Inflammatory plasma signature of chronic hand eczema: Associations with aetiological and clinical subtypes.

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.

Can moderate-intensity aerobic exercise ameliorate atopic dermatitis?

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.

Clinicopathologic overlap of psoriasis, eczema, and psoriasiform dermatoses: A retrospective study of T helper type 2 and 17 subsets, interleukin 36, and ß-defensin 2 in spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor-associated dermatitis.

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 ß-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.

[Using of specialized food for the workers with skin occupational eczema of perlite production].

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.

The relationship between maternal 25-hydroxyvitamin D status in pregnancy and childhood adiposity and allergy: an observational study.

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.

Upregulated expression of substance P (SP) and NK1R in eczema and SP-induced mast cell accumulation.

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.

Enhanced Expression of IL-18 and IL-18BP in Plasma of Patients with Eczema: Altered Expression of IL-18BP and IL-18 Receptor on Mast Cells.

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.

Associations of maternal and fetal 25-hydroxyvitamin D levels with childhood eczema: The Generation R Study.

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.

Identifying the heterogeneity of young adult rhinitis through cluster analysis in the Isle of Wight birth cohort.

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.

Hyper IgE in Childhood Eczema and Risk of Asthma in Chinese Children.

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.

Facial eczema management protocols used on dairy farms in the North Island of New Zealand and associated concentrations of zinc in serum.

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.

CCL28 Cannot Replace IgE for Severity by Objective SCORAD Index in Atopic Dermatitis in Children.

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.

Serum Vitamin D levels and Vitamin D supplementation do not correlate with the severity of chronic eczema in children.

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.

[Evolution of oxidant-antioxidant homeostasis in patients with eczema treated using different methods].

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".

Severe eczema and Hyper-IgE in Loeys-Dietz-syndrome - contribution to new findings of immune dysregulation in connective tissue disorders.

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 (TGFß) 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.

Circulating TSLP associates with decreased wheezing in non-atopic preschool children: data from the URECA birth cohort.

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.

Immunomodulation in patients with chronic hand eczema treated with oral alitretinoin.

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.