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Eczema is a common skin disease associated with inflammation. Interleukin (IL)-24 is crucial in the pathogenesis of inflammatory diseases like eczema. The study objective was the assessment of IL-24 serum levels and its gene polymorphisms in eczematic Iraqi patients. This retrospective case-control study involved 145 participants, divided into 82 patients with eczema and 63 healthy controls. An enzyme-linked immunosorbent assay measured serum IL-24, while polymerase chain reaction and Sanger DNA sequencing were used for genotype analysis. Serum IL-24 level was significantly higher (P value < .001) in patients compared to controls (41.6 [interquartile range (IQR): 28.9-53.6] vs 9.8 [IQR: 0.8-19.6] pg/mL, respectively). DNA sequence illustrated 2 SNPs with polymorphic frequencies (rs1150256 G/A and rs3093425 del/ins). The first SNP (rs1150256 G/A) showed 3 genotypes (GG, AA, and G/A), while the second SNP (rs3093425) showed 3 genotypes (-/G del/Ins, G Ins/Ins, and - del/del). The subsequent investigation revealed the presence of the following findings within the DNA sequence of the PCR amplified region (329bp). In the control group, all participants had GG/G (wild type) genotype/allele for the rs1150256 SNP, while in eczematic patients, 24.4% GG, 50% GA, and 25.6% AA. For the second SNP genotype (rs3093425 del/ins), the genotype frequencies in patients vs control were (24.4% vs 84.1%, 50.0% vs 11.1%, and 25.6% vs 4.8; Del/Del, Del/Ins, and Ins/Ins, respectively). The presence of Ins compared to Del increased the risk of eczema by 8.91 (4.66-17.03); OR (95% CI). In conclusion, IL-24 is a good predictor of eczema and A-allele carrier for rs1150256 SNP, and insertion-allele carrier for rs3093425 SNP is associated with elevated serum IL-24 and higher risk of eczema., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Chronic hand eczema (CHE) is a highly prevalent, heterogeneous, skin disease that encompasses different aetiological and clinical subtypes. Severe CHE without atopic dermatitis has been associated with systemic inflammation; yet it remains unknown if specific CHE subtypes leave distinct, systemic, molecular signatures., Objectives: To characterize the inflammatory plasma signature of different aetiological and clinical CHE subtypes., Methods: We assessed expression levels of 266 inflammatory and cardiovascular disease risk plasma proteins as well as filaggrin gene mutation status in 51 well-characterized CHE patients without concomitant atopic dermatitis and 40 healthy controls. Plasma protein expression was compared between aetiological and clinical CHE subgroups and controls both overall and according to clinical CHE severity. Correlation analyses for biomarkers, clinical and self-reported variables were performed., Results: Very severe, chronic allergic contact dermatitis (ACD) on the hands was associated with a mixed Type 1/Type 2 systemic immune activation as compared with controls. Circulating levels of Type 1/Type 2 inflammatory biomarkers correlated positively with clinical disease severity among CHE patients with ACD. No biomarkers were found, that could discriminate between aetiological subtypes, for example, between ACD and irritant contact dermatitis. Hyperkeratotic CHE showed a distinct, non-atopic dermatitis-like, systemic footprint with upregulation of markers associated with Type 1 inflammation and tumour necrosis factor alpha, but not Type 2 inflammation. Increased levels of CCL19 and CXCL9/10 could discriminate hyperkeratotic CHE from both vesicular and chronic fissured CHE, whereas no difference was found between the latter two subtypes., Conclusion: Profiling of systemic biomarkers showed potential for identifying certain CHE subtypes. Peripheral blood levels of inflammatory biomarkers were associated and correlated with the clinical disease severity of chronic ACD on the hands, underlining that this is a systemic disease. We question whether hyperkeratotic CHE should be classified as eczema., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Early-life vitamin D is a potentially modifiable risk factor for the development of eczema, but there is a lack of data on longitudinal associations., Method: We measured 25(OH)D3 levels from neonatal dried blood spots in 223 high-allergy-risk children. Latent class analysis was used to define longitudinal eczema phenotype up to 25 years (4 subclasses). Skin prick tests (SPTs) to 6 allergens and eczema outcomes at 6 time points were used to define eczema/sensitization phenotypes. Associations between 25(OH)D3 and prevalent eczema and eczema phenotypes were assessed using logistic regression models., Results: Median 25(OH)D3 level was 32.5 nmol/L (P25-P75 = 23.1 nmol/L). Each 10 nmol/L increase in neonatal 25(OH)D3 was associated with a 26% reduced odds of early-onset persistent eczema (adjusted multinomial odds ratio (aMOR) = 0.74, 95% CI = 0.56-0.98) and 30% increased odds of early-onset-resolving eczema (aMOR = 1.30, 95% CI = 1.05-1.62) when compared to minimal/no eczema up to 12 years. Similar associations were seen for eczema phenotype up to 25 years. We did not see any strong evidence for the association between neonatal 25(OH)D3 and prevalent eczema or eczema/sensitization phenotype., Conclusions: Higher neonatal 25(OH)D3 levels, a reflection of maternal vitamin D levels in pregnancy, may reduce the risk of early-onset persistent eczema.

Facial eczema (FE) is a significant metabolic disease that affects New Zealand ruminants. Ingestion of the mycotoxin sporidesmin leads to liver and bile duct damage, which can result in photosensitisation, reduced productivity and death. Strategies used to manage the incidence and severity of the disease include breeding. In sheep, there is considerable genetic variation in the response to FE. A commercial testing program is available for ram breeders who aim to increase tolerance, determined by the concentration of the serum enzyme, gamma-glutamyltransferase 21 days after a measured sporidesmin challenge (GGT21). Genome-wide association studies were carried out to determine regions of the genome associated with GGT21. Two regions on chromosomes 15 and 24 are reported, which explain 5% and 1% of the phenotypic variance in the response to FE, respectively. The region on chromosome 15 contains the β-globin locus. Of the significant SNPs in the region, one is a missense variant within the haemoglobin subunit β ( HBB ) gene. Mass spectrometry of haemoglobin from animals with differing genotypes at this locus indicated that genotypes are associated with different forms of adult β-globin. Haemoglobin haplotypes have previously been associated with variation in several health-related traits in sheep and warrant further investigation regarding their role in tolerance to FE in sheep. We show a strategic approach to the identification of regions of importance for commercial breeding programs with a combination of discovery, statistical and biological validation. This study highlights the power of using increased density genotyping for the identification of influential genomic regions, combined with subsequent inclusion on lower density genotyping platforms.

It has been shown that aerobic exercise improves atopic dermatitis (AD), although the mechanism is not clear. Here, we propose a hypothesis that moderate-intensity aerobic exercise improves AD in a mouse model through modulating allergic inflammation. The DNCB-treated mouse model for eczema was divided into 3 groups: (a) not subjected to aerobic exercise, (b) subjected to continuous aerobic exercise and (c) subjected to accumulated aerobic exercise. After given exercise using a treadmill device either 30 min/d or 10 min × 3/day at a speed of 16 m/min, for 9 days, respectively, dermatitis symptom score, thickness of epidermis/dermis and eosinophil infiltration were decreased in the 2 exercise groups compared to the sedentary living group. The serum levels of IgE, MCP-1 and MDC showed a significant decrease both in the continuous or accumulated exercise groups. Moderate-intensity aerobic exercise ameliorates dermatitis symptoms through immune modulation in the DNCB-treated mouse model for eczema., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: T helper (Th) type 17 and Th2 cells mediate psoriasis and eczema, respectively. Some dermatoses exhibit overlapping clinicopathologic features, and their immunopathology is relatively unexplored., Objective: To determine whether Th17 and Th2 subsets and interleukin (IL) 36 and β-defensin 2 (BD-2) markers of IL-17 signaling expression can discriminate between biopsy samples of psoriasis and eczematous/spongiotic dermatitis and to use those markers to immunophenotype cases with clinicopathologic overlap., Methods: A retrospective study was performed on biopsy samples of psoriasis, eczema/spongiotic dermatitis, sebopsoriasis, tumor necrosis factor α inhibitor-associated psoriasiform dermatitis, and ambiguous cases diagnosed as spongiotic psoriasiform dermatitis. Dual CD4/GATA3 and CD4/RORC, IL-36, and BD-2 immunohistochemistry was performed., Results: IL-36 and BD-2 were strongly expressed in biopsy samples of psoriasis compared with eczema/spongiotic dermatitis. No significant differences were observed in the percentages of Th2 and Th17 cells between disease types. Strong expression of IL-36 and BD-2 was observed in a subset of spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor-associated psoriasiform dermatitis biopsy samples., Limitations: This was an exploratory study with a small sample size. No multiple testing adjustment was done. Clinical follow-up was limited., Conclusions: In cases with clinicopathologic overlap between psoriasis and spongiotic dermatitis, IL-36, and to a lesser extent BD-2, may be used to assess for a psoriasis-like/IL-17 phenotype, which could inform therapeutic clinical decisions., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Neonatal antibiotics disturb the developing gut microbiome and are therefore thought to influence the developing immune system, but exact mechanisms and health consequences in later life still need to be elucidated. Therefore, we investigated whether neonatal antibiotics influence inflammatory markers at 1 year of age. In addition, we determined whether health problems during the first year of life, e.g., allergic disorders (eczema and wheezing) or infantile colics, were associated with changes in the circulating immune marker profile at 1 year of age. Methods: In a subgroup ( N = 149) of the INCA-study, a prospective birth-cohort study, a blood sample was drawn from term born infants at 1 year of age and analyzed for 84 immune related markers using Luminex. Associations of antibiotic treatment, eczema, wheezing, and infantile colics with immune marker concentrations were investigated using a linear regression model. The trial is registered as NCT02536560. Results: The use of broad-spectrum antibiotics in the first week of life, was significantly associated with different levels of inflammatory markers including sVCAM-1, sCD14, sCD19, sCD27, IL-1RII, sVEGF-R1, and HSP70 at 1 year of age. Eczema was associated with decreased concentrations of IFNα, IFNγ, TSLP, CXCL9, and CXCL13, but increased concentrations of CCL18 and Galectin-3. Wheezing, independent of antibiotic treatment, was positively associated to TNF-R2 and resistin. Infantile colics were positively associated to IL-31, LIGHT, YKL-40, CXCL13, sPD1, IL1RI, sIL-7Ra, Gal-1, Gal-9, and S100A8 at 1 year of age, independent of early life antibiotic treatment. Conclusion: In this explorative study, we identified that neonatal antibiotics are associated with immunological alterations at 1 year of age and that, independent of the antibiotic treatment, infantile colics were associated with alterations within gut associated markers. These findings support the importance of the first host microbe interaction in early life immune development., (Copyright © 2020 Oosterloo, van't Land, de Jager, Rutten, Klöpping, Garssen, Vlieger and van Elburg.)

Eczema and food allergy may impact diet. Using data from a cohort of Manitoba children born in 1995, we examined calcium intake, defined as the frequency and quality of calcium products consumed (with the exception of cheese), amongst Manitoba adolescents (12-14 years) with eczema or food allergy in childhood (7-8 years) or adolescence. At both ages, children were assessed by a physician for eczema and food allergy. Adolescents completed food frequency questionnaires. Calcium intake was defined as 1+ vs. <1 weekly. Linear and logistic regression was used as appropriate, with adjustments for confounders. Overall, 468 adolescents were included, of whom 62 (13.3%) had eczema only in childhood, 25 (5.3%) had food allergy only, and 26 (5.6%) had eczema and food allergy. Compared to children without eczema, those with eczema only had poorer calcium intake in adolescence (β -0.44; 95%CI -0.96; 0.00). Girls, but not boys, with eczema in childhood had poorer calcium intake in adolescence than girls without eczema (β -0.84; 95%CI -1.60; -0.08). These patterns persisted even if children experienced transient vs. persistent eczema to adolescence. Similar but non-significant trends were found for food allergy. Childhood eczema is associated with significantly lower calcium intake and consumption in adolescence. These differences persist to adolescence, even if a child "outgrows" their allergic condition., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Nipple eczema is a less common presentation of atopic dermatitis. No studies in the literature have correlated nipple eczema in pregnancy as a manifestation of atopic dermatitis., Objective: To evaluate whether nipple eczema presenting in pregnancy is a manifestation of atopic dermatitis., Methods: This was a prospective observational study including 100 women who presented with nipple eczema for the first time during pregnancy. The exclusion criteria were any patient with previous history of nipple eczema, those already on oral or topical treatment for atopic dermatitis or nipple eczema, and other disorders mimicking eczema. Patients were divided into two groups ‒ nipple eczema with atopic dermatitis and without atopic dermatitis. Demographic data, clinical features, total leukocyte count, differential leukocyte count, absolute eosinophil counts, and serum IgE levels were compared between the two groups to detect association between nipple eczema in pregnancy and atopic dermatitis., Results: Out of 100 patients, 39 were diagnosed with atopic dermatitis, whereas 61 were ruled out to have any features suggestive of atopic dermatitis. There were no statistically significant differences in mean age, mean duration of symptoms, and serum IgE levels. In patients with atopic dermatitis, bilateral symptoms were noted more commonly than in patients without the disease, but this was statistically insignificant., Study Limitations: Lack of long term follow-up and no large studies in literature to compare results., Conclusion: Nipple eczema in pregnancy follows a similar pattern as in other age groups. The clinical profile of patients is similar in cases with and without atopic dermatitis., (Copyright © 2019. Published by Elsevier España, S.L.U.)

Native C-reactive protein (nCRP) is a non-specific marker of inflammation being claimed as a bystander in several chronic disorders. Accumulating evidence indicates that nCRP dissociates to and acts primarily as the monomeric conformation (mCRP) at inflammatory loci. This suggests that mCRP may be a superior disease marker with improved specificity and clear causality to the underlying pathogenesis. However, the lack of a feasible assay to quantify mCRP in clinical samples precludes the assessment of that suggestion. Here we report the development of a sandwich ELISA assay for quantification of plasma mCRP using commercially available reagents. Our assay is reproducible and highly conformation-specific showing a reliable detection limit of 1 ng/mL. We further show that mCRP appears to be a better marker than nCRP in several skin-related autoimmune disorders. This assay thus provides a useful tool to examine the clinical significance and utility of mCRP.

Background & Aims: A role of vitamin D in the development of respiratory and allergic disease in children remains unclear. It may be likely that vitamin D has an effect on airway inflammation, but only few studies examined the effect in children. We aimed to examine whether serum 25-hydroxyvitamin D (25(OH) vitamin D) concentrations are associated with the fraction of exhaled nitric oxide (FeNO), airway interrupter resistance (Rint), physician diagnosed asthma ever, wheezing and eczema in a population-based cohort study in 6 year old children., Methods: Serum 25(OH) vitamin D concentration was assessed in 3815 children. 25(OH) vitamin D concentrations ≥75 nmol/L were considered as sufficient, between 50 and 75 nmol/L as insufficient, and <50 nmol/L as deficient. FeNO and Rint were measured at the research center. Data on physician diagnosed asthma, wheezing, and eczema were obtained by parent-reported questionnaires., Results: In comparison with sufficient 25(OH) vitamin D concentration, deficient concentrations were associated with elevated FeNO of ≥25 ppb (OR: 2.54; 95% CI: 1.34-4.80). In addition, deficient and insufficient 25(OH) vitamin D concentrations were associated with a lower Rint (Z-score: -1.26; 95% CI: -1.66 to -0.85) (ß: -0.75; 95% CI: -1.08 to -0.42), and increased risks of eczema (OR: 1.65; 95% CI: 1.13-2.41) (OR: 1.44; 95% CI: 1.06-1.95). Insufficient 25(OH) vitamin D concentration were associated with a decreased risk of physician diagnosed asthma ever (OR: 0.59; 95% CI: 0.38-0.94)., Conclusions: Our results indicate that lower 25(OH) vitamin D levels are associated with elevated FeNO levels, but lower Rint values. Lower 25(OH) vitamin D levels are also associated with a decreased risk for asthma diagnoses but an increased risk for eczema., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The research was conducted with participation of the perlite production workers with professional eczema (165 people in the main group and 152 from the control group without skin pathology). The effectiveness of the use of a specialized prophylactic food in the diet of workers was assessed on the basis of the study of the dynamics of the indicators of nutritional and clinical status. Inclusion of kissel, containing pectin, vitamin A (300% from RDA), vitamin E and zinc (40% from RDA), biologically active substances of plant origin in the diet of the examined against the background of the course of complex therapy, has resulted in a positive influence on individual laboratory values, demonstrating the optimization of metabolic processes, which characterize the pathogenesis of skin inflammation. Thus, the concentration of ascorbic acid in blood serum statistically significant (p<0.05) increased by 30.0%, tocopherol - by 36.3%, carotenoids - by 27.3%, phosphorus - by 28.9%, calcium level elevated by 16.3% (p<0.10). There was a decrease in the level of MDA in blood serum by 12.3% (p<0.05) and an increase in catalase activity by 12.2% (p>0.05). There was a tendency to reduce itching, infiltration, erythematous and eczematous manifestations of the disease. The data obtained make it possible to consider the use of a specialized food product of dietary preventive nutrition by workers in pearlite production as a mean to enhance the body's adaptive reserves and to prevent the occurrence, progression and development of occupational skin diseases (eczema) in the workplace., (Copyright© GEOTAR-Media Publishing Group.)

Background: Vitamin D insufficiency (defined as <75 nmol l -1 ) is widespread among pregnant women around the world and has been proposed to influence offspring outcomes in childhood and into adult life, including adiposity and allergy. Disorders, including asthma and eczema, are on the rise among children. Our aim was to investigate the relationship between maternal 25-hydroxyvitamin D status in pregnancy and offspring adiposity, asthma and eczema in childhood., Subjects and Methods: Maternal 25-hydroxyvitamin D concentrations were analysed in serum samples collected at 15 weeks' gestation from 1710 participants of the prospective Screening for Pregnancy Endpoints cohort study. The offspring of 1208 mothers were followed up at age 5-6 years. Data collected included height, weight, percentage body fat (PBF, measured by bioimpedance) and history of asthma and eczema. Multivariable analysis controlled for maternal body mass index (BMI), age and sex of the child and season of serum sampling., Results: Complete data were available for 922 mother-child pairs. Each 10 nmol l -1 increase in maternal 25-hydroxyvitamin D concentration at 15 weeks' gestation was associated with a decrease in offspring PBF of 0.2% (95% confidence interval 0.04-0.36%, P=0.01) after adjustment for confounders but was not related to child BMI z-score. Maternal mean (±s.d.) 25-hydroxyvitamin D concentration was similar in children who did and did not have asthma (71.7±26.1 vs 73.3±27.1 nmol l -1 , P=0.5), severe asthma (68.6±28.6 vs 73.3±26.8 nmol l -1 , P=0.2) and eczema (71.9±27.0 vs 73.2±27.0 nmol l -1 , P=0.5)., Conclusions: The finding of a relationship between maternal vitamin D status and adiposity in childhood is important, particularly because vitamin D insufficiency in pregnancy is highly prevalent. The association between maternal vitamin D supplementation in pregnancy and adiposity in the offspring merits examination in randomised controlled trials.

Substance P (SP) was reported to be associated with eczema and acts as a potent skin mast cell secretagogue. However, little is known of its expression in inflammatory cells in eczema and its ability in induction of mast cell accumulation. In the present study, we investigated expression of SP and neurokinin-1 receptor (NK1R) on peripheral blood leukocytes and mast cells from patients with eczema and influence of SP on mast cell accumulation by using flow cytometry analysis, trans-epithelial cell migration assay and mouse peritoneal model. The results showed that plasma SP and IL-17A levels in eczema patients were higher than that in healthy control subject. The percentages of SP+ and NK1R+ expression populations of monocytes, helper T cells, natural killer T cells and basophils in peripheral blood of eczema patients were markedly elevated. It was observed that not only absolute number of mast cells but also SP+ and NK1R+ mast cells are enhanced in the lesion skin of eczema. SP showed a potent chemoattractant action on mast cells as assessed by a mouse peritoneal model and a trans-endothelium cell migration assay. SP-induced mast cell accumulation appears a CD18/CD11a complex, L-selectin and ICAM-1-dependent event which can be blocked by a NK-1R antagonist RP67580. In conclusion, elevated expression of SP in patients with eczema and the ability of SP in induction of mast cell accumulation indicate strongly that SP is a potent proinflammatory mediator, which contributes to the pathogenesis of eczema. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of eczema.

IL-18 has been found to be associated with eczema. However, little is known of the role of IL-18 binding protein (BP) and IL-18 receptor (R) in eczema. We therefore investigated the expression of IL-18, IL-18BP, and IL-18R on mast cells by using flow cytometry analysis and mouse eczema model. The results showed that plasma free IL-18 and free IL-18BP levels in eczema patients were higher than those in healthy controls. IL-18 provoked up to 3.1-fold increase in skin mast cells. IL-18 induced also an increase in IL-18BP+ mast cells, but a reduction of IL-18R+ mast cells in mouse eczema skin. It was found that house dust mite allergen Der p1 and egg allergen OVA induced upregulation of the expression of IL-18, IL-18BP, and IL-18R mRNAs in HMC-1 cells following 2 and 16 h incubation. In conclusion, correlation of IL-18 and IL-18BP in eczema plasma suggests an important balance between IL-18 and IL-18BP in eczema. The decrease in molar concentration ratio of plasma IL-18BP/IL-18 and allergen-induced upregulated expression of IL-18 and IL-18R in skin mast cells of the patients with eczema suggests that anti-IL-18 including IL-18BP therapy may be useful for the treatment of eczema.

Background/aim: Psoriasis as multisystemic inflammatory dis-ease is related with an increased cardiometabolic risk. The aim of the study was to analyze risk biomarkers, peripheral and renal arteries ultrasonography and echocardiography for subclinical atherosclerosis and metabolic disease in 106 subjects (66 psoriasis patients and 40 controls, 20 eczema patients and 20 healthy volunteers)., Methods: In all exameenes following parameters were analyzed: body mass index (BMI), C-reactive protein, D-dimer, serum amyloid A (SAA), apolipoprotein (Apo) A1, ApoB, ApoB/Apo A1 index, fasting glucose, C-peptide, fasting insulinemia, homeostatic model assessment-insulin resistance (HOMA-IR), HOMA-β-cell, lipid profile, serum uric acid concentration (SUAC), 24-h proteinuria and microalbuminuria. Carotid, brachial, femoral and renal arteries ultrasonography, as well as echocardiography was also performed., Results: Five of 66 (7.6%) psoriasis patients had metabolic syndrome (not present in both control groups). The following variables were increased in patients with psoriasis compared to both control groups: BMI (p = 0.012), insulinemia (p < 0.001), HOMA-IR (p = 0.003), HOMA-β cell (p < 0.001), SUAC (p = 0.006), ApoB/ApoA1 ra-tio (p = 0.006) and microalbuminuria (p < 0.001). Also, increased C-peptide (p = 0.034), D-dimer (p = 0.029), triglycerides (p = 0.044), SAA (p = 0.005) and decreased ApoA1 (p = 0.014) were found in the psoriasis patients compared to healthy controls. HDL cholesterol was decreased in the psoriasis patients compared to the control group of eczema patients (p = 0.004). Common carotid (CIMT) and femoral artery intima-media thickness (FIMT) was significantly greater (p < 0.001) and the maximal flow speed (cm/s) in brachial artery significantly de-creased (p = 0.017) in the patients with psoriasis in comparison to both control groups. In multivariate logistic regression analysis, after the adjustment for confounding variables, the most important predictor of CIMT and FIMT was the diagnosis of psoriasis (p < 0.001).., Conclusion: Cardiometabolic risk biomarkers and ultrasonographic signs of early atherosclerosis are correlated with the diagnosis of psoriasis, and not to generalized eczema. Psoriasis was found to be an independent risk factor for subclinical atherosclerosis

Aims: To describe and evaluate the current practices used to manage and prevent facial eczema (FE) in North Island dairy herds, and determine the within-herd prevalence of cows with elevated activities of gamma glutamyl transferase (GGT), and with concentrations of Zn in serum <18 μmol/L., Methods: Between January and May 2014, 105 herd managers from throughout the North Island of New Zealand were invited to participate in the study when regional spore counts for Pithomyces chartarum started to rise towards 30,000 spores/g pasture. Managers selected 10 representative cattle that were weighed and blood-sampled by the herd veterinarian. Blood samples were analysed for concentrations of Zn in serum and GGT activity. Pasture samples were also collected and submitted for spore count estimation. Finally a survey of farm management practices relating to prevention of FE was completed by the herd manager. A mixed-effects logistic regression model was used to determine associations between herd-level and cow-level explanatory variables and the probability of a cow having a concentration of Zn in serum <18 µmol/L., Results: Of the 1,071 cows tested, 79 (7.3 (95% CI=5.8-9.0)%) had GGT activity in serum >300 IU/L, and 35/106 (33 (95% CI=24.2-42.8)%) herds had ≥1 of the 10 cows sampled with GGT activity >300 IU/L. Of the 911 cows that were being treated with Zn, concentrations of Zn were between 18-35 μmol/L in 398 (43.6 (95% CI=40.4-46.9)%) cows, were >35 μmol/L in 32 (3.5 (95% CI=2.4-4.1)%) cows, and <18 μmol/L in 479 (52.6 (95% CI=49.3-55.9)%) cows. After adjusting for the confounding effect of region, the odds of a cow having concentrations of Zn in serum <18 μmol/L were 5.5 (95% CI=1.1-29) times greater for cows supplemented with zinc in water compared with those supplemented by drenching. Of the 105 herd managers, 103 (98%) stated that they had access to regional spore count data, but only 35/105 (33%) reported that they measured spore counts on their own farm. Overall, 98/105 (93%) managers reported that they had some form of FE management programme in place. Fungicides were used on their own or in combination with zinc treatments in 10 herds, ZnSO4 in water troughs was used in 68 herds, oral drenching with ZnO in nine herds, and ZnO supplied in-feed in 26 herds. Estimated daily dose rates of zinc were less than that required to treat a 400 kg cow on 42/68 farms that administered ZnSO4 in the water or ZnO as a drench., Conclusion and Clinical Relevance: This study has shown that FE management on dairy farms in the North Island of New Zealand could be substantially improved. It is likely that improved FE management would occur if herd managers were provided with more feedback on the success (or otherwise) of their FE management programmes.

Background: Atopic eczema is a common childhood disease associated with high IgE and eosinophilia. We characterized the clinical features associated with hyper-IgE (defined as IgE > 2000 IU/L) in eczema., Methods: Nottingham Eczema Severity Score (NESS), family and personal history of atopy, skin prick test (SPT) for common food and aeroallergens, highest serum IgE ever and eosinophil counts were evaluated in 330 children eczema patients. Childhood-NESS (NESS performed at <10 years of age) and adolescent-NESS (NESS performed at >10 years of age) were further analyzed., Results: IgE correlated with NESS (spearman coefficient 0.35, p < 0.001) and eosinophil percentage (spearman coefficient 0.56, p = 0.001). Compared with IgE ≤ 2000IU/L (n = 167), patients with hyper-IgE (n = 163) were associated with male gender (p = 0.002); paternal atopy (p = 0.026); personal history of atopic rhinitis (p = 0.016); asthma (p < 0.001); dietary avoidance (p < 0.001); use of wet wrap (p < 0.001); traditional Chinese medicine use (TCM, p < 0.001); immunomodulant use (azathioprine or cyclosporine, p < 0.001); skin prick sensitization by dust mites (p < 0.001), cats (p = 0.012), dogs (p = 0.018), food (p = 0.002); eosinophilia (p < 0.001); more severe disease during childhood (p < 0.0001) and during adolescence (p < 0.0001), but not onset age of eczema or maternal atopy. Logistic regression showed that hyper-IgE was associated with personal history of asthma (exp(B) = 5.12, p = 0.002) and eczema severity during childhood and adolescence (p < 0.001). For patients <10 years of age, dust mite sensitization (p = 0.008) was associated with hyper-IgE. For patients >10years of age, food allergen sensitization was associated with hyper-IgE (p = 0.008)., Conclusions: Hyper-IgE is independently associated with asthma, more severe atopy and more severe eczema during childhood and adolescence. IgE > 2000 IU/L may be a tool to aid prognostication of this chronic relapsing dermatologic disease and its progression to asthma.

Background: Exposure to low levels of vitamin D in fetal life might affect the developing immune system, and subsequently the risk of childhood eczema. We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with the risk of eczema until the age of 4 years., Methods: In a population-based prospective cohort study of 3019 mothers and their children, maternal blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxyvitamin D levels (severely deficient <25.0 nmol/l, deficient 25.0-49.9 nmol/l, sufficient 50.0-74.9 nmol/l, optimal ≥75.0 nmol/l). Eczema was prospectively assessed by annual questionnaires until the age of 4 years. Eczema patterns included never, early (age ≤1 year only), late (age >1 year only), and persistent eczema (age ≤ and >1 year). Data were assessed using the generalized estimating equations and multinomial regression models., Results: Compared with the optimal 25-hydroxyvitamin D group, sufficient, deficient, and severely deficient groups of 25-hydroxyvitamin D level in mid-gestation were not associated with the risk of overall eczema (odds ratios [95% confidence interval]: 1.09 [0.82, 1.43], 1.04 [0.87, 1.25], and 0.94 [0.81, 1.10], p-values for trend >0.05), nor with eczema per year or eczema patterns in children up to the age of 4 years. Similarly, we observed no associations of 25-hydroxyvitamin D groups at birth with any eczema outcome., Conclusion: Our results suggest that levels of 25-hydroxyvitamin D in mid-gestation and at birth are not associated with the risk of overall eczema, eczema per year, or eczema patterns among children until the age of 4 years., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Population attributable risks from serum IgE and dust miteallergen concentrations and environmental chemicals for eczema are unclear. Therefore, it was aimed to examine serum IgE and allergen concentrations and environmental chemicals for eczema in adults and to calculate population attributable risks in a national and population-based setting. Data retrieved from the National Health and Nutrition Examination Survey, 2005-2006, was analyzed. Information on demographics and self-reported ever eczema was obtained by household interview. Bloods and urines (sub-sample) were also collected during the interview. Adults aged 20-85 were included. Statistical analyses were using chi-square test, t test, survey-weighted logistic regression modeling, and population attributable risk (PAR) estimation. Of all the included American adults (n = 4979), 310 (6.2%) reported ever eczema. Moreover, more eczema cases were observed in female adults but fewer cases in people born in Mexico. There were no significant associations observed between commonly known biomarkers (including vitamin D) and eczema or between dust mite allergens and eczema. Serum D. Farinae (PAR 1.0%), D. Pteronyssinus (PAR 1.1%), cat (PAR 1.8%), dog (PAR 1.6%), and muse (PAR 3.2%) IgE antibodies were associated with eczema. Adults with ever eczema were found to have higher levels of urinary trimethylarsine oxide concentrations (PAR 7.0%) but not other speciated arsenic concentrations. There were no clear associations between other environmental chemicals including heavy metals, phthalates, phenols, parabens, pesticides, nitrate, perchlorate, polycyclic hydrocarbons and eczema as well. Elimination of environmental risks might help delay or stop eczema up to 7% in the adult population.

Purpose of Review: The role of vitamin D in the development of food allergy is unclear. We summarize recent data on the epidemiologic link between sunlight (UVB) and food allergy, and evidence for and against a specific role for vitamin D status., Recent Findings: Since 2007, most epidemiologic studies have supported low sunlight (as measured by season of birth and latitude) as a risk factor for food allergy. Investigators have also looked directly at vitamin D status (as measured by serum 25OHD level) and its potential role. Although conflicting, the vitamin D studies suggest a more complicated association than a linear dose response in all individuals, with some studies indicating different associations based on host characteristics (e.g. concominant eczema, genetic polymorphisms, country of birth). Most studies have not fully examined the myriad effects of sunlight but have instead focused on a single maternal, neonatal or childhood 25OHD level., Summary: Many studies have linked sunlight with the development of food allergy but whether this is directly related to vitamin D status or a myriad of other sunlight-derived, seasonal and/or geographic factors remains uncertain. More studies are needed to investigate the role of sunlight and vitamin D status in food allergy because of their potential for primary prevention and disease modification.

Objective: to study the evolution of the oxidant-antioxidant homeostasis indices in patients with eczema using various methods of treating dermatosis. The study involved 63 patients with eczema (34 - males, 28 - females), aged 18-67 years, who were determined indices of pro- and antioxidant systems of blood. Patients with eczema were divided into 3 groups that were prescribed different treatments: the first comparative group (21 patients) - received a standard therapy; the second comparative group (20 patients) - had a standard therapy and additionally an antioxidant preparation "Mexidol", the third (basic group) - 22 patients, who were prescribed a complex therapy with a combination of two drugs with antioxidant effect: "Mexidol" and "Galavit." It was established that multimodality therapy for eczema while using two drugs with antioxidant action ("Mexidol", "Galavit") contributes to the most significant positive dynamics and normalization of the studied parameters of oxidant-antioxidant homeostasis of patients compared to a standard therapy of dermatosis or its combination with antioxidant preparation "Mexidol".

Background: Eczema is one of the most common chronic inflammatory skin diseases, affecting about 20% of children. The pathogenic mechanisms of eczema are still not fully understood, and current treatment of moderate-severe eczema is often difficult. Recently, it has been suggested that Vitamin D plays a key role in this disease, even if mechanisms are only partially known., Objective: The purpose of our study was to assess the 25-Hydroxyvitamin D serum levels in a pediatric population suffering from chronic eczema (IgE-mediated and non-IgE-mediated), and to correlate these phenotypes with the SCORAD severity and selected clinical and biological parameters. Moreover, we aimed to evaluate whether a supplementation of Vitamin D3 could affect the same clinical and laboratory parameters., Methods: 89 children with chronic eczema were enrolled in the study. Severity of eczema was assessed with the SCORAD index. Past and present history was taken, and patients were divided into two groups according to the state of sensitization. According to a randomization schedule, the enrolled children were assigned to the following groups: supplementation group, which received a daily oral Vitamin D3 supplementation (2000 IUs) for 3 months; control group which received no supplementation., Results: Vitamin D concentrations in patients with moderate and severe eczema were not statistically different from Vitamin D concentration detected in the serum of patients with mild eczema. Furthermore, we did not find any correlation between Vitamin D levels, total IgEs and SCORAD index, both in the Sensitized and in the Not-Sensitized group. The Vitamin D3 supplementation did not influence the SCORAD severity or the total IgEs concentration., Conclusion: To our knowledge, our study is the first one that shows no correlation between serum levels of Vitamin D, eczema severity and IgE sensitization in a pediatric population suffering from chronic eczema.

Background: Rhinitis affects many young adults and often shows comorbidity with asthma., Objective: We hypothesized that young adult rhinitis, like asthma, exhibits clinical heterogeneity identifiable by means of cluster analysis., Methods: Participants in the Isle of Wight birth cohort (n = 1456) were assessed at 1, 2, 4, 10, and 18 years of age. Cluster analysis was performed on those with rhinitis at age 18 years (n = 468) by using 13 variables defining clinical characteristics., Results: Four clusters were identified. Patients in cluster 1 (n = 128 [27.4%]; ie, moderate childhood-onset rhinitis) had high atopy and eczema prevalence and high total IgE levels but low asthma prevalence. They showed the best lung function at 18 years of age, with normal fraction of exhaled nitric oxide (Feno), low bronchial hyperresponsiveness (BHR), and low bronchodilator reversibility (BDR) but high rhinitis symptoms and treatment. Patients in cluster 2 (n = 199 [42.5%]; ie, mild-adolescence-onset female rhinitis) had the lowest prevalence of comorbid atopy, asthma, and eczema. They had normal lung function and low BHR, BDR, Feno values, and total IgE levels plus low rhinitis symptoms, severity, and treatment. Patients in cluster 3 (n = 59 [12.6%]; ie, severe earliest-onset rhinitis with asthma) had the youngest rhinitis onset plus the highest comorbid asthma (of simultaneous onset) and atopy. They showed the most obstructed lung function with high BHR, BDR, and Feno values plus high rhinitis symptoms, severity, and treatment. Patient 4 in cluster 4 (n = 82 [17.5%]; ie, moderate childhood-onset male rhinitis with asthma) had high atopy, intermediate asthma, and low eczema. They had impaired lung function with high Feno values and total IgE levels but intermediate BHR and BDR. They had moderate rhinitis symptoms., Conclusion: Clinically distinctive adolescent rhinitis clusters are apparent with varying sex and asthma associations plus differing rhinitis severity and treatment needs., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Recently, CC chemokine ligand28 (CCL28) has been reported as a severity marker in atopic dermatitis. We studied the association between objectively observed lesions and the level of CCL28 in children patients., Methods: A total of 105 children patients were grouped by the objective Scoring Atopic Dermatitis index (SCORAD). Total IgE, specific IgE, complete blood count, and serum level of CCL28 were evaluated., Results: The mean age of the subjects was 5.3 (range, 0 - 12 years). The median SCORAD was 21.4 and consisted of mild 70%, moderate 25%, and severe 6% disease. There were no statistical differences among severity groups for CCL28 or for total IgE. Total IgE showed positive correlation with eosinophil count (r = 0.429, p < 0.01), and SCORAD (r = 0.210, p < 0.05)., Conclusions: The disease severity of atopic dermatitis in children is not correlated to the level of CCL28, but rather related to that of total IgE.

Background: Specific immunoglobulins G and A (IgG and IgA) for common food items have been extensively measured as surrogate markers of food allergy, and dietary avoidance based on the test results advocated., Aim: We reviewed the prevalence of specific food IgG and IgA in children with eczema and evaluated outcome of dietary avoidance in these children., Methods: Specific immunoglobulins of 96 food items were measured for 30 consecutive atopic dermatitis (AD) patients and disease severity [SCORing atopic dermatitis (SCORAD) and Nottingham eczema severity score (NESS)], Children Dermatology Life Quality Index (CDLQI), skin hydration (SH), transepidermal water loss (TEWL), topical corticosteroid and oral antihistamine usage were evaluated. Twenty seven of these patients received dietary avoidance advice based on IgG and IgA data. General acceptability of treatment (GAT) was documented at the end of 3 months., Results: There were generally no correlations among levels of IgG or IgA of the 96 food items and disease severity, quality of life, SH or TEWL. Two-third patients reported very good or good and one-third reported fair or poor GAT following dietary avoidance advice. There was no difference in any clinical parameters between the two groups following dietary avoidance. Patient with lower sunflower seed IgA (p = 0.043), casein IgG (p = 0.041), milk IgG (p = 0.037) or whey IgG (p = 0.014) had improved SCORAD and objective SCORAD following dietary advice., Conclusion: Children with AD are sensitized to many food allergens via IgG and IgA mechanisms. Levels of food IgG or IgA do not seem to correlate with any clinical parameters in AD. Subjectively, two third of patients accepted dietary manipulations as very good or good for their AD. Objectively, dietary avoidance had few clinical effects on the clinical parameters. Sensitization should not be generalized to mean allergy to common food.

Background: Epidemiological studies have suggested an association between maternal vitamin D dietary intake during pregnancy and risk of asthma and allergy in the offspring. However, prospective clinical studies on vitamin D measured in cord blood and development of clinical end-points are sparse., Objective: To investigate the interdependence of cord blood 25-hydroxyvitamin D (25(OH)-Vitamin D) level and investigator-diagnosed asthma- and allergy-related conditions during preschool-age., Methods: Cord blood 25(OH)-Vitamin D level was measured in 257 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) at-risk mother-child cohort. Troublesome lung symptoms (TROLS), asthma, respiratory infections, allergic rhinitis, and eczema, at age 0-7 yrs were diagnosed exclusively by the COPSAC pediatricians strictly adhering to predefined algorithms. Objective assessments of lung function and sensitization were performed repeatedly from birth., Results: After adjusting for season of birth, deficient cord blood 25(OH)-Vitamin D level (<50 nmol/L) was associated with a 2.7-fold increased risk of recurrent TROLS (HR = 2.65; 95% CI = 1.02-6.86), but showed no association with respiratory infections or asthma. We saw no association between cord blood 25(OH)-Vitamin D level and lung function, sensitization, rhinitis or eczema. The effects were unaffected from adjusting for multiple lifestyle factors., Conclusion: Cord blood 25(OH)-Vitamin D deficiency associated with increased risk of recurrent TROLS till age 7 years. Randomized controlled trials of vitamin D supplementation during pregnancy are needed to prove causality.

Background: Mouse models of atopic march suggest that systemic, skin-derived thymic stromal lymphopoietin (TSLP) mediates progression from eczema to asthma., Objective: We investigated whether circulating TSLP is associated with eczema, allergic sensitization, or recurrent wheezing in young children., Methods: A prospective analysis of the relationship between plasma levels of TSLP to allergic sensitization and recurrent wheezing was conducted in the birth cohort from the Urban Environment and Childhood Asthma (URECA) study. Plasma TSLP levels were measured at 1, 2, and 3 years of age and analysed for correlation with clinical parameters in each of the three years. Only those children with consecutive samples for all three years were included in this analysis., Results: We detected TSLP in 33% of 236 children for whom plasma samples were available for all three years. Overall, a consistently significant association was not found between TSLP and eczema or allergic sensitization. With regard to recurrent wheezing, children with detectable TSLP at one year of age were significantly less likely to experience recurrent wheezing by 3 years compared with those children without detectable TSLP, but this was only seen in children without aeroallergen sensitization at 3 years (P < 0.01)., Conclusions and Clinical Relevance: Contrary to our expectations, circulating TSLP was not significantly associated with eczema, allergen sensitization, or recurrent wheezing during the first three years of life. Early presence of circulating TSLP was significantly associated with reduced incidence of recurrent wheeze in those children not sensitized to aeroallergen. These findings suggest a possible underlying distinction between pathogenesis of developing atopic vs. non-atopic recurrent wheeze., (© 2014 John Wiley & Sons Ltd.)

Reasons for Performing Study: Equine summer eczema, also known as insect bite hypersensitivity, affects horses recurrently during summer months. The treatment of this allergic pruritus is difficult and therefore there is a need for efficacious treatments. Autoserum therapy, based on the use of autogenous serum that is specifically prepared for oral administration and given when the animal shows clinical signs has been introduced recently. Lipids are thought to be responsible for the effect of this therapy., Objectives: The main aim of this study was to analyse the phospholipid content of autogenous serum preparations and to further assess whether these preparations have different lipid profiles depending on the clinical status of the horse. The hypothesis is that the major serum phospholipids typical of the horse are present in the autoserum preparation., Study Design: Descriptive controlled clinical study., Methods: Sera were collected from 10 affected and 6 healthy horses, prepared in a similar fashion and the lipids contained in the resulting autoserum preparations were analysed by electrospray ionisation mass spectrometry., Results: The major phospholipid classes detected were phosphatidylcholine, sphingomyelin, phosphatidic acid and traces of lysophosphatidylcholine. Horses with summer eczema had significantly abundant concentrations of phosphatidylcholine (P = 0.042) and sphingomyelin (P = 0.0017) in comparison with healthy horses, while the concentration of phosphatidic acid was significantly higher in healthy horses (P = 0.0075)., Conclusions: The autoserum preparation contains minute amounts of the main serum phospholipids in differing concentrations in healthy horses and horses with an allergic skin disease., (© 2013 EVJ Ltd.)

Objective: Schizophrenia is associated with atopy and increased inflammatory markers. We report a population-based longitudinal study of the associations between childhood atopic disorders, subsequent serum inflammatory markers, interleukin 6 (IL-6) and C-reactive protein (CRP), and the risk of psychotic experiences (PEs)., Method: PEs were assessed at age 13 years (n=6785). Presence of clinician-diagnosed atopic disorders (asthma and eczema) was determined from parent-completed questionnaires at age 10 years (n=7814). Serum IL-6 and CRP were measured at age 9 years (n=5076). Logistic regression examined the association between (1) atopy and PEs, (2) inflammatory markers and PEs, and (3) mediating effects of inflammatory markers on the atopy-PEs association. Linear regression examined the association between atopy and inflammatory markers. Age, gender, social class, ethnicity and body mass index were included as potential confounders., Results: At age 10 years, about 14% of the sample was reported to have asthma, 12% eczema, and 7% both asthma and eczema. Compared with children with no atopy, risk of PEs at age 13 years was increased for all of these groups; adjusted odds ratios (95% CI) were, respectively, 1.39 (1.10-1.77), 1.33 (1.04-1.69), and 1.44 (1.06-1.94). Atopy was associated with increased serum IL-6 and CRP; however, this did not mediate association between atopy and PEs. Inflammatory markers were not associated with later PEs., Conclusion: Childhood atopic disorders increase the risk of psychotic experiences in adolescence. Follow-up of these individuals will be useful to determine the effect of atopy and inflammation on different trajectories of early-life PEs., (© 2013. Published by Elsevier B.V. All rights reserved.)

Background: Oral alitretinoin (9-cis-retinoic acid; 9-cis-RA) has shown clinical efficacy in patients with chronic hand eczema (CHE). Herein, we investigated the impact of oral 9-cis-RA on the local and systemic immune response in patients with CHE., Methods: Twenty patients with CHE were treated with oral alitretinoin (10 or 30 mg/day) for at least 24 weeks. Blood samples were taken for flow cytometry, and serum samples were assessed by ELISA to determine immunoglobulin (Ig) levels. Skin biopsies from lesional skin were evaluated immunohistochemically., Results: Upon 9-cis-RA treatment, improvement of the CHE was observed in all patients. A significant decrease in plasmablasts in the peripheral blood and a significant reduction of serum IgE levels were determined. Furthermore, we detected a significant reduction of CD4+ cells and regulatory T cells in the peripheral blood upon treatment. By contrast, these cell subsets were significantly increased in the affected skin. Cytokine analysis of activated CD154-positive T cells showed a reduction of interleukin (IL)-17 but not of IL-4 or IFN-γ production., Conclusions: Overall, our data indicate a disease-modifying effect of 9-cis-RA, including a systemic decrease in IL-17-positive cells, but decreased serum IgE and CD23 expression. The increased frequency of FoxP3-positive cells in the skin upon treatment may suggest a mechanism by which hand eczema is therapeutically targeted by 9-cis-RA, but this will need to be proven in the future studies., (© 2014 S. Karger AG, Basel.)

Loeys-Dietz syndrome (LDS) is a connective tissue disorder caused by monoallelic mutations in TGFBR1 and TGFBR2, which encode for subunits of the transforming growth factor beta (TGFβ) receptor. Affected patients are identified by vascular aneurysms with tortuosity and distinct morphological presentations similar to Marfan syndrome; however, an additional predisposition towards asthma and allergy has recently been found. We describe two patients with a novel missense mutation in TGFBR1 presenting with highly elevated levels of IgE and severe eczema similar to autosomal-dominant Hyper-IgE syndrome (HIES). Mild allergic manifestations with normal up to moderately increased IgE were observed in 3 out of 6 additional LDS patients. A comparison of this cohort with 4 HIES patients illustrates the significant overlap of both syndromes including eczema and elevated IgE as well as skeletal and connective tissue manifestations., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The weak cationic chip (WCX2) and the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) were used to test the serum differential proteins in 20 healthy persons, 20 patients with chronic scrotal eczema, and 30 patients with scrotal Paget's disease and test the specificity and sensitivity of screening scrotal Paget's disease with differential proteins. We found that the differences between the 5 protein peaks of the normal group and the scrotal Paget's disease group in the range of 2000 to 30 000 Da were statistically significant (P < .01) and the difference of 3 protein peaks between the scrotal eczema group and the scrotal Paget's disease group in the range of 2000 to 30 000 Da was statistically significant (P < .05). SELDI-TOS-MS technique has certain application value in the early diagnosis of the scrotal Paget's disease and screening for the specific tumor markers.

Tolerance to allergens may partly depend on allergen-specific IgG and IgG subclasses and IgA antibodies. We investigated whether specific IgG and IgG subclasses and IgA antibodies to β-lactoglobulin, α-casein, and ovalbumin differed between infants who had verified cow's milk allergy (CMA) and infants with cow's milk (CM)-associated eczema, but negative CM oral challenge. The study population comprised 95 infants with clinical eczema that was by history associated with the consumption of CM. After an elimination period, a double-blind, placebo-controlled (DBPC) CM oral challenge confirmed CMA in 45 infants. Skin prick tests (SPT) were performed with CM and hen's egg. Serum levels of IgE antibodies to CM and hen's egg were measured with UniCAP (Phadia, Uppsala, Sweden), and levels of IgA, IgG, IgG1, and IgG4 antibodies to β-lactoglobulin, α-casein, and ovalbumin were measured with enzyme-linked immunosorbent assay. We observed that infants with CMA had lower IgG4 levels to β-lactoglobulin than infants with negative DBPC CM challenge (p = 0.004). Positive CM SPT was associated with lower IgG4 levels to α-casein (p = 0.04). The relation of CM IgE to β-lactoglobulin and α-casein IgG4 was higher in CMA than in infants with negative challenge (p < 0.002 and 0.0001). Positive egg SPT was associated with elevated levels of specific IgG to ovalbumin, β-lactoglobulin, and α-casein as well as IgA to α-casein (p < 0.04). Our study thus shows that low β-lactoglobulin-specific serum IgG4 levels may differentiate eczematous infants with CMA from infants who have eczema with only suspected association with CM., (© 2012 John Wiley & Sons A/S.)

Background: Eczema lesions are characterized by impaired expression of antimicrobial peptides such as cathelicidin, which play crucial roles in the innate immune defence against cutaneous infections. LL-37 corresponds to amino acids 134-170 of human cathelicidin and is a multifunctional host defence molecule essential for normal immune responses to infection and tissue injury., Objectives: The aim of this study was to investigate the relationship between childhood eczema and circulating LL-37 levels., Methods: One hundred and forty-four eczema children and 36 controls were recruited. Eczema severity was assessed by SCORing Atopic Dermatitis (SCORAD) and serum LL-37 concentration measured using enzyme immunoassay. Patients' skin hydration and transepidermal water loss at forearms were measured using Corneometer and Tewameter., Results: Patients' mean SCORAD was 49.2 and their disease was classified as mild (n=28; 12.8%), moderate (n=95; 43.6%) and severe (n=95; 43.6%). Serum LL-37 concentrations did not differ between eczema patients and controls (mean: 832 pg/mL vs. 952 pg/mL, P=0.471). However, serum LL-37 concentrations increased with increasing eczema severity among the patients (P=0.005 for trend). This biomarker shows weakly positive correlation with patients' objective SCORAD (r=0.207, P=0.013) and age (r=0.170, P=0.041), but not skin hydration or transepidermal water loss (P>0.09). Linear regression confirmed significant association between objective SCORAD and serum LL-37 when adjusted for age and gender as covariates (β=0.171, P=0.038). On the other hand, serum LL-37 did not differ between patients with and without heavy growth of staphylococci (P=0.151)., Conclusions: Circulating LL-37 may be a biomarker for severity of childhood eczema, which supports the importance of innate immunity in eczema pathogenesis., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Background: Leptin belongs to the helical cytokine family and has structural similarity to interleukin (IL)-6, IL-12, IL-15, prolactin, and growth hormone. It is mainly secreted by adipocytes but (at lower levels) also by stomach, skeletal muscle, and placenta. Initially, leptin was considered an antiobesity hormone, but experimental evidence has also shown pleiotropic effects on hematopoiesis, angiogenesis, lymphoid organ homeostasis, and T-lymphocyte functions. Recent evidence indicates that leptin modifies T-cell immunity by promoting T helper 1 proinflammatory immune response and production of cytokines., Objective: The aim of the present study was to evaluate leptin serum levels in patients with allergic contact dermatitis (ACD) and atopic dermatitis and to evaluate the correlation of these levels with different patterns of lymphocyte subpopulations., Methods: Serum leptin was assayed by enzyme-linked immunosorbent assay. Immunophenotypic analysis of peripheral blood was performed by flow cytometry., Results: We found that serum leptin levels were higher in ACD patients than in healthy controls (p = .02). In these patients, an inverse correlation between serum leptin and the percentage of CD4CD25 T lymphocytes was observed (p = .002)., Conclusion: These data seem to suggest that leptin might play a role in the pathogenesis of ACD and thus have implications for the therapy for ACD.

Interleukin-5 receptor α-subunit expression may be implicated in the development of allergic diseases. In a population-based birth cohort, we investigated the relationship between IL-5Rα and the development of allergic phenotypes in childhood, using soluble IL-5Rα (s-IL-5Rα) as a marker. Children (n = 510) were followed from birth and assessed at age 3, 5 and 8. Based on the onset and resolution of symptoms, we assigned children into the following wheeze and eczema phenotypes: never, transient, persistent, intermittent and late-onset. Specific IgE to common allergens, s-IL-5Rα (ELISA) and urinary eosinophilic protein X (U-EPX) levels was measured at age 5. s-IL-5Rα was significantly higher among atopic compared to non-atopic children (pg/ml, geometric means [95% CI], 152.4 [126.0-184.5] vs. 103.4 [94.0-113.9], p < 0.0001). While we found no association between s-IL-5Rα and current eczema at age 5, there was a significant association between eczema phenotypes and s-IL-5Rα (multiple anova model adjusted for gender and atopy, F = 2.56, p = 0.04). After adjustment for multiple comparisons, we found that children with late-onset eczema had significantly higher s-IL-5Rα compared to those who have never had eczema (mean difference [95% CI], 2.41 [1.03-5.62], p = 0.04) and those with intermittent eczema (2.63 [1.08-6.41], p = 0.02), with no difference between children who have never had eczema and other eczema phenotypes. We found no such association for wheeze phenotypes. There was a weak correlation between s-IL-5Rα and U-EPX (r = 0.16, p < 0.0001). Increased serum s-IL-5Rα level at age 5 was associated with contemporaneous atopic sensitization and with subsequent development of eczema by age 8., (© 2010 John Wiley & Sons A/S.)

Background: Association of genetic-variants in the FADS1-FADS2-gene-cluster with fatty-acid-composition in blood of adult-populations is well established. We analyze this genetic-association in two children-cohort-studies. In addition, the association between variants in the FADS-gene-cluster and blood-fatty-acid-composition with eczema was studied., Methods and Principal Findings: Data of two population-based-birth-cohorts in The Netherlands and Germany (KOALA, LISA) were pooled (n = 879) and analyzed by (logistic) regression regarding the mutual influence of single-nucleotide-polymorphisms (SNPs) in the FADS-gene-cluster (rs174545, rs174546, rs174556, rs174561, rs3834458), on polyunsaturated fatty acids (PUFA) in blood and parent-reported eczema until the age of 2 years. All SNPs were highly significantly associated with all PUFAs except for alpha-linolenic-acid and eicosapentaenoic-acid, also after correction for multiple-testing. All tested SNPs showed associations with eczema in the LISA-study, but not in the KOALA-study. None of the PUFAs was significantly associated with eczema neither in the pooled nor in the analyses stratified by study-cohort., Conclusions and Significance: PUFA-composition in young children's blood is under strong control of the FADS-gene-cluster. Inconsistent results were found for a link between these genetic-variants with eczema. PUFA in blood was not associated with eczema. Thus the hypothesis of an inflammatory-link between PUFA and eczema by the metabolic-pathway of LC-PUFAs as precursors for inflammatory prostaglandins and leukotrienes could not be confirmed by these data.

The Self-Administered Eczema Area and Severity Index (SA-EASI) is one of the few patient based atopic dermatitis (AD) disease activity scores and was found to be highly correlated with the EASI. Correlation with other frequently used scoring methods has not been investigated. The aim of this study was to evaluate the relation of the SA-EASI with two physician-based disease activity scores (objective SCORAD and SASSAD score) and with a serum marker for AD (Thymus and Activation-Regulated Cytokine [TARC]) in children with AD. Sixty children with moderate to severe AD were included. The SA-EASI was completed by caregivers, and the objective SCORAD and SASSAD scores were measured successively on the same day by a trained investigator. Blood for serum TARC measurement was drawn. The correlation between the SA-EASI and the objective SCORAD was high (ρ = 0.61, p = <0.001), mainly based on high correlation between the body surface area (BSA) measurements of both scores (ρ = 0.50, p = <0.001). The correlation with the SASSAD score (only severity measurement) was 0.43 (p = <0.001). The correlation with serum TARC levels was 0.46; p = <0.001, mainly based on the BSA score of the SA-EASI (ρ = 0.42, p = <0.001). Parents may have more difficulty in scoring severity of AD than scoring BSA involved. Educating parents in severity scoring of AD may improve agreement of the SA-EASI and the objective SCORAD, TARC, and SASSAD score. Additional use of the SA-EASI in routine clinical practice or in trials may then facilitate more frequent but still accurate assessment of AD., (© 2010 Wiley Periodicals, Inc.)