DERMATOLOGIC THERAPY, Issue 2 2006
Alfons Krol
ABSTRACT:, Atopic is the most common of the dermatitides seen in infancy and childhood, but there are numerous other diseases that can mimic the skin findings. These include seborrheic dermatitis, immunodeficiency, and psoriasis in infancy; scabies, tinea corporis infection, perioral, nummular, contact, and molluscum dermatitis in childhood. It is sometimes extremely difficult to differentiate between ichthyosis and AD, and it is also important to differentiate AD from erythrodermic conditions including acrodermatitis enteropathica, biotin deficiency, and Netherton syndrome. A rare condition in children that may mimic AD is mycosis fungoides. [source]

Exhaled nitric oxide in asthmatic and non-asthmatic children: Influence of type of allergen sensitization and exposure to tobacco smoke

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2001
Mario Barreto
Asthmatic bronchial inflammation is associated with increased nitric oxide concentrations in exhaled air (eNO). Recent data suggest that this effect arises from atopy. Our aim in this study was to find out whether atopy and sensitization to particular allergens influences eNO levels. A total of 213 subjects (41 asthmatics and 172 controls) (96 boys and 117 girls, 7.3,14 years of age) were studied. Parents completed a questionnaire that sought information on their children's respiratory symptoms and exposure to tobacco smoke. Subjects underwent skin-prick tests for the following common allergens: Dermatophagoides pteronyssinus (Dpt), cat fur, Aspergillus fumigatus, Alternaria tenuis, mixed grass, mixed tree pollen, Parietaria officinalis, egg, and cow's milk. eNO was collected in 1-l mylar bags (exhaled pressure 10 cmH2O, flow 58 ml/s) and analyzed by using chemiluminescence. Atopic and non-atopic children without a history of chronic respiratory symptoms had a similar geometric mean eNO (atopics, n = 28, 11.2 p.p.b.; non-atopics, n = 96, 10.0 p.p.b.; mean ratio 1.1, 95% confidence interval [CI]: 0.7,1.6). Conversely, atopic asthmatic subjects had significantly higher eNO values than non-atopic asthmatic subjects (atopics, n = 25, 24.8 p.p.b.; non-atopics, n = 16, 11.4 p.p.b.; mean ratio 2.2, 95% CI: 1.2,3.9, p=,0.000). In children with rhinitis alone (n = 15) and those with lower respiratory symptoms other than asthma (n = 33), eNO increased slightly, but not significantly, with atopy. eNO levels correlated significantly with Dpt wheal size (r = 0.51) as well with the wheal size for cat, mixed grass, and Parietaria officinalis (r = 0.30,0.29), and with the sum of all wheals (r = 0.47) (p=,0.000). Subjects sensitized only for Dpt (but not those subjects sensitized only for grass pollen or other allergens) showed significantly higher eNO levels than non-atopic subjects (16.4 p.p.b. vs. 10.2 p.p.b., mean ratio 1.6, 95% CI: 1.1,2.3, p=,0.002). In asthmatic subjects, Dpt sensitization markedly increased eNO levels (Dpt- sensitized subjects: 28.0 p.p.b.; Dpt- unsensitized subjects: 12.2 p.p.b.; mean ratio 2.3, 95% CI: 1.5,3.5, p=,0.000). Non-asthmatic Dpt- sensitized subjects also had significantly higher eNO values than non-asthmatic, non- Dpt -sensitized subjects (14.2 p.p.b. vs. 10.1 p.p.b.; mean ratio 1.4, 95% CI: 1.1,1.9, p=,0.008). No difference was found between eNO levels in asthmatic subjects and control subjects exposed or unexposed to tobacco smoke. In conclusion, eNO concentrations are high in atopic asthmatic children and particularly high in atopic asthmatics who are sensitized to house-dust mite allergen. [source]

Emollients in a propanol-based hand rub can significantly decrease irritant contact dermatitis

CONTACT DERMATITIS, Issue 6 2005
Günter Kampf
The objective of this study is to determine the effect of emollients in a propanol-based hand rub on skin dryness and erythema. In this prospective, randomized, controlled, double-blind trial, 35 subjects participated; of them approximately half were atopic (modified Erlanger atopy score ,8). 2 propanol-based formulations were tested in a repeated open application test, 1 contained a mixture of emollients (0.81%, w/w). 2 aliquots of 0.7 ml of each formulation were applied twice per day over 2 weeks to the cubital fossa of each subject after random assignment of the preparations. Treatment areas were assessed before each application and 3 days postfinal application by visual inspection for erythema and dryness according to a standard scale. The sum score over all assessment time-points served as primary parameter. The mean sum score for erythema and dryness was significantly lower for the hand rub with emollients (0.8 ± 2.4) in comparison with that for the hand rub without emollients (1.5 ± 3.5; P = 0.022; Wilcoxon signed rank test). A comparison of the atopic and non-atopic subjects revealed no significant difference for any of the products (P > 0.05; Mann,Whitney U -test). It is concluded that the addition of emollients to a propanol-based hand rub can significantly decrease irritant contact dermatitis under frequent-use conditions. [source]

P16 Eyelid dermatitis with positive patch test to coconut diethanolamide

CONTACT DERMATITIS, Issue 3 2004
Yves Dejobert
Objective:, The aim was to detect a possible allergen in a patient with eyelid dermatitis. Patient and methods: a non atopic 27-year-old female presented with eyelid dermatitis since 3 months. This dermatitis persisted despite the fact she had stopped the use of make up; she had acrylic artificial nails since 2 months and sometimes used hair dyes;patch tests were performed with Finn Chamber® tests with readings at D2 and D3, according ICDRG criteria, with European standard series, additional series (including toluenesulfonamide formaldehyde resin), cosmetic, acrylates, hairdressing series, in 3 patch test sessions, using Chemotechnique Diagnostics® allergens. Results:, The only positive patch test was coconut diethanolamide (0.5% pet.)++ at D2 and D3. After removal of the shampoo containing this allergen, the dermatitis cleared. Coconut diethanolamide (cocamide DEA), tensioactive synthesized with coconut oil is widely used in shampoos, soaps, shower gels, barrier creams, washing up liquids, metalworking fluids, hydraulic oils. Involvement of eyelids is not frequently described in the literature with this allergen. Conclusion:, Coconut diethanolamide should be added in cosmetic series, and it should be useful to test this allergen in patients with eyelid dermatitis. [source]

Lichen simplex chronicus (atopic/neurodermatitis) of the anogenital region

DERMATOLOGIC THERAPY, Issue 1 2004
Peter J. Lynch
ABSTRACT:, Lichen simplex chronicus (LSC) of the anogenital area is an eczematous disease characterized by unremitting itching and scratching. In most instances, it arises in individuals who are genetically atopic, and as such, LSC can be viewed as a localized variant of atopic/neurodermatitis. Common triggers for the development of the disease include psychological distress, and local environmental problems such as heat, sweating, and excess dryness. Lichen simplex chronicus may also develop as a superimposed condition in the presence of other anogenital diseases such as candidiasis, psoriasis, lichen sclerosus, tinea cruris, and neoplasia. Lichen simplex chronicus frequently persists as an itch-scratch cycle, even when environmental triggers are removed and the underlying disease is treated. For this reason, successful therapy requires attention not only to trigger factors, but also to repair of the damaged barrier layer, reduction in inflammation, and breakup of the itch-scratch cycle. [source]

Cross-priming with an epicutaneously introduced soluble protein antigen generates Tc1 cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2006
Li-Fang Wang
Abstract Epicutaneous sensitization with a protein antigen was demonstrated to induce a predominant type 2 CD4 T cell response with high IgE production in mice. On the other hand, its CD8 T cell responses have not been addressed probably partly because of the generally accepted concept that cross-priming of soluble protein is an inefficient process. Here, we used an established patch-applied murine model to demonstrate that cross-priming with an epicutaneously introduced soluble protein antigen, though inefficient, generated mainly Tc1 cells, but not Tc2 cells. In the presence of an irritant or hapten, the efficiency of this cross-priming process could be enhanced and more Tc1 cells were generated. CpG oligonucleotides also promote the generation of Tc1 cells. In contrast, lipopolysaccharide and poly (inosinic-cytidylic) acid [poly (I:C)] have no effect. Together, these results provide supportive evidence of the epicutaneous sensitization of human cutaneous lymphocyte-associated antigen-positive CD8 T cells found in the peripheral blood or tissues of patients. The surprising observation of the type 1 character of the generated CD8 T cells will also help us to better understand the complicated pathogenesis of atopic and cutaneous inflammatory diseases. [source]

CCL22-induced responses are powerfully enhanced by synergy inducing chemokines via CCR4: evidence for the involvement of first ,-strand of chemokine

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2005
Silvia Sebastiani
Abstract In an attempt to clarify how cells integrate the signals provided by multiple chemokines expressed during inflammation, we have uncovered a novel mechanism regulating leukocyte trafficking. Our data indicate that the concomitant exposure to CCR4 agonists and CXCL10/IP-10 strongly enhances the chemotactic response of human T lymphocytes. This enhancement is synergistic rather than additive and occurs via CCR4 since it persists after CXCR3 blockade. Besides chemotaxis, other cellular responses are enhanced upon stimulation of CCR4-transfected cells with CCL22/MDC plus CXCL10. Several other chemokines in addition to CXCL10 were able to increase CCL22-mediated chemotaxis. The first ,-strand of the chemokine structure is highly and specifically implicated in this phenomenon, as established using synergy-inducing and non-synergy-inducing chimeric chemokines. As shown in situ for skin from atopic and allergic contact dermatitis patients, this organ becomes the ideal environment in which skin-homing CCR4+ T lymphocytes can accumulate under the stimulus offered by CCR4 agonists, together with the synergistic chemokines that are concomitantly expressed. Overall, our results indicate that chemokine-induced synergism strengthens leukocyte recruitment towards tissues co-expressing several chemokines. [source]

Molecular epidemiology of molluscum contagiosum virus and analysis of the host-serum antibody response in Spanish HIV-negative patients

JOURNAL OF MEDICAL VIROLOGY, Issue 2 2002
Monica Agromayor
Abstract Molluscum contagiosum virus (MCV) lesions from Spanish human immunodeficiency virus (HIV)-negative patients were clinically examined and analyzed for virus detection and typing. In a study of 147 patients, 97 (66%) were children under 10 years, of whom 49% had atopic dermatitis. MCV lesions were morphologically indistinguishable among the different age groups, but atopic patients presented larger lesions compared with patients without the disorder. In adults, lesions were observed mainly on the genitals. MCVI was the predominant subtype. The deduced MCVI/MCVII ratio (146:1) was much higher than that found in other geographical areas. Protein preparations of the virus-induced lesions were immunoblotted with sera from 25 MCVI patients. The host-serum antibody response was weak and variable, although no significant differences were found between atopic and nonatopic patients. Three immunoreactive proteins of 74/80, 60, and 35 kDa were detected in almost all the analyzed sera. The 35 and 74/80-kDa proteins were virus specific, whereas the 60-kDa protein band was composed of a mix of human keratins. Immunoblotting of MCV lesions and vaccinia virus-infected cell extracts with either MCV patient serum or a rabbit antiserum against vaccinia virus showed no cross-reactivity of these two human poxviruses at the antigenic level. J. Med. Virol. 66:151,158, 2002. © 2002 Wiley-Liss, Inc. [source]

Intestinal B cell-activating factor: an indicator of non-IgE-mediated hypersensitivity reactions to food?

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010
G. Arslan Lied
Aliment Pharmacol Ther 2010; 32: 66,73 Summary Background, Medically confirmed hypersensitivity reactions to food are usually IgE-mediated. Non-IgE-mediated reactions are not only seldom recognized but also more difficult to diagnose. Aim, To examine B cell-activating factor (BAFF) in serum and gut lavage fluid of patients with self-reported food hypersensitivity, and to study its relationship to atopic disease. Methods, Gut lavage fluid was obtained from 60 and serum from another 17 patients with self-reported food hypersensitivity. Twenty healthy volunteers served as controls, gut lavage fluid was obtained in all, serum from 11 of 20. The patients were divided into atopic and non-atopic subgroups. BAFF was measured by ELISA in both serum and gut lavage fluid. Results, B cell-activating factor levels in serum and gut lavage fluid were significantly higher in patients than in controls (P < 0.03 and P < 0.002 respectively). Non-atopic patients had significantly higher levels of BAFF in serum than both atopic patients (P < 0.05) and controls (P < 0.05). There was no significant correlation between serum levels of BAFF and IgE. Conclusions, The results suggest that BAFF might be a new mediating mechanism in food hypersensitivity reactions. Significantly higher levels in non-atopic compared with atopic patients, and no correlation between BAFF and IgE, suggest that BAFF might be involved particularly in non-IgE-mediated reactions. [source]

Indications of ,atopic bowel' in patients with self-reported food hypersensitivity

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2010
K. LILLESTØL
Aliment Pharmacol Ther,31, 1112,1122 Summary Background, An association between atopic disease and gastrointestinal complaints has been suggested. Aim, To explore the association between atopic disease, gastrointestinal symptoms, and possible gastrointestinal manifestations of atopic disease in patients with self-reported food hypersensitivity. Methods, Symptoms, skin prick tests, serum markers of allergy and intestinal permeability were recorded in 71 adult patients. Eosinophils, tryptase- and IgE-positive cells were counted in duodenal biopsies. Results, Sixty-six (93%) patients had irritable bowel syndrome (IBS) and 43 (61%) had atopic disease, predominantly rhinoconjunctivitis. All 43 were sensitized to inhalant allergens, 29 (41%) to food allergens, but food challenges were negative. Serum total IgE and duodenal IgE-positive cell counts were significantly correlated (P < 0.0001) and both were significantly higher in atopic than in non-atopic patients (P < 0.0001 and P = 0.003 respectively). IgE-positive cells appeared to be ,armed' mast cells. Intestinal permeability was significantly elevated in atopic compared with non-atopic patients (P = 0.02). Gastrointestinal symptoms and numbers of tryptase-positive mast cells and eosinophils did not differ between groups. Conclusions, Patients with self-reported food hypersensitivity had a high prevalence of IBS and atopic disease. Atopic patients had increased intestinal permeability and density of IgE-bearing cells compared with non-atopic patients, but gastrointestinal symptoms did not differ between groups. [source]

Markers of eosinophilic and neutrophilic inflammation in bronchoalveolar lavage of asthmatic and atopic children

ALLERGY, Issue 8 2010
D. Snijders
To cite this article: Snijders D, Agostini S, Bertuola F, Panizzolo C, Baraldo S, Turato G, Faggian D, Plebani M, Saetta M, Barbato A. Markers of eosinophilic and neutrophilic inflammation in bronchoalveolar lavage of asthmatic and atopic children. Allergy 2010; 65: 978,985. Abstract Background:, Recent studies performing fiberoptic bronchoscopy in children have improved our understanding of asthma pathophysiology. Eosinophilic, but also neutrophilic, inflammation has been described in asthma, but the relationship with atopy was incompletely investigated. The aim of this study is to examine inflammatory cells and mediators in children with asthma compared to the appropriate controls, i.e. atopic children without asthma and children with no atopy or asthma. Moreover, asthmatic children were analysed separately based on the presence of atopy and stratified by age. Methods:, We recruited 191 children undergoing fiberoptic bronchoscopy for appropriate indications: 91 asthmatics (aged 1.4,17 years), 44 atopics without asthma (1.6,17.8 years) and 56 nonasthmatic nonatopic controls (1.4,14 years). In bronchoalveolar lavage, total and differential cell counts and inflammatory mediators, including ECP, eotaxin, IL-8 and TNF,, were analysed. Results:, Eosinophils and ECP levels were increased in asthmatic children when compared to controls (P = 0.002 and P = 0.01, respectively), but also atopic children without asthma had increased ECP levels compared to controls (P = 0.0001). Among asthmatic children, eosinophils and ECP levels were not different between atopic and nonatopic individuals. Neither neutrophils nor the related mediators (IL-8 and TNF,) differed significantly in the three groups. This pattern of inflammation was observed in both preschool and school-aged asthmatic children. Conclusions:, This study suggests that markers of eosinophilic, but not neutrophilic inflammation, are increased in asthmatic children and also in atopic children without asthma. Of interest, in asthmatic children, the activation of the eosinophilic response is not solely because of the presence of atopy. [source]

Characterization of the methylation patterns of MS4A2 in atopic cases and controls

ALLERGY, Issue 3 2010
M. A. R. Ferreira
To cite this article: Ferreira MAR, Oates NA, van Vliet J, Zhao ZZ, Ehrich M, Martin NG, Montgomery GW, Whitelaw E, Duffy DL. Characterization of the methylation patterns of MS4A2 in atopic cases and controls. Allergy 2010; 65: 333,337. Abstract Background:, It is largely unknown whether epigenetic modifications of key genes may contribute to the reported maternal effects in atopy. The aim of this study was to characterize the methylation patterns of the membrane-spanning 4-domains, subfamily A, member 2 gene (MS4A2) (,-chain of the IgE high-affinity receptor), a key gene in the allergic cascade. Methods:, Mass spectrometry and bisulphite sequencing were used to measure the methylation of two potential substrates for epigenetic regulation of MS4A2, namely a predicted promoter and a CpG-rich AluSp repeat. Methylation was measured in DNA extracted from peripheral blood lymphocytes of 38 atopic cases and 37 controls. Cases were positive for atopy, asthma, bronchial hyper-responsiveness and had high IgE levels. Both parents of eight atopic cases were also tested. Results:, The AluSp element was highly methylated across all individuals (mean 0.92, range 0.87,0.94), a pattern inconsistent with classical imprinting. Variation in methylation at this locus was not associated with age, sex, daily steroid use or atopic status, and there were no differences in methylation between mothers and fathers of atopic cases. Bisulphite sequencing analysis of the promoter region showed that it was also not imprinted, and there was no evidence for allele-specific methylation, but we were unable to test for association with atopy status. Conclusions:, Methylation levels at the AluSp repeat analysed in MS4A2 were inconsistent with classical imprinting mechanisms and did not associate with atopy status. The promoter region was less methylated but further analysis of this region in larger cohorts is warranted to investigate its role in allergic disease. [source]

Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure

ALLERGY, Issue 12 2009
M. L. A. Schuttelaar
Background:, Filaggrin gene (FLG) mutations contribute to the development of eczema and asthma, but their contribution to sensitization and hay fever remains unclear. Methods:,FLG mutations R501X, 2282del4 and R2447X were genotyped in the Prevention and Incidence of Asthma and Mite Allergy birth cohort (n = 934) to evaluate longitudinally, for up to 8 years, their association with eczema, sensitization, asthma, hay fever and their interaction with cat exposure. Results:, The combined FLG mutations were significantly associated with eczema at all ages when occurring in the first year of life (OR = 2.0; 95% CI: 1.4,2.8). Combined FLG mutations were associated with both atopic and nonatopic eczema, as well as asthma (OR = 3.7; 95% CI: 1.8,7.5). When the FLG 2282del4 mutation was analysed separately, it was significantly associated with the development of eczema during the first year, having eczema up to 8 years and sensitization at the age of 8 years, which was enhanced by early-life cat exposure (ORs being 8.2; 95% CI: 2.6,25.9, 6.0; 95% CI: 3.2,11.3 and 5.4; 95% CI: 1.2,23.6 respectively). FLG 2282del4 was significantly associated with hay fever from the age 5 years onwards (OR = 3.9; 95% CI: 1.5,10.5). Conclusions:,FLG mutations are associated both with atopic and nonatopic eczema starting in the first year of life. FLG mutations combined with eczema in the first year of life are associated with a later development of asthma and hay fever, a clear example of the atopic march. We confirm that cat exposure enhances the effect of a FLG mutation on the development of eczema and sensitization. [source]

Neutrophilic airway inflammation is a main feature of induced sputum in nonatopic asthmatic children

ALLERGY, Issue 11 2009
A. C. Drews
Background:, Asthma phenotypes are well described among children. However, there are few studies comparing airway inflammation in different clinical presentations of pediatric asthma. We tested the hypothesis that nonatopic asthma is associated with a predominant noneosinophilic inflammation in the airways, as assessed by induced sputum. The objective of this study was to evaluate the cytological characteristics of induced sputum (IS) in atopic (AA), nonatopic asthmatics (NAA) and nonatopic nonasthmatic children (NANA). Methods:, Of 90 selected children, 77 met eligibility criteria for performing IS and were classified as: AA, n = 28, NAA, n = 29 and NANA, n = 19. Subjects answered to a set of ISAAC-based questions and were skin-tested for common aeroallergens. A defined series of exclusion criteria was applied. Results:, Induced sputum was obtained from 54 (70.1%) subjects (21 AA, 20 NAA and 13 NANA). Demographic data and mean FEV1 were similar in the three groups. The proportion of eosinophils [median, inter quartile range (IQR)] was significantly higher in the sputum of AA [(6.0.)12)] compared with NAAs [0 (2)] and NANAs [0 (1)], P < 0.001. The proportion of children with sputum eosinophilia (eos > 3%) was also significantly higher in AA (71.4%) when compared with NAA (28.6%); none of the NANA had sputum eosinophilia. Nonatopic asthmatic children had significantly higher proportions and absolute number of neutrophils than AA and controls. Conclusions:, The results suggest that nonatopic children present IS with a cell pattern that is predominantly neutrophilic while eosinophilia is the hallmark of airway inflammation in the majority of atopic wheezing children not treated with inhaled steroids. [source]

Counter regulation of the high affinity IgE receptor, Fc,RI, on human airway dendritic cells by IL-4 and IL-10

ALLERGY, Issue 11 2009
A. Faith
Background:, Immunoglobulin E is a signalling molecule within the environment of the respiratory tract, the high affinity receptor for which, Fc,RI, is expressed by dendritic cells (DC). Little is known, however, of the expression and function of Fc,RI on DC in the human respiratory tract. Methods:, CD1c+ DC were purified from surgically resected nasal turbinates of 11 atopic and 12 nonatopic patients with chronic rhinosinusitis. Expression of Fc,RI was determined by flow cytometry. Cytokine production by DC was determined by cytometric bead array. Results:, Expression of Fc,RI was significantly elevated on respiratory tract dendritic cells (RTDC) from atopic as compared to nonatopic patients. Activation of RTDC through Fc,RI induced production of the pro-inflammatory cytokines IL-6 and TNF-,, and the anti-inflammatory cytokine IL-10. The production of IL-6 and TNF-, was elevated in atopic compared to nonatopic patients studied. Conversely IL-10 production was elevated in nonatopic patients. Concomitant activation of Fc,RI and stimulation of RTDC with IL-4 inhibited production of IL-10 by RTDC. Neutralization experiments with anti-IL-10 Ab enhanced whereas addition of exogenous IL-10 to RTDC inhibited Fc,RI-mediated inflammatory cytokine production. Conclusion:, The function of Fc,RI on RTDC from patients with rhinosinusitis is susceptible to counter regulation by IL-4 and IL-10. [source]

Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort

ALLERGY, Issue 9 2009
J. Julvez
Background:, Mental health has been reported to be associated with allergy, but only a few cohort studies have assessed if neurodevelopment predicts atopy. Objective:, To investigate if neurobehavioral status of healthy 4-year-old children was associated with specific immunoglobulin E (IgE) at the same age and skin prick test results 2 years later. Methods:, A population-based birth cohort enrolled 482 children, 422 of them (87%) provided neurobehavioral data, 341 (71%) had specific IgE measured at the age of 4 years; and 395 (82%) had skin prick tests completed at the age of 6 years. Atopy was defined as IgE levels higher than 0.35 kU/l to any of the three tested allergens at the age of 4 or as a positive skin prick test to any of the six tested allergens at the age of 6. McCarthy Scales of Child Abilities and California Preschool Social Competence Scale were the psychometric instruments used. Results:, Twelve percent of children at the age of 4 and 17% at the age of 6 were atopic. Neurobehavioral scores were negatively associated with 6-year-old atopy after adjustment for socio-demographic and allergic factors, A relative risk of 3.06 (95% CI: 1.30,7.24) was associated with the lowest tertile (scorings ,90 points) of the general cognitive scale. Similar results were found for verbal abilities, executive functions, and social competence. Asthma, wheezing, rhinitis, and eczema at the age of 6, but not at the age of 4, were associated with neurodevelopment at the age of 4. Conclusions:, Neuropsychologic functioning and later atopy are negatively associated in preschool age children. [source]

Chemokine responsiveness of CD4+ CD25+ regulatory and CD4+ CD25, T cells from atopic and nonatopic donors

ALLERGY, Issue 8 2009
D. Ahern
Background:, Allergic inflammation is associated with Th2-type T cells, which can be suppressed by CD4+ CD25+ regulatory T cells (Tregs). Both express chemokine receptors (CCR) 4 and CCR8, but the dynamics of expression and effect of atopic status are unknown. Objective:, To examine the expression of chemokine receptors by CD4+ CD25+ and CD4+ CD25, T cells from atopic and nonatopic donors, and document response to allergen stimulation in vitro. Methods:, Chemokine receptor expression was examined by flow cytometry and quantitative PCR of CD4+ CD25hi and CD4+ CD25, T cells from atopics and nonatopics. Responsiveness to chemokines was by actin polymerization. Dynamics of chemokine receptor expression in 6-day allergen-stimulated cultures was analysed by carboxyfluoroscein succinimidyl ester labelling. Results:, CD4+ CD25hi Tregs preferentially expressed CCR3, CCR4, CCR5, CCR6 and CCR8. CD4+ CD25hi Tregs responded to the chemokine ligands for CCR4, CCR6 and CCR8 (CCL17, 22, 20 and 1 respectively), with no differences between atopic and nonatopic donors. Over 6-day allergen stimulation, CD4+ CD25+ T-cells downregulated CCR4 and upregulated CCR7, in contrast to CD4+ CD25, effector cells, which downregulated CCR7 and upregulated CCR4. Conclusions:, CCR4, CCR6 and CCR8 have potential roles in localization of both CD4+ CD25+ regulatory and CD4+ CD25, effector T cells to sites of allergic inflammation. Upregulation of CCR7 and downregulation of CCR4 upon allergen stimulation of Tregs may allow their recirculation from sites of inflammation, in contrast to retention of effector T cells. [source]

Early production of thymic stromal lymphopoietin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjects

ALLERGY, Issue 7 2009
C. J. Corrigan
Background:, Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses through a receptor consisting of a heterodimer of the IL-7 receptor alpha (IL-7R,) chain and the TSLP receptor (TSLPR), which resembles the cytokine receptor common gamma chain. Dendritic cells activated by TSLP prime development of CD4+ T cells into Th2 cells contributing to the pathogenesis of allergic inflammation. We hypothesized that allergen exposure induces expression of TSLP and results in recruitment of TSLPR bearing cells in the cutaneous allergen-induced late-phase reaction (LPR) in atopic subjects. Methods:, Skin biopsies were obtained from atopic subjects (n = 9) at various times after cutaneous allergen challenge. In situ hybridization and immunohistochemistry were used to determine TSLP mRNA expression and to measure infiltration of TSLPR+ DC in skin LPR. RT-PCR and flow cytometry were employed to analyse TSLPR expression on isolated blood DC. Results:, Allergen-induced skin TSLP expression occurred as early as 1 h after allergen challenge, whereas TSLPR+ and CD11c+ cells infiltrated relatively late (24,48 h). The majority of TSLPR+ cells were DC co-expressing blood DC antigen-1 (BDCA-1) or BDCA-2. Freshly isolated blood DC expressed both TSLPR and IL-7R, chains. Maturation and stimulation with TSLP or polyriboinosinic,polyribocytidylic acid in vitro upregulated the expression of both TSLPR and IL-7R, chains in DC but not in chemoattractant receptor-homologous molecule expressed on Th2 cells+ CD4+ T cells. Conclusion:, The data suggest that TSLP plays a role in augmenting, through DC recruitment and activation, the development of Th2-type T cells in allergic inflammation. [source]

The importance of nasal provocation test in the diagnosis of natural rubber latex allergy

ALLERGY, Issue 6 2009
M. Ünsel
Background:, Most studies regarding natural rubber latex (NRL) allergy have concentrated on the prevalance using skin prick test (SPT) and specific IgE assay. The objective of this study is to examine the target organ (skin, nasal mucosa) responses in patients with positive SPT to NRL using the nasal provacation test (NPT) and glove use test (GUT). Methods:, Four thousand four hundred and twenty patients presented to our polyclinic between July 2003 and January 2007 were evaluated. One thousand six hundred and ninety-nine patients had positive SPT to one or more allergens (NRL and other inhaler allergens). Twenty-nine patients with positive SPT to NRL comprised the NRL sensitive group (group 1). Thirty-five randomized patients with positive SPT to an inhaler allergen other than NRL and negative NRL-specific IgE comprised atopic control group (group 2). Thirty healthy individuals who had no allergic diseases and had negative SPT and NRL-specific IgE comprised the healthy control group (group 3). Results:, The lowest NRL allergen concentration leading to NPT positiveness was 0.05 ,g/mL. NPT was negative in groups 2 and 3. NPT was found to have a sensitivity of 96%, specificity of 100%, negative predictive value of 98% and positive predictive value of 100%. GUT was found to have a sensitivity of 81%, specificity of 90%, negative predictive value of 75% and positive predictive value of 93%. Conclusions:, Nasal provocation test was successfully used for the first time in the diagnosis of NRL allergy. NPT is a more sensitive method as compared to GUT. [source]

A specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides induces a beneficial immunoglobulin profile in infants at high risk for allergy

ALLERGY, Issue 3 2009
E. Van Hoffen
Background:, It has been suggested that human breast milk oligosaccharides play a role in the development of the immune system in infants, and may consequently inhibit the onset of allergy. A specific prebiotic mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (GOS/FOS) has been shown to reduce the incidence of atopic dermatitis (AD) at 6 months of age in infants at risk for allergy. Aim of the study:, This study was aimed to analyze the effect of GOS/FOS on the immune response in these infants. Methods:, In a double-blind randomized placebo-controlled study, infants received a hypoallergenic whey formula with either 8 g/l GOS/FOS in a 9 : 1 ratio (IMMUNOFORTISTM) or 8 g/l maltodextrine (placebo) for 6 months. At 3 months of age, children were vaccinated with Hexavac against a.o. diphteria, tetanus, polio (DTP). At 6 months of age, plasma samples were collected from 84 infants (verum group n = 41, placebo group n = 43). Levels of total immunoglobulins (Ig) and of cow's milk protein (CMP-) and DTP-specific Ig were measured. Results:, GOS/FOS supplementation led to a significant reduction in the plasma level of total IgE, IgG1, IgG2 and IgG3, whereas no effect on IgG4 was observed. CMP-specific IgG1 was significantly decreased. DTP-specific Ig levels were not affected. Conclusions:, This study shows that GOS/FOS supplementation induces a beneficial antibody profile. GOS/FOS reduces the total Ig response and modulates the immune response towards CMP, while leaving the response to vaccination intact. This suggests that oral GOS/FOS supplementation is a safe method to restrain the atopic march. [source]

The effects of allergens in outdoor air on both atopic and nonatopic subjects with airway disease

ALLERGY, Issue 5 2008
P. G. J. Burney
Background:, Reports on air pollution and asthma exacerbations have been inconsistent, although effects of airborne allergen can be spectacular. With no generalized test for allergen in air, it is not known how far allergen is responsible for nonepidemic exacerbations of the disease. Methods:, Two hundred and ninety-seven patients using bronchodilators aged 18,64 years attending a London practice provided serum samples and were asked to report any acute respiratory events over the coming months. Small particles with a mean aerodynamic diameter <10 ,m (PM10) were collected using a high volume sampler on the roof of the practice. The ability of airborne particles to bind IgE from the patients was compared for particles sampled on the weekend before their reported exacerbation with particles sampled on the weekend 2 weeks before or after. Results:, Exacerbations were associated with a 25% increase in IgE binding to particles collected on the previous weekend compared with the control weekends (95% confidence interval: 10,43%; P = 0.00089). This increase was not higher in patients with positive skin tests or in those sensitized to grass or tree pollens. Conclusions:, Airborne allergen is an important cause of exacerbations even in those with ,intrinsic' asthma. It is important to identify the allergens responsible, as some of these may be controllable. Interpretation of associations of asthma exacerbations with other air pollutants is difficult in the light of these findings. [source]

Original article: Predictors of response to bronchial allergen challenge in 5- to 6-year-old atopic children

ALLERGY, Issue 4 2007
T. A. Douglas
Background:, The relationship between atopy and bronchial allergy in young children is not completely understood. Objective:, To examine the association between response to bronchial allergen challenge, immune markers of atopy and other clinical characteristics in 5- to 6-year-old children. Methods:, Children with positive skin test (SPT) to aeroallergen, together with a proportion of SPT negative children (as controls), were recruited from a birth cohort of 198 children at high risk of developing atopic disease and underwent allergen challenge. Results:, Thirty-seven children (26 atopic and 11 SPT negative), median age 74.5 months, were challenged: 31 with house dust mite and six with grass allergen. Only atopic children responded to challenge: n = 12/26 (46%). Wheal size [odds ratio (OR) 2.5 (1.2,5.3), P = 0.01], allergen-specific immunoglobulin E (IgE) [OR 3.4 (1.23,9.61), P = 0.02], total IgE [OR 8.6 (1.1,68.7), P = 0.04], current wheeze [OR 12 (1.7,81.7), P = 0.006] and persistent eczema [OR 11.0 (1.7,68.3), P = 0.006] emerged as the strongest independent predictors of response to allergen challenge. Prediction of response to allergen challenge was significantly improved when immune markers of atopy, and in particular wheal size, were combined with clinical characteristics. Conclusion:, The relationship between atopy and bronchial allergy is quantitative at this age. There may be potential to create more powerful indicators of the presence of respiratory allergy in young children when immunological markers of atopy are considered quantitatively and when combined with clinical history of coexistent allergic disease. [source]

Sublingual immunotherapy in the treatment of children

ALLERGY, Issue 2006
N. Pham-Thi
Children with controlled intermittent mild-to-moderate asthma, controlled rhinitis and a single sensitivity may be appropriate candidates for sublingual immunotherapy (SLIT). Positive effects of SLIT may depend on initiation in early childhood and a long duration of treatment. To ensure optimum compliance, sociological, economic and familial factors should also be taken in to consideration when prescribing SLIT. Evidence from recent long-term trials indicates that SLIT interfered with the atopic march and the allergic progression from rhinitis to asthma without any severe adverse side effects. Local immune response has been seen to be blunted with SLIT, which suggests that treatment has an immunomodulatory effect. In addition, it may also decrease the risk of new sensitizations. Ongoing developments in SLIT, particularly advances in dosing and new indications, such as food allergies, will increase the use of this treatment modality in children. [source]

High intestinal IgA associates with reduced risk of IgE-associated allergic diseases

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1-Part-I 2010
Kaarina Kukkonen
Kukkonen K, Kuitunen M, Haahtela T, Korpela R, Poussa T, Savilahti E. High intestinal IgA associates with reduced risk of IgE-associated allergic diseases. Pediatr Allergy Immunol 2010: 21: 67,73. © 2009 John Wiley & Sons A/S Development of oral tolerance and its stimulation by probiotics are still incomprehensible. Microbial stimulation of the gut may induce a subtle inflammation and induce secretion of mucosal IgA, which participates in antigen elimination. In a cohort of allergy-prone infants receiving probiotics and prebiotics or placebo we studied intestinal IgA and inflammation in the development of eczema, food allergy, asthma, and rhinitis (allergic diseases). We performed a nested unmatched case,control study of 237 infants participating in a randomized double-blind placebo-controlled allergy-prevention trial using a combination of four probiotic strains pre-natally and during 6 months form birth. We measured faecal IgA, ,1-antitrypsin (,1-AT), tumour necrosis factor-alpha (TNF-,), and calprotectin at the age of 3 and 6 months. By age 2 yr, 124 infants had developed allergic disease or IgE-sensitization (cases) and 113 had not (controls). In infants with high faecal IgA concentration at the age of 6 months, the risk of having any allergic disease before the age of 2 yr tended to reduce [odds ratio (OR: 0.52)] and the risk for any IgE-associated (atopic) disease reduced significantly (OR: 0.49). High faecal calprotectin at the age of 6 months associated also with lower risk for IgE-associated diseases up to age 2 yr (OR: 0.49). All faecal inflammation markers (,1-AT, TNF-,, and calprotectin) correlated positively with faecal IgA (p < 0.001). Probiotics tended to augment faecal IgA (p = 0.085) and significantly increased faecal ,1-AT (p = 0.001). High intestinal IgA in early life associates with minimal intestinal inflammation and indicates reduced risk for IgE-associated allergic diseases. [source]

Exhaled nitric oxide and exercise-induced bronchoconstriction in young wheezy children , interactions with atopy

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 7 2009
L. Pekka Malmberg
The association between exercise-induced bronchoconstriction (EIB) and exhaled nitric oxide (FENO) has not been investigated in young children with atopic or non-atopic wheeze, two different phenotypes of asthma in the early childhood. Steroid naïve 3- to 7-yr-old children with recent wheeze (n = 84) and age-matched control subjects without respiratory symptoms (n = 71) underwent exercise challenge test, measurement of FENO and skin prick testing (SPT). EIB was assessed by using impulse oscillometry, and FENO by standard online technique. Although FENO levels were highest in atopic patients with EIB, both atopic and non-atopic wheezy children with EIB showed higher FENO than atopic and non-atopic control subjects, respectively. In atopic wheezy children, a significant relationship between FENO and the severity of EIB was found (r = 0.44, p = 0.0004), and FENO was significantly predictive of EIB. No clear association between FENO and EIB or predictive value was found in non-atopic wheezy children. Both atopic and non-atopic young wheezy children with EIB show increased FENO levels. However, the association between the severity of EIB and FENO is present and FENO significantly predictive of EIB only in atopic subjects, suggesting different interaction between bronchial responsiveness and airway inflammation in non-atopic wheeze. [source]

Analysis of basophil activation by flow cytometry in pediatric house dust mite allergy

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 4 2008
Miguel González-Muñoz
Detection of allergen-induced basophil activation by flow cytometry has been shown to be a useful tool for allergy diagnosis. The aim of this study was to assess the potential of this technique for the diagnosis of pediatric house dust mite allergy. Quantification of total and specific IgE and basophil activation test were performed to evaluate mite allergic (n = 24), atopic (n = 23), and non-allergic children (n = 9). Allergen-induced basophil activation was detected as a CD63-upregulation. Receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cut-off value of activated basophils discriminating mite allergic and non-allergic children. ROC curve analysis yielded a threshold value of 18% activated basophils when mite-sensitized and atopic children were studied [area under the curve (AUC) = 0.99, 95% confidence interval (CI) = 0.97,1.01, p < 0.001] with a sensitivity and specificity of 96% for 16 ,g/ml mite extract. Analysis of the data obtained with 1.6 ,g/ml mite extract defined a cut-off value of 8% activated basophils (AUC = 0.96, 95% CI = 0.91,1.01; p < 0.001) with a sensitivity of 82% and specificity of 100%. Comparison between mite allergic and non-allergic children produced a cut-off of 8% activated basophils (AUC = 1.0) with 16 ,g/ml allergen extract and a sensitivity and specificity of 100%. The same threshold and specificity values were obtained with 1.6 ,g/ml extract (AUC = 97%, 95% CI = 0.92,1.02; p < 0.001) but sensitivity decreased to 83%. Two atopic children showed negative skin prick and basophil activation tests and high specific IgE (>43 kU/l) values for Dermatophagoides pteronyssinus allergen. They also showed positive prick (wheal diameter >1.0 cm) and basophil activation (>87%) tests and high specific IgE (>100 kU/l) with shrimp allergen. Shrimp sensitization was demonstrated by high levels of Pen a 1-specific IgE (>100 kU/l). Cross-reactivity between mite and shrimp was confirmed by fluorescence enzyme immunoassay (FEIA-CAP) inhibition study in these two cases. This study demonstrated that the analysis of allergen-induced CD63 upregulation by flow cytometry is a reliable tool for diagnosis of mite allergy in pediatric patients, with sensitivity similar to routine diagnostic tests and a higher specificity. Furthermore, this method can provide additional information in case of disagreement between in vivo and in vitro test results. [source]

Prevalence of latex sensitization and allergy in Portuguese children

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 6 2006
Arminda Jorge
The prevalence of latex allergy has been increasing not only in risk groups but also in the general population, where it is accepted to average 1%. In children, latex sensitization prevalence studies are scarce and involve different population sampling and allergy testing methods, which makes it difficult to compare across studies. Nevertheless, existing studies point towards a low prevalence of latex allergy in children, which still needs to be confirmed in the Portuguese population. Aiming at studying the prevalence of latex sensitization and allergy in a sample of Portuguese children, we studied 182 children from two different hospital outpatient clinics. A standardized questionnaire focusing on atopic background, previous history and allergic signs or symptoms on exposure to latex or fruits was given to all children and parents. Skin prick testing was performed with a battery of common aeroallergens as well as latex. Serum total IgE, Phadiatop, F × 5E and latex-specific IgE were determined in all children. Specific IgE to latex-crossreacting fruits was determined in latex-sensitized children. Based upon the questionnaire, the prevalence of latex allergy would be 0.5%. The prevalence of latex sensitization would be 3.8%, when based solely upon skin prick testing, and 12.1% (,0.35 IU/ml) or 6.6% (,0.70 IU/ml) when based singly upon determination of latex-specific IgE. When positive results for either test were considered, the prevalence of latex sensitization was 14.3%. All latex-sensitized children were atopic. Sensitivity to latex-crossreacting foodstuffs was demonstrated in 61.5% of latex-sensitized children (16/26). This study shows that the prevalence of latex allergy and sensitization in Portuguese atopic and non-atopic children, as analysed using various diagnostic methods, is similar to that observed in other countries. In addition, the assessment of latex allergy and sensitization should always include skin prick testing and determination of serum IgE. [source]

Basophil Activation Test and specific IgE measurements using a panel of recombinant natural rubber latex allergens to determine the latex allergen sensitization profile in children

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2006
María L. Sanz
There are no documented studies that describe natural rubber latex (NRL) sensitization in children with a history of surgical intervention but without any congenital malformation (urogenital anomalies, spina bifida, etc.), although some authors have studied NRL allergy in children without a history of surgical intervention. The aim of this work was to evaluate the sensitization profile to single NRL allergens in children without spina bifida and without repeated surgical interventions, by using different recombinant and natural latex allergens in two analytical techniques: specific serum immunoglobulin E (IgE) quantification and flow cytometry determination of activated basophils expressing CD63, after stimulating cells from patients with NRL allergens. A total of 23 patients and 10 healthy children were selected. Conjunctival and in-use NRL provocation tests were carried out, as well as specific IgE determination in all patients' and controls' sera with the recombinant NRL allergens: rHev b 1, rHev b 2, rHev b 3, rHev b 5, rHev b 6.01, rHev b 6.02, rHev b 8, rHev b 9 and rHev b 11 and with NRL (k82) using appropriate ImmunoCAPs. The Basophil Activation Test (BAT) was performed with whole latex extract and with the recombinant allergens rHev b 5 and rHev b 6.01, as well as with the natural allergen Hev b 6.02. The sensitivity and the specificity of NRL-specific IgE (k82) were 100%. Positive IgE responses to rHev b 5 were found in sera of 10 children, to rHev b 6.01 in 16 and for rHev b 6.02 in 15 children's sera. Specific IgE to rHev b 8 was found in four sera of the children. We only found significant differences in sensitization to rHev b 5 in children with two or more surgical interventions compared with the non-intervened group or those with only one intervention. Specific IgE in sera of children with latex-fruit syndrome recognized rHev b 6.02, but not to rHev b 11. The patients sensitized to Hev b 8, Hev b 9 and/or Hev b 11 were atopic. The four patients presenting a positive response to the NRL profilin Hev b 8 were allergic to pollen. The BAT against whole NRL extract was positive in 22 of 23 children; against rHev b 5 in 14 of the patients studied; against rHev b 6.01 in seven cases and against nHev b 6.02 in 19 children. In all the control subjects, the results using this technique were negative. If combined rHev b 5, rHev b 6.01 and nHev b 6.02 together, BAT could detect 20 of the 23 children with latex allergy. The combined use of ImmunoCAP with all the recombinant NRL allergens and BAT with rHev b 5, rHev b 6.01 and nHev b 6.02, enabled the identification of NRL allergy in 22 of 23 patients. There is a positive and significant correlation between sensitization to Hev b 5 and the number of interventions. BAT and allergen-specific IgE determination could be used as first-line in vitro diagnostic tests in patients with NRL allergy. [source]

Patterns of latex allergen recognition in children sensitized to natural rubber latex

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2006
Rafael Pamies
Single recombinant latex allergens permit the study of the pattern of sensitization to individual allergens. We aimed to quantify the IgE-response to individual latex allergens in children sensitized to latex. The study group included 31 latex-sensitized children: 26 operated at least twice, 20 of them with spina bifida; two children with one operation and three atopic non-operated children. IgE antibodies to rHev b 1, rHev b 3, rHev b 5, rHev b 6.01, rHev b 7.02 and rHev b 8, coupled to ImmunoCAPs, were measured in each serum. IgE responses to rHev b 1, rHev b 5 and rHev b 6.01 were found in 17 children each, and their mean ± s.d. levels were 5 ± 7.4, 16.8 ± 14 and 10 ± 18 kU/l, respectively. IgE responses to rHev b 3 (4 ± 5.4 kU/l) were found in eight children. Two children had IgE to rHev b 7 (1.7 and 3.2 kU/l), and none to rHev b 8. Four sera were negative to all tested recombinant allergens. We divided the patients in three groups: sensitized only to rHev b 1, sensitized only to rHev b 5 and/or rHev b 6.01, and sensitized to both rHev b 1 and to rHev b 5 and/or rHev b 6.01. The three groups had the same profile of clinical features. Hev b 5 induces the quantitatively higher IgE responses in children with multiple surgeries sensitized to latex. Responses to Hev b 6.01 equal those of Hev b 1. [source]

Cutaneous Manifestations of Cystic Fibrosis

PEDIATRIC DERMATOLOGY, Issue 2 2008
Megan L. Bernstein M.D.
Classic disease findings include chronic bacterial infection of airways and sinuses, malabsorption of fat, infertility in men, and elevated concentrations of chloride in sweat. Less well-recognized findings associated with cystic fibrosis include cutaneous findings, which can be primary or secondary manifestations of the disease process. Patients demonstrate more atopic and drug hypersensitivity reactions than the general population, but have similar rates of urticaria compared with the general population. In atypical presentations of cystic fibrosis, the nutrient deficiency dermatitis of the disease may aid with diagnosis, and notably can be the presenting sign. Other dermatologic manifestations of cystic fibrosis include early aquagenic skin wrinkling and cutaneous vasculitis, which can be associated with arthralgias. Familiarity with the nutrient deficiency dermatitis of this entity may play a role in the timely diagnosis of the disease, and the other cutaneous findings add to our understanding of the protean nature of its manifestations. [source]