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Rapidly increasing knowledge on the complex background of atopic dermatitis (AD) on the genetic, immunological and environmental level in combination with the continuous improvement in our diagnostic options has initiated an ongoing discussion on factors, which primarily promote the disease on one hand and mechanisms which emerge rather secondarily as a consequence of disease-specific modifications, on the other hand. Beside a sustained search for reliable and meaningful diagnostic tools for elicitors of the disease, novel therapeutic approaches are required, as most of the treatments of AD are limited to symptomatic therapies. In contrast, therapeutic approaches selectively regulating aberrant pathophysiological mechanisms in AD itself would be much more effective and promising. [ABSTRACT FROM AUTHOR]

Background:  Allergic contact dermatitis prevalence is reported as equal in atopic and nonatopic dermatitis. Atopic dermatitis is under-represented in those with allergic contact dermatitis to agents having cutaneous and dietary exposure. We compared rates of atopic dermatitis between patients with allergic contact dermatitis arising out of individual fragrance chemicals with known oral/cutaneous exposure against exclusively cutaneous exposure. Methods:  Between 1982 and 2007, 37 065 dermatitis patients were tested with Fragrance mix I. Those who were positive were tested for individual fragrance allergy. Chemicals were categorized according to whether their exposure pattern was solely cutaneous, oral or mixed. Current and past atopic dermatitis rates were compared between the whole population and groups allergic to individual fragrances. Age and gender were controlled. Results:  Cinnamic alcohol and cinnamal allergy groups had reduced rates of both ‘current’ [24/266 (9.0%) P = 0.0008, 38/364 (10.4%) P = 0.0005] and ‘past’ atopic dermatitis [44/266 (16.5%) P = 0.009, 70/346 (19.2%) P = 0.037]. Atopic dermatitis rates in groups allergic to Evernia prunastri and hydroxycitronellal (cutaneous exposure only) were not reduced [120/597 (20.1%) and 41/153 (26.8%)]. Groups allergic to cinnamic alcohol ( P < 0.0001, P < 0.0001) and cinnamal ( P < 0.0001, P < 0.004) had reductions in ‘current’ and ‘past’ atopic dermatitis, compared with Evernia prunastri. Conclusions:  Patients allergic to individual fragrances with dietary exposure have reduced rates of atopic dermatitis. This suggests that patients with atopic dermatitis have heightened oral tolerance to dietary haptens, in contrast to the known close association of atopic dermatitis with food-protein allergy. Haptens may interfere with food protein tolerance by binding to soluble protein to alter its configuration and immunogenic profile. [ABSTRACT FROM AUTHOR]

Background: There are frequent concerns about early immunizations among the parents of children at heightened risk for atopy. The study assessed the effect of vaccine immunization before the first birthday on eczema severity and allergic sensitization in the second year of life. Methods: A total of 2184 infants, aged 1–2 years, with established atopic dermatitis and a family history of allergy, from 97 study centres in 10 European countries, South Africa and Australia were included. Exposure to vaccines (diphtheria, tetanus, pertussis, polio, Haemophilus influenzae Type B, hepatitis B, mumps, measles, rubella, varicella, BCG, meningococci and pneumococci) and immunization dates were recorded from immunization cards. Immunoglobulin E (IgE) was determined by RAST and eczema severity was assessed by scoring atopic dermatitis (SCORAD). Results: Immunization against any target was not associated with an increased risk of allergic sensitization to food or inhalant allergens. Varicella immunization (only 0.7% immunized) was inversely associated with total IgE > 30 kU/l (OR 0.27; 95% CI 0.08–0.87) and eczema severity (OR 0.34; 95% CI 0.12–0.93). Pertussis immunization (only 1.7% nonimmunized) was inversely associated with eczema severity (OR 0.30; 95% CI 0.10–0.89). Cumulative received vaccine doses were inversely associated with eczema severity ( P = 0.0107). The immunization coverage of infants before and after the onset of atopic dermatitis was similar. Conclusion: In children at heightened risk for atopy, common childhood immunization in the first year is not associated with an increased risk of more severe eczema or allergic sensitization. Parents of atopic children should be encouraged to fully immunize their children. [ABSTRACT FROM AUTHOR]

Background: An increased understanding of the ocular surface at cellular level in the conjunctiva and the cornea may help explain the pathogenesis and the subsequent clinical appearance of atopic ocular allergies, which may be potentially blinding. Purpose: To investigate the MUC16 and MUC5AC alterations, tear function and the ocular surface disorder in patients with atopic keratoconjunctivitis (AKC). Methods: Thirty-six eyes of 18 AKC patients as well as 28 eyes of 14 age- and sex-matched normal subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), fluorescein and Rose-Bengal staining of the ocular surface, conjunctival impression cytology and brush cytology. Impression cytology samples underwent periodic acid schiff and immunohistochemical staining with MUC16 and MUC5AC antibodies. Brush cytology specimens underwent evaluation for inflammatory cell numbers and quantitative real-time polymerase chain reaction (PCR) for MUC16 and MUC5AC mRNA expression. Results: The mean corneal sensitivity and BUT values were significantly lower in patients with AKC, compared with controls ( P < 0.001). Brush cytology specimens from AKC patients revealed significantly higher numbers of inflammatory cells ( P < 0.001). Specimens from patient eyes showed positive staining for MUC5AC and MUC16. MUC16 mRNA expression was significantly upregulated with significant downregulation of MUC5AC mRNA expression in eyes with AKC compared with the eyes of control subjects. Conclusion: Ocular surface inflammation, decline in corneal sensitivity, tear film instability, changes in conjunctival epithelial MUC5AC and MUC16 mRNA expressions were thought to be important in the pathogenesis of atopic ocular surface disease. [ABSTRACT FROM AUTHOR]

Background: Long-term treatment for atopic dermatitis (AD) using low dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent relapses. This 12-month, European, multicentre, randomized study investigated whether the proactive use of 0.1% tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations (DE). Methods: During the initial open-label period, 257 adults with AD applied 0.1% tacrolimus ointment twice daily (b.i.d.) for up to 6 weeks to affected areas. When an Investigator Global Assessment (IGA) score of ≤2 was achieved, the patient entered the disease control period (DCP) and was randomized to either proactive tacrolimus ( n = 116) or vehicle ointment ( n = 108) twice weekly for 12 months. Exacerbations were treated with 0.1% tacrolimus ointment b.i.d. until an IGA ≤2 was regained, then randomized treatment was restarted. The primary endpoint was the number of DEs during the DCP that required a substantial therapeutic intervention. Results: Proactive tacrolimus 0.1% ointment application significantly reduced the number of DEs requiring substantial therapeutic intervention (median difference 2; P < 0.001; Wilcoxon rank sum test), the percentage of DE treatment days (median difference: 15.2%; P < 0.001; Wilcoxon rank sum test) and increased the time to first DE (median 142 vs 15 days; P < 0.001; stratified log-rank test). The adverse event profile was similar for the two treatment approaches. Conclusion: A 12-month, twice weekly proactive tacrolimus ointment application was an effective treatment in most study patients which prevented, delayed and reduced the occurrence of AD exacerbations. [ABSTRACT FROM AUTHOR]

Background: Monocyte chemotactic protein (MCP-1/CCL2), the ligand for CCR2 and CCR5, and macrophage inflammatory protein-1α (MIP-1α/CCL3), the ligand for CCR1 and CCR5, are potent chemo-attractants in vitro and produce lesions in experimental animals, which resemble immediate and delayed-type hypersensitivity (DTH) reactions. CCL3 induces mononuclear cell and granulocyte infiltration in human atopic and nonatopic skin. Whether CCL2 (MCP-1) has comparable activity in man is uncertain as is the capacity of both the chemokines to elicit immediate- and DTH-like reactions in humans. Methods: Inflammatory cells were counted by immunohistochemistry in 24 and 48-h skin biopsies from atopics and nonatopics after intradermal injection of CCL2 and CCL3. Immediate (15 min) wheals-and-flares and delayed (24 and 48 h) indurations were also recorded. Results: Both chemokines induced immediate- (15 min) and delayed (24 and 48 h) reactions, which were associated with significant infiltrations of CD68+ macrophages, CD3+, CD4+ (but not CD8+) T cells, neutrophils, and eosinophils in biopsies from injection sites. CCL2, but not CCL3, also induced infiltration of basophils. Neither chemokine produced significant changes in the numbers of tryptase+ cutaneous mast cells. There were no differences in the pattern of skin reactivity or the numbers of infiltrating leukocytes in response to CCL2 and CCL3 between atopic and nonatopic subjects. In general, maximal infiltration of inflammatory cells was observed at the 24-h, rather than the 48-h, time point. Conclusions: CCL2 and CCL3 induce both immediate and delayed skin reactions in atopics and nonatopics, and evoke a similar profile of local T cell/macrophage and granulocyte recruitment which, in general, confirm previous in vitro findings and in vivo experimental animal data. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is often complicated by an enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus. Toll-like receptors (TLR), especially TLR-2 recognizes cell wall components of S. aureus, e.g. lipoteichoic acid (LTA) and peptidoglycan (PGN). A heterozygous TLR-2 R753Q polymorphism occurs in a frequency of 11.5% in adult AD patients and has been shown to be associated with a severe phenotype of AD. Methods: The aim of this study was to investigate the impact of TLR-2 agonists (LTA, PGN and Pam3Cys) on cytokine production in human monocytes from AD patients with the TLR-2 R753Q polymorphism compared with that of AD patients with ‘wild type’ TLR-2 and control individuals to elucidate the functional role of the TLR-2 R753Q polymorphism. Results: Monocytes from AD patients with the TLR-2 R753Q mutation produced significantly more IL-6 and IL-12 compared with that of AD patients with nonmutated TLR-2 upon stimulation with TLR-2 agonists. Conclusion: We show for the first time functional differences in TLR-2 responsiveness of monocytes from AD patients with the TLR-2 R753Q mutation compared with wild type AD patients in a ligand-dependent manner. Clinical implication: Our data support the emerging concept that AD patients have a dysbalance in innate and aquired immunity. TLR-2 may be essential in the pathogenesis and maintenance of AD and may be involved in the enhanced susceptibility to skin infections with S. aureus and in a higher inflammatory response in patients with AD carrying the TLR-2 polymorphism. [ABSTRACT FROM AUTHOR]

Background: Sensitization to atopens is an early phenomenon that overlaps with the onset of atopic dermatitis (AD) in infancy. Early epidermal barrier impairment may facilitate the epicutaneous penetration of atopens. Objective: To correlate transepidermal water loss (TEWL) and aeroallergen sensitization in infants with AD. Methods: In this cross-sectional study we enrolled 59 AD children and 30 controls aged 3–12 months. Transepidermal water loss in uninvolved skin, specific immunoglobulin E, atopy patch test (APT) and skin prick tests were performed with respect to seven aeroallergens, i.e., Dermatophagoides pteronyssinus, D. farinae, cat, dog, birch pollen, ambrosia, and cockroach. Environmental conditions were assessed by a questionnaire, and the house dust mite (HDM) concentration was determined in dust samples. Results: Eighty-nine percent of AD infants had a positive APT vs one out of eleven controls. AD infants had a significantly higher mean TEWL than controls (27.4 vs 11.1 g/m2/h, P < 0001). Children with two or more positive APT had higher TEWL than the others (31.1 vs 19.0 g/m2/h, P < 0.025). No correlation was found between indoor APT results and exposure to HDM, cats, and dogs at home. Conclusions: This study confirms the high prevalence of delayed sensitization to indoor and outdoor aeroallergens in AD infants, and shows that the higher the TEWL, the higher the prevalence of sensitization to aeroallergens. These data are in favor of a major role of a constitutive epidermal barrier impairment in determining early atopen sensitization in infants with AD. [ABSTRACT FROM AUTHOR]

Background: There is still uncertainty about the determinants of atopic eczema (AE). To explain the heterogeneity of the disease, different phenotypes of AE have been suggested. Methods: The cross-sectional PARSIFAL study included 14 893 school-age children of farmers or children attending Steiner schools and their respective reference groups. A detailed questionnaire was completed, and house dust was collected for the measurement of endotoxin and glucans. Atopic sensitization was defined by allergen-specific IgE levels in the serum. Results: In multivariate analyses, helping with haying was the only variable related to a farming environment having a consistent inverse association with both current symptoms and a doctor’s diagnosis of AE [aOR = 0.65 (95% CI: 0.46–0.93) and 0.73 (0.51–1.05)], respectively. Severe lower respiratory tract infections (LRTI) in the first 2 years of life and usage of antibiotics ever were found to be positively related only to asthma-associated AE, whereas the effect of LRTI on AE without asthma had an opposite effect. Levels of β(1→3)-glucans in mattress dust were inversely related to a doctor’s diagnosis of asthma-associated AE [aOR = 0.75 (0.57–0.98)], and endotoxin levels to current symptoms of asthma-associated AE [aOR = 0.73 (0.57–0.94)]. Conclusions: The analyses of the PARSIFAL study revealed two different phenotypes of AE, depending on the association with asthma and wheezing ever. With regard to the hygiene hypothesis, help with haying, exposure to β(1→3)-glucans and endotoxin were found to be inversely associated with the AE phenotype associated with asthma and wheezing. [ABSTRACT FROM AUTHOR]

The prevalence of atopic diseases, including eczema, allergic rhinoconjunctivitis and asthma, has increased worldwide, predominantly in westernized countries. Recent epidemiological studies and experimental research suggest that microbial stimulation of the immune system influences the development of tolerance to innocuous allergens. The gastrointestinal microbiota composition may be of particular interest, as it provides an early and major source of immune stimulation and seems to be a prerequisite for the development of oral tolerance. In this review the observational studies of the association between the gut microbiota and atopic diseases are discussed. Although most studies indicated an association between the gut microbiota composition and atopic sensitization or symptoms, no specific harmful or protective microbes can be identified yet. Some important methodological issues that have to be considered are the microbiological methods used (traditional culture vs molecular techniques), the timing of examining the gut microbiota, the definition of atopic outcomes, confounding and reverse causation. In conclusion, the microbiota hypothesis in atopic diseases is promising and deserves further attention. To gain more insight into the role of the gut microbiota in the etiology of atopy, large-scale prospective birth cohort studies using molecular methods to study the gut microbiota are needed. [ABSTRACT FROM AUTHOR]

Background: Topical treatments of atopic dermatitis (AD) may be responsible for cutaneous allergies. Percutaneous sensitization to oat used in emollients/moisturizers has already been reported. Our objectives were to measure the prevalence of oat sensitization in AD children, to assess its relevance, and to look at related parameters. Methods: We recruited prospectively children with AD referred for allergy testing between June 2001 and December 2004. Atopy patch tests (APT) and skin prick tests (SPT) to oat proteins (1%, 3% and 5%) and to the European standard series were performed followed by oral food challenge (OFC) and repeated open application test (ROAT) in the oat-sensitized group. Results: About 302 children were enrolled. Oat APT and SPT were positive in 14.6% and 19.2% of cases, respectively. Children under 2 years of age were more likely to have positive APT. In oat-sensitized children, OFC and ROAT were positive in 15.6% (five of 32) and 28% (seven of 25) of cases, respectively. Thirty-two percentage of oat cream users had oat-positive atopy patch test (APT) vs 0% in the nonusers group. Conclusions: Oat sensitization in AD children seen for allergy testing is higher than expected. It may be the result of repeated applications of cosmetics with oats on a predisposed impaired epidermal barrier. We suggest avoiding topical-containing oat proteins in infants with AD. [ABSTRACT FROM AUTHOR]

Background: Some studies have suggested that supplementation of food with lactobacilli may prevent or improve atopic dermatitis in children. This study was designed to investigate the therapeutic effect of Lactobacillus rhamnosus GG (LGG) as a food supplement in infants suffering from atopic dermatitis. Methods: Infants aged 3–12 months suffering from mild-to-moderate atopic dermatitis (severity scoring of atopic dermatitis or SCORAD index of 15–40) without current antiinflammatory treatment were randomized to receive LGG (5 × 109 colony forming units b.i.d.) or placebo as a food supplement for 12 weeks. Severity scoring of atopic dermatitis index and use of hydrocortisone 1% ointment as rescue medication (2 points per application) were recorded at 4, 8, and 12 weeks of treatment and combined as symptom load (SL). Results: Fifty-four infants (LGG group, mean ± SD SCORAD index 24.6 ± 8.8) and 48 infants (placebo group, SCORAD index 23.6 ± 7.8) were randomized and completed the treatment period (intention-to-treat analysis). Symptom load generally improved over time at 4 weeks (LGG vs placebo, 23.8 ± 12.4 vs 20.6 ± 9.9), 8 weeks (22.5 ± 14.6 vs 17.9 ± 13.1), and 12 weeks (19.6 ± 15.4 vs 15.1 ± 12.1), without statistically significant group differences. When stratified for age, eczema severity or use of rescue medication, no statistically significant group differences, in improvement, were found. No significant group differences were found for the use of rescue medication (0.8 ± 45.0 g vs 3.5 ± 29.8 g), increase in mean logarithmic total serum IgE (0.17 ± 0.30 kU/l vs 0.26 ± 0.45 kU/l), and newly developed allergic sensitization against hen’s egg or cow’s milk (18.8% vs 10.0%). Conclusion: This placebo-controlled trial showed no therapeutic effect of LGG against mild-to-moderate atopic dermatitis in infancy. [ABSTRACT FROM AUTHOR]

Background: Recent studies point to the pathophysiological role of the peroxisome proliferators-activated receptor gamma (PPARγ) in the inflammatory immune response. We have showed that activation of PPARγ by specific ligands attenuates the allergic immune response via monocytes and lymphocytes. The objective of this study was to analyse the PPARγ expression and its regulation via inflammatory cytokines. Methods: We examined the PPARγ expression in the lesional and nonlesional skin of atopic patients by immunohistochemistry. The expression patterns of PPARγ mRNA and its isoforms were investigated in peripheral mononuclear blood cells of atopic and nonatopic donors and in cytokine-stimulated populations by quantitative real-time RT-PCR. Results: Our data show an increased PPARγ expression in lesional skin from atopic dermatitis patients. The analysis of PPARγ mRNA reveals a significantly up-regulated expression of PPARγ1 but not of PPARγ2 in monocytes and CD4+ T-cells from atopic dermatitis patients. Furthermore, we demonstrate that Th-cytokines, like IL-4, IL-13 and IFNγ, which regulate the biphasic atopic immune response, directly regulate the expression of PPARγ1. Conclusion: Taken together, these data demonstrate that PPARγ isoforms are differently expressed and regulated by the local cytokine-milieu. Whether the increased expression of the PPARγ1 receptor may be beneficial or not for a PPARγ ligand-based treatment of atopic dermatitis, is currently under investigation. [ABSTRACT FROM AUTHOR]

Background: Eosinophils are recruited into the affected tissue of asthma and atopic dermatitis (AD) patients. IL-5 and IL-5R are highly expressed in the AD skin lesions, yet the reported levels of IL-8 are controversial. Method: We genotyped 17 singlenucleotide polymorphisms (SNPs) from five genes of the 1120 case-control samples (646 AD and 474 controls). We measured the serum IL-5 concentrations in 87 individuals [36 ADe (AD extrinsic), 18 ADi (AD intrinsic) and 33 controls] by ELISA, and compared the results among these groups. Result: The rs2522411SNP and haplotype T-A in the IL-5 gene were significantly associated with the ADe. The serum IL-5 concentration was higher in the ADe than that in the ADi patients without any correlation with the rs2522411SNP. In the IL-5RA gene, the rs334809SNP showed a weak association with AD, and the rs6771148SNP and the haplotype T-C-T of the three adjacent tagged SNPs had an effect on the blood eosinophil counts and the serum ECP levels in the AD patients. However, we could not detect any relationship between AD and the SNPs in the IL-8 and IL-8R genes. Conclusion: We found that the rs2522411SNP and the haplotype T-A in the IL-5 gene and the serum IL-5 levels were strongly associated with the allergic type of AD, but not with the nonallergic type of AD. The association of the rs6771148SNP and the haplotype T-C-T in the IL5RA gene with the blood eosinophil counts and the serum ECP levels indicates that the IL5RA gene has a role for controlling eosinophils in the peripheral blood. [ABSTRACT FROM AUTHOR]

Although controlled oral food challenges are considered to be the gold-standard in the diagnosis of food related symptoms, especially if performed in a double-blind, placebo-controlled food challenges (DBPCFC) manner, there are still many unanswered questions and newer aspects, which may explain some pitfalls encountered during oral food challenges. For stopping an oral food challenge and declaring a challenge as positive or negative, symptoms should be objective and/or repetitive. The time interval between administering the food and observing the clinical reaction is an ambivalent factor. Possible reasons for false negative assessments include inadvertent drug use during oral challenges, and the fact that a short-term specific oral tolerance induction (SOTI) may be induced as increasing amounts of the offended food are administered during a titrated oral food challenge. Possible reasons for false positive assessments are the difficulty to maintain an appropriate strict diet throughout the oral challenge procedure, and that the elimination diet implemented before the oral food challenge in children with atopic eczema and suspected food related symptoms may itself be responsible for immediate type clinical symptoms, which had not been reported by the parents before. Finally augmentation factors are among the most plausible explanations for the inadequate reproducibility of an oral food challenge. Although a 100% standardization of the challenge procedure does not seem realistic, efforts should be made to improve the methodology used so far. On the contrary, the possible relation of DBPCFC and SOTI may offer potential advantages for future therapeutic approaches of food allergy. [ABSTRACT FROM AUTHOR]

Food allergy and atopic eczema (AE) may occur in the same patient. Besides typical immediate types of allergic reactions (i.e. noneczematous reactions) which are observed in patients suffering from AE, it is clear that foods, such as cow’s milk and hen’s eggs, can directly provoke flares of AE, particularly in sensitized infants. In general, inhaled allergens and pollen-related foods are of greater importance in older children, adolescents and adults. Clinical studies have revealed that more than 50% of affected children with AE that can be exacerbated by certain foods will react with a worsening of skin eczema either alone or in addition to immediate symptoms. Adolescents and adults may also react to foods, but reactions to ‘classical’ food allergens, such as hen’s eggs and cow’s milk, are not as common as in childhood. Some patients with AE do react to pollen-associated foods. Food-induced eczema should not be neglected by the allergologist: On the one hand, food can be a relevant trigger factor of persistent moderate-to-severe AE; on the other hand, unnecessary diets which are not based on a proper diagnosis may lead to malnutrition and additional psychological stress on patients suffering from AE. Eczematous reactions to food can only be diagnosed by a thorough diagnostic procedure, taking into account the patient’s history, the degree of sensitization and the clinical relevance of the sensitization. The latter has often to be proven by oral food challenges. Upon oral food challenge it is most important to evaluate the status of the skin with an established score (e.g. SCORAD, EASI) after 24 h and later because otherwise worsening of eczema will be missed. [ABSTRACT FROM AUTHOR]

Background: Staphylococcal superantigens (SsAgs) contribute to the persistence of allergic skin inflammation in atopic dermatitis (AD). The aims of this study were to (1) determine whether there are differences between AD patients and healthy subjects in SsAg-induced caspase-3 activation and SsAg-induced changes of anti-apoptotic protein Bcl-2 and Bcl-2 mRNA levels of CD4+ T cells; (2) investigate the effect of interleukin (IL)-4 on SsAg-induced caspase-3 activation and SsAg-induced changes of Bcl-2 and Bcl-2 mRNA levels of CD4+ T cells. Methods: Using immunofluorescence staining followed by flow cytometric analysis and real-time PCR, we analyzed peripheral blood mononuclear cells with or without staphylococcal enterotoxin B (SEB) stimulation in the presence or absence of recombinant IL-4 or anti-IL-4 neutralizing antibodies in 16 AD patients and 14 healthy subjects. Results: SEB-reactive (TCRV β3+, V β12+, and V β17+) CD4+ T cells from AD patients were more resistant to SEB-induced caspase-3 activation and SEB-induced decrease of Bcl-2 and Bcl-2 mRNA than those from healthy subjects. Exogenously added IL-4 inhibited SEB-induced caspase-3 activation and SEB-induced decrease of Bcl-2 and Bcl-2 mRNA in SEB-reactive CD4+ T cells from healthy subjects. Inhibition of endogenous IL-4 by using anti-IL-4 neutralizing antibodies up-regulated SEB-induced caspase-3 activation and SEB-induced decrease of Bcl-2 and Bcl-2 mRNA in SEB-reactive CD4+ T cells from AD patients. Conclusions: Following SsAg stimulation, IL-4 produced by T cells in AD patients down-regulates SsAg-induced caspase-3 activation and apoptosis of CD4+ T cells through inhibiting the decrease of Bcl-2. This may impair deletion of SsAg-activated T cells and resolution of allergic skin inflammation. [ABSTRACT FROM AUTHOR]

Background: Cystatin A ( CSTA) is a strong candidate for atopic dermatitis (AD) because it maps to AD susceptibility locus on chromosome 3q21 and it does inhibit Der p 1 and Der f 1, major house dust mite cysteine proteases and environmental triggers for AD and asthma. Objective: To examine any association between polymorphisms in CSTA and AD and study the effect on the CSTA mRNA expression level. Methods: We identified three polymorphisms and characterized the linkage disequilibrium mapping of the CSTA gene. All three CSTA polymorphisms were genotyped in 100 AD patients and 203 matched controls. Subsequently, we performed transfection-based RNA stability assays. Results: We found a significant association between the CSTA +344C variant and AD [odds ratio (OR) = 1.91; P = 0.024]. When further 61 control samples were genotyped. The association with CSTA +344C allele was enhanced OR = 2.13; P = 0.006. To test whether the CSTA +344 affected the CSTA transcriptional activity, the decay rates of RNAs transcribed from the CSTA +344C and CSTA +344T variants were investigated. COS-7 cells were transfected with a pcDNA3.1−CSTA+344C or a pcDNA3.1−CSTA+344T construct and cultured in the presence or absence of actinomycin D. Real-time RT-PCR revealed that CSTA +344C mRNA is more than two times less stable than the CSTA +344T mRNA ( P < 0.001). Conclusion: These results suggest that the CSTA +344C allele associated with unstable mRNA could result in failing to protect the skin barrier in AD patients from both exogenous and endogenous proteases [ABSTRACT FROM AUTHOR]

Background: Asymptomatic skin sensitization (AS) is a risk factor for the development of allergic symptoms. A meticulous definition of this condition requires a systematic assessment of clinical symptoms before inclusion. Objective: To examine the concordance between retrospective assessment of seasonal allergic symptoms and prospective seasonal symptom registration among subjects with AS. Methods: On the basis of a population survey, autumn 2002, including skin prick tests (positive if ≥3 mm) and a screening questionnaire, 87 subjects with AS to birch and/or grass pollen, birch and/or grass pollen allergic symptomatic subjects ( n = 63) and healthy controls ( n = 40) were included in January to March 2003, completed diary cards on symptom and medication use during the relevant seasons 2003, and were examined at follow up in autumn 2003. Allergy: positive SPT and symptoms ≥ seven diary days. Results: Eleven AS subjects (birch: n = 10) subsequently developed allergic symptoms, yet nine admitted, at follow up, to have had symptoms before inclusion, or even denied pollen-related symptoms despite a significant diary. Compared with AS subjects sensitized to grass pollen, AS subjects sensitized to birch pollen had significantly larger skin prick reactions and more often and severe pollen symptoms. Conclusion: In the context of double-sensitization, retrospective symptom assessment is not a reliable method for ensuring that subjects classified, as asymptomatically skin sensitized, are truly, asymptomatic. This matter should be considered in studies on allergy development. [ABSTRACT FROM AUTHOR]

Background: Topical glucocorticosteroids are the gold standard in treatment of atopic dermatitis (AD). Recently, topical calcineurin inhibitors have been developed for treatment of this condition. This study compared efficacy and safety of 0.1% methylprednisolone aceponate (MPA) ointment with 0.03% tacrolimus ointment for 3 weeks, in children and adolescents with severe to very severe flare of AD. Methods: The primary end point was treatment success, defined as a score of ‘clear’ or ‘almost clear’ in the static Investigator's Global Assessment (IGA) score. Secondary end points were the percentage change in the Eczema Area and Severity Index (EASI) and patients’ assessment of itch and sleep, Children's Dermatology Life Quality Index, patient's assessment of global response, affected Body Surface Area and medication costs. Results: 265 patients were randomized to either MPA ( n = 129) or tacrolimus ( n = 136) treatment, 257 patients completed the study. Methylprednisolone aceponate 0.1% ointment once daily provided rapid and relevant clinical benefit. Tacrolimus 0.03% ointment twice daily was equally effective with regard to success rate. Methylprednisolone aceponate was superior to tacrolimus for EASI, itch and sleep. Both treatments were well tolerated. Drug-related adverse events were only observed in the tacrolimus group. Medication costs were significantly lower for MPA. Conclusions: While both treatment groups showed similar efficacy results regarding treatment success (IGA), significant advantages were observed for EASI, itch and sleep with MPA 0.1%. These advantages and the significantly lower treatment costs highlight the benefits of MPA treatment, underlining its first-line role in treatment of children and adolescents with severe AD. [ABSTRACT FROM AUTHOR]

A number of scientific reports have been published on patch tests with protein allergens performed on patients with atopic eczema (AE). Evaluation of eczematous skin lesions with an atopy patch test (APT) can be used as a diagnostic tool in characterizing patients with aeroallergen- and food-triggered AE. Indications for testing with APT, choice of allergens (aeroallergens and foods), test materials and technique, including present knowledge on sensitivity and specificity, are reviewed on the basis of available literature. This position paper also points out the need for future research on the clinical use of the APT. [ABSTRACT FROM AUTHOR]

Background: Atopic skin diathesis is a clinical term to describe skin atopics with previous, present or future atopic eczema/dermatitis syndrome (AEDS). In clinical practice, an unequivocal assessment of atopic skin diathesis in non-eczematous patients may be difficult. The majority of the known clinical features included in diagnostic scores are characteristic, but not specific markers of atopy. Especially, the vasoreactivity of atopic skin is disturbed. This is manifested by white dermographism, an irregular vascular response to thermal stimuli, and paradoxic skin reactions to histamine, cholinergic agents, and nicotinates. Objective: The aims of our study were to investigate the clinical morphology of palmar vascular reactions in skin atopic and non-atopic individuals, and to determine whether this abnormal vascular reaction is more pronounced in skin atopic individuals. Methods: Forty persons, 20 of them skin atopics, assessed by the Erlangen Atopy Score and an elevated serum IgE level (>150 U/ml), were included in a prospective single-centre study. Standardized digital photographs of the palms were presented in a blinded manner to five dermatologists in random order by means of the computerized imaging analysis system KS400 3.0. Results: Evaluation of the original rgb (red, green, blue) color images and modified gray-level images showed that a pronounced reticular pattern of erythema of the palms was significantly ( P < 0.0001) more common in skin atopics (72% and 69.6%, respectively). Conclusion: The gross vascular pattern of the palm might be an additional diagnostic feature of atopy, and further studies are needed to establish its exact prevalence. [ABSTRACT FROM AUTHOR]

Background: Different lifestyle factors seem to be associated with the risk for atopic diseases and some studies suggest that stress increases the risk of allergic sensitization, asthma and atopic eczema. Only few studies have investigated the association of early stressful life events and atopic eczema (AE) in children. Subjects and Methods: Parents of participants of the ongoing LISA birth cohort study were asked to give information on life events, such as severe disease or death of a family member, unemployment, or divorce of the parents. Lifetime prevalence of AE and incidence after the assessment period for life events were compared. Results: Prevalence of AE until the age of 4 years was 21.4%. Reported life events within the first 2 years were: severe disease (17.5%) or death (8.4%) of a family member, divorce/separation (3.4%), and unemployment (2.7%). Divorce/separation was associated with a significantly [odds ratio (OR) 3.59, 95% confidence interval (CI) 1.69–7.66] increased and disease with a significantly (OR 0.29, 95% CI 0.13–0.68) decreased incidence of AE for the subsequent 2 years of life. No effect was seen for unemployment. Conclusions: Divorce/separation of the parents and severe disease of a family member influence the risk of developing AE. [ABSTRACT FROM AUTHOR]

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, α-integrins and β-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. [ABSTRACT FROM AUTHOR]

Background: Climate and sunlight (ultraviolet radiation) influence activity of atopic eczema. Objective: To evaluate the effect of moving from a subarctic/temperate climate to a sunny subtropical climate on children's atopic eczema. Methods: Children, 4–13 years, with severe atopic eczema were randomized to stay 4 weeks in Gran Canary (index patients = 30) and home in Norway (controls = 26), with a follow up of 3 months. SCORing of Atopic Dermatitis (SCORAD) was primary variable, and secondary were Children's Dermatology Life Quality Index (CDLQI), Staphylococcus aureus skin colonization and pharmacological skin treatment. Results: SCORing of Atopic Dermatitis decreased from 37.2 (29.4–44.9) to 12.2 (9.0–15.4) [mean (95% confidence intervals)] after 4 weeks and 21.2 (17.2–25.1) 3 months thereafter in index patients ( P < 0.0005), much less in controls. Children's Dermatology Life Quality Index in the index group improved from 8.7 to 2.2 and 4.5 after 4 weeks and 3 months ( P < 0.0005), not in controls. Bacterial skin colonization with S. aureus decreased in the index group from 23/30 (77%) to 12/30 (40%; P = 0.001) and 12/30 (40%; P = 0.005) after 1 month and 3 months, and the use of local steroids decreased in index patients but not in controls. Conclusions: The change from a subartic/temperate to a subtropical climate for 4 weeks improved significantly skin symptoms (SCORAD) and quality of life, even for 3 months after return. [ABSTRACT FROM AUTHOR]

The author reflects on the interdisciplinary approach of the European Academy of Allergy and Clinical Immunology (EAACI) and Global Allergy and Asthma European Network (GA²LEN) to allergies and skin. He claims that the skin is frequently involved in several allergic reactions such as drug allergy, atopic eczema and angioedema. An overview on the activities of EAACI and GA²LEN and the clinical findings of atopic dermatitis is offered.

Background: Prevalences of childhood asthma and other atopic diseases are increasing worldwide, and so is the number of diagnostic methods and definitions used. We determined the occurrence of atopic diseases in Cuban children with a range of diagnostic approaches commonly used or proposed in epidemiological studies, and compared the different outcome measures. Methods: A total of 398 Cuban schoolchildren between 5 and 13 years of age were diagnosed by International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, clinical examination, pre- and post-exercise spirometry, and skin prick testing. All results were considered separately, as well as jointly by using scores and definitions as described in the literature. Results: Using questionnaire-based approaches, 21-39% of the children were positive for asthma, 9-19% for atopic dermatitis, and 15-46% for rhinoconjunctivitis. With spirometry, 7% of the children had asthma. Definitions based on a combination of questionnaire and spirometry results yielded asthma rates of 5%. Of all children, 6% wheezed on clinical examination, and only one child showed clinical signs of atopic dermatitis. Eleven percent of the children had a positive skin prick test. In total, 254 children (64%) had an atopic disease as based on the ISAAC questionnaire, and 263 (66%) based on all approaches used. Conclusion: Diagnostic outcomes on atopic diseases vary considerably depending on definition and methodology. Our results clearly demonstrate the need for consensus on diagnosing asthma and other atopic diseases in epidemiological studies. Based on the most commonly used ISAAC questionnaire, our data suggest prevalences of atopic diseases in Cuban children that rival those found in some other Latin American countries and developed nations with the highest prevalences in the world. [ABSTRACT FROM AUTHOR]

Background: Dry skin in atopic eczema depends on increased water loss. The mechanisms behind this are poorly understood. The aim of this work was to identify genes that may contribute to water loss in eczema. Methods: Affymetrix DNA microarrays U133A were used to analyse gene expression in skin biopsies from 10 patients with atopic eczema and 10 healthy controls. Results: DNA microarray analysis showed up-regulation of 262 genes and down-regulation of 129 genes in atopic eczema. The known functions of these genes were analysed using Gene Ontology to identify genes that could contribute to increased water loss. This led to identification of aquaporin 3 ( AQP3), which has a key role in hydrating healthy epidermis. Increased expression of AQP3 was found in eczema compared with healthy skin. This was confirmed with real-time polymerase chain reaction ( P < 0.001). In healthy skin, epidermal AQP3 immunoreactivity was weak and mainly found in the stratum basale. A gradient was formed with decreasing AQP3 staining in the lower layers of the stratum spinosum. By contrast, in acute and chronic atopic eczema strong AQP3 staining was found in both the stratum basale and the stratum spinosum. Conclusions: Aquaporin 3 is the predominant aquaporin in human skin. Increased expression and altered cellular distribution of AQP3 is found in eczema and this may contribute to water loss. [ABSTRACT FROM AUTHOR]

Background: Allergic reactions to β-lactam antibiotics represent the most frequent cause of immunological drug reactions. Objective: This study evaluates the involvement of genetic susceptibility factors in patients with immediate allergic reactions to β-lactams. We examined 15 single nucleotide polymorphisms (SNP) of genes coding proteins implicated in immunoglobulin (Ig)E synthesis regulation. Methods: We performed a case–control study involving 44 patients with immediate β-lactam allergy and 44 control subjects, all matched for sex and atopy. Interleukin (IL)-4, IL-13, IL-4R α, signal transducer and activator of transcription 6 (STAT6), interferon (IFN)- γR1, IFN- γR2 and Fc ℇ RI β gene polymorphisms were determined using polymerase chain reaction (PCR) restriction fragment length polymorphism, and IL-21R gene and IL-10 promoter polymorphisms by direct sequencing. Results: Our analysis did not reveal differences in the distribution of the 15 SNPs between allergic patients and controls. However, among atopic subjects, we found two distinct significant associations between immediate β-lactam allergy in women and the Ile75Val variant of IL-4R α gene ( P = 0.012, OR = 5.4, CI: 1.16–27.7), and two linked IL-10 promoter gene polymorphisms, −819C>T and −592 C>A ( P = 0.023, OR = 17.5, CI: 1.26–533.07). In contrast, we observed no association in allergic male subjects in the atopic population. Interestingly, the IL-4R α Ile75Val variant could have a paradoxal protective effect in atopic male patients ( P = 0.004, OR = 0.07, CI: 0.01–0.66). Conclusion: Our findings suggest that polymorphisms in the IL-10 promoter and IL-4R α genes are genetic factors that favour β-lactam immediate allergies in female patients with atopy. [ABSTRACT FROM AUTHOR]

Background: The opportunistic yeast Malassezia is a trigger factor in atopic eczema (AE). Around 30–80% of patients with AE have an IgE and/or T-cell reactivity to the yeast. Several IgE-binding components have been identified in Malassezia extracts and 11 allergens have been cloned and sequenced. The pH of the skin surface in patients with AE is higher than that of normal healthy skin. We here investigate whether different pH conditions mimicking those of AE skin and healthy skin can influence the production and release of Malassezia allergens. Methods: Malassezia sympodialis (ATCC strain 42132) was cultured in Dixon broth at pH 6.1 to 5.0 for 1–15 days. Culture supernatants were analysed for the presence of IgE-binding components by immunoblotting. The M. sympodialis cells were analysed for allergen expression and production with immunocytochemistry and quantitative polymerase chain reaction. Results: We found that M. sympodialis cells produce, express and release allergens to a greater extent when cultured at the higher pH. This was particularly true of a 67-kDa major allergen designated Mala s 12. Conclusions: The data suggest that the skin barrier in AE patients provides an environment that can enhance the release of allergens from M. sympodialis, which can contribute to the inflammation. [ABSTRACT FROM AUTHOR]

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies. [ABSTRACT FROM AUTHOR]

Background: Changing occurrence rates of asthma, allergic rhinitis and atopic dermatitis are of public health concern and require surveillance. Changes in prevalence rates of these atopic diseases were monitored during 10 years and their trend with time was determined taking into account the influence of personal and environmental risk factors. Methods: Four cross-sectional surveys in 5–7-year old children were performed in seven different communities in Switzerland between 1992 and 2001. Prevalence of respiratory and allergic symptoms and of affecting risk factors including parental environmental concern were assessed using a standardized parental questionnaire. Results: A total of 988 (74.1%), 1778 (79.0%), 1406 (82.6%) and 1274 (78.9%) children participated, respectively, in the 1992, 1995, 1998 and 2001 surveys. Prevalence rates of asthma and hay fever symptoms remained quite stable over time (wheeze/past year: 8.8%, 7.8%, 6.4% and 7.4%, sneezing attack during pollen season: 5.0%, 5.6%, 5.4% and 4.6%). Rates of reported atopic dermatitis symptoms (specific skin rash/past year: 4.6%, 6.5%,7.4% and 7.6%) showed an increase over time, but those of diagnosis of eczema did not show a clear pattern (18.4%, 15.7%, 14.0% and 15.2%). Stratified analysis by parental environmental concern and by parental atopy showed similar trends. Rates of atopic dermatitis symptoms showed significant increase in girls but stayed stable in boys. Conclusion: Results of these four consecutive surveys suggest that the increase in prevalence of asthma and hay fever in 5–7-year old children living in Switzerland may have ceased. However, symptoms of atopic dermatitis may still be on the rise, especially among girls. [ABSTRACT FROM AUTHOR]

The role of atopic eczema (AE) as risk factor for the development of allergic contact dermatitis is discussed controversially, as well as its influence on patch test results due to increased irritability. In this study, we analysed the pattern of positive patch test results to most frequent contact allergens in patients with AE ( n = 9020) and age matched nonatopic ( n = 15 263) individuals. The pattern and the frequencies of the observed sensitizations did not differ greatly from nonatopic individuals. Bufexamac is an exception: in AE patients sensitization is observed three times more often. For the other substances tested only minor differences were detected. Moreover, the frequencies of single, double or polyvalent sensitizations were nearly identical between the two groups. The analysis of the anatomical sites of dermatitis shows differences between the groups: in AE patients, the face (7.2%) and hand dermatitis (6.6%) was more common, and leg dermatitis (4.0%) less common. Analysis of occupation, suspected allergen source, and accompanying factors revealed no major differences between the both groups. Conclusion: The chronic and long-term exposure to external drugs and emollients presumably carries a risk for sensitization against specific contact allergens in AE patients. However, the sensitization of contact allergens differs surprisingly little between patients with or without AE. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a hereditary, pruritic, chronic, relapsing, inflammatory skin disease resulting from multiplex interactions between genes and environmental factors. We have previously found several loci showing suggestive linkage on chromosomes 3q14, 13q14, 15q14-15 and 17q21, and weaker linkage to chromosomes 1p32, 4q24-26 and 21q21 in 109 Swedish families. Methods: In order to confirm the linkage to chromosome 21, we carried out a replication linkage analysis with additional microsatellite markers on chromosome 21 in another set of 295 families. Results: In the extended material, the Z-score was 2.40 ( P < 7.4 × 10−4) in the region 21q21 for a semi-quantitative variable measurement; the severity of AD. When combining the two data sets into 404 families and stratifying according to asthma status, suggestive linkage was found only in the group of AD patients who also had asthma ( Z-score 2.45, P < 7.4 × 10−4 and 2.69, P < 7.4 × 10−4) in two different regions. Conclusions: Our results suggest that 21q21 could contain a susceptibility gene modulating the severity of AD especially in combination with asthma. [ABSTRACT FROM AUTHOR]

Background: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis patients. We studied the effect of pretreatment with topical tacrolimus 0.1% on APT in nonlesional skin of patients with atopic dermatitis. Methods: Nonlesional skin of the back of patients with atopic dermatitis ( n = 8) was treated once daily for 3 weeks with tacrolimus 0.1% ointment. Cetomacrogol ointment (placebo) was used as a negative control and triamcinolone acetonide 0.1% ointment as positive control. Twenty-four hours after the last APT application, samples were taken from the three treated areas ( t = 0 and 24 h) for immunohistochemical analysis. Results: Pretreatment with tacrolimus ointment did not suppress nonlesional skin infiltrate, in contrast to triamcinolone acetonide. Furthermore, tacrolimus did not inhibit the induction of the APT macroscopically ( t = 24 h). An equal influx of T cells, eosinophils, dendritic cells, CD64+ and Fc ℇRI-positive cells was present compared with placebo. Only CD36+ and CD68-positive cells were inhibited compared with placebo. All cell types were significantly inhibited in triamcinolone acetonide-treated sites compared with placebo. Conclusions: Pretreatment with tacrolimus 0.1% ointment does not inhibit the APT reaction in patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease commonly associated with respiratory allergies such as rhinitis and asthma, and a high serum level of IgE. In contrast to the ‘classic’ IgE-mediated allergic (extrinsic) form of AD, approximately 20% of the patients are reported to show normal IgE levels, lack of sensitizations towards environmental allergens, and absence of associated respiratory allergies. Accordingly, these patients are assigned to a nonallergic (intrinsic) form of the disease. Objectives: In order to define these two forms of AD more closely, 259 adult patients with AD were investigated. Results: After a thorough diagnostic workup there were 18 patients (6.9%), who fulfilled the criteria of intrinsic AD. After follow-up, four additional patients had developed respiratory allergies or IgE-mediated sensitizations resulting in an overall proportion for intrinsic AD of 5.4%. Conclusions: Based on these figures the nature and relevance of the intrinsic form of AD deserves further evaluation. [ABSTRACT FROM AUTHOR]

Background: Appropriate use of prebiotics and optimal combinations of probiotics and prebiotics (synbiotics) could allow significantly better results to be obtained in the treatment of atopic dermatitis (AD). Objective: To evaluate the efficiency of synbiotics when compared with prebiotics alone (control group) in the treatment of moderate and severe AD in children aged 2 years and over. Methods: Double-blind prospective randomized study performed on children aged at least 2 years presenting AD with a minimum SCORing Atopic Dermatitis (SCORAD) score of 15. A dose of 1.2 × 109 colony-forming units Lactobacillus rhamnosus Lcr35 plus prebiotic preparation or an identically appearing prebiotic preparation alone was given three times a day for 3 months. Patients’ diet and usual treatment for AD remained unchanged during the study period. Efficiency was evaluated using the SCORAD score. Use of topical drugs was noted. Results: A total of 48 patients were originally enrolled; nine did not complete the study. In synbiotic group, the mean values of the total SCORAD score was 39.1 before treatment vs 20.7 after 3 months of treatment ( P < 0.0001). In the prebiotic group, the mean of the total SCORAD score was 39.3 before the treatment vs 24.0 after 3 months ( P < 0.0001). After 3 months of treatment, no statistical differences between the two treatment groups with regard to the total SCORAD score were noted ( P = 0.535). Neither were there any statistical differences in the total use of ointment between patients receiving prebiotics or synbiotics ( P = 0.966) over the study period. Tolerance was excellent in both groups. Conclusions: Both synbiotics and prebiotics used alone seem able to significantly improve the manifestations of AD in children aged 2 years and over. [ABSTRACT FROM AUTHOR]

Background: Food allergy is not always correctly diagnosed in children with atopic eczema dermatitis syndrome (AEDS) and treatment with an avoidance diet is not without danger. Methods: After admission to our clinic, 11 children with a prolonged cow's milk (CM) elimination diet because of AEDS and sensitization underwent double-blind placebo-controlled food challenge (DBPCFC). Retrospectively, the exposure to CM, sensitization and reactions to accidental ingestion were carefully documented. The DBPCFC was used to evaluate the childrens’ current status. Results: Before the elimination period (median 2.3 years; started before the admission) all 11 children with AEDS were sensitized and had ingested CM (four bottle-fed; seven breast-fed without CM diet of the mother) without the development of acute reactions. The diagnosis of CM allergy was not confirmed by DBPCFC previously. After elimination the AEDS had not improved, but nevertheless the diet was continued. During the elimination period, eight of 11 children developed severe acute allergic reactions to CM after accidental ingestion. In evaluation, in our clinic all 11 children experienced acute allergic reactions to CM during DBPCFC. Conclusion: There is a considerable chance of developing acute allergic reactions to CM after elimination in children with AEDS without previous problems after CM intake. [ABSTRACT FROM AUTHOR]

Background: Pimecrolimus cream 1% (Elidel, Novartis Pharmaceuticals AG) effectively improves/relieves pruritus associated with atopic dermatitis (AD), but few data are available regarding the timing of relief. The purpose of this study was to investigate the timing of pruritus relief produced with pimecrolimus in adults with mild/moderate AD and moderate/severe pruritus. Methods: Patients were randomized to 7 days of treatment with pimecrolimus ( n = 100) or vehicle ( n = 98). Pruritus severity was assessed daily on a 4-point scale (0 = absent, 3 = severe), reflecting the previous 24 h experience. Patients who completed this core study were eligible to enter a voluntary 5-week, open-label extension study. Results: A significant effect was noted within 48 h of treatment, with pruritus improving in 56% of pimecrolimus-treated patients and 34% of vehicle-treated patients ( P = 0.003). Pruritus relief was maintained during the remainder of the core and extension phases, and was accompanied by an improvement in the Investigator's Global Assessment score. Conclusion: Pimecrolimus cream 1% significantly reduced pruritus within 48 h. [ABSTRACT FROM AUTHOR]

Background: The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose–response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. Methods: Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD ≥40 and allergic sensitization to house dust mites [CAP-FEIA ≥3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation ( Dermatophagoides pteronyssinus/ D. farinae) applying maintenance doses of 20, 2000 and 20 000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. Results: The SCORAD declined in the three dose groups in a dose-dependent manner ( P = 0.0368, Jonckheere–Terpstra test) and was significantly lower in the two high-dose groups (2000, 20000 SQ-U) compared with the low-dose group of 20 SQ-U ( P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses ( P = 0.0007, Mantel–Haenszel chi-square test). Conclusions: Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease. [ABSTRACT FROM AUTHOR]

Background: When skin prick testing (SPT) young children with atopic dermatitis (AD) for suspected food allergy, we frequently found positive reactions with turnip rape ( Brassica rapa) and oilseed rape ( Brassica napus). We performed food challenge to examine whether these children react clinically to turnip rape. Methods: A total of 1887 children were screened with SPTs for sensitization to turnip rape and oilseed rape. Twenty-eight children with clearly positive SPT (≥5 mm) were first subjected to labial challenge with turnip rape seeds followed, if negative, by open oral challenge for up to 7 days. Twenty-five children with AD but negative SPT to turnip rape and oilseed rape served as controls. Results: Two-hundred and six (10.9%) children had positive SPT to turnip rape and/or oilseed rape. Twenty-five (89%) of 28 children showed a positive challenge reaction to turnip rape. Seventeen reacted with labial whealing, and eight in oral challenge with facial urticaria, flare-up of AD or abdominal symptoms. All 25 control children remained negative in the labial challenge. Conclusions: Turnip rape and oilseed rape seem to be new important food allergens in young children with AD. The modes of exposure to these allergens and the possible routes of sensitization remain to be established. [ABSTRACT FROM AUTHOR]

Background: Staphylococcal colonization may influence the course of allergic diseases such as atopic dermatitis or allergic rhinitis. The frequency of Staphylococcus aureus (SA) nasal carriage and its possible influence on persistent allergic rhinitis was investigated. Methods: In nasal lavages from 22 patients with house dust mite allergy and 18 healthy controls, the number of SA colony forming units per ml were assessed and related to nasal symptom scores, the concentrations of three inflammatory cell activation markers, nasal total IgE and 17 cytokines in nasal secretions. Results: SA was found in 15/22 allergic patients and 4/18 controls ( P < 0.01). Comparing allergic SA carriers with allergic noncarriers, nasal symptom scores tended to be higher ( P < 0.1), and the cell activation markers ECP (102.23±0.33 vs 101.45±0.50 ng/ml; P < 0.05) and elastase (102.70±0.21 vs 102.12±0.34 ng/ml; P < 0.01), and nasal total IgE-levels (101.66±0.38 vs 101.2±0.28 kU/ml; P < 0.05) were significantly higher in allergic SA carriers. Nasal SA carriers had a higher nasal IL-13/IFN- γ ratio ( P < 0.01), and this was correlated with higher nasal total IgE in allergic patients ( r = 0.6, P < 0.05). Conclusion: Nasal SA carriage is frequent in patients with persistent allergic rhinitis. The data of this study suggest that they are not only secondary bystanders, but actively modulate the disease by promoting local IgE production. [ABSTRACT FROM AUTHOR]

The genetic background of atopic dermatitis (AD) is not clearly understood. Interleukin (IL)-10 is a powerful Th-2 cell cytokine produced by lymphoid cells that exerts its function by inhibiting macrophage/monocyte and T-cell lymphocyte replication and secretion of inflammatory cytokines [IL-1, tumour necrosis factor- α (TNFA), IL-6, IL-8 and IL-12]. In an effort to discover additional polymorphism(s) in genes whose variant(s) have been implicated in total immunoglobulin E (IgE) level in AD patients, we scrutinized the single nucleotide polymorphisms (SNPs) in the IL10 gene as a potent candidate for contributing to the level of IgE in serum. We recruited 334 AD patients and assayed their serum total IgE levels using the LIPA-200 system. Four SNPs in the IL10 gene were genotyped using the single-base extension (SBE) method. Logistic regression analyses were performed with single polymorphisms and haplotypes (ht) to determine their association with the level of serum total IgE. Genetic association analysis of total serum IgE in AD patients revealed that one of the IL10 ht, IL10-ht2, was associated with decreased serum total IgE in gene dose-dependent manner ( P = 0.02–0.001). It was predicted that the inhibition of innate immunity by increased IL-10 production in IL10-ht2-bearing individuals might be associated with decreased total serum IgE levels among AD patients. The greater effects of IL10 ht on decreased total serum IgE levels suggest that the effect of IL-10 polymorphism might be the result of a combined genotype (ht) rather than single polymorphisms. [ABSTRACT FROM AUTHOR]

During the last decades there has been extensive epidemiological research to explore the increasing prevalence of asthma and allergy in childhood. The worldwide variations in prevalence of these diseases necessitate regional rapports. Furthermore, time-trend analyses with comparable methods are important in order to monitor the rapidly changing prevalence of these diseases.Three cross-sectional questionnaire-based studies of asthma and allergy in schoolchildren were conducted in the counties of Troms and Finnmark, in northern Norway in 1985, 1995 and 2000. The two former studies included children from randomly selected primary schools (n = 1794/1985,n = 1432/1995). The latter study was a part of ISAAC-II Europe study (n = 3853). Identical items of asthma and allergy were employed. The analyses comprised only children 9–11 years of age.The prevalence of asthma was 9.3, 13.2 and 13.8% in 1985, 1995 and 2000, respectively. However, great gender differences were detected; the prevalence of asthma increased in males from 1995 to 2000, from 14.1 to 17.0%, RR = 1.2 (95% CI 1.0–1.5), but decreased in females 1995 to 2000, from 12.3 to 10.5%, RR = 0.9 (95% CI 0.7–1.1). Furthermore, in children with asthma, a changing trend was found in the external factors that perceived symptoms, from typical allergens towards other, unspecific agents. The prevalence of self-reported atopic eczema/dermatitis syndrome (AEDS) was 13.4, 21.1 and 20.8% in 1985, 1995 and 2000, respectively. The prevalence of self-reported allergic rhinoconjunctivitis was in 16.5, 24.7 and 29.6% 1985, 1995 and 2000, respectively, RR (2000/1995) = 1.2 (95% CI 1.1–1.3).The prevalence of asthma in girls has reached a plateau and even decreased from 1995 to 2000 which is in contrast to the asthma prevalence in boys that tends to continuously increase. The prevalence of AEDS which increased substantially between 1985 and 1995 did not change from 1995 to 2000. However, the prevalence of allergic rhinoconjunctivitis increased steadily from 1985, 1995 to 2000. [ABSTRACT FROM AUTHOR]

Information needs and preferences in treatment decision-making of parents caring for infants with atopic dermatitis (AD) are unknown, despite emphasis on quality information-giving and involvement of health-care users in treatment decisions.To explore information needs and decisional role-preferences of parents caring for infants with AD.Qualitative study. Purposive sample: 31 parents caring for infants with AD. Tape-recorded focussed conversation-style interviews. Interview topic-guide literature-derived. Control Preferences Scale (5 sort-card vignettes‘very active’ to‘very passive’ role) adapted for use with parents; used to facilitate discussion. Thematic analysis of verbatim transcripts.Nine core information needs identified: AD-causation, role of diet, medication-use, medication-side-effects, exacerbating factors, new/alternative medication, nonpharmacological treatments, AD-prevention, AD and other atopic conditions. Parents desired verbalandwritten information. Many felt their baby's condition was not taken seriously, leading to delayed diagnosis and treatment. They had to be more active than they wished to obtain information/treatment. Parents preferred sharing decisions with their doctor.Parents caring for infants with AD have clearly defined, unmet information needs, forcing them into more active roles in the treatment decision-making process than they desire. The study-findings may inform the development of written information specifically for these parents and improve partnership during consultations. [ABSTRACT FROM AUTHOR]