Manifestations Of Atopic Disease Research Articles

ATOPIC DERMATITIS

Abstract:Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease with a wide range of severity, and is usually the first manifestation of atopic disease. It is one of the most common skin disorders in developed countries, affecting approximately 20% of children and 1–3% of adults. Symptoms such as eczematous papules, plaques, and itch, and their associated consequences, such as sleep disturbance, can significantly impact the quality of life of the patient and family. Key words: atopic dermatities, epidemiology,phenotypes,clinical features

Maternal antioxidant intake during pregnancy and the development of cows' milk allergy in the offspring.

Cows' milk allergy (CMA) is the most common food allergy in young children, and it is often the first manifestation of atopic diseases. Accordingly, very early environmental factors, such as maternal diet during pregnancy, may play a role in the development of CMA, but the evidence is limited. The aim of this study was to investigate the association between maternal intake of antioxidant nutrients during pregnancy and the subsequent development of CMA in the offspring in a prospective, population-based birth cohort within the Finnish Type 1 Diabetes Prediction and Prevention Study. Maternal dietary information during pregnancy was collected with a detailed, validated FFQ. The maternal dietary information and the information on putative confounding factors were available for 4403 children. Information on diagnosed CMA (n 448) was obtained from a medical registry and queried from the parents up to child's age of 3 years. The Finnish food composition database was used to calculate the average daily intake of nutrients. Logistic regression was applied for statistical analyses, and the nutrient intakes were adjusted for energy intake. OR are presented per 1 sd increment of the particular nutrient intake. Maternal total and dietary intake of β-carotene was associated with an increased risk of CMA in the offspring when adjusted for the putative confounding factors (total OR 1·10, 95 % CI 1·02, 1·20; dietary OR 1·10; 95 % CI 1·01, 1·19). Using dietary supplements containing antioxidants in addition to a balanced diet may not confer any additional benefits.

The Role of the Microbiome in Food Allergy: A Review.

Food allergies are common and estimated to affect 8% of children and 11% of adults in the United States. They pose a significant burden—physical, economic and social—to those affected. There is currently no available cure for food allergies. Emerging evidence suggests that the microbiome contributes to the development and manifestations of atopic disease. According to the hygiene hypothesis, children growing up with older siblings have a lower incidence of allergic disease compared with children from smaller families, due to their early exposure to microbes in the home. Research has also demonstrated that certain environmental exposures, such as a farming environment, during early life are associated with a diverse bacterial experience and reduced risk of allergic sensitization. Dysregulation in the homeostatic interaction between the host and the microbiome or gut dysbiosis appears to precede the development of food allergy, and the timing of such dysbiosis is critical. The microbiome affects food tolerance via the secretion of microbial metabolites (e.g., short chain fatty acids) and the expression of microbial cellular components. Understanding the biology of the microbiome and how it interacts with the host to maintain gut homeostasis is helpful in developing smarter therapeutic approaches. There are ongoing trials evaluating the benefits of probiotics and prebiotics, for the prevention and treatment of atopic diseases to correct the dysbiosis. However, the routine use of probiotics as an intervention for preventing allergic disease is not currently recommended. A new approach in microbial intervention is to attempt a more general modification of the gut microbiome, such as with fecal microbiota transplantation. Developing targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy. Similarly, fecal microbiota transplantation is being explored as a potentially beneficial interventional approach. Overall, targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy.

К вопросу о профилактике формирования атопического фенотипа у детей, рожденных от матерей с бронхиальной астмой

Influence of feeding type on manifestation of atopic diseases in children born from the mothers suffering from bronchial asthma was studied. It was shown that one of the ways of prevention of early manifestation of food allergy clinical symptoms, if breast feeding is impossible, may be use of deep hydrolysis mixtures.

PREBIOTICS IN NUTRITION OF CHILDREN OF EARLY AGE

Abstract. Proper nutrition is the key factor of growth and development of the child. Early artificial feeding and irrational introduction of complementary food is one of the problems of infants leading to development of functional disorders of the gastrointestinal tract, impaired immunological protection and manifestation of atopic diseases. We described the effects of the main pre-biotic components of functional nutrition in children of early age. Also we demonstrated the importance of prebiotics for the formation of intestinal microflora, including the development of local mucosal homeostasis due to immunomodulatory action.

Maternal dietary folate, folic acid and vitamin D intakes during pregnancy and lactation and the risk of cows' milk allergy in the offspring.

Maternal nutrient intake during pregnancy and lactation potentially influences the development of allergic diseases. Cows' milk allergy (CMA) is often the first manifestation of atopic diseases, but the impact of early nutritional influences on CMA has not been explored. The associations between maternal intakes of folate, folic acid and vitamin D during pregnancy and lactation were addressed in a prospective, population-based birth cohort within the Finnish Type 1 Diabetes Prediction and Prevention Study. Mothers of 4921 children during pregnancy and 2940 children during lactation provided information on maternal dietary intake during the 8th month of pregnancy and the 3rd month of lactation using a detailed, validated FFQ. Information on diagnosed CMA in the offspring was obtained from a medical registry as well as queried from the parents. The Finnish food composition database was used to calculate nutrient intake. Logistic regression was applied for statistical analyses. Folate intake and folic acid and vitamin D supplement use were associated with an increased risk of CMA in the offspring, whereas vitamin D intake from foods during pregnancy was associated with a decreased risk of CMA. Thus, maternal nutrient intake during pregnancy and lactation may affect the development of CMA in offspring. Supplementation with folic acid may not be beneficial in terms of CMA development, especially in children of allergic mothers. The association between dietary supplement use and CMA risk can at least partly be explained by increased health-seeking behaviour among more educated mothers who also use more dietary supplements.

Anti-Immunoglobulin E in the Treatment of Refractory Atopic Dermatitis

Atopic dermatitis (AD) is a common diagnosis seen in both children and adults, and it is often the first manifestation of atopic disease. Research has shown a strong correlation between serum IgE levels, the severity of atopic dermatitis, and co-existing asthma and/or allergic rhinitis. Omalizumab (Xolair, East Hanover, NJ; Genentech, South San Francisco, CA) is a monoclonal antibody to human IgE and is currently Food and Drug Administration (FDA) approved for the treatment of asthma. We present 3 patients with severe, treatment resistant atopic dermatitis whose cutaneous symptoms significantly improved by treatment with omalizumab.

Fatty acid composition of serum lipid classes in mice following allergic sensitisation with or without dietary docosahexaenoic acid-enriched fish oil substitution

Dietary fatty acids have been shown to influence allergic sensitisation. Both n-3 and n-6 PUFA are involved in targeted mediation of inflammatory responses during allergic sensitisation and manifestation of atopic diseases. In the present experiments we investigated whether supplementation of DHA-enriched fish oil partly substituting dietary sunflower-seed oil, in comparison with sunflower-seed oil, supplemented to mice influences fatty acid composition of serum lipid classes. The effects of the two different diets were also investigated depending on allergic sensitisation. Supplementation of DHA and EPA in doses of 2 and 0.12 % (w/w) to non-sensitised and sensitised mice resulted in significantly increased percentile contributions of DHA to all lipid classes. In contrast, serum values of the n-6 PUFA arachidonic acid (AA) were significantly lower, both in non-sensitised and sensitised mice fed the DHA-enriched diet. The fatty acid composition of serum lipids also reflected allergic sensitisation: the EPA:AA ratio in TAG, cholesteryl esters and phospholipids in non-supplemented animals fell to 23, 29 and 29 % respectively of the original value after allergic sensitisation, whereas it decreased to 70, 80 and 76 % respectively only in the animals supplemented with DHA. In summary, allergic sensitisation alone decreased significantly the EPA:AA ratios in serum TAG, while concomitant supplementation of DHA-enriched fish oil ameliorated this decrease. We postulate from the present results that the amelioration of the severity of allergic sensitisation after DHA supplementation may be linked to altered ratios of the eicosanoid precursors EPA and AA as well as DHA needed for further metabolic activation to pro- or anti-inflammatory bioactive lipids.

Helminth Infection withLitomosoides sigmodontisInduces Regulatory T Cells and Inhibits Allergic Sensitization, Airway Inflammation, and Hyperreactivity in a Murine Asthma Model

Numerous epidemiological studies have shown an inverse correlation between helminth infections and the manifestation of atopic diseases, yet the immunological mechanisms governing this phenomenon are indistinct. We therefore investigated the effects of infection with the filarial parasite Litomosoides sigmodontis on allergen-induced immune reactions and airway disease in a murine model of asthma. Infection with L. sigmodontis suppressed all aspects of the asthmatic phenotype: Ag-specific Ig production, airway reactivity to inhaled methacholine, and pulmonary eosinophilia. Similarly, Ag-specific recall proliferation and overall Th2 cytokine (IL-4, IL-5, and IL-3) production were significantly reduced after L. sigmodontis infection. Analysis of splenic mononuclear cells and mediastinal lymph nodes revealed a significant increase in the numbers of T cells with a regulatory phenotype in infected and sensitized mice compared with sensitized controls. Additionally, surface and intracellular staining for TGF-beta on splenic CD4(+) T cells as well as Ag-specific TGF-beta secretion by splenic mononuclear cells was increased in infected and sensitized animals. Administration of Abs blocking TGF-beta or depleting regulatory T cells in infected animals before allergen sensitization and challenges reversed the suppressive effect with regard to airway hyperreactivity, but did not affect airway inflammation. Despite the dissociate results of the blocking experiments, these data point toward an induction of regulatory T cells and enhanced secretion of the immunomodulatory cytokine TGF-beta as one principle mechanism. In conclusion, our data support the epidemiological evidence and enhance the immunological understanding concerning the impact of helminth infections on atopic diseases thus providing new insights for the development of future studies.

Relationship between atopic manifestations, family history of atopic disease and cord blood IgE levels in children

Background The incidence of atopic disease tends to increaseover the past few decades and its morbidity interferes with thequality of life and health. Prediction of the disease is importantfor early prevention.Objective To evaluate the relationship between atopicmanifestations, family history (FH) of atopic disease and cordblood IgE (CB-IgE) levels.Methods We conducted an analytic observational study withcohort retrospective design on children with an average age of 3years whose CB-IgE had been measured at delivery inKiaracondong Primary Health Care during October–December2004. Manifestations of atopic disease were recorded using ISAACquestionaire for allergy. Chi-square, Mann-Whitney test, andlogistic regression analysis were used for analysis.Results Cord blood IgE was measured on 124 children after birth.Only 94 children (76%) fulfilled the inclusion criteria. Atopicdisease was found in 17 children (18%), consisting of 8 childrenwith atopic dermatitis, 4 with allergic rhinitis, and 5 suffered fromboth. There were significant differences in the mean value of CB-IgE (Z M-W =4.60; P<0.001) and FH (x 2 =19.059; P<0.001)between atopic and non atopic children. Cut off point of the CB-IgE concentration was 1.4 IU/mL (77.7%). The highest probabilityfor atopic manifestations was found in children who had highCB-IgE and positive FH (P=45%). Relative risk of children withhigh CB-IgE level in positive FH group was 3.636 (95% CI0.943;14.016).Conclusion CB-IgE level and family history of atopic disease arerisk factors for the development of atopic manifestation.

Association of a STAT 6 haplotype with elevated serum IgE levels in a population based cohort of white adults

Background: Several studies have shown linkage of chromosome 12q 13–24 with atopy related phenotypes. Among candidate genes in this region is STAT6 (signal transducer and activator of transcription), which is...

Allergen-specific CD8(+) T cells and atopic disease.

Considerable evidence suggests that IL-10 may have a role in the manifestation of atopic disease. We sought to test the hypothesis that at the single cell level, allergen-specific T cells have diminished IL-10 production capacity in severely affected atopics compared with asymptomatic atopics. We defined three A*0201-restricted Der p 1 CD8(+) T cell epitopes. Using human leukocyte antigen-A*0201-peptide (HLA-A*0201-peptide) tetrameric complexes and enzyme-linked immunospot assays to analyze peripheral blood mononuclear cells from A*0201-positive severely symptomatic atopics, asymptomatic atopics, and nonatopic controls, we observed a significant association between the frequency of the Der p 1-specific CD8(+) T cells and disease activity. The specific T cells expressed an antigen-experienced cell surface phenotype, and 45.7% were positive for cutaneous lymphocyte-associated antigen. The specific T cells were able to produce IFN-gamma efficiently, but their IL-10 production was significantly reduced in severely affected atopics. In contrast, viral-specific CD8(+) T cells were able to produce equivalent amounts of IL-10 in the severely affected atopics compared with asymptomatic atopics and nonatopics. Through defining the first human atopic allergen HLA class I epitopes, we have provided a possible cellular mechanism to link the previous association of low IL-10 levels and severe atopic disease. These data are consistent with a role for CD8(+) T cells in atopic disease pathogenesis and may provide a basis for future T cell immunotherapy strategies.

Allergen-specific CD8+ T cells and atopic disease

Considerable evidence suggests that IL-10 may have a role in the manifestation of atopic disease. We sought to test the hypothesis that at the single cell level, allergen-specific T cells have diminished IL-10 production capacity in severely affected atopics compared with asymptomatic atopics. We defined three A*0201-restricted Der p 1 CD8+ T cell epitopes. Using human leukocyte antigen-A*0201–peptide (HLA-A*0201–peptide) tetrameric complexes and enzyme-linked immunospot assays to analyze peripheral blood mononuclear cells from A*0201-positive severely symptomatic atopics, asymptomatic atopics, and nonatopic controls, we observed a significant association between the frequency of the Der p 1–specific CD8+ T cells and disease activity. The specific T cells expressed an antigen-experienced cell surface phenotype, and 45.7% were positive for cutaneous lymphocyte-associated antigen. The specific T cells were able to produce IFN-γ efficiently, but their IL-10 production was significantly reduced in severely affected atopics. In contrast, viral-specific CD8+ T cells were able to produce equivalent amounts of IL-10 in the severely affected atopics compared with asymptomatic atopics and nonatopics. Through defining the first human atopic allergen HLA class I epitopes, we have provided a possible cellular mechanism to link the previous association of low IL-10 levels and severe atopic disease. These data are consistent with a role for CD8+ T cells in atopic disease pathogenesis and may provide a basis for future T cell immunotherapy strategies.

Allergen-specific CD8+ T cells and atopic disease

Considerable evidence suggests that IL-10 may have a role in the manifestation of atopic disease. We sought to test the hypothesis that at the single cell level, allergen-specific T cells have diminished IL-10 production capacity in severely affected atopics compared with asymptomatic atopics. We defined three A*0201-restricted Der p 1 CD8+ T cell epitopes. Using human leukocyte antigen-A*0201–peptide (HLA-A*0201–peptide) tetrameric complexes and enzyme-linked immunospot assays to analyze peripheral blood mononuclear cells from A*0201-positive severely symptomatic atopics, asymptomatic atopics, and nonatopic controls, we observed a significant association between the frequency of the Der p 1–specific CD8+ T cells and disease activity. The specific T cells expressed an antigen-experienced cell surface phenotype, and 45.7% were positive for cutaneous lymphocyte-associated antigen. The specific T cells were able to produce IFN-γ efficiently, but their IL-10 production was significantly reduced in severely affected atopics. In contrast, viral-specific CD8+ T cells were able to produce equivalent amounts of IL-10 in the severely affected atopics compared with asymptomatic atopics and nonatopics. Through defining the first human atopic allergen HLA class I epitopes, we have provided a possible cellular mechanism to link the previous association of low IL-10 levels and severe atopic disease. These data are consistent with a role for CD8+ T cells in atopic disease pathogenesis and may provide a basis for future T cell immunotherapy strategies.

Atopy and asthma genes--where do we stand?

Atopy and asthma genes--where do we stand?

Enhanced IL-4 but normal interferon-gamma production in children with isolated IgE mediated food hypersensitivity.

Atopic disorders such as atopic dermatitis and asthma have been characterised by an imbalance in interferon-gamma (INF-gamma) and IL-4. Whether similar imbalances are found in atopic disorders with different clinical manifestations, such as IgE mediated immediate food hypersensitivity, is not clear. We have examined the in vitro production of INF-gamma and IL-4 in peripheral blood mononuclear cells (PBMC) following phytohaemagglutinin stimulation from children with isolated immediate IgE mediated food hypersensitivity (egg, milk, "nut"), children with moderate and severe atopic dermatitis, and normal children. Children with immediate food reactions were excluded if they had a history or evidence of atopic dermatitis or asthma. PBMC from children with IgE mediated food hypersensitivity produced significantly more IL-4 (p = 0.013) but equivalent INF-gamma (p = 0.26) compared to PBMC from control children. In contrast, PBMC from children with atopic dermatitis produced significantly less INF-gamma (p < 0.001) and more IL-4 (p < 0.008) than PBMC from normal children. In addition, there was no difference in IL-4 (p = 0.74) but significantly less INF-gamma (p < 0.001) produced by PBMC from the children with atopic dermatitis than food hypersensitivity. We demonstrate that children with IgE mediated food hypersensitivity and no other manifestation of atopic disease have enhanced IL-4 production without the defect in INF-gamma production observed in childhood AD and asthma. We postulate that isolated IL-4 enhancement promotes the development of IgE mediated hypersensitivity disorders such as food allergy, whilst the combination of defective INF-gamma and enhanced IL-4 production promotes inflammatory atopic disorders such as AD and asthma.

Atopic eczema and other manifestations of atopy: results of a study in East and West Germany.

Within an environmental health study, dermatologic examination of 1273 pre-school-age children (5-7 years old) was carried out in selected areas of East (n = 287) and West (n = 987) Germany in spring 1991. On the basis of comparable genetic background, the influence of a different exposure to air pollutants on the manifestation of atopic diseases was investigated. Halle an der Saale (East Germany) and Duisburg (North/South) as well as Essen (West Germany) were chosen as polluted study areas, whereas the countryside town of Borken (West Germany) served as a control region. Outdoor pollution with particles and SO2 was significantly higher in Halle an der Saale. Of the total study group, 12.9% suffered from atopic eczema at the time of examination. The prevalence was highest in East Germany (17.5%; adjusted odds ratio [OR] 1.39, confidence intervals [GI] 0.77-2.52, compared to Borken). The reported frequencies of hay fever and asthma in the total study population were 2% and 1.3%, respectively, without significant differences between study sites. Some 34.7% of the children showed at least one positive skin prick test reaction; significantly (P < 0.001) higher sensitization rates were obtained in western regions (Essen, Duisburg-South) than in the control region (Borken) and East Germany. Multivariate analysis of the prevalence of atopic eczema showed associations with parental predisposition (OR 1.52, CI 1.03-2.25), sex (for boys, OR 0.63, CI 0.43-0.92), location (Duisburg-South vs Borken OR 0.52, CI 0.30-0.96), month of investigation (May vs April, and March vs February OR 0.55, CI 0.37-0.81), contact with rabbits (for girls, OR 2.90, CI 1.36-6.19), animal fur in bedrooms (2.17, 1.01-4.67), indoor use of gas without hood (1.68, 1.11-2.56), and distance of homes from a busy road (< 50 m 1.71, 1.07-2.73). Nonsignificant associations were observed for history of helminthic infections (OR 1.61, CI 0.98-2.64) and high parental education level (OR 1.83, CI 0.83-4.02). In East and West Germany, atopic eczema seems to follow a course different from that of respiratory allergic diseases and specific sensitization, a fact which underlines the need for a differentiated analysis.

Allergen avoidance in infancy and allergy at 4 years of age

In an attempt to prevent or reduce the manifestations of atopic disease, a group of infants considered to be genetically at high risk of atopy was entered in a prenatally randomized, controlled study. A prophylactic group (n = 58) was either breast-fed with their mothers excluding foods regarded as highly antigenic from their diets, or given an extensively hydrolysed formula. In addition, strenuous efforts were made to reduce exposure to the house-dust mite by application of acaricide to the bedroom and living room carpets and upholstered furniture. A control group (n = 62) was fed conventionally by breast or on formula, and no specific environmental measures were taken. The results (previously reported) after 1 year showed significantly less total allergy, asthma, and eczema in the prophylactic group. Similar results were obtained at 2 years although the reduction in asthma no longer achieved statistical significance. However, there was significantly less sensitization, as shown by a battery of skin prick tests (SPTs), to both dietary allergens and aeroallergens in the prophylactic group. All the children have now been reviewed at the age of 4 years, and SPTs to a wide range of dietary allergens and aeroallergens have been performed. The control group continues to show more total allergy (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.21-6.13, P < 0.02), definite allergy (allergic symptoms plus positive SPT) (OR 5.6, CI 1.8-17.9, P < 0.005), and eczema (OR 3.4, CI 1.2-10.1, P < 0.05). More control children have positive SPTs (OR 3.7, CI 1.3-10.0, P < 0.02). A dual approach to the prevention of allergic disease, avoiding as far as possible sensitization to food and aeroallergens, significantly reduces the risk of atopic disease. This should be reserved for infants considered at very high risk of atopy, and close medical and dietetic supervision must be available.

Atopic family history. Validation of instruments in a multicenter cohort study.

In order to identify newborns at risk for atopic diseases, we developed a family questionnaire and selected specific answers which were suitable to identify atopic family members. The validity of the questionnaire was evaluated by the Phadiatop test results of 793 mothers and 353 fathers. As both screening instruments do not measure the same, the Phadiatop test identifies sensitization to inhalant allergens and the history reflects the clinical manifestation of atopic disease, the agreement between sensitization and manifestation is incomplete. Sensitivity and specificity of the questionnaire screening conditions to reproduce the Phadiotop test result was 64% and 84% for mothers, and 58% and 88% for fathers, respectively. The relative risk for lifetime prevalence of atopic manifestations in Phadiatop positive over negative mothers was calculated to be 3.88 (95% confidence interval = 3.12 to 4.81), and for Phadiatop positive over negative fathers to amount 4.84 (95% confidence interval 3.25 to 7.23). A few relevant answers of 20 were identified by logistic regression analysis to predict the Phadiatop test result nearly, as well as the total questionnaire.