Correlation between skin prick test using commercial extract of cow''s milk protein and fresh milk and food challenges

The skin prick test (SPT) is regarded as an important diagnostic measure in the diagnostic work-up of cow's milk protein allergy. It is not known whether commercial extracts have any advantage over fresh milk. The aims of the study were to (i) compare the diagnostic capacity of SPTs for the three main cow's milk proteins (alpha-lactalbumin, casein and beta-lactoglobulin) with fresh milk and (ii) determine a cut-off that discriminates between allergic and tolerant children in a controlled food challenge. A study was carried out on 104 children consecutively attending two paediatric allergy clinics for suspected cow's milk allergy. A clinical history, SPTs with fresh cow's milk and commercial extracts of its three main proteins and a challenge test were performed on all the children. A study of the validity of the prick test was also performed by taking different cut-off points for fresh milk and its proteins. Twenty-eight of 104 challenge tests (26.9%) were positive. At a cut-off point of 3 mm, fresh milk showed the greatest negative predictive value (98%), whereas casein showed the greatest positive predictive value (PPV, 85%). Calculation of 95% predicted probabilities using logistic regression revealed predictive decision points of 12 mm for lactalbumin, 9 mm for casein, 10 mm for beta-lactoglobulin and 15 mm for fresh cow's milk. We found that the greater the number of positive SPTs for milk proteins, the more likely the positive response to challenge. Having a positive SPT for all three milk proteins had PPV of 92.3% and would seem more clinically useful than any cut-off. Both fresh milk and cow's milk extract of the three main proteins could be useful in the diagnostic work-up of cow's milk allergy. Finding positivity to all three cow's milk proteins seems to be a simpler and more useful way of avoiding oral food challenges.     

The diagnostic value of skin prick testing in children with food allergy

The diagnostic accuracy of the skin prick test (SPT) in food allergy is controversial. We have developed diagnostic cut-off levels for SPT in children with allergy to cow milk, egg and peanut. Based on 555 open food challenges in 467 children (median age 3.0 yr) we defined food-specific SPT weal diameters that were '100% diagnostic' for allergy to cow milk (>or=8 mm), egg (>or=7 mm) and peanut (>or=8 mm). In children < 2 yr of age, the corresponding weal diameters were >or=6 mm, >or=5 mm and >or=4 mm, respectively. These SPT cut-off levels were prospectively validated in 90 consecutive children 相似文献   

Predictive factors for the persistence of cow’s milk allergy

Santos A, Dias A, Pinheiro JA. Predictive factors for the persistence of cow’s milk allergy.
Pediatr Allergy Immunol 2010: 21: 1127–1134.
© 2010 John Wiley & Sons A/S Cow’s milk allergy (CMA) is usually transient, but recent studies have shown a later acquisition of tolerance to CM. Our aims were to characterize a population of Portuguese children with CMA and to identify predictive factors for the persistence of this food allergy. Children with CMA observed in our Paediatric Allergy Clinic between 1997 and 2006 were selected. Demographic and clinical data were collected from medical records. The group of children who tolerated CM before the age of 2 was compared with the group of children who tolerated CM beyond that age or persisted with CMA until the end of the study. Multivariate logistic regression analysis was used to investigate independent predictive factors for the persistence of CMA beyond the age of 2. In the subgroup of children with IgE‐mediated CMA, the acquisition of tolerance was analysed using Cox regression. In this population of 139 children, the majority presented more than one symptom (73%) affecting more than one organ (51%), with cutaneous (81%), gastrointestinal (55%), respiratory (16%) manifestations and/or anaphylaxis (3%). Thirty‐two per cent developed asthma, 20% atopic eczema, 20% rhinoconjunctivitis and 19% other food allergies over time. The acquisition of tolerance was different in the whole population versus the subgroup with IgE‐mediated CMA: 34%versus 0% at the age of 2, 55%versus 22% at the age of 5 and 68%versus 43% at the age of 10. Immediate allergic symptoms, asthma and other food allergies were independent factors for the persistence of CMA beyond the age of 2. Higher maximum weal diameter on skin prick test to CM and higher maximum level of specific IgE to CM were associated with reduced likelihood of acquiring tolerance in the subgroup of children with IgE‐mediated CMA. In conclusion, children with IgE‐mediated CMA acquire tolerance to CM at older age. Clinical parameters and allergy tests may be helpful in defining prognosis. CM‐allergic children tend to develop other atopic conditions and need specialized follow‐up in the long term.     

Diagnosis of IgE‐mediated food allergy among Swiss children with atopic dermatitis

Diagnosis of food allergy in children with atopic dermatitis (AD) relies on a good knowledge of the prevalence of the disease and of the foods most frequently involved. Our objective was to define these characteristics in a population of Swiss children with AD. Patients referred to a pediatric allergist or a dermatologist for AD were routinely tested by skin‐prick test (SPT) to seven common food allergens (milk, egg, peanut, wheat, soy, fish, and nuts), and to all other foods suspected by history. Patients with positive SPTs were further evaluated for specific serum immunoglobulin E (IgE) antibodies (by using the CAP System FEIA^?). CAP values were interpreted following previously published predictive values for clinical reactivity. Patients with inconclusive results (between the 95% negative predictive value [NPV] and the 95% positive predictive value [PPV]) were challenged with the suspected food. A total of 74 children with AD were screened for food allergies. Negative SPTs excluded the diagnosis in 30 subjects. Nineteen patients were diagnosed by histories suggestive of recent anaphylactic reactions to foods and/or CAP values above the 95% PPV. Forty‐three food challenges (35 open challenges and eight double‐blind, placebo‐controlled in children with persistent lesions of AD despite aggressive topical skin treatment) were performed in patients with positive SPTs but with inconclusive CAP values. Six patients were diagnosed as positive to 15 foods. Challenges were not performed to high‐allergenic foods in young children (under 12 months of age for egg and fish, and under 3 years of age for peanuts and nuts). Altogether, 33.8% (25 of 74) of the AD patients were diagnosed with food allergy. The prevalence of food allergy was 27% (seven of 25) in the group referred to the dermatologist for primary care of AD. The foods most frequently incriminated were egg, milk, and peanuts. The prevalence of food allergy in our population was comparable to that in other westernized countries, suggesting an incidence of food allergy in approximately one‐third of children with persistent lesions of AD. Together with milk and eggs, peanuts were most frequently involved in allergic reactions.     

Large number of CD19+/CD23+ B cells and small number of CD8+ T cells as early markers for cow's milk allergy (CMA)

Assessment of activation of immune mechanisms is valuable in the early diagnosis of cow's milk allergy (CMA). The purpose of this study was to evaluate peripheral blood lymphocyte subclasses in children suspected of having CMA and healthy infants in order to detect an early marker for food allergy. Altogether 47 breast-fed infants, aged from 0.4 to 10 months were followed-up prospectively from birth because of atopic heredity. Twenty-three of the infants were healthy and 24 infants had a strong suspicion of and later challenge-proven cow's milk allergy. Leucocyte subsets were determined from peripheral blood mononuclear cells by flow cytometry. In response to a clinical cow's milk challenge, seven infants developed urticaria, 11 infants had eczema, three patients had loose stools, diarrhoea or vomiting and three infants had eczema and diarrhoea, loose stools or vomiting. The total percentage of B cells and also the proportion of B cells bearing a low-affinity IgE receptor as a marker for activation were significantly higher, whereas the percentage of CD8+ T cells was significantly lower in infants with challenge-proven CMA than in healthy controIs. These results imply that infants with active CMA have a defect in regulation of B-cell function. Further, they suggest that imbalance of the ratio of suppressor and helper T cells might be an important factor in the etiopathogenesis of CMA. Our results show that large numbers of activated CD19 B cells and low numbers of CD8+ T cells could be considered as early markers for food allergy since they are already detectable in peripheral blood during the earliest symptoms of CMA.     

Food allergy after liver transplantation in children: a prospective study

Food allergy has been increasingly reported in children who had orthotopic liver transplantation (OLT). We aimed to conduct a prospective study to investigate the prevalence of sensitizations and food allergy in pediatric OLT recipients. We also aimed to identify potential risk factors. The study group consisted of 28 children (14 male, 14 female, mean age 4.96 ± 0.76 yrs) who had OLT. Total eosinophil count (TEC), total IgE, and specific IgEs were studied before and 3, 6, 12 months after OLT. Six patients (21%) developed multiple food allergies. Mean age of six patients at OLT who developed food allergy was younger compared to the non‐food allergy group (10.2 months vs. 68.9 months, p < 0.05). Food allergy has been developed within 1 yr in 5, and in 20 months in one patient after OLT. All six patients had cow’s milk and egg allergy after OLT. Five children developed wheat, one children developed lentil and another one developed peach allergy in addition to cow’s milk and egg allergy. Out of six food‐allergic patients after OLT, four children developed Epstein–Barr virus (EBV) infection prior to food allergy. Before OLT, TECs and total IgE levels were not differed among food allergic and non‐food allergic patients (p > 0.05). Mean of TECs were significantly higher in food allergic group compared to non‐food allergic group at each time point after OLT (p < 0.05). Though statistically insignificant, mean of total IgE levels were also higher in the food allergic group (p > 0.05). These findings suggest that food allergy should be considered after OLT in patients who are younger than 1 yr of age, who developed hypereosinophilia, high total IgE levels or EBV viremia.     

Natural history of soy allergy and/or intolerance in children, and clinical use of soy-protein formulas

Atopic diseases of infants and children are common, debilitating, chronic and sometimes even life-threatening. Several well-conducted studies in high risk babies have demonstrated a significant reduction in the prevalence and severity of atopic diseases with dietary and environmental manipulations. The currently available cow's milk (CM) substitutes for infants are soy protein (SP) formulas (SPFs), hydrolyzed formulas (HF), and home-made meat-based formulas. Soybeans have been cultivated in Eastern countries for many centuries and were first used to feed US babies with CM allergy (CMA) in 1929. Since then, SPFs containing purified SP, a mixture of vegetable oils, and purified carbohydrate have been developed. From a nutritional point of view, SPFs are adequate, support normal growth, protein status, bone mineralization, are well accepted, and economical. SPFs are used for different conditions including CMA, lactose and galactose intolerance and in the management of severe gastroenteritis, and some studies show that feeding SPFs for the first six months of life significantly reduces the prevalence of atopic diseases in high risk babies. Although gastrointestinal symptoms and atopic dermatitis (AD) may occur in some SPF-fed children, anaphylaxis following the ingestion of soybean is extremely rare in children. However, in the past few years the antigenicity/allergenicity of SPFs has been over-emphasized in the medical literature. In this paper on the natural history of soy antigenicity/allergenicity we discuss all the pros and cons of SPFs, their composition and nutritional value, the basic immune definitions, chemistry and characterization of SPs. We then discuss the antigenicity and allergenicity of SPFs in animals, recent data on the use of SPFs and the incidence of soy allergy in children, clinical reactions to SPFs, and the clinical relevance of skin testing and IgE antibodies to soy, challenge test procedure, clinical indication of SPFs, and their relevance in the prevention of atopy. We have meta-analyzed 17 different studies and conclude that history-based SPF allergy incidence totals 27%, in skin prick tests (SPT) RAST-oral food challenge (OFC)/double-blind food challenge (DBFC)-based epidemiological studies attains 3%, and in challenge test studies 4%. We suggest that double-blind placebocontrolled food challenge (DBPCFC) studies in larger cohorts of babies may establish a more reliable prevalence of SPF allergy in different disorders associated with CMA.     

Milk and soy allergy

Cow's milk allergy (CMA) affects 2% to 3% of young children and presents with a wide range of IgE and non-IgE-mediated clinical syndromes, which have a significant economic and lifestyle effect. It is logical that a review of CMA would be linked to a review of soy allergy because soy formula is often an alternative source of nutrition for infants who do not tolerate cow's milk. This review examines the epidemiology, pathogenesis, clinical features, natural history, and diagnosis of cow's milk and soy allergy. Cross-reactivity and management of milk allergy are also discussed.     

Development of natural tolerance and induced desensitization in cow’s milk allergy

Cow’s milk allergy (CMA) affects 2–3% of infants. It resolves in the great majority spontaneously during childhood. CMA encompasses a spectrum of clinical and immunologic characteristics. Non‐IgE‐mediated allergy typically resolves earlier than IgE‐mediated allergy. The most documented prognostic characteristic is that intense‐specific IgE response predicts persistence of CMA. Low serum levels of cow’s milk (CM)‐specific IgG4 are also associated with persistent CMA. Natural development of tolerance involves an immunologic shift where Th2 responses diminish, and Th1 as well as T regulatory cell responses strengthen. Accordingly, specific IgE levels decrease and specific IgG4, possibly also IgA, levels increase in serum. Specific oral immunotherapy (OIT) with CM induces desensitization in most cases where spontaneous recovery has not yet occurred. Data on long‐term tolerance induction are still scarce. According to current research data, the immunologic changes induced by OIT resemble those seen during natural development of tolerance.     

婴幼儿鸡蛋与牛奶过敏食物皮肤点刺试验的诊断价值

目的 通过对皮肤点刺试验疹团平均直径与开放性食物激发试验的相关性研究,获得有确诊食物过敏价值的皮肤点刺试验界值点,为简化临床诊断程序提供依据.方法 采用前瞻性研究,选择重庆医科大学附属儿童医院儿保科可疑食物过敏儿童173名,均进行皮肤点刺试验及开放性食物激发试验.测量并记录皮肤点刺试验疹团平均直径,通过开放性食物激发试验确诊食物过敏患儿.采用SPSS 13.0软件包进行统计学处理.将开放性食物激发试验作为诊断的金标准,通过四格表计算疹团平均直径的敏感度、特异度、阳性预测值及阴性预测值.通过受试者工作特征曲线及曲线下面积对疹团平均直径诊断价值进行评价;同时获取具有100%诊断价值的平均直径界值点.结果 173名婴幼儿年龄范围1～24个月,平均(9.39±5.67)个月共进行271次食物激发试验(其中阳性结果123次),99例婴幼儿被确诊为食物过敏.食物激发试验诱发症状主要表现为皮肤症状(87.0%),其次是胃肠道症状(9.8%).蛋白、蛋黄、牛奶皮肤点刺试验的受试者工作特征曲线的曲线下面积分别为0.794、0.804及0.904.当皮肤点刺试验疹团平均直径≥3 mm时,敏感度在71%～87%之间,特异度在31%～57%之间.当蛋白、蛋黄、牛奶皮肤点剌试验疹团平均直径分别≥8.5、5.5、5.5 mm时,皮肤点刺试验对食物过敏的诊断准确率可达100%.结论 皮肤点刺试验疹团平均直径对食物过敏的临床诊断准确性较好,通过其100%诊断界值点,可避免部分可疑食物过敏患儿进行食物激发试验.

Abstract：

Objective Mean diameter is the most common used parameter for wheal response assessment after skin prick test.This study aimed to investigate the diagnostic capacity of mean diameter according to the outcome of oral food challenge, and to determine the cut-off points that could render food challenges unnecessary.Method Data of 173 children referred to the Division of Primary Child Health Care for the evaluation of suspected food allergy were prospectively studied.All children underwent skin prick test and open food challenge to the relevant food(s) in clinic.The mean wheal diameter of skin prick test was measured, and open food challenge was performed to confirm food allergy. The SPSS software package version 13.0 for windows ( SPSS, Chicago, IL,USA) was used for all statistical analysis.Open food challenge was taken as the gold standard for diagnosis.Diagnostic capacity of skin prick test, including the sensitivity, specificity, positive predictive value, negative predictive value, was calculated by cross-table.In addition, receiver operating characteristic curve ( ROC ) was plotted and area under the curve ( AUC ) was calculated to quantify the accuracy of the parameter.Result For the 173 children,271 open food challenges were performed with egg white, egg yolk and cow's milk, In which 123 were positive, 99 children were diagnosed as food allergy.Cutanuous symptoms ( 87.0% ) were most common, followed by gastrointestinal symptoms (9.8% ).The AUC of mean diameter was 0.794 for egg white, 0.804 for egg yolk and 0.904 for cow's milk.The sensitivity of skin prick test with a cut-off value of ≥3 mm was ranged from 71% to 87%,while the specificity was between 31% and 57%.The authors also defined food specific skin prick test mean diameters that were 100% diagnostic for allergy to egg white ( ≥8.5 mm), egg yolk ( ≥5.5 mm), cow's milk ( ≥5.5 mm).Conclusion Predictive decision points for a positive outcome of food challenges can be calculated for egg and cow's milk using mean diameter.It may help to simplify the diagnostic procedure of food allergy.     

CLINICAL AND IMMUNOLOGICAL ASPECTS OF FOOD ALLERGY IN CHILDHOOD I. Estimation of IgG, IgA and IgE Antibodies to Food Antigens in Children with Food Allergy and Atopic Dermatitis

Abstract Sixtynine children with case histories of food intolerance and 30 food tolerant children with atopic dermatitis have been investigated regarding serum IgE levels and IgE-, IgG, and IgA-antibodies to some common foods. Children with food intolerance had significantly higher IgE levels and to a larger extent specific IgE antibodies to the tested allergens. IgE antibodies to cow's milk were found in 71% of the children with histories of cow's milk allergy but occurred also in similar titers in 27% of milk tolerant children with other food allergies. IgE antibodies to egg-white occurred in 88% of egg allergies, but low and moderate titers were also found in 17% of children without food intolerance. However, all children with high titers had symptoms of egg allergy. IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to soy-bean and green peas were found less consistently. The level of serum IgA antibodies to milk was similar in both groups. The IgG antibody titers to all tested food antigens seemed to parallel the IgE antibody titer to the same food. It was not possible to correlate the IgG antibody titers to symptoms.     

儿童IgE相关食物过敏消化道临床特点及随访研究

目的　探讨儿童IgE相关食物过敏的消化道临床表现特点及其预后。方法　选取2012年3月至2013年11月首都医科大学附属北京儿童医院消化科174例IgE相关食物过敏患儿作为研究对象,结合过敏原IgE抗体检测结果,对致敏食物进行饮食回避,设计标准化调查问卷,对患儿的临床表现及预后进行定期随访。结果　174例过敏原特异性IgE抗体检测中,牛奶、鸡蛋为主要过敏原,分别占66.1%和27.6%,轻度敏感以牛奶为主（65.5%）,中度敏感以鸡蛋白为主（5.2%）。婴儿组消化道症状以腹泻为主（51.3%）,幼儿组以呕吐为主（37.5%）,学龄期及青春期组以腹痛为主要表现（43.5%）。牛奶过敏以腹泻为主要表现,占20.7%。以腹泻为主要临床表现患儿在过敏原特异性IgE浓度高低、过敏原数目方面,差异无统计学意义（P＞0.05）。牛奶特异性IgE 2级的患儿获得耐受的时间（7.54±5.11）个月长于牛奶特异性IgE 1级的患儿（3.50±3.53）个月,差异有统计学意义（P＜0.05）。结论　IgE相关的食物过敏患儿以牛奶和鸡蛋为主要的过敏原,患儿的消化道临床表现依据年龄组不同而有所差异,牛奶过敏患儿特异性IgE浓度越高越不易获得耐受。     

Clinical and immunological aspects of food allergy in childhood. I. Estimation of IgG, IgA and IgE antibodies to food antigens in children with food allergy and atopic dermatitis

Sixtynine children with case histories of food intolerance and 30 food tolerant children with atopic dermatitis have been investigated regarding serum IgE levels and IgE-, IgG, and IgA-antibodies to some common foods. Children with food intolerance had significantly higher IgE levels and to a larger extent specific IgE antibodies to the tested allergens. IgE antibodies to cow's milk were found in 71% of the children with histories of cow's milk allergy but occurred also in similar titers in 27% of milk tolerant children with other food allergies. IgE antibodies to egg-white occurred in 88% of egg allergies, but low and moderate titers were also found in 17% of children without food intolerance. However, all children with high titers had symptoms of egg allergy. IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to soy-bean and green peas were found less consistently. The level of serum IgA antibodies to milk was similar in both groups. The IgG antibody titers to all tested food antigens seemed to parallel the IgE antibody titer to the same food. It was not possible to correlate the IgG antibody titers to symptoms.     

The almond milk: a new approach to the management of cow-milk allergy/intolerance in infants

AIM: Elimination of the offending food is imperative in the management of children with cow-milk allergy/intolerance (CMA/CMI). Herein we report the result of randomized clinical trial carried out to test the efficacy and safety of a new almond-based food (hereinafter named almond milk) in a group of infant with CMI/CMA. METHODS: A group of 52 infants aged 5 to 9 months and with documented CMI/CMA was enrolled and randomized to: almond milk (Group A, n=26); soy-based formula (Group B, n=13); protein hydrolysate-based formula (n=13). The main efficacy outcomes were the improvement in clinical symptoms and the decrease in serum levels of soluble CD30 (a potential marker for atopic disorders; sCD30). RESULTS: Elimination of the offending food and supplementation with a milk protein-free formula produced a considerable improvement of clinical manifestations within 5-12 days in all cases examined (at the onset of the study: 26.4+/-5.4 U/mL and 7.9+/-5.2 U/mL in IgE+ and IgE- infants respectively, after 6 months of supplementation: 16.6+/-4.8 U/mL and 7.1+/-4.5 U/mL in IgE+ and IgE- infants respectively). No difference in growth rate (increment of weight, length and head circumference) was found, during the entire study, between infants given the almond milk and babies given the soy-based formula or the protein hydrolysate-based formula. Supplementation with the soy-based and protein hydrolysate-based formulas caused the development, in some subjects, of a secondary sensitization (23% to soy-based and 15% protein hydrolysate-based formula), whereas supplementation with the almond milk did not. CONCLUSIONS: Though preliminary, the present findings seem to demonstrate that the almond milk may an efficacious substitute of cow milk in infants with CMA/CMI. One could speculate that some active principles contained in the almond milk could contribute to its beneficial effect observed in CMI/CMA-affected infants.     

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??Objective??To observe the clinical characteristics and prognosis of children with IgE-related food allergy??Methods??The study was enrolled 174 children with food allergy in Beijing Children Hospital between March 2012 and November 2013. All patients were given treatment of avoid allergic food and filled out the standard questionnaire and followed up . Results??The sIgE positive rates of milk and eggs were higher than other food??were 66.1% and 27.6%. Mildly sensitive to milk was 65.5%??moderately sensitive to chicken protein was 5.2%. Main clinical manifestations of children with food allergy were vary in different age groups . In the infant group, diarrhea was the main manifestation??51.3%????and in the toddler group??vomiting was the main manifestation??37.5%??. In the school age and adolescence group??abdominal pain was the main manifestation??43.5%??. The severity of diarrhea are not connected with the types and concentration of allergens IgE. The results of follow-up analysis showed that patients of milk sIgE 2 level??7.54±5.1?? months need more longer time to acquire tolerance than sIgE 1 level??3.50±3.53?? months. Conclusion??Milk and eggs are the main allergens. The gastrointestinal symptoms of children with IgE-related food allergy were different with age. Children with high concentration of milk specific IgE is not easy to acquire food tolerance. The concentration of milk specific IgE had certain predictive value for the patient’s tolerance.     

The diagnosis of IgE-mediated food allergy in childhood

IgE-mediated food allergy is a common condition in childhood and a recognized public health concern. An accurate diagnosis of food allergy facilitates the avoidance of the allergen – and cross-reactive allergens – and allows for safe dietary expansion. The diagnosis of food allergy relies on a combination of rigorous history, physical examination, allergy tests [skin prick tests (SPT) and/or serum-specific IgE] and oral food challenges. Diagnostic cut-off values for SPT and specific IgE results have improved the diagnosis of food allergy and thereby reduced the need to perform oral food challenges. This clinical case series seeks to highlight a contemporary approach to the diagnosis of food allergy in children strategies.     

The predictive value of skin prick testing for challenge-proven food allergy: a systematic review

Immunoglobulin E-mediated (IgE) food allergy affects 6-8% of children, and the prevalence is believed to be increasing. The gold standard of food allergy diagnosis is oral food challenges (OFCs); however, they are resource-consuming and potentially dangerous. Skin prick tests (SPTs) are able to detect the presence of allergen-specific IgE antibodies (sensitization), but they have low specificity for clinically significant food allergy. To reduce the need for OFCs, it has been suggested that children forgo an OFC if their SPT wheal size exceeds a cutoff that has a high predictability for food allergy. Although data for these studies are almost always gathered from high-risk populations, the 95% positive predictive values (PPVs) vary substantially between studies. SPT thresholds with a high probability of food allergy generated from these studies may not be generalizable to other populations, because of highly selective samples and variability in participant's age, test allergens, and food challenge protocol. Standardization of SPT devices and allergens, OFC protocols including standardized cessation criteria, and population-based samples would all help to improve generalizability of PPVs of SPTs.     

The clinical significance of food specific IgE/IgG4 in food specific atopic dermatitis

Food is closely associated with the pathogenesis of atopic dermatitis. Food allergy is usually mediated by IgE antibody to specific food proteins and determination of specific IgE antibody is the basis of the common diagnostic test for food allergy. IgG4 have been reported as blocking antibody and the protective effects of blocking antibody may be clear in inhalant allergy. However, the role of IgG4 in food allergy is still a matter of debate. In this study, the clinical significance of food allergen-specific IgE/IgG4 in atopic dermatitis was investigated and compared with that of IgE. A total of 97 patients who fulfilled the diagnostic criteria for atopic dermatitis participated in this study. Skin prick test and allergy patch test were performed. Specific IgE and IgG4 concentration were measured using allergy protein chip, 'AllergyChip'. Double blinded placebo controlled food challenge test (DBPCFC) was performed for the diagnosis of allergy to milk, egg white, wheat, and soybean. DBPCFCs for milk, egg white, soybean, and wheat were performed. The positive rates were 31.7% (19/60) in milk, 36.7% (18/49) in egg white, 30.4% (7/23) in soybean, and 34.8% (8/23) in wheat. Mean IgE/IgG4 levels in DBPCFC (+) subjects is higher than those in DBPCFC (-) subjects in all food items studied. Of them, there were significantly different between two groups in egg white and wheat (Egg white in DBPCFC (+) vs. (-): 0.4 +/- 0.3 vs. 0.2 +/- 0.2, wheat in DBPCFC (+) vs. (-): 1.2 +/- 1.2 vs. 0.3 +/- 0.3, p < 0.05). Allergen-specific IgE/IgG4 may provide one of the clues to understand the mechanism of food allergy in atopic dermatitis. The present study suggests that protein microarray can be one of the useful methods to assess ongoing status of allergic diseases.     

Towards better triage of infants suspected of cow's milk allergy: development of a preliminary multivariable diagnostic index

The double-blind placebo-controlled food challenge (DBPCFC) is currently the gold standard to diagnose cow's milk allergy (CMA). However, DBPCFCs are burdensome, expensive and require specialised facilities. For primary care physicians, selective and consistent referral to DBPCFC of infants suspected of CMA may be difficult. The objective of this study was to assess the predictive value of clinical parameters for a positive DBPCFC in infants suspected of CMA. Clinical data from 124 infants suspected of CMA that had undergone a DBPCFC were collected. Out of a total of 23 parameters, nine candidate predictors were selected on clinical grounds. We used bootstrapped logistic regression analysis to find a more parsimonious and practical model. The prevalence of a positive DBPCFC was 34.7 % (95 % CI from 27 to 43). A well-calibrated diagnostic model containing as predictors abdominal cramps, inconsolable crying and the objective SCORAD index discriminated moderately well between infants with and without a positive DBPCFC. The area under the ROC curve was 0.68 (95 % CI from 0.58 to 0.78). The fifth and 95th percentiles of the positive DBPCFC predictive probability distribution were 17 and 73 % (17 and 59 % after correction for over-optimism). We conclude that a diagnostic model with three clinical parameters may be used for better referral of children suspected of CMA and the decision to either initially perform an open food challenge or directly perform a DBPCFC. Large prospective studies are needed to validate these findings and provide additional precision.     

Fractional exhaled nitric oxide in infants during cow's milk food challenge

Cow's milk allergy (CMA) is the most common food allergy in early childhood. The golden standard for the diagnosis of CMA is a food challenge after a period of elimination. Increased levels of fractional exhaled nitric oxide (FE_NO) have been shown after bronchial allergen provocation. We evaluated whether FE_NO may also be a predictor of a positive reaction during cow's milk challenge in infants. Forty-four infants [mean age (range): 4.2 (3.7–4.6) months] suspected of CMA underwent an open food challenge with cow's milk formula administered in ascending quantities, starting with 2 ml and then 6, 20, 60 and 200 ml until a clinical reaction occurred. Off-line FE_NO samples were obtained during tidal breathing by means of a facemask covering infants' nose and mouth. FE_NO was measured twice before the challenge (baseline), immediately before each new dose of milk and after a positive reaction or after the last dose of milk. Eleven children showed immediate positive clinical responses to cow's milk, whereas 13 infants presented only a late-type reaction. FE_NO values before or after a positive reaction (either immediate or late) were not different from FE_NO values at baseline. Baseline FE_NO in infants with a positive reaction did not differ from FE_NO in infants without a reaction at any time point. We conclude that FE_NO values are not predictive and not related to the occurrence of a positive reaction during a cow's milk challenge in infants, suggesting that a positive reaction may not result from eosinophilic activation.