sphingosines and acid ceramidase (r = 0.65, p < 0.01) or ceramides (r = 0.70, p < 0.01) in the upper stratum corneum from the same patients with atopic dermatitis. Collectively, our results suggest the possibility that vulnerability to bacterial colonization in the skin of patients with atopic dermatitis is associated with reduced levels of a natural antimicrobial agent, sphingosine, which results from decreased levels of ceramides as a substrate and from diminished activities of its metabolic enzyme, acid ceramidase.     

Stratum Corneum pH in Atopic Dermatitis

Recent studies have provided new insights into the occurrence, causes, and pathogenetic consequences of changes in the skin pH in atopic dermatitis, particularly with respect to skin barrier function and colonization with Staphylococcus aureus. Growing evidence suggests an impaired release of proton donors, such as amino acids, urocanic acid, and lactic acid, to the stratum corneum in atopic dermatitis, as a result of reductions in filaggrin proteolysis and sweat secretion. In addition, an impaired formation of free fatty acids from sebaceous lipids and epidermal phospholipids seems to be involved. Because both lipid organization and lipid metabolism in the stratum corneum requires an acidic pH, these alterations might contribute to the disturbance of skin barrier function observed in atopic dermatitis. Furthermore, bacterial growth and virulence of S. aureus, as well as defensive host mechanisms, have increasingly been delineated as pH dependent, giving rise to a new understanding of the pathophysiology underlying increased skin colonization seen in atopic dermatitis.     

Microanalysis of an antimicrobial peptide, beta-defensin-2, in the stratum corneum from patients with atopic dermatitis

Background  Antimicrobial peptides, such as defensin and cathelicidin, have recently been reported to play important roles in host defence and in cutaneous innate immunity. Although β-defensin-2 has been reported to be downregulated in the skin of patients with atopic dermatitis (AD), little is known about its role in the colonization of Staphylococcus aureus in the stratum corneum of patients with AD. A precise evaluation of these peptides in the stratum corneum as an antimicrobial barrier against S. aureus colonization has not yet been performed.
Objectives  To compare β-defensin-2 levels in the skin of patients with AD and healthy controls.
Methods  We developed a microanalytical technique to measure β-defensin-2 in the stratum corneum using a combination of immunoprecipitation and Western blotting.
Results  β-Defensin-2 in the stratum corneum was significantly higher in AD lesional skin compared with healthy control skin. The β-defensin-2 content in AD lesional skin also increased in proportion to the severity of the disease. Counting bacterial colonies revealed higher populations of S. aureus on lesional and nonlesional skin surfaces of patients with AD compared with healthy controls. Comparison of S. aureus colony numbers and β-defensin-2 levels demonstrated a positive correlation ( r  =   0·342, P  =   0·004, n  =   67) between both factors.
Conclusions  Collectively, these findings suggest that β-defensin-2 is induced in response to bacteria, injury or inflammatory stimuli and is not associated with vulnerability to S. aureus colonization in the skin of patients with AD.     

The effect of antibiotics on the production of superantigen from Staphylococcus aureus isolated from atopic dermatitis

Staphylococcus aureus (S. aureus) often colonizes on the skin of patients with atopic dermatitis. It is known that superantigens which are staphylococcal enterotoxins can activate T cells without processing by antigen presenting cells. It has been suggested that activated T cells release various cytokines which may exacerbate or prolong the cutaneous inflammation associated with atopic dermatitis. Reduction of bacterial colonization from skin lesions has been reported to be effective in the treatment of atopic dermatitis. Therefore, antimicrobial therapy using antibiotics may be a treatment option for atopic dermatitis in selected patients. We examined the effect of antibiotics on the production of superantigen from S. aureus in vitro to determine the action mechanism of antibiotics in the treatment of atopic dermatitis. It was found that antibiotics with inhibitory effect on protein synthesis can suppress the production of superantigen. On the other hand, the superantigen production was not suppressed by antibiotics having either the inhibitory effect on cell wall synthesis or on nucleic acid synthesis. Levels of the suppressive effect on superantigen production by S. aureus varied with strains tested in this study. Moreover, we demonstrated that replication of DNA coding of superantigen produced by S. aureus was suppressed only by roxithromycin (ROX), which is a new macrolide. This finding suggests that ROX may have an effect at the gene level. These results suggested that the suppressive effects of antimicrobial agents that act as inhibitors of protein synthesis on superantigen production from S. aureus may be useful in the treatment of atopic dermatitis.     

Antimicrobial activity of sphingosines.

The antimicrobial activity of stratum corneum lipids was examined by screening in vitro various representative phospholipids and sphingolipids. Of mixed galacto-cerebrosides; phosphatidic acid; phosphatidic acid-monomethylester-dioleoyl; phosphatidylethanolamine; phosphatidylethanolamine-beta-oleoyl-gamma-palmitoyl; phosphatidylcholine; D-sphingosine; D,L-sphinganine; 4-D-hydroxysphinganine; oleoyl-sphingosine; N,N-dimethylsphingosine; and stearylamine, only the sphingosines and, to a lesser extent, stearylamine were clearly and profoundly effective against Staphylococcus aureus (4-log reduction at 6.25 micrograms/ml [20 microM]; 2-log reduction at 0.78 mu/ml [2.5 microM]). The sphingosines were similarly active against Streptococcus pyogenes, Micrococcus luteus, Propionibacterium acnes, Brevibacterium epidermidis, and Candida albicans, moderately active against Pseudomonas aeruginosa, and ineffective against Escherichia coli and Serratia marcescens. Both erythro- and threo-isomers were effective. Optimal inhibition was at 60 min incubation at 37 degrees C and at pH 6.5. Antimicrobial activity, which was Ca++ dependent, was confirmed in vivo by topical application and microbial challenge. Because free sphingosines are available in the stratum corneum and other epidermal layers, these lipids may contribute to the cutaneous antimicrobial barrier.     

The adherence of Staphylococcus aureus to human corneocytes

Staphylococcus aureus has a peculiar ability to colonize the skin of patients with atopic dermatitis. We examined the possibility that this might be due to a specific ability of this pathogenic staphylococcus to adhere to atopic stratum corneum. We used an in vitro model to show that S aureus does have an unusual ability to adhere to atopic corneocytes when compared with corneocytes obtained from patients with other cutaneous diseases, including psoriasis. Protein A--a component of the staphylococcal cell wall--may be responsible in part for this adherence phenomenon. This trait did not extend to the other gram-positive bacteria tested.     

Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin?

Stratum corneum lipids are an important determinant for both water-retention function and permeability-barrier function in the stratum corneum. However, their major constituent, ceramides, have not been analyzed in detail in skin diseases such as atopic dermatitis that show defective water-retention and permeability-barrier function. In an attempt to assess the quantity of ceramides per unit mass of the stratum corneum in atopic dermatitis, stratum corneum sheet was removed from the forearm skin by stripping with cyanoacrylate resin and placed in hexane/ethanol extraction to yield stratum corneum lipids. The stratum corneum was dispersed by solubilization of cyanoacrylate resin with dimethylformamide, and after membrane filtration, the weight of the stratum corneum mass was measured. The ceramides were quantified by thin-layer chromatography and evaluated as microgram/mg stratum corneum. In the forearm skin of healthy individuals (n = 65), the total ceramide content significantly declined with increasing age. In atopic dermatitis (n = 32-35), there was a marked reduction in the amount of ceramides in the lesional forearm skin compared with those of healthy individuals of the same age. Interestingly, the non-lesional skin also exhibited a similar and significant decrease of ceramides. Among six ceramide fractions, ceramide 1 was most significantly reduced in both lesional and non-lesional skin. These findings suggest that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry skin.     

pH in nature,humans and skin

The pH plays an important physiological role in nature and humans. pH varies from 1 to 8 in human organs with tight regulation in blood and epithelia of barrier organs. The physiological pH of the stratum corneum is 4.1–5.8 and several mechanisms contribute to its formation: filaggrin degradation, fatty acid content, sodium‐hydrogen exchanger (NHE1) activation and melanosome release. First, the acidic pH of the stratum corneum was considered to present an antimicrobial barrier preventing colonization (e.g. by Staphylococcus aureus and Malassezia). Later on, it was found that the pH influences skin barrier function, lipid synthesis and aggregation, epidermal differentiation and desquamation. Enzymes of ceramide metabolism (e.g. β‐glucocerebrosidase or acid sphingomyelinase) as well as proteases (e.g. chymotryptic enzyme or cathepsin D linked to epidermal differentiation and desquamation) are regulated by the pH. Experimental disruption of the physical barrier leads to an increase of pH, returning to normal levels only after many hours. Inflammatory skin diseases and diseases with an involvement of the epidermis exhibit a disturbed skin barrier and an increased pH. This is known for atopic dermatitis, irritant contact dermatitis, ichthyosis, rosacea and acne, but also for aged and dry skin. Normalizing the pH by acidification through topical treatment helps to establish a physiological microbiota, to repair skin barrier, to induce epidermal differentiation and to reduce inflammation.     

Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sézary syndrome

Background  Mycosis fungoides (MF) and Sézary syndrome (SS), variants of cutaneous T-cell lymphoma, may arise from antigen-driven clonal expansion and accumulation of helper-memory T cells. Superantigens from Staphylococcus aureus can stimulate T cells.
Objectives  (i) To determine the prevalence of S. aureus carriage in nares and skin in patients with MF/SS compared with historical rates in other conditions. (ii) To determine whether eradication of S. aureus carriage is associated with clinical improvement.
Methods  Skin and nares cultures were performed prospectively. Patients with positive nares and skin cultures were treated with oral antibiotics and intranasal mupirocin 2% and samples were taken for reculturing at 3 days, 4 weeks and 8 weeks. An exact binomial test was used to compare the carriage rates among different groups.
Results  Among 106 patients with MF/SS, 67 (63%) had skin colonization and 57 (54%) had nasal colonization. Staphylococcus aureus was isolated from 44 patients, 33 (31%) each from skin and nares. Colonization was highest in erythrodermic SS (48%), similar to atopic dermatitis (64%), and lowest in MF without erythroderma (26%), psoriasis (21%), and the general population (10%). Oral and topical antibiotics eradicated S. aureus colonization in nares in 28 of 33 (85%) patients and in MF skin lesions in 30 of 33 (91%) patients at 4–8 weeks, with rapid clinical improvement seen in 58% of S. aureus -colonized patients.
Conclusions  Staphylococcal carriage in nares and skin lesions of patients with MF is similar to that in atopic dermatitis. Eradication of staphylococci from the skin is possible with treatment and was associated with clinical improvement.     

Aberrant lipid organization in stratum corneum of patients with atopic dermatitis and lamellar ichthyosis

There are several skin diseases in which the lipid composition in the intercellular matrix of the stratum corneum is different from that of healthy human skin. It has been shown that patients suffering from atopic dermatitis have a reduced ceramide content in the stratum corneum, whereas in the stratum corneum of lamellar ichthyosis patients, the amount of free fatty acids is decreased and the ceramide profile is altered. Both patient groups also show elevated levels of transepidermal water loss indicative of an impaired barrier function. As ceramides and free fatty acids are essential for a proper barrier function, we hypothesized that changes in the composition of these lipids would be reflected in the lipid organization in stratum corneum of atopic dermatitis and lamellar ichthyosis patients. We investigated the lateral lipid packing using electron diffraction and the lamellar organization using freeze fracture electron microscopy. In atopic dermatitis stratum corneum, we found that, in comparison with healthy stratum corneum, the presence of the hexagonal lattice (gel phase) is increased with respect to the orthorhombic packing (crystalline phase). In lamellar ichthyosis stratum corneum, the hexagonal packing was predominantly present, whereas the orthorhombic packing was observed only occasionally. This is in good agreement with studies on stratum corneum lipid models that show that the presence of long-chain free fatty acids is involved in the formation of the orthorhombic packing. The results of this study also suggest that the ceramide composition is important for the lateral lipid packing. Finally, using freeze fracture electron microscopy, changes in the lamellar organization in stratum corneum of both patient groups could be observed.     

DNase1L2 suppresses biofilm formation by Pseudomonas aeruginosa and Staphylococcus aureus

BACKGROUND: The formation of biofilms, which is an important step in bacterial colonization, can be inhibited by deoxyribonuclease (DNase)-mediated breakdown of extracellular DNA. We have recently demonstrated that epidermal keratinocytes strongly express DNase1-like 2 (DNase1L2) in a differentiation-associated manner. OBJECTIVES: To determine whether enzymatically active DNase1L2 is present in human stratum corneum and whether it is able to suppress bacterial biofilm formation. METHODS: DNase1L2 was extracted from normal human stratum corneum, immunocaptured and incubated with plasmid DNA. DNA hydrolysis was monitored by gel electrophoresis and ethidium bromide staining. The effect of DNase1L2 on biofilm formation was assayed by cultivation of Pseudomonas aeruginosa and Staphylococcus aureus in the presence or absence of purified recombinant DNase1L2 in microtitre plates and subsequent quantification of biofilm-forming bacteria by crystal violet staining. RESULTS: DNase1L2 was found to be present in an enzymatically active form in the stratum corneum of human skin. In an in vitro assay, purified recombinant DNase1L2 efficiently suppressed the formation of biofilms by P. aeruginosa and S. aureus. CONCLUSIONS: Our data suggest that DNase1L2 is a novel component of the innate antimicrobial defence of the epidermis.     

Stratum corneum and nail lipids in patients with atopic dermatitis. Decrease in ceramides--a pathogenetic factor in atopic xerosis?

Dry skin is seen in many patients with atopic dermatitis and correlates with a disturbed epidermal barrier function demonstrated by such features as increased transepidermal water loss and diminished stratum corneum hydration. With regard to the importance of stratum corneum lipids for the permeability barrier, we have analysed plantar (n = 8) and lumbar (n = 20) stratum corneum and nail lipids (n = 15) of atopic subjects by high-performance thin-layer chromatography (HPTLC). Compared with controls our investigations show a decrease in the ceramide fraction as a percentage of total lipid and a diminished ratio of ceramides and free sterols in atopic subjects. This implies that impaired ceramide synthesis may be a factor in the pathogenesis of atopic xerosis.     

特应性皮炎皮损金黄色葡萄球菌检出情况的研究

目的 :　探讨特应性皮炎 (AD)皮损微生物定植情况 ,为临床合理选用抗菌药物有效控制该病提供依据。方法 :　无菌生理盐水浸湿的棉拭子于 4 3例AD患者皮损处取标本 ,同时对 39例患者非皮损处及 10例健康人取标本作对照 ,进行细菌培养及菌落计数 ,金葡菌予常规药敏试验。结果 :　AD患者皮损细菌阳性率为 74 .4 2 % ,金葡菌为主要的致病菌 ,占 6 5 .6 3% ;非皮损处也可分离出细菌 ,但金葡菌阳性率及密度均明显低于皮损处 (P <0 .0 0 1)。结论 :　微生物感染因素 ,尤其金葡菌感染或定植 ,在AD的发病中起着重要的作用     

Methicillin-resistant Staphylococcus aureus colonization in children with atopic dermatitis

Children with atopic dermatitis are more frequently colonized with Staphylococcus aureus than children without atopic dermatitis. However, little epidemiological data exist regarding the prevalence of methicillin-resistant S. aureus among children with atopic dermatitis. Recent studies have revealed an increasing prevalence of community-associated methicillin-resistant S. aureus among patients presenting to hospitals with serious bacterial infections, particularly those with cutaneous and soft tissue infections. As many atopic dermatitis patients are treated empirically with antibiotics for secondary skin infections, an understanding of the epidemiology of bacterial colonization and superinfection is essential for directing proper treatment in the atopic patient population. This study investigates the prevalence of risk factors for community-associated, methicillin-resistant S. aureus colonization among pediatric atopic dermatitis patients encountered at an academic pediatric dermatology clinic. An observational cross-sectional study was conducted at the Children's Hospital of Philadelphia in which 54 patients previously diagnosed with atopic dermatitis were enrolled. A detailed patient questionnaire, a complete cutaneous examination, and an evaluation of eczema severity according to the Eczema Area and Severity Index were completed at the time of enrollment. Bacterial cultures from the skin and nares were obtained to determine the frequency of colonization with either methicillin-sensitive S. aureus or methicillin-resistant S. aureus. Although most atopic dermatitis patients studied were colonized with S. aureus (43/54 [80%]), methicillin-resistant S. aureus was isolated from only seven atopic dermatitis patients (7/43 [16%]). Patients colonized with S. aureus were more likely to be male, to have been previously hospitalized, to have used a topical calcineurin inhibitor in combination with a topical steroid, and less likely to have used topical antibiotics. Bivariable analysis, however, revealed that only previous hospitalization was independently associated with an increased risk of methicillin-resistant S. aureus colonization. We observed that 80% of atopic dermatitis patients were colonized with S. aureus, and that of these patients, 16% of colonized patients were colonized with a methicillin-resistant strain. Methicillin-resistant S. aureus colonization was found to be significantly associated with previous hospitalization. Evidence also indicates that topical calcineurin inhibitors used in conjunction with topical steroids is associated with increased S. aureus colonization, while topical antibiotic use appears to decrease S. aureus colonization.     

Ceramide profiles of the uninvolved skin in atopic dermatitis and psoriasis are comparable to those of healthy skin

Ceramides are sphingolipids consisting of sphingoidbases, which are amide-linked to fatty acids. In the stratum corneum, they represent the major constituent of the free extractable intercellular lipids and play a significant role in maintaining and structuring the water permeability barrier of the skin. Using thin layer chromatography, which represents the method of the first choice in analyzing the stratum corneum ceramides, at least seven classes can be distinguished. Each ceramide class contains various species, which have the same head group and different chain lengths. As in many other skin disorders, atopic dermatitis and psoriasis show derangements in content and profile of the ceramides. Such derangements were reported for both the lesional involved as well as for the normal-appearing uninvolved skin. In this study, we focused on investigating the stratum corneum ceramides of the uninvolved skin in atopic dermatitis and psoriasis patients compared to healthy skin. The aim of the investigations was to explore possible significant and specific differences which can be accomplished for purposes of early diagnostics. The skin lipids were collected by means of an in vivo topical extraction procedure using an extraction mixture consisting of n-hexane and ethanol, (2:1). An automated multiple development-high performance thin layer chromatography (AMD-HPTLC) method with photodensitometric detection were applied to separate the ceramides and to estimate their contents. For studying their molecular profile within each ceramide class, a new method of normal phase HPLC with atmospheric pressure chemical ionization mass spectrometry were used. The results obtained by AMD-HPTLC exposed no significant alterations regarding the relative composition of the major stratum corneum lipids and primarily the ceramides. In addition, the mass spectrometric profiles within each ceramide class were similar in the patients and the healthy control subjects. In conclusion, this study revealed that the normal-appearing uninvolved skin of atopic dermatitis and psoriasis patients does not prove significant or specific deficiencies with respect to the free extractable major stratum corneum lipids and mainly the ceramides, when compared to healthy skin. Thus, they cannot be used for diagnostic purposes. Furthermore, our data are not consistent with the concept that impairments in the ceramide composition represent an obligate etiologic factor for both diseases.     

Bacterial superantigens and inflammatory skin diseases

Bacteria seem to play an important role in the induction and maintenance of inflammatory skin diseases such as psoriasis and atopic dermatitis. Toxins from bacteria including Streptococcus and Staphylococcus aureus, have been shown to function as a new type of allergen termed 'superantigen'. Superantigens bypass the normal control of T-cell activation and activate all T-cell clones bearing certain types of variable chain on the T-cell receptor: this leads to vigorous T-cell activation and cytokine release. These bacterial superantigens may be involved in induction and aggravation of inflammatory skin diseases. Guttate psoriasis is often preceded by a streptococcal throat infection and T cells specific for streptococcal superantigens have been identified in the skin of patients. The skin of patients with atopic dermatitis is often colonized with superantigen-releasing Staph. aureus, and application of a staphylococcal superantigen to human skin induces an eczematoid reaction.     

Biomarkers of Th2 polarity are predictive of staphylococcal colonization in subjects with atopic dermatitis

Background  Staphylococcal colonization of the skin is commonly observed in subjects with atopic dermatitis (AD) and correlates with disease severity. Little is known about whether the degree of T-helper 2 (Th2) polarity in these subjects can also affect the frequency of bacterial colonization in this disease.
Objectives  To determine if there is a correlation between markers of Th2 polarity [serum total IgE, eosinophilia and presence of another atopic disease (allergic rhinitis)] and skin colonization with Staphylococcus aureus in subjects with AD.
Methods  A retrospective chart review was performed of an academic dermatology clinic focused on the treatment of AD with a single provider.
Results  Staphylococcus aureus colonization was more commonly observed in subjects with AD who had peripheral eosinophilia, elevated serum IgE levels, and/or a history of or active allergic rhinitis.
Conclusions  Results suggest that Th2 polarity may enhance subjects' risk for bacterial colonization.     

In vitro and in vivo antistaphylococcal activity of human stratum corneum lipids

Despite the assumption that sebum-derived fatty acids are responsible for cutaneous antimicrobial defense, no studies have assessed the contribution of epidermis-derived lipids. Herein, we tested the antistaphylococcal effects of human stratum corneum lipids, enriched in endogenous, keratinocyte-derived species obtained by lipid extraction and thin-layer chromatography, for antimicrobial activity in both in vitro and in vivo systems. Whereas the most potent species in vitro were the free fatty acids, polar lipids and glycosphingolipids also demonstrated antistaphylococcal activity in vitro, while other neutral lipids displayed virtually none, results that were confirmed with authentic standards in vitro. In a pilot study on delipidized forearm test sites in human volunteers, naturally occurring free fatty acids, polar lipids, and glycosphingolipids exhibited significantly more antistaphylococcal activity than other stratum corneum lipids or vehicle controls. Finally, biopsy specimens of incubated skin sites demonstrated penetration of staphylococci through lipid-enriched intercellular domains. These results provide the first evidence that endogenous, epidermis-derived skin lipids may contribute to cutaneous antimicrobial resistance.     

特应性皮炎和湿疹皮肤金黄色葡萄球菌肠毒素及中毒休克综合征毒素-1的检测

目的 探讨皮肤金黄色葡萄球菌(金葡菌)肠毒素及中毒休克综合征毒素-1(TSST-1)在特应性皮炎及湿疹中的致病作用。方法 反向被动乳胶凝集法测定来自117例特应性皮炎和199例湿疹患者皮肤共140株金葡菌的肠毒素/TSST-1。结果 140株金葡菌中60株产生超抗原,阳性率为42.9%,其中43株只产生一种超抗原,17株产生至少两种超抗原。特应性皮炎组超抗原总阳性率为51.5%,皮损与非皮损处无差别。湿疹组超抗原总阳性率为34.7%,阳性株均为皮损处菌。特应性皮炎组超抗原总阳性率、皮损处超抗原总阳性率及中毒休克综合征毒素-1阳性率均高于湿疹组。结论 与湿疹相比,特应性皮炎与金葡菌超抗原的关系较为密切。     

Reevaluation of the non-lesional dry skin in atopic dermatitis by acute barrier disruption: an abnormal permeability barrier homeostasis with defective processing to generate ceramide

Atopic dermatitis is characterized by disruption of the cutaneous barrier due to reduced ceramide levels even in non-lesional dry skin. Following further acute barrier disruption by repeated tape strippings, we re-characterized the non-lesional dry skin of subjects with atopic dermatitis, which shows significantly reduced levels of barrier function and ceramide but not of beta-glucocerebrosidase activity. For the first time, we report an abnormal trans-epidermal water loss homeostasis in which delayed recovery kinetics of trans-epidermal water loss occurred on the first day during the 4 days after acute barrier disruption compared with healthy control skin. Interestingly, whereas the higher ceramide level in the stratum corneum of healthy control skin was further significantly up-regulated at 4 days post-tape stripping, the lower ceramide level in the stratum corneum of subjects with atopic dermatitis was not significantly changed. In a parallel study, whereas beta-glucocerebrosidase activity at 4 days post-tape stripping was significantly up-regulated in healthy control skin compared with before tape stripping, the level of that activity remained substantially unchanged in atopic dermatitis. These findings indicate that subjects with atopic dermatitis have a defect in sphingolipid-metabolic processing that generates ceramide in the interface between the stratum corneum and the epidermis. The results also support the notion that the continued disruption of barrier function in atopic dermatitis non-lesional skin is associated with the impaired homeostasis of a ceramide-generating process, which underscores an atopy-specific inflammation-triggered ceramide deficiency that is distinct from other types of dermatitis.