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1.
IgE Antibodies to Pityrosporum orbiculare in Children with Atopic Diseases   总被引:1,自引:0,他引:1  
Abstract. IgE antibodies to Pityrosporum orbiculare and 16 other species of fungi were measured with the radioallergosorbent test (RAST) in sera of 131 children. The children were 7-18 years old, suffered from atopic diseases and showed a varied allergic profile on a skin prick test (SPT). IgE antibodies to P. orbiculare were found in the sera of 26 of the 131 children. A higher proportion of the P. orbiculare RAST positive children than of the negative ones had current eczema (p<0.0001). In a stepwise logistic regression analysis of SPT and RAST data, the occurrence of serum IgE antibodies to P. orbiculare had the highest explanatory value for current eczema. Ten of 15 children with current atopic eczema and total serum IgE of >500 kU/1 had serum IgE antibodies to P. orbiculare. Twenty-four of the 26 P. orbiculare RAST positive children harboured serum IgE antibodies to other fungi. The strong relationship between atopic eczema and the occurrence of IgE antibodies to P. orbiculare indicates that these antibodies may be pathogenetically important in at least some patients with atopic eczema and this gives another dimension to this common skin disease.  相似文献   

2.
IgE antibodies to Pityrosporum orbiculare in children with atopic diseases   总被引:2,自引:0,他引:2  
IgE antibodies to Pityrosporum orbiculare and 16 other species of fungi were measured with the radioallergosorbent test (RAST) in sera of 131 children. The children were 7-18 years old, suffered from atopic diseases and showed a varied allergic profile on a skin prick test (SPT). IgE antibodies to P. orbiculare were found in the sera of 26 of the 131 children. A higher proportion of the P. orbiculare RAST positive children than of the negative ones had current eczema (p less than 0.0001). In a stepwise logistic regression analysis of SPT and RAST data, the occurrence of serum IgE antibodies to P. orbiculare had the highest explanatory value for current eczema. Ten of 15 children with current atopic eczema and total serum IgE of greater than 500 kU/l had serum IgE antibodies to P. orbiculare. Twenty-four of the 26 P. orbiculare RAST positive children harboured serum IgE antibodies to other fungi. The strong relationship between atopic eczema and the occurrence of IgE antibodies to P. orbiculare indicates that these antibodies may be pathogenetically important in at least some patients with atopic eczema and this gives another dimension to this common skin disease.  相似文献   

3.
It is estimated that at least one out of three children with recurrent wheezing is atopic. Reliable diagnostic tools are needed in primary care that allow for adequate identification of these children. The purpose of this study was to assess the value of ImmunoCAP® Rapid (ICR) Wheeze‐Rhinitis Child in the identification of atopy with the use of 10 selected allergens in children with recurrent episodes of wheezing. A multicenter population study is based on primary care. It included children managed consecutively at the health center, who had three or more episodes of wheezing, at least one of them in the last 12 months. Each child completed a physical examination, an epidemiological survey, one capillary blood sampling (110 μl) for ICR, and one venous blood sampling for determination of Phadiatop Infant, total IgE and 10 specific IgE measurements. The children were identified as atopic, based on their clinical signs and symptoms and at least one positive specific IgE (0.35 kUA/l or higher), before knowing the results of ICR, Phadiatop Infant and total IgE. ICR was read by two independent observers. Six classes were evaluated, negative without any color and five positive degrees of pink‐red color. Two hundred and fifteen children aged between 1 and 14 years were studied (138 boys); 50.7% were identified as atopic, 39.1% were sensitized only to inhalant allergens, 6.5% to food allergens and 5.1% to both. The predominant allergen was the dust mite (39.3%). For ICR, there were 2134 valid double observations. The Kappa index, comparing the negative results vs. any positive result, was 0.91 (95% CI: 0.88–0.94). The intraclass correlation coefficient was 0.98 (95% CI: 0.98–0.99). In the identification of a child as atopic, the positive post‐test probability of ICR depended on the color degrees considered: 88.4% for any positive and 97.6% for the most intense tones. The positive post‐test probability of Phadiatop Infant and total IgE was 95.6% and 68.2% respectively. ICR showed good reliability for the most prevalent allergen, the dust mite, with a sensitivity of 90.5% (95% CI: 82.1–95.8) and specificity of 88.5% (95% CI: 81.7–93.4). The analysis of the other allergens was limited by the small number of sensitized children. The analysis of receiver operating characteristic curves revealed an area under the curve of 0.84 (95% CI 0.80–0.88) for the cut‐off point of specific IgE of 0.35 kUA/l and of 0.94(CI 0.91–0.97) for 2 kUA/l. A greater intensity of color of the lines of ICR was related to higher levels of specific IgE in blood. ICR is a reliable test for the identification of atopy in children, which identifies most children as atopic, and shows a good correlation in allergen‐by‐allergen identification. This suggests that it should be regarded as a first‐rate tool, in the primary care clinic, for the evaluation of children with recurrent wheezing.  相似文献   

4.
The prevalence of latex allergy has been increasing not only in risk groups but also in the general population, where it is accepted to average 1%. In children, latex sensitization prevalence studies are scarce and involve different population sampling and allergy testing methods, which makes it difficult to compare across studies. Nevertheless, existing studies point towards a low prevalence of latex allergy in children, which still needs to be confirmed in the Portuguese population. Aiming at studying the prevalence of latex sensitization and allergy in a sample of Portuguese children, we studied 182 children from two different hospital outpatient clinics. A standardized questionnaire focusing on atopic background, previous history and allergic signs or symptoms on exposure to latex or fruits was given to all children and parents. Skin prick testing was performed with a battery of common aeroallergens as well as latex. Serum total IgE, Phadiatop, F x 5E and latex-specific IgE were determined in all children. Specific IgE to latex-crossreacting fruits was determined in latex-sensitized children. Based upon the questionnaire, the prevalence of latex allergy would be 0.5%. The prevalence of latex sensitization would be 3.8%, when based solely upon skin prick testing, and 12.1% (>/=0.35 IU/ml) or 6.6% (>/=0.70 IU/ml) when based singly upon determination of latex-specific IgE. When positive results for either test were considered, the prevalence of latex sensitization was 14.3%. All latex-sensitized children were atopic. Sensitivity to latex-crossreacting foodstuffs was demonstrated in 61.5% of latex-sensitized children (16/26). This study shows that the prevalence of latex allergy and sensitization in Portuguese atopic and non-atopic children, as analysed using various diagnostic methods, is similar to that observed in other countries. In addition, the assessment of latex allergy and sensitization should always include skin prick testing and determination of serum IgE.  相似文献   

5.
The purpose of this study was to investigate the value of a new multiantigen radioallergosorbent test, Phadiatop Paediatric, in the diagnosis of atopy in children less than 7 years of age. The diagnosis of atopic disease was established by history, physical examination, total serum IgE concentration, and the results of prick skin tests or radioallergosorbent tests or both, and then compared with the result of the Phadiatop Paediatric test for each patient. One hundred two patients (62 boys) between the ages of 4 months and 7.3 years were enrolled (median age 3.2 years). After the history and physical examination, 42% of the patients were believed to be atopic and 32% to be nonatopic; the diagnosis was uncertain in 26%. Skin prick test reactions to a variety of foods and inhalants were positive in 41 of 63 children tested; results of radioallergosorbent tests were positive in 35 of 61 children. Overall, atopy was diagnosed in 53 children and 49 were found to be nonatopic. When the clinical diagnosis was used as the gold standard, the Phadiatop test resulted in a correct diagnosis of atopy in 49 of 53 cases and of no atopy in 43 of 49 cases: sensitivity = 92%, specificity = 88%, and efficiency = 90%. Although the Phadiatop Paediatric test does not indicate specific sensitivities, it provides the clinician with a useful screening test for atopic disease in children 7 years of age or less, and the researcher with a means of validating atopic populations.  相似文献   

6.
BACKGROUND: The incidence of atopic diseases such as eczema is increasing in westernized societies. The suggestion that there is a "protective" association between the unique fatty acid composition of breast milk, particularly the omega-3 (n-3) and omega-6 (n-6) essential polyunsaturated fatty acid content, and the development of atopic disease in children was investigated in a cohort study of 263 infants born into families with a history of allergy (one or both parents had asthma, hayfever, eczema). The objectives of this study were to determine the lipid profile [specifically in relation to long-chain polyunsaturated fatty acid (LC-PUFA) composition] in maternal breast milk samples collected at 6 wk and at 6 months following birth, and to investigate the potential role of these fatty acids in modulating the phenotype of children at high genetic risk of developing atopic disease. METHOD: Breast milk samples were available from 91 atopic mothers at their child's ages of 6 wk and 6 months. These samples were analysed for the fatty acid spectrum. Analysis of variance was used to detect differences between groups of outcomes (no atopy or eczema, non-atopic eczema, atopy, atopic eczema) at ages 6 months and 5 yr, and a multiple comparisons procedure was conducted to isolate the parameters producing the different results (F-test, LSD test). For the exposure variables, n-3 and n-6 fatty acids are expressed as weight percentage and as a ratio (at both time-points). RESULTS: The fatty acid profiles of maternal breast milk at 6 wk and 6 months were similar. An increased ratio of n-6: n-3 fatty acids in both 6 wk and 6 month milk samples was associated with non-atopic eczema (p < 0.005) but not atopy alone or atopic eczema. CONCLUSION: We found milk fatty acids were a significant modulator of non-atopic eczema but not atopy or atopic eczema in infants at 6 months. In mothers with a history of asthma, hayfever or eczema, their 6-month-old infants were more likely to develop non-atopic eczema if their milk had a higher ratio of n-6: n-3 LC-PUFA.  相似文献   

7.
During a prospective study of 1654 children, followed from birth for 11 years, we evaluated the validity of a detailed questionnaire for establishing the prevalence of atopic disease in preadolescence. In 133 randomly selected children the questionnaire-based diagnoses were accurate in 128 (96.2%). If the cord blood IgE concentration was high (≥ 0.9 kU/l) then it was 1.7 times more common to have any prevalent atopic disease. The corresponding relative risk for multiple atopic disease was 11.5. Boys had high IgE levels significantly more often than girls, regardless of the degree of pubertal maturation. Sensitization to timothy pollen developed more often in children born during May compared to November. At least one allergy test (IgE, Phadiatop or SPT) was positive in 20 of 70 (28.6%) 11-year-old children with no history of atopic disease, indicating latent allergy. Among the healthy children with positive tests, those with cord blood IgE ≥ 1.3 kU/l were over-represented. IgE concentrations at 11 years of age corresponded poorly with neonatal IgE concentrations, indicating that after birth environmental influences are more important for the present IgE level than genetic factors.  相似文献   

8.
Type 1 allergy against natural rubber latex is an increasing problem in health care workers and children with spina bifida or urogenital malformations. The aim of our study was to evaluate the prevalence of latex IgE antibodies and cross-reacting fruit antibodies in patients with spina bifida compared with atopic and non-atopic controls. Risk factors for sensitization should be determined. Sera of 148 patients with spina bifida and 98 controls (44 with atopy) were screened for IgE antibodies against latex, banana and kiwi by fluorescence enzyme immunoassay (CAP system). Atopies, allergic symptoms after latex contacts and the number of operations were compiled by a questionnaire. Patients with spina bifida developed latex IgE antibodies (≥0.7 kU/l) more frequently (40.5%) than atopic children (11.4%) or healthy controls (1.9%). All 18 symptomatic patients belonged to the spina bifida group and had high values of latex antibodies. The risk for developing latex antibodies increases with the number of operations. There was no difference in the history of atopic diseases and in a screening test of IgE antibodies against inhalative allergens between latex sensitized and not sensitized children with spina bifida. Antibodies against banana were more frequent in the latex sensitized children with spina bifida. (18.3% vs 3.4%, P = 0.002). Conclusion The high prevalence of latex antibodies in children with spina bifida justifies a primary prophylaxis by avoiding latex contacts, especially during anaesthesia and surgery, a correlation between the number of operations and the development of latex antibodies exists. Received: 30 March 1996 and in revised form: 19 March 1997 / Accepted: 20 March 1997  相似文献   

9.
Sensitivity and allergy to latex in atopic and non-atopic children   总被引:2,自引:0,他引:2  
To study the sensitivity and allergy to latex in children, we investigated sera of 306 atopic md 303 non-atopic children (median age 4. 5 years) for specif-ic IgE to latex. In patients with specific IgE to latex, a questionnaire was sent to families and provocation tests were carried out. 60/306 atopic children (20. 8%) and 1/303 non-atopic children (0. 3 %) showed specific IgE to latex in serum. The proportion of atopic. latex-sensitized and provocation positive children was 12/48 (25 %). Specific IgE to latex was significantly higher (p < 0.03) in symptomatic compared to non-symptomatic patients. Specificity of a positive history was 92 %, sensitivity 50 %. Atopic dermati-tis tended to be more prevalent among the 12 provocation positive atopic children (75 %) compared to 36 provocation negative children (58 %). There was a tendency that children of the symptomatic group underwent surgical interventions more frequently compared to non-symptomatic children. In conclusion, latex sensitization and latex allergy seem to have oc-cured more often in atopic children than previously known. Risk factors for the development of a sensitization to latex are atopy and the clinical diagno-sis of atopic dermatitis; risk factors for a clinically manifest allergy to latex are an elevated specific IgE to latex, a positive history upon contact to mate-rial containing latex and probably frequent operations. Provocation tests should be performed to plan avoidance measures in latex-allergic children especially before surgical interventions.  相似文献   

10.
Data on the pathogenic mechanisms underlying the development of non-atopic asthma in children are scarce. Our aim was to evaluate the association and compare the atopic status, pulmonary functions, bronchial hyperresponsiveness and serum total immunoglobulin E (IgE) levels of parents of atopic and non-atopic asthmatic children by using objective methods. Fifty-one asthmatic children aged 4–16 yr and their parents were included into the study. Initially the American Thoracic Society's Respiratory Disease questionnaire inquiring data on symptoms of asthma, rhinitis and past medical history was filled in. Afterwards, skin prick test with aeroallergens, pulmonary function and methacholine bronchial provocation tests and serum sampling for total IgE level determinations were carried out. Bronchial hyperresponsiveness to methacholine was significantly more common in the mothers of non-atopic children compared to those of atopic ones, although no significant difference was observed in the skin prick test reactivity, pulmonary function test parameters and serum IgE levels. Questionnaire data revealed that the presence of asthmatic symptoms such as wheezing and phlegm and doctor-diagnosed asthma were more common in the mothers of non-atopic children. Meanwhile, asthmatic symptoms were also found to be significantly more common in fathers of non-atopic children. Logistic regression analyses revealed that maternal PC20 was the only predictive factor for the risk of displaying non-allergic asthma in children. The results demonstrate that among the risk factors studied, maternal bronchial hyperreactivity was associated with the development of asthma in non-atopic children.  相似文献   

11.
Expression of low-affinity receptors for IgE (FcɛRII) on T and B cells was examined with monoclonal antibodies to cell surface antigens of FcɛRII (CD23), T cells (CD3) or B cells (CD 19) by two-dimensional analysis under laser flow cytometry system. The majority of cells bearing FcɛRII were B cells; however, a small proportion of T cells (1. 6%) bore FcɛRII in children with atopic asthma and elevated serum level of IgE. The occurrence of FcɛRII positive B cells was also increased in children with atopic asthma compared with non-atopic controls (p < 0.001). The numbers of T and B cells hearing Fc receptors for IgG (FcɛR) did not differ between atopic and non-atopic children. T cells were isolated from venous blood by rosetting with sheep erythrocytes, and then cultured in vitro with phytohemagglutinin plus phorbol-myristate-acetate. The amount of IgE-binding factors (IgE-BF), a soluble form of FcɛRII, was determined by means of enzyme-linked immunosorbent assay. The level of IgE-BF was increased in cultures from children with a atopic asthma compared with non-atopic controls (p < 0.01). The possible involvements of FcɛRII on T cells and their soluble products, IgE-BF, in the pathogenesis of atopic asthma is discussed.  相似文献   

12.
Suboptimal immune responses to vaccination have been suggested among atopic infants. The aim of this study was to assess the influence of atopy and atopic asthma on the humoral response to Bordetella pertussis vaccination. Immunoglobulin (Ig)G and IgA specific antibodies were measured by enzyme linked-immunosorbent assay in 102, 10-yr-old atopic children (66 of them also being asthmatics) and compared with 76 non-atopic and 53 non-atopic non-asthmatic controls of similar age. The levels of antibodies and the percentage of positives to B. pertussis were comparable in all groups. Children with a very high total serum immunoglobulin (Ig)E (Percentile (Pct) > 90th) showed higher (p = 0.01) IgG pertussis antibodies than children with very low serum IgE (Pct < 10th). In conclusion, we found normal pertussis antibody levels in atopic and in atopic asthmatic children in late childhood, thus overriding any possible suboptimal response during infancy.  相似文献   

13.
Phadiatop和sIgE检测在儿童哮喘诊断中的应用   总被引:3,自引:1,他引:2       下载免费PDF全文
目的:探讨CAP过敏原检测系统中吸入性过敏原过筛试验(Phadiatop)检测和特异性IgE(sIgE)检测在小儿哮喘病因诊断中的价值。方法:应用荧光酶联免疫法,对153例小儿哮喘、40例支气管肺炎进行Phadiatop,sIgE和血清总IgE检测。结果:哮喘患儿Phadiatop和尘螨sIgE阳性率分别为 66.01%和59.48%,而支气管肺炎患儿两者阳性率分别为 12.5%和7.5%,两组间差异有显著性(P<0.05)。Phadiatop,sIgE灵敏度分别为0.66和0.59,特异度分别为0.88和0.93,两种检测的一致性高。结论:Phadiatop检测是哮喘病因诊断简便、可靠的体外过筛试验,Phadiatop阳性患儿应进一步作sIgE检测。  相似文献   

14.
A search for IgE antibodies was performed in 224 children, aged 0–15 yr, with symptoms compatible with IgE-mediated allergy, employing total IgE. RAST with up to 17 allergens and the Phadiatop® test. Fiftysix of 113 children (50%), aged 0–3 yr, and 80 of 111 children (72%) aged 4–15 yr had specific IgE antibodies. The most common allergens during the first 4 yr were egg white, a mixture of nuts (hazel nut, peanut, almond, coconut and Brazil nut) and milk. During the 2nd yr of life inhalant allergens became more important. From the 3rd yr they became more common than food allergens as sensitizers. Among the children aged 4–15 yr timothy, cat and nut mix were the most common allergens. Among the children with specific IgE antibodies Phadiatop was positive in 58% of the children younger than 4 yr, and in 91% of the children over that age. Fifty-three of the children with IgE antibodies against nut mix were further investigated for antibodies against hazel nut, peanut and almond, and 48 (91%) were positive against at least one of them. The parents of 41 of these patients answered a questionnaire about adverse symptoms against nuts, and 26 (63%) were aware of clinical sensitivity. In conclusion, IgE antibodies against food allergens dominated in children under 2 yr, and thereafter antibodies against inhalants became more important. An unexpectedly high prevalence of IgE antibodies against nut mixture was found. Phadiatop was a good screening method for identification of children 4 yr or older with IgE antibodies against inhalants.  相似文献   

15.
体内和体外变应原测定在过敏性哮喘诊断中的联合应用   总被引:1,自引:2,他引:1  
目的分析变应原皮肤点刺试验(SPT)和血清吸入性变应原筛查(Phadiatop)及特异性IgE测定联合应用在过敏性哮喘变应原诊断中优势。方法对57例诊断哮喘患儿进行吸入性变应原SPT测定和Phadiatop测定。对其中33例进行血清户尘螨特异性IgE测定。分析本组哮喘患儿SPT结果分布,SPT与Phadiatop结果符合率,户尘螨SPT与其特异性IgE结果符合率。结果儿童哮喘吸入性致敏原分布最常见的为尘螨、真菌、宠物等室内变应原。本组SPT和Phadiatop阳性检出率分别为86%、79%,SPT与Phadiatop符合率86%。5例Phadiatop阴性患儿经SPT和真菌特异性IgE测定证实存在真菌过敏。户尘螨SPT和特异性IgE结果符合率为97%。结论在儿童哮喘相关吸入性变应原诊断中,联合应用体内和体外变应原测定方法可互为补充,有助于提高变应原诊断的敏感性和特异性。  相似文献   

16.
Few epidemiological studies have compared the risk factors of asthma or wheezing between atopic and non-atopic children. The objective of this study was to determine if there are specific risk factors for current wheezing related to atopic status in schoolchildren. Schoolchildren 9-12 yr of age from three Spanish cities (n = 2720) were subject to a cross-sectional study of asthma risk factors (by questionnaire) and atopy (by skin prick test) according to the ISAAC phase-II protocol. Risk factors for current wheezing (in the last 12 months) as reported by parents were investigated among the atopic (positive prick test to at least one allergen) and the non-atopic (negative prick test) children. The prevalence of current wheezing was 13.1% in the whole group, 22.1% in the atopic group and 7.8% in the non-atopic group. However, only 62.4% of children with current wheezing were atopic. Male gender and asthma in the mother and/or the father were both significant and independent risk factors for current atopic wheezing, whereas maternal smoking in the first year of the child's life and mould stains on the household walls were for current non-atopic wheezing. In summary, this study shows that atopic and current non-atopic wheezing children in Spain do not share identical environmental and family risk factors.  相似文献   

17.
The association between exercise-induced bronchoconstriction (EIB) and exhaled nitric oxide (FENO) has not been investigated in young children with atopic or non-atopic wheeze, two different phenotypes of asthma in the early childhood. Steroid naïve 3- to 7-yr-old children with recent wheeze (n = 84) and age-matched control subjects without respiratory symptoms (n = 71) underwent exercise challenge test, measurement of FENO and skin prick testing (SPT). EIB was assessed by using impulse oscillometry, and FENO by standard online technique. Although FENO levels were highest in atopic patients with EIB, both atopic and non-atopic wheezy children with EIB showed higher FENO than atopic and non-atopic control subjects, respectively. In atopic wheezy children, a significant relationship between FENO and the severity of EIB was found ( r  = 0.44, p = 0.0004), and FENO was significantly predictive of EIB. No clear association between FENO and EIB or predictive value was found in non-atopic wheezy children. Both atopic and non-atopic young wheezy children with EIB show increased FENO levels. However, the association between the severity of EIB and FENO is present and FENO significantly predictive of EIB only in atopic subjects, suggesting different interaction between bronchial responsiveness and airway inflammation in non-atopic wheeze.  相似文献   

18.
Forty children with atopic dermatitis were evaluated for history, clinical features and allergologic-immunologic parameters. Lichenoid skin lesions were found in 67.5%, follicular lesions in 57.5%, and eczematoid lesions in 50% in children. 25% of children suffered from associated food allergy, 15% from respiratory atopy, and 5% from contact urticaria. The diagnostic efficiency to show specific sensitization was 93% for Pediatric Phadiatop, 90% for Food-Multidisc (fx5 Pharmacia), 88% for skin tests (Prick), 73% for elevated total serum IgE, 65% for Phadiatop, and 60% for family history. The classification of atopic dermatitis into an extrinsic type with specific sensitizations to allergens and into an intrinsic type without specific sensitizations appears to be useful because specific sensitizations significantly correlate with severer skin condition and disease course.  相似文献   

19.
Aim: To evaluate the diagnostic value of the skin-prick test and the atopy patch test in diagnosing basic food allergy in young children suffering from atopic eczema/dermatitis syndrome.

Methods: 141 children, the majority under 2 y of age (mean 16 mo) with atopic eczema/dermatitis syndrome were investigated using skin-prick and atopy patch tests for milk, egg, wheat and rye. Open diagnostic elimination challenge was done since this has been reported to be a reliable method in young children.

Results: A positive challenge response was found to milk in 63 (45%), egg in 78 (55%), wheat in 61 (43%) and rye in 61 (43%). Sensitivity/specificity of the atopy patch test was 60%/97% for milk, 71%/97% for egg, 90%/94% for wheat and 93%/90% for rye. For the skinprick test the corresponding figures were 41%/99%, 60%/97%, 13%/98% and 15%/99%.

Conclusion: Patch testing was found to be a more sensitive method than the skin-prick test in diagnosing food allergy in children with atopic eczema/dermatitis syndrome, especially in those under 2 y of age. Many children with a negative skin-prick test result have a positive patch test result, especially in the case of cereals. A diagnosis of food allergy should be confirmed by elimination and in the research setting also by challenge.  相似文献   

20.
Serum IgE concentrations and the presence of allergen-specific IgE were determined in a series of 23 children with atopic dermatitis. In this group 83% had significantly elevated serum levels of IgE, 91% had coexistent respiratory allergy, 70% had radioallergosorbent test (RAST) evidence of pollen hypersensitivity, and 43% gave a history and demonstrated a RAST score consistent with milk or egg hypersensitivity. In patients with eczema a significant proportion of the elevated serum IgE appears to be antigen specific.  相似文献   

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