Association between mast cell chymase genotype and atopic eczema: comparison between patients with atopic eczema alone and those with atopic eczema and atopic respiratory disease

BACKGROUND: It has remained unclear whether genetic background of patients with atopic eczema (AE) alone is identical to that of patients with both AE and atopic respiratory disease. OBJECTIVE: We aimed to assess whether there is a genetic difference between these two groups of AE patients. METHOD: We determined the genotype with regard to an allelic polymorphism in the gene for mast cell chymase (MCC; a serine protease secreted from mast cells) in 169 AE patients. RESULTS: MCC genotype was significantly associated with pure AE patients who did not have a predisposition to atopic respiratory disease and whose serum IgE concentration was < 500 IU/mL. The distribution of MCC genotypes also differed significantly between the latter patients and those AE patients with bronchial asthma and a serum IgE concentration of > 2000 IU/mL. CONCLUSION: These results suggest that pure AE is associated with genetic variants of MCC, and that the genetic basis of pure AE differs from that of AE associated with atopic asthma.     

Putative association of a TLR9 promoter polymorphism with atopic eczema

BACKGROUND: Toll-like receptors (TLR) play a pivotal role in the induction of first-line defense mechanisms of the innate immune system and trigger adaptive immune responses to microbial pathogens. Genetic variations in innate immunity genes have been reported to be associated with a range of inflammatory disorders. Deficiencies on the level of immunity receptors such as pathogen-recognition receptors are suspected to affect the maturation of our immune system and to avail thereby the high prevalence of atopic diseases and susceptibility of atopic patients to microbial infections. AIMS OF THE STUDY: We evaluated TLR9 as susceptibility gene for atopic eczema (AE). METHODS: Analyses of four tag single-nucleotide polymorphisms in two panels of families containing a total of 483 parent-affected offspring trios as well as a cohort of 274 unrelated adult AE cases and 252 hypernormal population-based controls have been performed. RESULTS: In both family cohorts, polymorphism C-1237T, which is located within the promoter region of the TLR9 gene, was significantly associated with AE, in particular the intrinsic subtype of AE. No associations were seen in the case-control cohort. Luciferase reporter gene assays revealed significantly higher promoter activity of the TT allelic variant at this single nucleotide polymorphism site. CONCLUSION: These observations suggest that the TLR9 promoter polymorphism C-1237T might affect AE susceptibility in particular in patients with the intrinsic variant of AE.     

Maternal oral contraceptive use and atopic diseases in the offspring

BACKGROUND: This study examined the association of maternal oral contraceptive (OC) use - before and after birth - and atopic manifestations in the offspring. METHODS: A total of 2754 East German children aged 5-14 years participated in a cross-sectional survey in 1998-99. The standardized parental questionnaire in 1998-99 included data on atopic diseases, socio-economic factors, parental atopy and maternal OC use. Specific immunoglobulin E against common inhalant allergens was measured by radioallergosorbent test (RAST). RESULTS: Maternal OC use before birth was associated with a higher risk of atopic diseases in the offspring compared with children of mothers who had never taken OC [asthma: odds ratio (OR) 1.6; 95% confidence interval (CI): 0.9-3.0; allergic rhinitis: OR 1.5; CI: 0.96-2.2; atopic eczema: OR 2.6; CI: 1.6-4.3; atopic sensitization: OR 1.5; CI: 0.97-2.2]. However, the effect estimates for maternal OC use after birth compared with the never users showed quite similar effects for these atopic conditions. No relations were observed between the prevalences of atopic diseases and maternal age at beginning of OC use, the duration of OC use, the type of contraceptive or maternal age at birth. CONCLUSION: This study raises doubts in a true biological association between OC use and atopic diseases.     

Worm infestation and the negative association with eczema (atopic/nonatopic) and allergic sensitization

BACKGROUND: Worm infestations may play a role in preventing allergies. There is a lack of epidemiological information from Western countries on the association between worm infestation and eczema. OBJECTIVE: To investigate the association between worm infestation and eczema in a proper temporal sequence and under consideration of allergic sensitization. METHODS: Two surveys were performed in East German school children. Questionnaire data included the history of eczema and worm infestation and their time of onset. Specific IgE antibodies to five common aeroallergens were measured and used to define nonatopic and atopic eczema. Logistic regression analyses were performed to control for relevant confounders (age, sex, parental school education and history of allergies). In order to confirm the findings a corresponding conditional regression analysis was applied on cases and controls matched by age and sex. RESULTS: A total of 4169 children participated (response 75 and 76%) who were, on average, 9.2 years old (47% girls). Overall 17.0% reported a prior worm infestation (Ascaris 44%, Oxyuris 33%) and 18.1% had a history of eczema. Eczema occurred significantly less frequent in children who had a worm infestation (prior to the onset of eczema) compared with children without such a history (8.1%vs 16.5%, OR(adj): 0.45, 95% CI: 0.33-0.60). The finding was confirmed by the corresponding matched case-control analysis (OR(adj): 0.57, 95% CI: 0.41-0.79). Atopic eczema was affected more by a prior worm infestation (OR(adj): 0.31, 95% CI: 0.18-0.56) than the nonatopic eczema (OR(adj): 0.58, 95% CI: 0.40-0.84). A total of 29.1% exhibited specific IgE antibodies to at least one aeroallergen. Sensitized children gave significantly less frequent a history of worm infestation (14.2%vs 18.3%, OR(adj): 0.74, 95% CI: 0.60-0.92). Stratified analysis revealed that this effect most pronounced for a sensitization to house dust mite. CONCLUSIONS: A worm infestation is associated with a reduced frequency of subsequent eczema, especially the atopic type. Furthermore allergic sensitization, especially to house dust mite, and worm infestation are negatively associated. The data support the concept that a lack of immune-stimulation by parasitic infections contributes to the development of allergies.     

Monoamine and diamine oxidase activities in atopic eczema

Increased plasma histamine levels were associated with significantly lowered diamine and type B monoamine oxidase activities in platelet rich plasma of atopic eczema patients.     

Maternal distress across the postnatal period is associated with infant secretory immunoglobulin A

Employing a longitudinal design, relationships between maternal distress (i.e., perceived stress, negative affect, depressive symptomology), and infant secretory immunoglobulin A (sIgA) across the peripartum period were examined in 51 mother–infant dyads. Indices of maternal distress were assessed at four time periods: third trimester of pregnancy and 1, 3, and 6 months postpartum. Infant saliva samples were collected at each of the three time points in the postpartum period to assess sIgA levels. No relationships were found between prenatal maternal distress and infant sIgA. Results indicated that during the postnatal period, higher concurrent maternal distress was associated with reduced infant sIgA. Maternal distress did not prospectively predict infant sIgA. These findings advance our understanding of the social-context of infant development, highlighting the significance of maternal regulation of infant immunity.     

Dietary exclusions for improving established atopic eczema in adults and children: systematic review

Atopic eczema is the most common inflammatory skin disease of childhood in developed countries. We performed a systematic review of randomized controlled trials to assess the effects of dietary exclusions for the treatment of established atopic eczema. Nine trials (421 participants) were included, most of which were poorly reported. Six were studies of egg and milk exclusion ( n  = 288), one was a study of few foods ( n  = 85) and two were studies of an elemental diet ( n  = 48). There appears to be no benefit of an egg- and milk-free diet in unselected participants with atopic eczema. There is also no evidence of benefit in the use of an elemental or few-foods diet in unselected cases of atopic eczema. There may be some benefit in using an egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs – one study found 51% of the children had a significant improvement in body surface area with the exclusion diet as compared with normal diet (95% CI 1.07–2.11) and change in surface area and severity score was significantly improved in the exclusion diet as compared with the normal diet at the end of 6 weeks (MD 5.50, 95% CI 0.19–10.81) and end of treatment (MD 6.10, 95% CI 0.06–12.14). Despite their frequent use, we find little good quality evidence to support the use of exclusion diets in atopic eczema.     

Breast-feeding and atopic eczema dermatitis syndrome: protective or harmful?

Numerous studies have addressed the potential of breast-feeding to protect for the development of allergic diseases, and in particular of atopic eczema dermatitis syndrome (AEDS). Although the majority of studies, as well as several meta-analyses, are strongly in favour of breast-feeding, there are some conflicting results and open issues. Furthermore, breast-feeding might be detrimental in a subgroup of young infants with severe early manifestations of AEDS and immunoglobulin E sensitizations to common foods. The aim of this review is not to analyse systematically the current literature, but to suggest a scientifically and clinically based analysis of the benefits of breast-feeding in atopic infants.     

Maternal stress and behavior modulate relationships between neonatal stress, attention, and basal cortisol at 8 months in preterm infants

There is evidence that the developmental trajectory of cortisol secretion in preterm infants is altered, with elevated basal cortisol levels observed postnatally through at least 18 months corrected age (CA). This alteration is possibly due to neonatal pain-related stress. High cortisol levels might contribute to greater risk of impaired neurodevelopment. Since maternal factors are important for the regulation of infant stress responses, we investigated relationships between infant (neonatal pain-related stress, attention, cortisol) and maternal (stress, interactive behaviors) factors at age 8 months CA. We found that interactive maternal behaviors buffered the relationship between high neonatal pain-related stress exposure and poorer focused attention in mothers who self-reported low concurrent stress. Furthermore, in preterm infants exposed to high concurrent maternal stress and overwhelming interactive maternal behaviors, higher basal cortisol levels were associated with poor focused attention. Overall, these findings suggest that maternal factors can influence the cognitive resilience at 8 months of preterm infants exposed to early life stress.     

Different expression of adhesion molecules and tetraspanins of monocytes of patients with atopic eczema

BACKGROUND: Atopic eczema (AE) and psoriasis vulgaris (Pso) represent the most frequent chronic inflammatory skin diseases, which have a high number of characteristics in common but differ in their clinical picture and immunological background. A shared feature of both AE and Pso is a high recruitment of distinct proinflammatory cells from the blood into the skin at the initiation of the disease. A multistep adhesion cascade via different adhesion receptors consisting of 'tethering' and 'rolling' mediated by selectins, alpha-integrins and beta-integrins and the 'arrest' of the cells is initiated during this process. AIMS OF THE STUDY: To evaluate the expression of adhesion molecules and tetraspanins of monocytes of patients with AE and Pso in comparison with healthy controls. METHODS: We analysed the expression of adhesion molecules and tetraspanins on monocytes freshly isolated from the peripheral blood of patients with AE (n = 40) and Pso (n = 65) during exacerbation of their disease in comparison with healthy, non-atopic controls (n = 50). RESULTS: A high number of similarities between monocytes of patients with AE and patients with Pso, and disease-related differences in the expression of CD62L, CD62P, CD11a, CD11b, CD11c, CD49b, CD49d, CD49e and CD18 and the tetraspanins CD9, CD53, CD63 and CD151, which were elevated on monocytes of patients with AE could be observed. CONCLUSION: A distinct expression pattern of adhesion molecules and tetraspanins on monocytes of patients with AE and Pso might influence the recruitment process of inflammatory precursor cells and facilitate new approaches for therapeutic strategies aimed at interrupting the very earliest steps of the fateful recruitment process.     

Food adverse reactions in patients over 14 years of age suffering from atopic eczema

Adverse reactions to food represent one of the most common complaints in the general population and particularly in childhood. Only few population-based data exist on the association of food adverse reactions and atopic eczema (AE). The objective of this study was an assessment of anamnestical data in patients with AE obtained in questionnaires and statistical evaluation of the relations among individual parameters monitored, which include the occurrence of adverse food reactions, the onset of AE, occurrence of asthma bronchiale (AB), occurrence of seasonal or perennial rhinoconjunctivitis (RC). Our findings have demonstrated that the onset of AE before 5 years of age is statististically significantly related to a greater incidence of adverse food reactions at an adult age and to more frequent flare-ups of AE caused by food. Our study demonstrates that there is a significant association between the severity of AE and the incidence of perennial RC, AB, and the worsening of AE in relation to food.     

Serum, cheek cell and breast milk fatty acid compositions in infants with atopic and non-atopic eczema

BACKGROUND: The major theory implicating diet with allergic diseases is associated with altered food consumption and subsequent changes in fatty acid composition. OBJECTIVE: To investigate fatty acid compositions among infants with atopic and non-atopic eczema and healthy infants and to evaluate the expediency of non-invasive cheek cell phospholipid fatty acid composition as a marker in patients with eczema. METHODS: Diagnosis of eczema in infants was confirmed clinically and by positive (atopic eczema, n=6) or negative (non-atopic eczema, n=6) skin prick testing in comparison with controls (n=19). The fatty acid compositions of infant cheek cell and serum phospholipids and breast milk total lipids were analysed by gas chromatography. RESULTS: The distinction between atopic and non-atopic eczema was manifested in cheek cell phospholipids as linoleic acid (14.69 (13.67-15.53)% of total fatty acids; the median (interquartile range)), the sum of n-6 fatty acids (19.94 (19.06-20.53)%) and the sum of polyunsaturated fatty acids (22.70 (21.31-23.28)%) were higher in infants with atopic eczema compared with non-atopic eczema (12.69 (10.87-13.93); 17.72 (15.63-18.91) and 19.90 (17.64-21.06), respectively; P<0.05) and controls (12.50 (12.16-13.42); 18.19 (17.43-18.70) and 20.32 (19.32-21.03), respectively; P<0.05). Serum phospholipid gamma-linolenic acid was lower in both atopic and non-atopic eczema compared with controls (P<0.05) and additionally eicosapentaenoic acid was higher in atopic eczema compared with controls (P<0.05). CONCLUSION: These preliminary results suggest differences in fatty acid compositions between the two types of eczema, calling for further evaluation in a larger setting. The two types of eczema may be regulated by different immunological processes, and fatty acids may have a more profound role in the atopic type.     

Temporal variations in early gut microbial colonization are associated with allergen‐specific immunoglobulin E but not atopic eczema at 2 years of age

Background Intestinal microbiota undergoes substantial development during the first 2 years of life, important for intestinal immunologic development and maturation influencing systemic immune responses. Objective We aimed to investigate, using a prospective study design, whether allergen‐specific IgE (sIgE) and atopic eczema are associated with variations in gut microbial colonization patterns in an unselected population during the first 2 years of life. Methods Faeces from 94 infants were repeatedly sampled from 10 days, 4 months, 1 and 2 years postnatal and analysed for 12 different bacterial species by quantitative real‐time PCR. Venous blood samples from the infants were collected at 2 years of age and were analysed for sIgE for 12 specific allergens. The temporal gut colonization patterns for 42 sIgE‐positive (sIgE?0.35 kU/L) and 52 sIgE‐negative children (sIgE<0.1 kU/L) were then compared. The association between colonization pattern and phenotype as atopic eczema according to UK Working Party (UKWP) criteria were also described. Results Subjects with atopic sensitization had lower levels of Escherichia coli at 4 months and 1 year, higher levels of Bifidobacterium longum at 1 year and lower levels of Bacteroides fragilis at 2 years. For E. coli and B. longum, the differences were only transient and had disappeared by 2 years of age. For other species, there were no differences in colonization patterns, and we found no association between colonization pattern and atopic eczema. Conclusions and Clinical Relevance We found temporal and transient variations in gut microbial colonization patterns associated with differences in sIgE sensitization at 2 years of age. A full understanding of the principles and mechanisms that underlie intestinal microbial colonization and diversity and host–microbiota relationships will be pivotal for the development of therapeutic approaches that manipulate the intestinal microbiota to maintain human health. [Registration number: ISRCTN28090297] Cite this as: O. Storrø, T. Øien, Ø. Langsrud, K. Rudi, C. Dotterud and R. Johnsen, Clinical & Experimental Allergy, 2011 (41) 1545–1554.