Serum concentrations of CCR4 ligands in relation to clinical severity of atopic dermatitis in Egyptian children

T helper 2 (Th2) lymphocytes, the key effector cells in pathogenesis of atopic dermatitis (AD), express CCR4 receptors. CCR4 ligands (macrophage-derived chemokine ‘MDC’ and thymus and activation-regulated chemokine ‘TARC’) direct trafficking and recruitment of Th2 cells into lesional skin in AD. These chemokines appear to be useful inflammatory markers for assessing severity of AD in adults. However, the same results have not been replicated in children. Therefore, we were stimulated to elucidate the expression of CCR4 ligands in children with AD and their relation to clinical disease severity. To investigate this, serum concentrations of CCR4 ligands were determined in 60 children, of whom 30 had AD and 30 were healthy matched subjects. Patients were classified into mild (n = 8), moderate (n = 12) and severe (n = 10) according to the objective scoring AD (obj-SCORAD) index. Serum concentrations of MDC and TARC were significantly increased in children with AD (2697 ± 982.6 pg/ml and 945.5 ± 494.7 pg/ml, respectively) compared with controls (357.2 ± 233.2 pg/ml and 214.2 ± 116.6 pg/ml, respectively, p < 0.0001). Serum levels of both chemokines went hand in hand with disease severity as they were significantly higher in severe than moderate and in moderate than mild AD. In addition, they correlated positively with obj-SCORAD (r = 0.99 for both, p < 0.0001). Furthermore, both chemokines had significant positive correlations to blood eosinophil counts and serum immunoglobulin E. In conclusion, serum CCR4 ligands may be useful inflammatory markers for assessing AD severity in children. Further studies may pave way for CCR4 ligands antagonism among the adjuvant therapeutic strategies of AD.     

Predictive features for persistence of atopic dermatitis in children

Allergen exposure plays an important role in atopic dermatitis (AD). Because immunological mechanisms underlying asthma and AD have great similarities, we evaluated whether features such as allergen sensitization, immune response, disease severity and duration or allergen exposure could be considered predictive for AD persistence. Seventy-one AD children (age range 14–158 months) were enrolled and followed for 3 consecutive years for AD severity using the SCORAD index (SI). At enrollment, reactivity to inhalant and food allergens using the skin prick test (SPT) and house dust mite (HDM) atopy patch test (APT), and HDM allergens in house dust were evaluated. After 3 years, 38 children outgrew their AD (AD^– group), while in 33 AD persisted (AD⁺ group). At enrollment, AD⁺ children had a higher SI, higher rate of positivity to SPT and APT for mites (p = 0.001), and higher environmental exposure to HDM allergens (p = 0.035). The AD⁺ children developed more respiratory symptoms in comparison to AD^– children (p < 0.001). None of the AD^– children presented APT positivity. In our study population, positivity of SPT and APT for HDM, environmental allergen exposure levels and severity of the disease at enrollment presented a significant predictive power towards AD persistence. Subjects with positive skin reactivity to HDM should be considered at risk of AD persistence and of possible development of allergic respiratory disorders.     

Does the severity of atopic dermatitis correlate with serum IgE levels?

Recent studies suggest an association between atopic phenotypes and serum IgE levels. In contrast to asthma, this association has not been proven for atopic dermatitis. For 345 children (mean age 2.9 years), we investigated a correlation of the severity of eczema (defined by SCORAD score) and serum IgE levels. Additionally, the data was analyzed for differences between children with high and low SCORAD quartile. Parameters such as genetic background, the prevalence of other atopic phenotypes such as bronchial asthma, allergic rhinoconjunctivitis, and allergic sensitization were recorded. Our results indicate a significant correlation between SCORAD and serum IgE levels (R = 0.31, p < 0.001), but the standard deviation was large. Children with atopic dermatitis showed a high prevalence of sensitization to foods independent of the IgE levels; children with high SCORAD levels showed a sensitization to aeroallergens significantly more often (p < 0.02). No differences were found in prevalences of atopic family background, or a number of additional atopic symptoms such as asthma and allergic rhinoconjunctivitis. These results suggest that serum IgE levels seem to correlate with the degree of eczema. Children with severe atopic dermatitis and high IgE levels are at risk for sensitization to food allergens and aeroallergens.     

Scoring of atopic dermatitis by SCORAD using a training atlas by investigators from different disciplines

The ETAC (Early Treatment of the Atopic Child) study, a multi-national double-blind placebo-controlled randomized trial, has been in progress since 1994. Fifty-six centers in Europe and Canada participate in this study. A total of 817 children with atopic dermatitis [AD] were recruited. The severity of AD was scored using the SCORAD (objective criteria). Ninety-eight investigators (mostly pediatricians) were trained by three members of the European Task Force on Atopic Dermatitis [ETFAD] to standardize their objective SCORAD scoring (system developed by the ETFAD). The experts selected photographs and prepared a training atlas. The percentages of photographs assessed by the 98 non-expert investigators below, within and above the range of evaluations by the three experts were calculated. Taking over- and underscoring together, edema/papulation was the easie. st intensity item to score (82% within the range by the experts). The global symptom score, as well as lichenification. edema/papulation. oozing and excoriation registered by physicians with dermatological experience were not statistically significantly different from those by others. Erythema was statistically significantly better scored by those with dermatological experience. The results of the Euclidean Distance method showed that the item excoriations gave the largest distance. Erythema and excoriations were scored better by dermatologically experienced physicians (t-test, p=0.042 and p=0.063 respectively), but lichenification was better scored by non-dermatologically experienced physicians (p=0.013). The extent of surface area involved in the disease was calculated on 3 sets of photographs. Most evaluations by the 98 nonexpert investigators were within the range of the experts. Dermatologically experienced physicians scored significantly better than the others (Mest, p=0.006). This training program is useful for standardizing the scoring in AD and indicates that SCORAD can be used by investigators from different disciplines.     

IgE antibody responses in young children with atopic dermatitis

In 2184 young children aged 13–24 months with atopic dermatitis (SCORAD 5–59) serum IgE antibodies to a standard panel of food and inhalant allergens were assayed. The frequency of positive IgE responses (>0.35 kU/l) increased with greater severity of skin disease. A significant minority of infants had levels of IgE antibody to foods to suggest they were at risk of acute reaction to those foods (7% to hen's egg, 3% to cow's milk, 4% to peanut). Our findings indicate that the frequency of positive IgE responses is related to disease severity and suggest that differences in the time course of the development of IgE responses to food, which are at maximum prevalence within the first year of life, while inhalant allergies, are still developing between 1 and 2 yr and beyond.     

A randomized, single-blind and crossover study of an amino acid-based milk formula in treating young children with atopic dermatitis

Cow's milk and soy protein allergies are commonly associated with atopic dermatitis (AD) in young children. Amino acid (AA)-based elemental milk formula may improve AD control in these patients. This study investigates the efficacy of AA-based formula in treating young AD patients irrespective of their food allergy status. AD patients younger than 3 yr old were eligible. Sensitization to food allergens was ascertained by skin prick tests and allergen-specific immunoglobulin E (IgE) assay. Patients were then randomly allocated to take either active treatment or pre-existing formulae (placebo) for 6 wk. They were allowed a 6-wk washout period before crossed over to the other intervention for another 6 wk. Fifteen AD patients, with median (interquartile range, IQR) age of 1.4 (0.6-2.6) yr, were recruited. Their median (IQR) SCORAD score was 23.9 (10.5-29.7). Seven of them were sensitized to cow's milk or soybean. Among 11 patients who completed the study, the median changes for all scores and urinary eosinophil protein X (EPX) concentration were not statistically significant. There was also no evidence of carry-over effects for SCORAD and its various components and global health score, except for urinary EPX concentration (p = 0.05). Our results do not support the use of AA-based elemental milk formula in treating young children with AD irrespective of their food allergy status.     

Serum levels of Th2 chemokines,CCL17, CCL22, and CCL27, were the important markers of severity in infantile atopic dermatitis

Atopic dermatitis (AD) is considered to be Th2 cell‐mediated disorder. In most infants with AD, AD may be induced by food allergy. In the early stage of infantile AD, it is unclear whether there are changes in serum Th2 chemokines or in Th2 chemokine production by peripheral blood mononuclear cells (PBMC). Thirty‐four patients with AD were examined (mean age, 4.5 months; female:male, 18:16). Ten age‐matched infants with no history of allergic disease were used as controls. Thirty of these 34 patients were sensitized with ovalbumin (OVA; radioallergrosolvent score of >2). Serum levels of CCL17, CCL22, and CCL27 were measured with enzyme‐linked immunosolvent assay (ELISA) kits and their correlation with the severity of skin lesions, defined by the scoring atopic dermatitis (SCORAD) index, was analyzed. The amounts of TNF‐α, CCL17, CCL22, and CCL27 in the culture supernatants of PBMC from OVA‐sensitized AD infants after stimulation with OVA were estimated with ELISA kits. Elevated serum CCL17, CCL22, and CCL27 levels significantly correlated with SCORAD index (r = 0.7181, p < 0.001; r = 0.5354, p < 0.005; r = 0.8312, p < 0.0001, respectively). CCL22 levels produced by PBMC from OVA‐sensitized infants with AD reflected serum CCL22 levels. Only six of 30 OVA‐sensitized patients in whom the skin signs increased immediately after OVA intake showed markedly high titers of TNF‐α produced by PBMC after stimulation with OVA. These high TNF‐α titers correlated significantly with serum CCL27 levels (r = 0.7181, p < 0.001). Serum concentrations of CCL17, CCL22, and CCL27 correlate well with the extent and intensity of AD in infants. Of the three Th2 chemokines examined, serum CCL27 correlated most significantly with the severity of AD. Thus, the peripheral immune responses of infantile AD patients are skewed to a Th2 dominant bias.     

Food hypersensitivity in two groups of children and young adults with atopic dermatitis evaluated a decade apart

There is an impression that children today are experiencing allergic reactions to an increasing variety of foods. We compared two separate groups of children and young adults with atopic dermatitis evaluated a decade apart and found no difference in sensitization rates or overall clinical reactivity to a variety of foods. Allergies to egg, milk, wheat, soy, peanut, tree nuts, and seafood continue to account for ≈ 90% of food‐allergic reactions over the past decade.     

Cytokine production, activation marker, and skin homing receptor in children with atopic dermatitis and bronchial asthma

T cells are known to develop a critical role in the pathogenesis of atopic dermatitis (AD) and bronchial asthma. T cells involved in AD express the skin homing receptor CLA, but no lung homing receptor has been identified in bronchial asthma. We compared different cell markers and the cytokine production in T cells from children with AD or bronchial asthma. We studied the involvement of CLA+ and CLA- T-cell subpopulations in these diseases. We studied 20 children with acute AD lesions, 15 with mild persistent asthma, and 15 non-atopic controls. All patients were sensitized to house dust mite (DP) and evaluated during the acute phase. Total and specific IgE were measured by immunoassay and the expression of different cell markers and the cytokine production was analyzed by flow cytometry in peripheral blood mononuclear cells. Total IgE was significantly higher in AD children and IgE to DP in the asthmatic children. There was a significant increase in CD25+ CD4+ cells in asthmatic children and in HLA-DR+ CD4+ and HLA-DR+ CD8+ cells in AD. In the CD4+ subsets, there was an increase in IL-13, IL-5 and TNF-alpha in AD compared to controls, a decrease in IFN-gamma in asthmatic children compared to controls, and an increase in IL-13, IL5, IL2, TNF-alpha, and IFN-gamma in the AD compared to asthmatic children. Changes in cytokine production were mainly detected in CLA+ cells in AD and in CLA- cells in asthma. Differences exist in total and specific IgE, activation markers, and cytokine patterns between AD children and children with asthma, with the former expressing a Th2 pattern whereas in asthmatic children we only detected a decrease in IFN-gamma. Moreover, the subpopulations (CLA+ vs. CLA-) expressing these changes were different, indicating that the underlying mechanisms in the two diseases are not exactly the same.     

Soluble CD30 serum levels in atopic dermatitis and bronchial asthma and its relationship with disease severity in pediatric age

CD30 is a transmembrane molecule that may be expressed on a proportion of activated T-lymphocytes and has been reported to be a marker of Th2 phenotype. A soluble form of CD30 (sCD30) is released by CD30+ cells in vivo. Our objective was to evaluate serum sCD30 levels in children with atopic dermatitis (AD) or bronchial asthma and to investigate its relation to disease severity. This study included of 60 infants and children, of whom 18 had AD, 22 had bronchial asthma and 20 were healthy matched subjects. Severity of AD was assessed according to the objective Scoring Atopic Dermatitis (obj-SCORAD) index. Laboratory investigations included complete blood count, serum total immunoglobulin E (IgE) and serum sCD30 by ELISA. Serum levels of sCD30 in AD (77.7+/-27.9 U/ml) and asthmatic patients (49.2+/-21.5 U/ml) were significantly increased compared with the control group (18.2+/-7.0 U/ml) (t=8.8, p<0.0001; t=6.4, p<0.0001, respectively). In patients with AD, sCD30 levels were shown to correlate with obj-SCORAD (r=0.96, p<0.0001). Patients with moderate persistent asthma had significantly elevated sCD30 levels than those with mild persistent asthma (t=3.4, p<0.01). In addition, sCD30 was inversely correlated to peak expiratory flow rate (r=-0.78, p<0.0001). Levels of sCD30 did not correlate with age, disease duration or serum total IgE (p>0.05). In conclusion, serum sCD30 levels correlate with the severity of AD and bronchial asthma. It appears to be an additional objective marker that may be useful for follow up and may help to improve research and management of these diseases.     

儿童特应性皮炎严重度与维生素D水平的相关性

目的探讨儿童特应性皮炎(AD)疾病严重程度与维生素D水平的相关性。方法纳入152例AD患儿,以AD严重程度评分(SCORAD)评估AD严重度,液相色谱-串联质谱法检测血清25-羟维生素D[25 (OH)D],分析AD严重程度与血清25(OH)D水平的相关性。结果 152例AD患儿中,男81例、女71例,中位年龄3.5岁。轻度、中度、重度AD患儿分别为51例(33.6%)、80例(52.6%)、19例(12.5%)。血清25(OH)D充足55例(36.2%),不足65例(42.8%),缺乏32例(21.1%)。AD患儿SCORAD评分与血清25(OH)D水平无显著相关性(r=-0.047,P=0.567),与血清总IgE呈显著正相关(r=0.244,P=0.003),与血嗜酸性粒细胞比例呈显著正相关(r=0.239,P=0.004)。结论 AD儿童中血清维生素D缺乏和不足者较多,但AD的严重程度与血清25(OH)D水平无显著相关性。     

Web-based consultations for parents of children with atopic dermatitis: results of a randomized controlled trial

Aim: To analyse how web-based consultations for parents of children with atopic dermatitis affect self-management behaviour, health outcome, health resource use and family costs.
Methods: Ninety-eight children with atopic dermatitis were randomly assigned to intervention and control groups. The intervention group received remote dermatology consultations through a secure web-based communication system. The control group was encouraged to seek treatment through traditional means such as general practitioner visits and hospital care. Both groups received an extensive individual educational session prior to the intervention.
Results: Thirty-eight percent of the intervention group used web-based consultations 158 times ranging from 1 to 38 consultations per patient. We found no change in self-management behaviour, health outcome or costs. The intervention group tended to have fewer visits to practitioners offering complementary therapies than the control group, and we found a positive correlation between emergency visits at baseline and messages sent. Both groups, however, reduced the mean number of skin care treatments performed per week and had fewer total health care visits after the intervention.
Conclusion: We found no effect of supplementing traditional treatment for childhood dermatitis with web-based consultations. This study showed that web consultations is feasible, but more research is needed to determine its effect on self-management skills, health outcome and resource use.     

Cutaneous lymphocyte‐associated antigen expression in children with atopic dermatitis and non‐atopic healthy children

Cutaneous lymphocyte‐associated antigen (CLA) is a cell surface glycoprotein which has been implicated in the homing of lymphocytes to cutaneous sites. It is postulated to play an important role in T‐cell migration to skin in atopic dermatitis; however, the expression of CLA in both normal children and children with atopic dermatitis has not been extensively studied. If CLA expression on T cells were important in the traffic of lymphocytes to atopic dermatitis skin lesions, it might be expected that the proportion of CLA⁺ T cells in unstimulated peripheral blood from children with atopic dermatitis would be elevated. We have examined the proportion of CLA⁺ T cells in children with atopic dermatitis and non‐atopic age‐matched controls. The proportion of CLA⁺ T cells in non‐atopic children was highly associated with and increased with increasing age ( r  = 0.88, p < 0.001). There was no difference between the proportion of T cells expressing CLA in the unstimulated PBMC from children with severe or mild/moderate atopic dermatitis and age‐matched non‐atopic controls (p = 0.18, p = 0.3, respectively). Despite this, children with atopic dermatitis did show evidence of perturbation of CLA expression, as unlike the non‐atopic children the proportion of CLA⁺ T cells in the atopic children did not correlate with age. These findings suggest that while CLA expression may play a role in atopic dermatitis, other as yet undefined surface markers are likely to principally determine the migration of T cells to skin in atopic dermatitis.     

Changes in serum lactate dehydrogenase activity in children with atopic dermatitis

Background: In recent years an increase has been seen in the number of patients with severe atopic dermatitis (AD) accompanied with generalized typical eruptions. Some markers indicating the severity of the disease and symptom changes are very useful, and therefore the purpose of the present study was to investigate serum lactate dehydrogenase (LDH) as such a marker. Methods: A total of 58 children with AD were enrolled. The severity of the disease was graded on the basis of the extent of eruptions and the severity of atopic symptoms. The fraction of serum LDH, number of eosinocytes in the peripheral blood, and serum IgE levels were also determined. Results and Conclusion: There was a close correlation between the severity of cutaneous symptoms and serum LDH activity, and between severity and eosinocyte count, but no relationship was seen between serum IgE levels and severity of the disease. The aforementioned factors were determined in a time‐related way. As the patients' condition improved, serum LDH activity tended to decline, but there were no consistent changes in eosinocyte count in the peripheral blood or serum IgE level. On LDH isozyme the levels of LDH4 and LDH5 were high. Tissue showed high LDH activity, especially in epidermides. These results suggest that serum LDH activity is a useful marker.     

Antimicrobial susceptibility of Staphylococcus aureus in children with atopic dermatitis

Background: Skin infection and/or nasal carriage of Staphylococcus aureus in children with atopic dermatitis (AD) is a risk factor for exacerbating disease or subsequent recurrent S. aureus infection. The purpose of the study is to evaluate the antibiotic susceptibilities of S. aureus strains from AD children and determine the most appropriate choice of antibiotics. Methods: Nasal swabs from 168 healthy children with AD and 20 AD children with concurrent skin and soft‐tissue infections (SSTI) were collected in 2005–2008. S. aureus strains were further analyzed for and compared with antibiotic susceptibilities. Results: There were 78 (46.4%) healthy children with AD colonized with S. aureus, and 24 (30.8%) were methicillin‐resistant S. aureus (MRSA). Among the 20 SSTI‐infecting strains, 12 (60%) were MRSA. Antimicrobial susceptibility testing showed that, after penicillin, colonizing and SSTI‐infecting strains had the highest rates of resistance to erythromycin (50% and 70%, respectively). All isolated strains were susceptible to vancomycin, rifampin, and mupirocin. Multi‐drug resistance was found in 70% of the colonizing and 50% of the SSTI‐infecting strains. D‐test assay revealed inducible clindamycin resistance in 75% of the colonizing strains. The most prevalent resistance gene was ermB which was present in 94.9% and 92.9% of colonizing and SSTI‐infecting strains, respectively. Conclusions: This study found that colonizing and SSTI‐infecting strains of S. aureus from AD children had a high prevalence of MRSA and multi‐drug resistance. Trimethoprim‐sulfamethoxazole, rifampin, fusidic acid and mupirocin appear to be more suitable for treatment and decolonization of S. aureus in AD children.     

Reduced plasma c-AMP levels in children with atopic dermatitis

Plasma levels of cAMP and serum concentrations of IgE have been determined in children with acute atopic dermatitis (AD) and in a healthy control group, to illuminate the pathophysiological mechanisms that cause AD.
There were significantly lower plasma levels of cAMP (P < 0,001) and significantly higher levels of serum IgE (P < 0.004) in children with AD, in comparison with a healthy control group. It is possible that defective control of c-AMP levels could contribute to the immunopathogenesis of AD and monitoring levels may be of value in the clinical evaluation of the disease.