Early atopic disease and early childhood immunization--is there a link?

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.

IgE antibody responses in young children with atopic dermatitis.

In 2184 young children aged 13-24 months with atopic dermatitis (SCORAD 5-59) serum IgE antibodies to a standard panel of food and inhalant allergens were assayed. The frequency of positive IgE responses (>0.35 kU/l) increased with greater severity of skin disease. A significant minority of infants had levels of IgE antibody to foods to suggest they were at risk of acute reaction to those foods (7% to hen's egg, 3% to cow's milk, 4% to peanut). Our findings indicate that the frequency of positive IgE responses is related to disease severity and suggest that differences in the time course of the development of IgE responses to food, which are at maximum prevalence within the first year of life, while inhalant allergies, are still developing between 1 and 2 yr and beyond.

Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: an international study.

BACKGROUND: Studies of Australian infants have reported that more than 80% of those with moderate atopic eczema (AE) have high levels of IgE food sensitization (IgE-FS) that are commonly associated with IgE food allergy. OBJECTIVES: To explore the relationship between high levels of IgE-FS and AE in a large cohort of young children with eczema participating in a multi-centre, international study. METHODS: Two thousand one hundred and eighty-four subjects (mean age 17.6 months, range 11.8-25.4; 1246 males) with active eczema from atopic families from 94 centres in 12 countries were studied. Clinical history, Scoring Atopic Dermatitis index as a measure of eczema severity and CAP-FEIA measurements for total IgE and IgE antibody levels to cow milk, egg and peanut were entered into a database. If CAP-FEIA levels exceeded previously reported age-specific cut-off levels for 95% positive predictive values (PPVs) for food allergy, subjects were defined as having high-risk IgE-FS (HR-IgE-FS). RESULTS: Serum was available from 2048 patients; 55.5% were atopic. The frequency of HR-IgE-FS to milk, egg and/or peanut was the greatest in patients whose eczema developed in the first 3 months of life and the least in those whose eczema developed after 12 months (P<0.0001). In a regression analysis to allow for potential confounding factors, children with HR-IgE-FS had the most severe eczema and the youngest age of onset (P<0.001); 64% of infants with severe eczema of onset-age <3 months had HR-IgE-FS. CONCLUSION: Early-onset severe eczema in infancy was associated with HR-IgE-FS. Clinical implications Food allergies should be routinely assessed in infants with moderate or severe eczema. Capsule summary In eczematous infants, the earlier the age of onset, and the greater the severity of eczema, the greater the frequency of associated high levels of IgE-FS.

Do patients with skin allergies have higher levels of anxiety than patients with allergic respiratory diseases? Results of a large-scale cross-sectional study in a French population.

BACKGROUND: Psychological comorbidity is a known aspect of allergic disease. However, there is recent evidence that a large proportion of allergic patients remains undiagnosed and untreated for psychological disease. In addition, the complexities of the anxiety-allergy relationship, i.e. differences for current and past disease, or differences among allergic disease types, are not well understood. OBJECTIVES: To measure the level of anxiety in a large allergic population in France using a standardized measure, the State/Trait Anxiety Inventory (STAI). METHODS: Allergy patients in France (n = 3939) who visited their allergy specialists participated in the study. The patients completed a questionnaire which was then linked to the questionnaire completed by their physician. Only patients with both subject and physician questionnaire were kept in the analyses. Mean STAI scores for the State (S) and Trait (T) scales were obtained for each allergic disease. ANCOVA models testing group differences on the mean scores, using the categories "current disease", "past disease" and "allergic disease ever", were assessed along with relevant confounders. RESULTS: Allergic rhinitis (AR), asthma and atopic dermatitis (AD) were the most prevalent conditions of the 12 allergic diseases assessed in the study. Women had higher mean STAI S/T scores than men and age was also found to be associated with higher S scores; therefore, both age and gender were included as covariates where relevant. A single ANCOVA model for each STAI scale showed a statistical difference among the various allergic diseases. Using the category "current disease" each allergic disease was assessed separately regarding the presence or absence of that disease. Higher, statistically significant mean STAI scores were found for AD and allergic urticaria on the S scale and for AD on the T scale. Similarly, for the category "allergic disease ever", AD and allergic urticaria reached statistical significance on the S scale, while on the T scale only AD was statistically significant. When patients were assessed for anxiety based on their past disease, asthma, AR and sinusitis were significant on the S scale while asthma and nasal polyps were statistically significant on the T scale. When asthma and AD were tested simultaneously, only the latter was significant. CONCLUSIONS: High mean scores for State and Trait anxiety were mostly associated with AD.

Epidemiological characterization of the intermittent and persistent types of allergic rhinitis.

BACKGROUND: A new classification of allergic rhinitis (AR) has been proposed by the allergic rhinitis and its impact on asthma (ARIA) workgroup. The validity of this new classification is still largely unknown, especially the extent to which it differs from the classical seasonal/perennial (SAR/PAR) classification, and how and whether intermittent and persistent types of AR, as defined by ARIA, differ from each other. METHODS: Two-step cross-sectional, population-based, in six Western Europe countries; telephone interview followed by clinical diagnosis [including specific immunoglobulin E (IgE) measurements] in a selected subset. RESULTS: Within the population with AR, 29% of the subjects had persistent AR. There was no association between the intermittent/persistent and the SAR/PAR classifications. Subjects with persistent AR had more severe symptoms, and higher rate of self-awareness and previous diagnosis of AR; they were also clearly distinct in their sensitization pattern and medication use. CONCLUSIONS: The classic types of SAR/PAR cannot be used interchangeably with the new classification of intermittent/persistent, as they do not represent the same stratum of disease. There is also evidence that the persistent type describes a distinct group with characteristics that differentiates them from intermittent AR. These results support the validity of the new ARIA classification.

Prevalence and rate of diagnosis of allergic rhinitis in Europe.

To measure the prevalence of allergic rhinitis among European adults and the proportion of undiagnosed subjects, a two-step, cross-sectional, population-based survey in Belgium, France, Germany, Italy, Spain, and the UK was undertaken. Step one of the study involved screening for allergic rhinitis by telephone interview, based on history of symptoms and/or self-awareness of the condition. Step two undertook confirmation of allergic rhinitis in a subset of the subjects screened positive; this was performed by a clinical diagnosis conducted in three to five clinical centres per country, including specific immunoglobulin E tests and a disease-specific questionnaire. A total of 9,646 telephone interviews were conducted between February and April 2001. Self-awareness of allergic rhinitis was reported by 19% of the subjects. Physician-based diagnosis of allergic rhinitis was reported by 13% of the subjects. In step two, 725 clinical assessments were conducted between May and August 2001. A total of 411 of patients, who underwent step two, had investigator-confirmed allergic rhinitis. Among patients with investigator-confirmed allergic rhinitis, 45% had not reported a previous diagnosis by a physician. Prevalence of subjects with clinically confirmable allergic rhinitis estimated by combining step one and step two data ranged from 17% in Italy to 29% in Belgium with an overall value of 23%. This large-scale study confirms that allergic rhinitis has a high prevalence in western Europe and is frequently undiagnosed.

'Vertition' of integumental organs in mites revisited: a case of fluctuating asymmetry.

Vertition in mites is defined as a meristic variation for a bilateral integumental organ with a separate genetic control for each body side. A prominent hypothesis expressed by Grandjean is the role of vertition in the evolutionary trend towards a reduced number of hair-like organs (mechano- and/or chemo-receptors) known to have occurred in many mite groups. Observations on leg setae in the two-spotted spider mite Tetranychus urticae do not support this hypothesis. Meristic variation for leg setae rather conforms to the notion of fluctuating asymmetry: the difference between the number of leg setae on the right and left sides of the body had a unimodal distribution with a mean of zero. Moreover, lack of heritability for left/right absences of leg setae in an inbred laboratory strain suggests that vertition could be purely environmental. It is therefore argued that meristic variation for hair-like organs in mites is caused by random developmental accidents not corrected by homeostatic mechanisms normally resulting in a perfect bilateral symmetry.

Population genetic structure in a Robertsonian race of house mice: evidence from microsatellite polymorphism.

Genetic evidence was assessed for inbreeding and population subdivision in a Robertsonian fusion (Rb) race of the western European form of house mouse, Mus musculus domesticus, in central Belgium. Inbreeding, and the factors responsible for subdivision (genetic drift and extinction-recolonization) can theoretically influence the fixation of underdominant Rb variants. The data consisted of allele frequencies of eight microsatellite loci and of the Rb(4.12) and Rb(5.10) chromosomes. Six populations were sampled once, and a seventh was sampled successively over 3 years. No evidence for inbreeding within populations was found. Levels of between-population subdivision were high (theta = 0.15-0.39), and showed no association with either karyotype or geographical distance over 8-60 km. In addition, low values of effective size were found in the successively sampled population (Ne = 5-20). Cases of significant two-locus disequilibria were associated with the most closely linked pair of microsatellite loci (r = 0.15): also consistent with small effective sizes. These results suggest that both the lack of inbreeding, and the combined effects of genetic drift and extinction-recolonization, may promote Rb polymorphism in M. m. domesticus.

Clutch desertion and re-nesting in pied flycatchers: an experiment with progressive clutch removal

Clutch desertion and re-nesting are important components of fitness when predation is frequent. In nestbox populations however, nest predation and desertion are rare but can be studied by experimental manipulations. We experimentally reduced clutches of pied flycatcher, Ficedula hypoleucaby removing one egg per day until desertion occurred. The size of the clutch at desertion and whether females re-nested or not were used as measures of the female response. Of the deserting females, 74% re-nested in our study area. Re-nesting frequency was correlated with date but not with the size of the clutch laid. The majority of the non-re-nesting females deserted empty nests, while the majority of re-nesting females deserted one egg. Clutch size at desertion was not correlated with the size of the clutch laid nor with laying date; it was smaller than the size predicted by an optimality analysis of the value of both the current (deserted) and the replacement clutch. For the re-nesting females, there was a negative correlation between fledging rate of the replacement clutch and the size of the clutch at desertion. Our predictions, made under the hypothesis that desertion and re-nesting are adaptive behaviours, were partly supported by the data; we explain the discrepancy by the constraint of searching for a new nest site or mate for re-nesting.

Segregation and fertility in Mus musculus domesticus (wild mice) heterozygous for the Rb(4.12) translocation.

Analysis of the progeny of wild mice heterozygous for the Rb(4.12) shows that fertility and segregation are normal. This study, and others with similar results, suggests that our view of the chromosomal evolution of the house mouse should be revised.