Fecal IgE levels in infants at 1 month of age as indicator of atopic disease

Fecal IgE levels were investigated in 165 asymptomatic infants at 1 month of age under two nutritional regimens, breast-feeding and formula feeding, and the possibility of predicting by fecal IgE levels the onset of atopic disease was studied in these infants. IgE levels were measured by time-resolved fluoroimmunometric assay. IgE antibodies are detectable in fecal extracts, and we have already reported that IgE levels are increased in food-allergy patients after administration of food allergens, and this increase in fecal IgE levels may be a specific consequence of the local immune response to food-allergen stimulation in the gut mucosa. The presence of atopic disease and the feeding method during the nursing period were surveyed by questionnaire in 89 of these 165 infants when they were 18 months old. In an analysis of the present results, IgE values above 0.015 U/ml, the lower limit of measurement, were considered to be high. Forty-eight (29%) of the 165 subjects showed a high fecal IgE level. Thirty-seven (35%) of 105 formula-fed infants had high fecal IgE levels, whereas only 11 (18%) of 60 breast-fed infants had high levels (P<0.05). With respect to atopic family history, 30(39%) of the 77 infants with atopic family history had high fecal IgE levels, as compared with 18 (20%) of the 88 infants without atopic family history (P<0.01). When the relationship between fecal IgE levels at 1 month of age and presence of atopic disease in the first 18 months was investigated, the prevalence of atopic disease was significantly higher in subjects with high fecal IgE levels (50%) than in subjects with low fecal IgE levels (14%) (P<0.01). We conclude that cow's milk proteins or dietary antigens in breast milk consumed by infants, in addition to genetic predisposition, may stimulate IgE immune response in the developmental gut mucosa, and that fecal IgE level at 1 month of age is an important and noninvasive factor for predicting the development of atopic disease during infancy and early childhood.     

Predictive value of cord blood IgE in the development of atopic disease and role of breast-feeding in its prevention

The predictive value of cord blood IgE in the development of atopic disease was evaluated in a prospective study of two groups of infants. Total serum IgE level was ≥ 0.7 U/ml in 44.3% of the infants with positive family history of atopy and in 16.0% among those with negative family history. The level of cord blood IgE correlated significantly with the subsequent development of atopic disease in both groups. Cord blood IgE higher than 0.7 U/ml was associated with a high risk of development of atopic eczema and wheezing, 52.8% and 58.8% respectively in the groups with or without family history of atopy; compared with 13.4% and 1.1% in the groups with IgE levels less than 0.7 U/ml. Among newborns fed exclusively on breast milk for a minimum of 3 months, the incidence of eczema and wheezing was significantly lower (12%) compared with findings in the formula-fed group (32%).     

Serum IgE in non-atopic adults and in dermatitis patients

Total serum IgE was determined with the PRIST technique, and specific reaginic antibodies against 10 allergens were measured in 163 healthy adults with no personal or family history of symptoms indicative of atopy (Group A). 103 non-atopic adults with a family history of atopic diseases were similarly investigated (Group B). When all subjects who at the second interview presented with a history of atopic symptoms and those with positive RAST results were excluded, the geometric mean serum IgE value for Group A was 14.5 (SD = 2) - 94.4 U/ml and for Group B 14.4 (SD = 2) - 130.2 U/ml. There was no significant difference in the IgE values between men and women. Subjects under 40 years of age had significantly higher IgE values than subjects over 40 years. In the series of 276 dermatitis patients the geometric mean IgE value for the men was significantly higher (46.8) than for the women (28.8 U/ml). There was a highly significant difference in the mean serum IgE levels between the patients with a personal history of atopic diseases and the other patients. Patients with present atopic disease had significantly higher mean IgE values than those with past atopic disease while no significant difference was discernible in the mean IgE levels between the non-atopic patients from atopic families and those with no personal and family atopy. Three years later, total serum IgE was controlled in subjects with initial IgE levels greater than 100 U/ml. During this time, eight subjects had developed an atopic disease. In most cases, there were only slight variations in the IgE values.     

Cord blood IgE. II. Prediction of atopic disease

Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985–1986) in Denmark ( n = 1189 + 1625). For follow-up we chose all infants with cord blood IgE ≥ 0.5 kU/1 and a randomly chosen group of the same size with cord blood IgE < 0.5 kU/1. A total of 762 infants were clinically evaluated at 18 months of age. A diagnosis of definite atopy, probable atopy or no atopy, including both IgE and non-IgE mediated disease was established. Applying different cord blood IgE cut-off values (0.3, 0.5, 0.8, 1.1) we did not find an excess of atopic infants among those with elevated cord blood IgE irrespective of the chosen cut-off value. Atopic predisposition or family history of atopic disease was defined as at least one parent or older siblitig with atopic disease. Significantly more infants with a family history developed atopy at 18 months. In the 2 series the positive predictive values of cord blood IgE≥0.5 were 43% and 46% and the sensitivities were 17% and 15%. The predictive values of having a family history were 48% and 44% and the sensitivities were 55% and 58%.
Clinical aspects
Cord blood IgE analysed by Phadebas IgE PRIST was a poor predictor of infants developing atopic disease before the age of 18 months.     

Increased levels of serum IgE in children of mothers with systemic lupus erythematosus

Various allergic diseases have been described in patients with systemic lupus erythematosus (SLE). In the present study, we evaluated the prevalence of allergic disease and serum IgE levels in 36 children of 26 mothers with SLE. None of the subjects had any rheumatic symptoms. There was at least one type of allergic disease in 28 (78%) of the 36 children of mothers with SLE, as compared with 30% in Japanese control children ( P <0.01). The prevalence of atopic dermatitis and bronchial asthma was higher in children of mothers with SLE (64% and 28%) than in controls (19% and 9%) ( P <0.01, respectively). Fourteen of the 36 subjects (39%) had higher levels of serum IgE than those of normal range for age-matched healthy Japanese children with no atopic family disease in the immediate family history, and these children had atopic disease. Among the 14 children with high serum-IgE levels, seven had neither immediate nor remote family history of atopic disease, while the others had an immediate family history of atopic disease. We think that genetic factors may influence the presence of allergic disease in children of mothers with SLE, and that the increased serum IgE levels in children of SLE mothers with no allergic family history may be a part of subclinical immunologic abnormalities related to SLE.     

Predictors of atopy in newborn babies

The capacity of laboratory tests and clinical signs to predict allergic manifestations up to 18 months of age was assessed in 129 newborn babies, most of whom had family members with atopic disease. The parameters assessed included family history; skin dryness; erythema toxicum; skin reactivity to histamine and IgE levels; eosinophil counts; and peripheral white blood cell, leukocyte diflferential, and platelet counts in cord blood (CB). Erythema toxicum and white blood cell and platelet counts were of no value as predictors of allergy. The sensitivity of family history, skin dryness, and sensitivity to histamine, as well as IgE levels and eosinophil counts, varied 25–79% and the specificity 40–74%. The efficiency was never higher than 58%. Logistic regression, applied in order to evaluate the joint predictive power of the five parameters, showed a P value of <0.001. The estimated probability for atopy before 18 months of age was 0.33 for neonates with normal skin texture, a CB IgE of less than 0.5 kU/l, and a history of fewer than two family members with atopy. The probability increased to 0.89 for babies with a dry skin, a history of two or more atopic family members, and a CB IgE of ≥0.5 kU/1. In conclusion, not one parameter nor any combination of them seems suitable for general screening. However, a combination of family history and CB IgE and skin assessment may be used to identify babies at high risk of allergy for participation in prevention studies.     

Predictive value of cord blood IgE levels in 'at-risk' newborn babies and influence of type of feeding

Cord serum IgE levels were examined in 101 newborn infants ofatopic parents, and reviewed at the ages of 3, 6, 9, 12, 15, 18, 21 and 24 months, in order to determine any relation with signs and symptoms of allergic rhinitis, bronchial asthma, atopic dermatitis, urticaria and food allergy. Cord blood IgE levels were 1.06+ 1.02 U/ml in the group of infants who developed atopic disease, and 0.34 + 0.79 U./ml in the group of infants who did not develop atopy (P < 0.001). In the breast-fed group 37.5, of the infants with cord blood IgE more than 0.8 U/ml and 11.5% with IgE below 0.8 U/ml had atopic disease. In the soy-fed group 33.3% of the infants with cord blood IgE more than 0.8 U/m! and 15.8% with cord blood IgE less than 0.8 U/ml developed atopy. Ninety percent of the cow's milk-fed infants with cord blood IgE above 0.8 U/ml and 16% with cord blood IgE below 0.8 U/ml showed atopy during the follow-up period. No correlation was found between the IgE levels in maternal and respective cord blood.     

Cost-effectiveness of neonatal IgE-screening for atopic allergy before 7 years of age

Obvious atopic diseases developed in 18% of 1651 non-selected children before 7 years of age. More than 80% of newborns with high IgE concentrations in cord blood developed atopic diseases before this age. Although the sensitivity of the IgE test is rather low (40%), most cases (94%) of severe, long-lasting atopic disease show a high neonatal IgE concentration, and the specificity of the test is high (94%), Calculations of total costs of screening were made on the basis of family history alone compared with neonatal IgE-screening in two groups: (i) all newborn infants, or (ii) infants with a family history of atopic disease. The cost of preventive measures and treatment costs were included in the total patient compliance) then IgE-screening was cost-effective in both groups, which screening solely on a basis of family history was not. In Sweden there was a total saving of approx, 20 million SEK or 3 million USS per annum. Thus, IgE-screening of cord blood to select newborns for preventive measures is also economically worthwhile.     

Relationship between active and passive smoking and total serum IgE levels in Japanese women: baseline data from the Osaka Maternal and Child Health Study

BACKGROUND: Many studies have shown that cigarette smoking is associated with elevated concentrations of total serum IgE. Few studies, however, have examined total IgE in relation to passive smoking exposure, especially in adults. This cross-sectional study investigated the association of active and passive smoking exposure with levels of total serum IgE in Japan. METHODS: Study subjects were 981 pregnant women in Osaka. Total IgE levels were measured using UniCAP 1000 and were defined as elevated if they exceeded 170 ml/UI. Age, gestation, parity, family history of asthma, atopic eczema and allergic rhinitis, indoor domestic pets, family income, education and the mite allergen level in house dust were selected as potential confounding factors. RESULTS: Current smoking of at least 15 cigarettes a day and 8.0 or more pack-years of smoking were independently related to an increased prevalence of elevated total serum IgE (adjusted odds ratios 3.40 and 2.51, 95% confidence intervals 2.12-5.47 and 1.55-4.06, respectively), and both cigarette smoking status and pack-years of smoking were significantly positively associated with total serum IgE levels, especially in subjects with a positive familial allergic history. There was no measurable association of exposure to environmental tobacco smoke (ETS) at home or at work with total serum IgE concentrations among those who had never smoked. CONCLUSIONS: Our results corroborate a positive relationship between active smoking and total serum IgE levels; however, this study failed to substantiate a positive association of ETS exposure with total IgE. Investigations with more precise and detailed exposure measurements are warranted.     

Serum levels of interleukin-4, soluble CD23 and IFNγ in relation to the development of allergic disease during the first 18 months of life

Serum levels of Interleukin (IL)-4, Interferon (IFN)-γ and soluble CD23 (sCD23) were analysed in a prospective study of 64 infants who were monitored from birth to 18 months of age. The findings were related to family history of atopy and the development of allergic disease in the infants. Low levels of IL-4 were detected in 10 of 63 cord blood samples (median 0.14 and range 0.32 μg/1). The levels then increased, both in healthy and atopic infants, reaching a peak at either 6 or 9 months and then decreased up to 18 months of age. The children who developed atopic disease during the first 18 months of life had significantly higher IL-4 median levels than those who did not, i.e. 0.24 (range 0.40) vs <0.10 μg/1 at 3 months, (P< 0.001), 0.40 (range 0.95) vs 0.13 (0.19) μg/1 at 6 months (P < 0.01), 0.46 (range 0.78) vs 0.10 (0.24) μg/1 at 9 months (P< 0.001) and 0.30 (range 1.38) vs 0.10 (0.36) μg/1 at 18 months (P< 0.001). The IFNγ levels were below the detection level, i.e. < 100 ng/1 in all but 49 of the 196 serum samples that were analysed. There was no significant relationship with clinical outcome, nor with S-IgE levels. Soluble sCD23 levels increased in the infants with age. There was no association with either atopic disease, family history of allergic disease or IgE antibody levels. In conclusion, IL-4 levels in serum, but not sCD23 and IFN7 are associated with allergic disease in infancy. Elevated levels were recorded before the onset of clinical symptoms. The findings support that atopic disease is associated with a primary abnormality of T-cell function.     

Extraordinarily high serum IgE levels and consequences for atopic phenotypes.

BACKGROUND: IgE plays a central role in allergic diseases. Recent studies have postulated an association between serum IgE levels and bronchial asthma. OBJECTIVE: To examine the differences of atopic phenotypes in a group of individuals with extraordinarily high serum IgE levels (>10,000 kU/L) compared with children with moderately elevated IgE levels (400-1,000 kU/L). METHODS: We investigated 20 children with serum IgE levels greater than 10,000 kU/L and compared them with 56 age-matched children with serum IgE levels of 400 to 1,000 kU/L regarding prevalences of atopic dermatitis, bronchial asthma, allergic rhinoconjunctivitis, allergic sensitization, and history of anaphylaxis. RESULTS: The mean eczema severity score as determined by the Severity Scoring of Atopic Dermatitis Index was 56 vs 18 (P < 0.003), and anaphylactic reactions were reported in 20% of the group with very high serum IgE levels vs 7% in the group with moderate levels (P < 0.02). Sensitization to both aeroallergens and food allergens was detected in 80% of the group with very high serum IgE levels vs 32% of the group with moderate levels (P < 0.001). CONCLUSIONS: Our results indicate that children with very high serum IgE levels are at risk for anaphylactic reactions and more severe atopic dermatitis.     

High anti-IgE levels at birth are associated with a reduced allergy prevalence in infants at risk: a prospective study

Development of atopic disease was prospectively studied in 148 children from birth to the age of 18 months and related to serum levels of IgG anti-IgE antibody. Children with a dual heredity of allergy, but remaining healthy, had significantly higher IgG anti-IgE levels at birth than children with a similar predisposition to allergy, who became allergic. Children with increased allergy risk, defined by elevated IgE levels at birth (>= 0.53 kU/l) and with probable allergy symptoms had also significantly higher IgG anti-IgE levels at birth than children of the same risk group, developing definite allergy. Independent of allergy risk, there was a significantly lower prevalence of atopic disease in children with cord serum levels of IgG anti-IgE above 350AU.1 than in children with lower levels. Additionally, we showed that the allergy predictive capacity of IgE levels in cord serum was slightly improved in specificity, sensitivity and efficiency by including not only the family history of allergy, but also cord serum levels of IgG anti-IgE. Our results thus raise the possibility that high levels of IgG anti-IgE protect children of increased allergy risk from early development of atopic disease and reduce the severity of symptoms.     

Trichophyton-specific IgE in patients with dermatophytosis is not associated with aeroallergen sensitivity

BACKGROUND: It has been proposed that Trichophyton infection is associated with atopy and allergy. OBJECTIVES: Our purpose was (1) to confirm whether atopy predisposes to chronic dermatophytosis and (2) to investigate whether Trichophyton infection induces atopic disease. METHODS: Patients attending dermatology clinics and suspected of having dermatomycosis underwent in a prospective manner fungal culture and Trichophyton and inhalant skin tests, and blood serum was collected for total IgE and Trichophyton radioallergosorbent testing. Personal and family history of atopic diseases was also investigated. RESULTS: According to mycologic culture, atopic history, and inhalant skin test results, patients were classified into 4 groups: (1) atopy plus mycosis (n = 28), (2) atopy (n = 26), (3) mycosis (n = 35), and (4) no atopy, no mycosis (n = 33). Patients with active mycosis (groups 1 and 3) demonstrated significantly increased positivity of Trichophyton skin tests compared with patients without fungal infection (groups 2 and 4), regardless of their atopic status, whereas atopic patients (those in groups 1 and 2) had significantly increased levels of total serum IgE compared with nonatopic subjects. Trichophytosis was not more prevalent in atopic than in nonatopic subjects, and atopic diseases were not more frequent in culture-positive than in culture-negative patients. CONCLUSIONS: Our results indicate that Trichophyton -specific IgE is observed in patients with trichophytosis regardless of atopy.     

Expression of sCD23 in atopic and nonatopic blood donors: correlation with age, total serum IgE, and allergic symptoms

Although structure, biologic activities, and expression of the low-affinity IgE receptor (Fc_eRII, CD23) have been investigated, the diagnostic value for allergies of this molecule and its soluble circulating fragment (sCD23) remains unclear. Therefore, serum sCD23 levels were measured in 203 blood donors. They were divided into atopic and nonatopic subjects by allergy history, physical findings of allergic symptoms, and corresponding specific circulating IgE antibodies. The group consisting of nonatopic subjects was divided into four age categories in order to exclude age-dependent variations in the expression of the low-affinity IgE receptor. In our study population, sCD23 serum levels were not influenced by age. Furthermore, no significant differences, especially no decrease in serum sCD23 levels, between the four nonatopic age groups were detected. There was no significant increase of sCD23 serum levels in atopic subjects in comparison with nonatopic blood donors. In addition, no correlation between total IgE levels and sCD23 serum levels could be detected, in either the group of atopic donors or the group of nonatopics. Our data suggest that the circulating low-affinity IgE receptor does not appear to be an additional general marker for the diagnosis of allergies, as previously suggested.     

Clinical symptoms and IgE responses to common food proteins in atopic and healthy children

The appearance of symptoms suggestive of allergy through the first 4 years of life was studied prospectively in eighty-six healthy newborn babies. Blood samples were obtained at birth, at 3,8,25 and 48 months of age and analyzed for levels of total serum IgE and for IgE antibodies to some common foods. The occurrence of IgE antibodies was related to atopic manifestations and to a detailed history of infant feeding and family history of allergy. All infants with elevated cord blood IgE (more than 1.3 kU/1) developed manifestations of atopy. Specific IgE antibodies against egg, cow's milk and soy were demonstrated at 3, 8, 25 and 48 months in nine, twenty-three, six and two children respectively. Egg was a more potent sensitizing agent than cow's milk, IgE antibodies to egg being present in thirty-one samples, to cow's milk in eleven and to soy in five samples. Nine infants developed IgE antibodies to eggs or cow's milk before the introduction of these nutrients into the food. The IgE antibody levels were generally low in healthy non-atopic children and did, with one exception, not reach RAST class 1. In contrast, the levels of IgE antibodies to egg or cow's milk were higher in eleven blood samples from atopic children. We conclude that transient low IgE antibody responses to food proteins appear relatively often even in healthy infants. High concentrations of IgE antibodies however are almost exclusively seen in infants with atopic disease. Sensitization may appear early in infancy sometimes even before the offending food has been introduced into the diet.     

Development of atopic disease during childhood and its prediction by Phadiatop Paediatric

Background Evaluating in vivo and/or in vitro tests for ‘early’ prediction of childhood allergy is of interest in paediatric allergology. Objective To determine whether the measurement of Phadiatop Paediatric (PP) during early childhood could be used to predict the development of atopic disease during the first 5 years of life among infants with a family history of atopic disease. Methods Phadiatop Paediatric was evaluated in 134 infants. The analysis was performed at 6 months, at 18 months and at 5 years of age and the numbers of available serum samples were 61, 85 and 134, respectively. The potential capacity of the test to predict the development of atopic disease was studied by relating the result of the test, a positive or a negative score, to the cumulated incidence of atopic diseases from birth to 18 months of age and from birth to 5 years of age. Results Three of four children with a positive PP at 6 months of age developed clinical signs/symptoms of atopic disease before 18 months and all four before 5 years of age. The predictive value of a positive test at 18 months for symptoms before 5 years of age was 80% (12/15). If the diagnostic criterion, instead of clinical signs/symptoms of atopic disease, was at least one positive skin-prick test to major food or inhalant allergens, the predictive value of a positive PP-test at 18 months decreased to 53% (8/ 15). Conclusion Although the presence of circulating IgE antibodies, as detected by Phadiatop Paediatric, can predict the development of atopic diseases during childhood, the usefulness of the test is limited by its low sensitivity (22-47%).     

IgE levels in cord blood and at 4–5 days of age: relation to clinical symptoms of atopic disease up to 18 months of age

To evaluate the variation in serum IgE levels during the neonatal period and its relation to the development of atopy, 83 infants with a heredity of atopy were studied with regard to the concentration of IgE in cord blood (CB) and capillary blood on the fourth or fifth day of life. During the neonatal period, the average IgE level remained unchanged in the whole group but there were large individual changes. Among 22 infants with CB-IgE levels greater than or equal to 0.9 kU/l the IgE concentrations in 50% decreased below this value on days 4-5. The correlation between maternal IgE and CB-IgE concentrations (rs = 0.41; P less than 0.001) was interpreted as indicating a probable contamination with maternal blood. This view was supported by the presence of an elevated IgA level and of IgE antibodies against inhalant allergens in 16% of the cord blood samples of which 69% had an IgE level exceeding 0.9 kU/l. It therefore seems preferable to collect the blood samples on the fourth or fifth day. However, in the 74 infants available for atopic classification at 18 months of age, the positive predictive value of IgE determinations was low: on days 4-5 25-38% and in CB 42%. A high CB-IgE level may merely be an indication of the mother's atopic state.     

Normative data for total serum immunoglobulin E measurements in children of three ethnicities

BACKGROUND: It is about 20 years since IgE measurements were published for children without atopic disease. It is possible that the recent increase in atopic disease is reflected in altered measurements in subjects who have no clinical expression of atopy. If the measurement of IgE is to be used as a marker for atopy to characterize disease categories, contemporary normative data must be available. OBJECTIVE: To measure total serum IgE in healthy children of three ethnicities born and living in an inner city environment. METHODS: Subjects were aged 1 to < or = 12 years, of Afro-Caribbean, Bangladeshi and white British ethnicities, with no personal history of current atopic disease. An extra 1 mL of blood for the measurement of total serum IgE was collected when blood was taken for other purposes or when a surgical procedure was being undertaken. RESULTS: Measurements were taken from 151 boys (median age 5.4 years) and 106 girls (median age 6.0 years), who included 127 Bangladeshis, 58 Afro-Caribbeans and 72 white British children. Measurements increased with age but were not related to gender or ethnicity. The data were significantly higher than previous measurements by sixfold. CONCLUSION: These contemporary normative data allow the generation of z scores for total IgE measurements for clinical or epidemiological use.     

Cord serum IgE in relation to family history and as predictor of atopic disease in early infancy

Cord serum IgE was assayed by particle counting immunoassay (PACIA) in an unselected series of European newborns (n = 190; geom mean = 0.37 IU/ml) and a cutoff limit established (≥ 1.20 IU/ml) for prediction of atopy. At control follow-up by questionnaire 18 months after birth, 38 infants (20.0%) had developed definite (9.5%) or probable (10.5%) atopy with a significant predominance of boys ( P < 0.03). Infants with a positive immediate family history (IFH) had a higher risk of developing atopy ( P < 0.0025) and also had a higher incidence of elevated cord IgE ( P < 0.02) than infants with a negative IFH. Maternal atopy influenced cord IgE levels significantly ( P < 0.00005), whereas paternal atopy did not ( P = 0.23). No fetal IgE antibodies against five common allergens could be demonstrated in 36 cord sera tested. Breast-feeding for 3 months was not sufficient to prevent atopic symptoms. The predictive value of cord IgE was high since 26 of 36 newborns (positive predictive value = 72.2 %) with elevated cord IgE had developed atopic symptoms before follow-up. Of the 38 infants who developed atopic symptoms, 26 had elevated cord IgE (sensitivity = 68.4%) compared to only 10 (6.6%) of the 152 atopy-free infants (P < 0.00005). The data indicate that elevated cord IgE as determined by PACIA is a good predictor of early-onset atopy, better than family history ( P < 0.008), and that primarily maternal atopy seems to affect fetal IgE synthesis.     

Markers for early sensitization and inflammation in relation to clinical manifestations of atopic disease up to 2 years of age in 133 high-risk children

BACKGROUND: The combination of genetic susceptibility and environmental factors induce allergic sensitization and subsequently local inflammation, resulting in atopic manifestations. OBJECTIVE: To examine whether immunological features reflecting sensitization (total and specific IgE levels, allergen-induced proliferative responses and skin tests) and markers of inflammation (plasma sE-selectin and blood eosinophils) are related to the clinical expression of atopy and whether they precede atopic disease in children up to 2 years of age. METHODS: The development of these markers during the first 2 years of life was studied prospectively in 133 newborns at high risk to develop atopic disease. RESULTS: The prevalence of atopic disease increased from 25% at 12 months to 32% at 24 months of age. The children with food allergy at 12 months, who all had atopic dermatitis (AD), turned out to have asthma-like disease in 40% and AD in 100% at the age of 24 months. Total IgE levels increased with time and from 12 months onward levels started to differ markedly between atopics and nonatopics. Food-specific IgE antibodies were significantly associated with AD (relative risk [RR] = 2.39), food (RR = 1.32) and upper-airway allergy (RR = 1.20), and house dust mite-specific IgE antibodies with upper-airway allergy (RR = 5.00). A positive skin test was significantly associated with AD (RR = 2.90) and food allergy (RR = 1.36). The inflammation markers investigated, were not related to the clinical expression or preceded atopic disease at 2 years of age in high-risk children. CONCLUSION: Positive skin tests and specific IgE to food or inhalant allergens were related to the clinical expression of different atopic diseases. The combination of AD and food allergy at 12 months reflected the strongest risk factor in this high risk cohort for the development of asthma-like disease at 24 months of age.