A pilot study to explore the usefulness of antibody array in childhood atopic dermatitis.

BACKGROUND: The pathophysiology of childhood atopic dermatitis (AD) involves complex interactions among cellular, humoral, cytokine and chemokine systems. OBJECTIVE: To evaluate protein expressions using antibody microarray. METHODS: Severity-nine proteins were assayed using antibody microarray on AD patients age < 18 years. Disease severity was assessed with the SCORing Atopic Dermatitis (SCORAD) and Nottingham Eczema Severity Score (NESS), and quality of life with the Children Dermatology Life Quality Index (CDLQI). Serum IgE levels were also assessed. Normal subjects without atopy were used as controls. Cytokines, chemokines and a wide array of proteins were assayed with RayBio Human Cytokine Antibody Array V (RayBiotech, Norcross, GA). RESULTS: Nine Chinese children with AD and four normal subjects were recruited. The median SCORAD was 60.7. Among the 79 proteins, the levels of BDNF, Fit-3 ligand, IL-8, IL-16, LIGHT, MIP-1beta, MIP-3alpha, NAP-2, PARC, TGF-beta2 and TIMP-2 were significantly different from the controls. Nevertheless, no significance was found when adjusted for multiple comparisons using p = 0.0006. Some of these markers showed significant correlations with various components of SCORAD, NESS and CDLQI. The serum IgE level as a marker of atopy correlates significantly with BDNF, LIGHT, PARC and TIMP-2. CONCLUSIONS: The serum levels of BDNF, LIGHT, PARC and TIMP-2 correlate to IgE as a marker of atopy. Although targeting chemokines and chemokine receptors may offer new opportunities for therapeutic interventions in AD, protein assay with cytokine antibody array was generally not helpful in identifying specific molecules pertinent to AD activity.

Comparison of skin hydration evaluation sites and correlations among skin hydration, transepidermal water loss, SCORAD index, Nottingham Eczema Severity Score, and quality of life in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is characterized by dryness of the skin, pruritus and involvement of the skin flexures. Skin hydration (SH) and integrity, as measured by transepidermal water loss (TEWL), are important parameters for objectively quantifying AD research. OBJECTIVES: To evaluate if sites in the forearm are equivalent to the antecubital fossa for standard SH and TEWL measurements; and to determine the correlations among these measurements and scores of disease severity and quality of life. METHODS: We evaluated SH and TEWL under standardized conditions at three common measurement sites in the forearm (antecubital flexure, 2 cm below the antecubital flexure, mid-forearm), and determined the SCORing Atopic Dermatitis (SCORAD) score, Nottingham Eczema Severity Score (NESS), and Children's Dermatology Life Quality Index (CDLQI). RESULTS: Significant correlations between clinical scores, SH, and TEWL were obtained at a site 2 cm below the antecubital fossa (r = -0.553, p < 0.001 for SH and SCORAD; r = 0.596, p < 0.001 for TEWL and SCORAD). SH and TEWL were also correlated with long-term severity of AD as measured by NESS (r = -0.494, p = 0.001 for SH; r = 0.430, p = 0.004 for TEWL), while TEWL was significantly correlated with CDLQI (r = 0.323, p = 0.035). Overall, similar significant correlations were obtained at the mid-forearm, but less so at the antecubital fossa. CONCLUSION: In AD research, three sites on the forearm appear to be convenient for determination of SH and TEWL. This is the first report to demonstrate that significant correlations are obtained among acute and chronic scores of AD disease severity, quality of life, and the bioengineering parameters.

Efficacy and problems associated with using a wet-wrap garment for children with severe atopic dermatitis.

Use of a wet wrap for short-term relief of itch in children with severe atopic dermatitis has been advocated but objective determination of its efficacy has been difficult and many issues associated with its use are yet to be defined. We tested a new garment for the wet-wrap procedure in six patients with atopic dermatitis and objectively determined whether a 3-day usage could indeed relieve the distressing symptom of itch using a wrist motion monitor. The garments were effective in the short-term improvement of itching, severity of atopic dermatitis and quality of life in these children. Many issues associated with its use were identified. Clear instructions and individualized regimes (such as the choice of emollient, bathing ointment and topical corticosteroid) are essential for optimal outcome.

Eczema exacerbation and food atopy beyond infancy: how should we advise Chinese parents about dietary history, eczema severity, and skin prick testing?

Issues related to empirical dietary restriction are important, but they have been inadequately studied among children with atopic dermatitis (AD). To evaluate whether any association exists between food atopy, food avoidance, and AD severity, investigators in the present study reviewed all skin prick tests (SPTs) performed between January 2005 and April 2006 at a pediatric dermatology clinic and correlated findings with history of food avoidance and eczema severity. Only 13% of 114 children with AD had a positive SPT for beef. The most commonly sensitized foods were egg yolk (53%), egg white (42%), shrimp (35%), peanuts (31%), and crab (29%). Disease severity was not associated with prevalence of sensitization to these foods. The investigators concluded that immediate immunoglobulin E reaction to beef, as suggested by positive SPT findings, is unlikely to occur in most children with AD. SPT information may be useful in reassuring parents about the unlikelihood of a severe and immediate reaction to beef. As for other foods, it is sensible to advise parents about specific avoidance strategies only in more severely affected children with a definite history of eczema exacerbation by specific food allergens.

Apoprotein E isoform-dependent expression and secretion of pro-inflammatory cytokines TNF-alpha and IL-6 in macrophages.

The anti-atherogenic properties of human apoprotein E-associated lipoproteins have been partially attributed to its anti-inflammatory properties. We studied if endogenously expressed apoprotein E (apoE) elicits isoform-dependent effects on pro-inflammatory cytokine expression and secretion. Mouse J774A.1 peritoneal macrophages without native expression of apoE were used to establish cell lines with stable expression of the three human apoE isoforms, apoE2, apoE3 and apoE4. In the presence of lipopolysaccharide (LPS), expression and secretion of TNF-alpha and IL-6 in cells expressing different apoE isoforms were determined by RT-PCR, immunoblotting and ELISA assays. ApoE3-expressing cells have significantly lower expression and secretion levels of the two cytokines as compared to cells with apoE2 and apoE4 expression. Such observations were accompanied with the lowest ERK1/2 activity in apoE3-expressing cells. Further study shows that the apoE isoform-dependent variations of TNF-alpha and IL-6 expression/secretion in macrophages are diminished in the presence of ERK1/2 inhibitor U0126. In conclusion, apoE elicits isoform-dependent effects on macrophage TNF-alpha and IL-6 expression as well as secretion. The ERK1/2 signaling pathways are involved in mediating such apoE isoform-dependent effects.

Are age-specific high serum IgE levels associated with worse symptomatology in children with atopic dermatitis?

BACKGROUND: Atopic dermatitis (AD) is a distressing disease associated with excoriations, pruritus, sleep disturbance, and elevation of serum total immunoglobulin E (IgE) levels. OBJECTIVE: To evaluate whether serum IgE levels correlate with the symptomatology and plasma chemokine levels in children with AD. METHODS: AD patients aged younger than 18 years were recruited from the pediatric dermatology clinic of a university teaching hospital, and the AD severity was evaluated using the SCORing Atopic Dermatitis (SCORAD) index. Concentrations of serum total IgE, eosinophil count, and plasma AD-associated chemokines [cutaneous T-cell-attracting cytokine (CTACK), thymus and activation-regulated chemokine (TARC)] were measured. RESULTS: One hundred and seventeen Chinese children with AD (64 boys and 53 girls), with an age (mean +/- standard deviation) of 10.7 +/- 4.4 years, were recruited. Their overall SCORAD index (mean +/- standard deviation) was 51.1 +/- 22.8. The total serum IgE level divided by the age-specific upper limit (AE) correlated well with the extent and intensity of AD, except for oozing/crusting, which was significant only in males. There was a significant correlation between AE and pruritus or sleep loss only in females. Levels of IgE, CTACK, and TARC, and eosinophil count, differed significantly between patients with mild, moderate, and severe disease. AE correlated well with TARC (r = 0.50, P < 0.001) and eosinophil count (r = 0.41, P < 0.001), but not with CTACK (r = 0.11, P = 0.270). The prediction of moderate to severe eczema by AE gave an area under the receiver-operating characteristic curve of 0.76 (95% confidence interval, 0.65-0.86; P = 0.004). An optimum positive predictive value of 94.2% was achieved with a cut-off point of AE of 2.95, sensitivity of 75.0%, and specificity of 66.7%. CONCLUSION: AE correlates significantly with various objective clinical scores and chemokine markers of AD, and is a useful indicator for predicting moderate to severe AD in children.

Steroid fears in children with eczema.

BACKGROUND: Topical glucocorticoids (GCs) are the mainstay of treatment for eczema, but GC phobia and fears are very common among the parents of paediatric patients. AIM: To survey the nature and extent of "fears" of GC use, and to evaluate if disease severity is associated with such fears. METHODS: Patients with eczema managed in the paediatric dermatology outpatient clinic of a university hospital were recruited in this survey. Disease severity and various aspects of belief and practices of GC use were assessed with the Nottingham Eczema Severity Score and a questionnaire. RESULTS: GC "fears" were present in two fifths of informants with non-eczematous skin disease and mild eczema, but three fifths in moderate-to-severe disease. Requests for steroid-sparing medications (such as tacrolimus or pimecrolimus) had been made in nearly 50% of cases with moderate-to-severe eczema, and many parents would wait until eczema had worsened or apply GC only as a last resort to avoid potential side effects. "Fears" were predominantly interpersonal and rarely iatrogenic in nature. Skin problems (in particular skin thinning) and adverse effects on growth were the side effects of GC of most concern. However, fewer than half of the informants had discussed their concerns with doctors. CONCLUSION: Our results suggest the importance of understanding the nature and extent to which GC fears, regardless of eczema severity, are prevalent so that sound advice can be offered in a timely manner to parents and patients.