Severe atopic dermatitis is associated with a high burden of environmental Staphylococcus aureus

Background About 90% of patients with atopic dermatitis (AD) are colonized with Staphylococcus aureus. S. aureus worsens AD by secreting superantigens and structural molecules within the cell wall that induce skin inflammation. Therefore, S. aureus in the home may contribute to persistent skin inflammation and disease severity. Objective To quantify S. aureus burden in homes of participants with AD of varying severities. Methods Participants with mild (n=18), moderate (n=14), severe (n=15), and no AD (n=15), collected dust from their bed and bedroom floor, and from their home vacuum cleaner bag. DNA was extracted from dust samples, and the S. aureus‐specific femB gene was quantified using quantitative real‐time PCR. Data was log‐transformed, and then statistically analysed with anova , student's t‐test, and Spearman's r. Results Participants with severe AD (geometric mean: 14.67 pg/mg dust) had significantly more S. aureus DNA in their bed dust than those with moderate (0.41 pg/mg dust, P<0.0001), mild (1.42 pg/mg dust, P=0.0051), and no AD [0.09 pg/mg dust, P<0.0001 (t‐test)]. Similar patterns were observed for dust from the bedroom floors and vacuum bags. S. aureus DNA was highest in dust from beds as compared with bedroom floors or vacuum bags (medians: 1.51, 0.69, 0.21 pg/mg dust, respectively; P=0.007). Eczema Area and Severity Index scores correlated with S. aureus DNA from the bed (Spearman's r=0.7263; P=0.0004) and floor (0.6846; P=0.0002) dust, but not with the vacuum bag dust (0.3783; 0.0684). Conclusions In the home and especially the bedroom, higher levels of S. aureus may contribute to disease severity and persistence in AD patients.     

Possible influences of Staphylococcus aureus on atopic dermatitis — the colonizing features and the effects of staphylococcal enterotoxins

BACKGROUND: Heavy colonization of atopic dermatitis (AD) with Staphylococcus aureus is well documented. This phenomenon suggests that S. aureus in AD lesions influences the disease processes of AD. OBJECTIVE: We describe the importance of the presence of S. aureus and staphylococcal enterotoxins A and B (SEA, SEB) in AD lesions. METHODS: We investigated the colonizing features of S. aureus in AD lesions using electron microscopy, the distribution of SEB in the eczematous skin of AD using immunofluorescence, the effects of SEA and SEB on normal human epidermal keratinocytes in organ culture, and the presence of specific IgE antibodies to SEA and/or SEB in serum of AD patients by enzyme immunoassay. RESULTS: S. aureus in AD lesions colonized on and in the horny layers of the eczematous skin. SEB produced by S. aureus was distributed mainly on the dermal-infiltrated cells, especially on eosinophils. SEA and SEB stimulated expression of ICAM-1 and HLA-DR in normal human keratinocytes. More than half of the AD patients in the present study had specific IgE antibodies to SEA and/or SEB in their serum. CONCLUSION: S. aureus and SEs have important roles in the exacerbation and prolongation of AD.     

Reduction of Staphylococcus aureus in atopic skin lesions with acid electrolytic water - a new therapeutic strategy for atopic dermatitis

The subjects studied were 22 pediatric patients newly diagnosed with atopic dermatitis (AD); 11 were treated with acid electrolytic water (AEW), which has a strong bactericidal activity (AEW group), and the other 11 with tap water (placebo group). AEW or tap water, 1 ml/cm² (body surface area), was sprayed on their skin lesions with a spray gun each twice a day for a week. There were no significant differences between the two groups in regard to sex, age, serum IgE, peripheral eosinophil counts, grading scores of AD, and duration of AD. The study was designed as a randomized, placebo-controlled, double-blind clinical trial. Colony counts of Staphylococcus aureus on skin lesions in the AEW group, both 3 min after spraying ( P < 0.05) and after 1 week of skin treatment ( P < 0.01), were significantly decreased as compared with colony counts before treatment, while there was no significant difference in the placebo group before and after treatment. Grading scores of AD also decreased in the AEW group ( P <0.01), but not in the placebo group. Both the subjects' guardians' evaluation and a referee physician's evaluation of treatment effect were significantly higher in the AEW group than in the placebo group ( P < 0.01). AEW may be potentially effective in preventing a staphylococcal chronic inflammation in AD because of its strong bactericidal activity.     

Hyper-response of serum IgG1 to Staphylococcus aureus peptidoglycan in patients with hyper-IgE syndrome.

The hyper-IgE (HIE) syndrome is characterized by high IgE serum levels, chronic dermatitis and recurrent infections. To determine whether an impairment of the antibody response to Staphylococcus aureus contributes to infections in this syndrome we measured total serum IgG subclass, specific IgG1 and IgG2 levels against peptidoglycan (PG), the immunodominant cell wall component of S. aureus and serum opsonic activity to PG. Of the 14 patients with HIE syndrome, nine had increased level of serum IgG1 and six had IgG2 subclass deficiency. In regard to specific response of IgG1 and IgG2 antibodies to PG, patients were divided into five groups related to ages and compared with 10 control subjects for each age cohort. Patients with HIE syndrome had significant high levels of serum-specific IgG1 to PG and significant decreased levels of serum-specific IgG2 to PG in all five groups. Additionally, serum opsonic activity in patients was significantly higher than that in normal control subjects. It is concluded that IgG2 deficiency or poor IgG2 antibody response to S. aureus is not the explanation of the abnormal susceptibility to S. aureus infections of HIE patients.     

Lipoteichoic acid from Staphylococcus aureus enhances allergen-specific immunoglobulin E production in mice

BACKGROUND: Our previous study demonstrated that lipoteichoic acid (LTA) from Staphylococcus aureus induced T helper type 2 (Th2)-prone dermatitis resembling that seen in atopic dermatitis (AD) patients in mice sensitized percutaneously with an allergen. However, the effects of LTA on allergen-specific IgE production in such sensitized mice have not been elucidated. OBJECTIVE: The purpose of this study was to determine the effects of LTA from S. aureus on allergen-specific IgE production in mice sensitized percutaneously with a house dust mite antigen (MA). METHODS: Mice were sensitized with a single topical application of MA and/or LTA to barrier-disrupted abdominal skin. One to 5 weeks later, MA-specific IgE antibodies in sera from sensitized mice were detected by an enzyme-linked immunosorbent assay (ELISA). Expression of B7.1 (CD80), B7.2 (CD86) and CD40L molecules by CD40-positive (CD40+) and CD4-positive (CD4+) cells in the lymph nodes of sensitized mice were analysed by flow-cytometry (FACS). RESULTS: Simultaneous sensitization with MA and LTA increased IgE production 3 weeks later, significantly more than sensitization with MA alone. FACS analysis of CD40+ cells in the lymph nodes from sensitized mice showed that simultaneous sensitization with MA and LTA did not enhance CD80- or CD86-expression by antigen-presenting cells such as B lymphocytes and dendritic cells more than sensitization with MA alone. However, analysis of CD4+ cells in the lymph nodes showed that simultaneous sensitization with MA and LTA increased the number of CD40L-expressing Th cells more than sensitization with MA alone. CONCLUSION: These results suggest that LTA enhances allergen-specific IgE production by a mechanism associated with up-regulation of CD40L-expressing Th cells and this might explain the role of skin colonization with S. aureus in AD patients.     

Children with atopic dermatitis who carry toxin-positive Staphylococcus aureus strains have an expansion of blood CD5- B lymphocytes without an increase in disease severity

Toxin-positive strains of Staphylococcus aureus (T + S. aureus) are present on the skin of some but not all patients with atopic dermatitis. Many staphylococcal toxins are superantigens, which can stimulate the immune response and thus may potentially lead to the very high levels of IgE characteristic of this condition, as well as exacerbating the clinical disease. The aim of this study was to determine whether the presence of T + S. aureus on the skin of children with atopic dermatitis was associated with in vivo evidence of a heightened humoral immune response, higher IgE levels and more severe clinical disease. Toxin gene expression in S. aureus isolated from the eczematous lesions of 28 children with atopic dermatitis was assessed by PCR. Clinical and immune data were also collected from this cohort. Thirteen of the 28 children (46%) were colonized with T + S. aureus strains. The presence of T + S. aureus was associated with a significant expansion in peripheral blood CD5- B cells (P = 0.01), and the more toxin types identified the greater the B-cell expansion (P = 0.002). However, in this cohort of children with atopic dermatitis, despite th in vivo expansion of B cells in children harbouring T + S. aureus, there was no associated increase in IgE levels or in clinical disease severity scores.     

Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters

BACKGROUND: Staphylococcus aureus has important implications for the pathogenesis of atopic dermatitis (AD). In some patients S. aureus can be eradicated from the skin during anti-inflammatory treatment, while in others bacterial colonization is persistent. Potential mechanisms and features of these two distinct groups of patients are not known. OBJECTIVE: Accordingly, we studied relationships between the ability to eliminate S. aureus during an anti-inflammatory treatment and selected clinical and immunological features. METHODS: Quantitative assessment of S. aureus on the skin, in nasal vestibule and throat, serum IgE levels, CD4/CD8 T-cell ratio, lymphocyte proliferation and phagocyte oxidative burst were determined during the exacerbation and after 4 and 12 weeks of the treatment using topical steroid and oral antihistamine in 34 patients with AD. RESULTS: S. aureus was found on the skin of all 34 patients during exacerbation. Disease severity scoring of atopic dermatitis (SCORAD) correlated with the density of bacteria. Treatment with oral antihistamine and topical steroid resulted in a significant alleviation of symptoms, which correlated with the elimination of S. aureus from the skin in 70% of patients. In the remaining 30% of patients, dense (more than 10(10)/cm2) S. aureus skin colonization, persisted despite the treatment. Patients with persistent S. aureus presented with higher serum IgE levels, lower lymphocyte proliferation in response to staphylococcal enterotoxin B, phytohaemagluttinin and anti-CD3. Persistence of S. aureus was more common in men. CONCLUSIONS: Patients with AD differ in the ability to clear S. aureus from the skin during anti-inflammatory treatment, which appears to be related to the abnormalities in immunological parameters. Local antibiotic therapy should be considered only in patients with persistent S. aureus colonization.     

Staphylococcus aureus isolated from tonsillectomized adult patients with recurrent tonsillitis

The aim of this study was to analyze the prevalence and antibiotic resistance of Staphylococcus aureus strains from 118 tonsillectomized adults due to recurrent tonsillitis (RT). The study included strains isolated from the tonsillar surface prior to tonsillectomy, recovered from the tonsillar core at the time of surgery, and from the posterior throat 2–4 weeks after the procedure. Susceptibility of isolates to 19 antibiotics was tested in line with the Clinical and Laboratory Standards Institute recommendations. Irrespective of the stage, the most commonly isolated bacteria were gram‐positive cocci, and among them S. aureus. The tonsillar core was the most common site of S. aureus isolation (30.5%), followed by the tonsillar surface (10.8%) and the posterior pharynx (5.9%). This difference turned out to be statistically significant (p < 0.001). Beta‐hemolytic streptococci, most often Streptococcus pyogenes (5.1%), were isolated from 2.5% to 10.2% of patients. Staphylococcal isolates were susceptible to most tested antibiotics (except from penicillin and ampicillin) and rarely showed methicillin resistance (n = 1). Staphylococcus aureus seems to be the most common pathogen isolated from patients tonsillectomized due to RT. Staphylococcal isolates associated with RT are present mostly within the tonsillar core and susceptible to most antibiotics. They are typically isolated from patients between 21 and 30 years of age. Tonsillectomy results in less frequent isolation of S. aureus strains.     

Urine eosinophil protein X (EPX) is an in vitro parameter of inflammation in atopic dermatitis of the adult age

BACKGROUND: Eosinophils are important effector cells in several atopic diseases. The levels of eosinophil granule-derived mediators (ECP, EPX) in serum and body fluids have been proven to be correlated with disease activity in atopic respiratory diseases and atopic dermatitis. The study aimed to demonstrate an interrelationship between urine EPX and disease activity in adult patients with atopic dermatitis. METHODS: We determined urine EPX concentration, serum ECP concentration, and peripheral blood eosinophil count in 40 adult patients with mild to severe atopic dermatitis and compared it with the disease activity as assessed with the SCORAD index. RESULTS: Urine EPX and serum ECP concentrations were significantly higher in patients with severe atopic dermatitis than in patients with mild or moderate disease (median values 123.5 vs 78.3 microg/mmol creatinine, P<0.0001; 25.4 vs 14.9 microg/l, P<0.0001, respectively). We found a significant correlation between urine EPX levels, serum ECP levels, and the SCORAD (r=0.36, P<0.0001 and 0.34, P<0.0001, respectively). CONCLUSION: Urine EPX is a useful in vitro parameter of inflammation in atopic dermatitis of the adult age.     

The molecular evolution of methicillin-resistant Staphylococcus aureus

Staphylococcus aureus is a potentially pathogenic bacterium that causes a broad spectrum of diseases. S. aureus can adapt rapidly to the selective pressure of antibiotics, and this has resulted in the emergence and spread of methicillin-resistant S. aureus (MRSA). Resistance to methicillin and other β-lactam antibiotics is caused by the mecA gene, which is situated on a mobile genetic element, the Staphylococcal Cassette Chromosome mec (SCC mec ). To date, five SCC mec types (I–V) have been distinguished, and several variants of these SCC mec types have been described. All SCC mec elements carry genes for resistance to β-lactam antibiotics, as well as genes for the regulation of expression of mecA . Additionally, SCC mec types II and III carry non-β-lactam antibiotic resistance genes on integrated plasmids and a transposon. The epidemiology of MRSA has been investigated by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), spa typing and SCC mec typing. Numerous MRSA clones have emerged and disseminated worldwide. SCC mec has been acquired on at least 20 occasions by different lineages of methicillin-sensitive S. aureus . Although most MRSA strains are hospital-acquired (HA-MRSA), community-acquired MRSA (CA-MRSA) strains have now been recognised. CA-MRSA is both phenotypically and genotypically different from HA-MRSA. CA-MRSA harbours SCC mec types IV or V, and is associated with the genes encoding Panton–Valentine leukocidin. The prevalence of MRSA ranges from 0.6% in The Netherlands to 66.8% in Japan. This review describes the latest developments in knowledge concerning the structure of SCC mec , the molecular evolution of MRSA, the methods used to investigate the epidemiology of MRSA, and the risk-factors associated with CA-MRSA and HA-MRSA.     

Role of gamma/delta T cell receptor-expressing lymphocytes in cutaneous infection caused by Staphylococcus aureus

The high number of gamma/delta-expressing T cells found in the epithelial lining layer suggests that they form a first line of defence against invading pathogens. To evaluate the role of gamma/delta T cell-receptor (TCR)-expressing cells in cutaneous infection caused by Staphylococcus aureus, mice lacking gamma/delta-expressing T cells (TCRdelta-/-) were inoculated intradermally with S. aureus, and compared with S. aureus-infected congeneic TCRdelta+/- control mice. The number of bacteria recovered from the skin of TCRdelta-/- mice was significantly higher (P = 0.0071) at early time-points after inoculation compared to the number of bacteria isolated from infected TCRdelta+/- congeneic controls. Nevertheless, inflammatory responses measured as serum IL-6 levels, were significantly lower in TCRdelta-/- mice than in the control group. A possible explanation for this discrepancy was the observation of significantly decreased overall numbers of infiltrating cutaneous T lymphocytes, which are important producers of IL-6. These results support the notion that the gamma/delta-expressing T cells that reside at the epithelial lining layer of the skin is of importance for early containment of the bacteria, thereby limiting their replication and spread.