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.     

Is maternal age at delivery related to childhood food allergy?

The prevalence of food allergies is increasing. Concurrently, the average maternal age at birth is also increasing. We conducted a preliminary study to evaluate whether maternal age at the time of delivery is associated with a food allergy in children. Case and control patients were identified among consecutive patients seen by one of us (AD) in the Allergy/Immunology program at the Children's Hospital Boston between 11/1/98 and 2/28/00. Case patients were born in Massachusetts and had evidence of clinical sensitivity and IgE to one or more food allergens (n = 58). Control patients were those born in Massachusetts who had a negative skin test and/or RAST to inhalant and/or food allergens (n = 96). A second comparison group consisted of all live births in Massachusetts in 1999 (n = 80,866). Information on maternal age at birth was missing from 3/58 (5%) of patients with a food allergy and 4/96 (4%) of the control patients, so these patients were not included in the analysis. The proportion of children whose mother was aged 30 and over at their birth was significantly higher in children with a food allergy than control patients (78% vs. 55% p = 0.005) and higher than all births in Massachusetts (78% vs. 53% p = 0.0002). Mothers of children with a food allergy had about three times greater odds of being aged 30 or over at the time of delivery than mothers in either of the comparison groups. Further exploration of the data using logistic regression showed that maternal age over 30 at delivery and being first born were independent predictors of the child having a food allergy. In this study, the presence of a food allergy in children was related to older maternal age at delivery. Additional studies are needed to further evaluate this relationship and its potential implication in preventive strategies for food allergies in children.     

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   

Labial food challenge in children with food allergy

The current increase in the prevalence of food allergies appears to have several causes including better screening, improved diagnosis and changes in both the techniques used by food manufacturers and eating habits. Labial food challenge (LFC)is simple, rapid to perform and is associated with only low risks of systemic reaction. It is thus an appealing alternative to the oral food challenge (OFC) for pediatric use.
We report a series of 202 LFC performed over two years in 142 children with food allergy suspected from the case history, positive skin prick tests and specific serum IgE assays: 156 LFC were positive; and 46 negative, followed by positive single-blind, placebo-controlled food challenges (SB-PCFC). The foods provoking reactions were egg white (75 cases), peanut (60 cases), mustard (23 cases), cow's milk (13 cases), cod (8 cases), kiwi fruit, shrimp (4 cases each), chicken, peanut oil (3 cases each), hazel nuts (2 cases), and snails, apple, fennel, garlic, chilli peppers, pepper, and duck (1 case each). LFC positivity was mostly (89. 7% of cases) manifested as a labial edema with contiguous urticaria. There were systemic reactions in 4. 5% of cases: generalized urticaria, hoarseness and rapid-onset and generalized eczema. The 46 infants with negative LFC results had positive SBPCFC. The reactions were in 34 cases generalized urticaria, 10 cases asthma attacks, 2 cases early and generalized eczema, and in one case general anaphylactic shock. The sensitivity of the LFC was 77%. The LFC was easy to perform with children. Positive results indicate the presence of food allergy, but negative results require further investigations preferably double-blind, placebo-controlled food challenge (DBPCFC)     

Is caesarean delivery associated with sensitization to food allergens and IgE-mediated food allergy: A systematic review

Several studies have shown differences in the composition of the gastrointestinal flora of children who develop sensitization to food allergens compared with non-allergic children. It has been hypothesized that changes in the gut microbiota resulting from caesarean section delivery could increase a child’s risk of developing food allergy; however, studies examining the relationship between mode of delivery and food allergy have produced conflicting results. The objective of this review was to determine whether there is sufficient evidence to support an association between delivery by caesarean section and the development of sensitization to food allergens and immunoglobulin E (IgE) mediated food allergy. Using predefined inclusion and exclusion criteria, MEDLINE and PubMed were searched for studies investigating the relationship between caesarean section delivery and food allergy. The information on the quality of the studies and results were extracted and analysed systematically. The search identified four relevant studies as per our protocol. Symptomatic food allergy was used as the outcome in two studies and was found to occur more frequently in children born by caesarean section in one study while the second study found no association between food allergy diagnoses and mode of delivery. The other two studies measured levels of food antigen-specific IgE, with both studies showing an increase in sensitization to food allergens among children born by caesarean section. Overall, there is evidence that the risk of developing IgE-mediated sensitization to food allergens is increased among children delivered by caesarean section, however further studies using objectively diagnosed food allergy as the outcome are needed to verify whether this equates to an increase in confirmed food allergy. Future birth cohort studies should control for the effects of mode of delivery when investigating environmental modifiers of food allergy.     

Combining skin prick, immediate skin application and specific-IgE testing in the diagnosis of peanut allergy in children

Previous studies have suggested various diagnostic cut-offs of allergy tests for the diagnosis of clinical peanut allergy in children. There are few data relating to the use of combinations of these tests in children. We aimed to determine the validity of previously reported diagnostic cut-off levels of peanut allergen skin tests and peanut specific-immunoglobulin (Ig) E, as well as the usefulness of combinations of these, for predicting clinical peanut allergy in our Allergy Clinic. Children attending the Allergy Clinic with a positive peanut skin prick test (SPT; n = 84) were included in the study. Immediate skin application food tests (I-SAFT) using 1 g of peanut butter (positive if any wheals were detected at 15 min), peanut specific-IgE levels and open-label peanut food challenges were performed. Fifty-two of 85 peanut challenges were positive. Skin prick test specificity was 67% at >or=8 mm and 100% at >or=15 mm. The I-SAFT was 82% specific. A peanut specific-IgE level of 0.37 kU/l was 98% sensitive but 33% specific. A level of 10 kU/l was 100% specific. Combinations of a SPT of >or=8 mm with a positive I-SAFT and a peanut specific-IgE >or=0.37 kU/l were 88% specific with a sensitivity of 38%. Using challenge outcomes as the standard, available in vitro and in vivo diagnostic tests for peanut allergy have poor sensitivity and specificity and combining them does not significantly improve their clinical usefulness. Previously described diagnostic cut-off levels do not have general applicability. Allergy practitioners may need to interpret results of allergy tests in the context of their own practices.     

婴儿期食物过敏的预后研究

目的了解婴儿期食物过敏（FA）的预后及影响因素。方法对119例患儿进行回顾性研究,采用Kaplan-Meier法计算食物耐受的累积概率,非条件Logistic回归模型分析食物耐受形成的预测因素和其他过敏性疾病发生的影响因素。结果鸡蛋、牛奶耐受的累计概率在诊断后1年分别为31％、42％;2年为62％、63％;3年为80％、77％;4年后均可达100％。牛奶、鸡蛋过敏患儿的皮肤点刺试验阳性强度是持续牛奶、鸡蛋敏感的预测因素（OR=2．535,95％CI：1．159～5．543;OR=2．654,95％CI：1．302～5．410,P均〈0．05）。本组13例患儿发生其他FA,危险因素是持续鸡蛋敏感（OR=6．109,95％CI：1．818～20．527,P〈0．05）;4例发生变态反应性鼻炎,15例发生支气管哮喘,危险因素是持续鸡蛋敏感和呼吸道过敏症状（OR=3．596,95％CI：1．429～9．045;OR：4．235,95％CI：1．152～15．563,P均〈0．05）。结论至少75％的鸡蛋或牛奶过敏患儿在诊断后3年内可获耐受。10．9％、12．6％和3．4％的FA儿童发生其他FA、支气管哮喘和变态反应性鼻炎。加强持续FA高危儿的筛查和管理,可能有助于改善FA的预后。     

The impact of oral food challenges for food allergy on quality of life: A systematic review

Background

Food allergy significantly impairs health‐related quality of life (HRQL). Currently, it is still unknown whether diagnostic interventions for food allergy improve HRQL. We aim to assess the impact of diagnostic interventions for food allergy on HRQL.

Methods

A systematic search was performed in MEDLINE, Embase, Cochrane Library, and CINAHL focused on patients with a (suspected) food allergy who underwent diagnostic interventions (ie, skin prick test, specific IgE, or oral food challenges [OFC]) and in whom HRQL was assessed. The mean difference between HRQL before and after the diagnostic intervention was calculated. A minimal clinically important difference of 0.5 was considered clinically relevant for the food allergy quality of life questionnaire.

Results

Seven of 1465 original identified publications were included in which the impact of an OFC on HRQL was investigated (total patients n = 1370). No other diagnostic interventions were investigated. Food allergy‐specific parent‐reported HRQL improved significantly after an OFC irrespective of the outcome in children with a suspected food allergy in two publications. The change was considered clinically relevant in one of two publications. In addition, parent‐reported HRQL improved after an OFC to assess the eliciting dose in children with a confirmed food allergy. The parental burden was significantly reduced after an OFC to assess resolution of food allergy. A meta‐analysis could not be performed due to the limited numbers of, and considerable heterogeneity between, eligible publications.

Conclusion

An OFC is associated with an improved food allergy‐specific HRQL and a reduced parental burden of food allergy.     

Sesame food allergy and sensitization in children: the natural history and long-term follow-up

Sesame food allergy (SFA) in children is an increasingly recognized one in many countries. Our objective was to describe the course and natural history of SFA. Seventy-four patients sensitized to sesame were evaluated using clinical records, questionnaires, skin prick tests (SPT), in vitro specific immunoglobulin (sIg) E, and oral challenges (OC) and categorized into three groups: group A: patients who experienced allergic reaction after ingestion of sesame-containing food (n = 45); group B: patients evaluated for atopic dermatitis and found to be sesame SPT-positive (n = 11); group C: patients with sensitization to sesame allergen (n = 18). Group A patients were followed for an average of 6.7 yr. Analysis of our results revealed that 76% of patients in group A developed the allergy by the age of 2. The median age at onset of allergy in these patients was 1 yr. Immediate reaction to a minimal amount of sesame was characteristic. Skin was the most common site of involvement, followed by respiratory and gastrointestinal systems. Tolerance developed in only 20% of the patients. High sIgE (>0.15 IU) was demonstrated only in 75% of those in which it was examined. Sixteen patients performed oral sesame food challenge which was found positive in 88%. No correlation was found between the size of SPT and the level of in vitro sesame IgE antibodies, the outcome of OC results, and the development of tolerance to sesame. In conclusion, SFA tends to appear early in life, but unlike cow's milk and egg allergy, persists in 80% of the cases. Typical reactions combined with positive sesame SPT are reliable for diagnosis.     

Which cereal is a suitable substitute for wheat in children with wheat allergy?

Wheat is one of the main food allergens. It is among widely used cereals and there is an extensive cross-reaction between cereals. The aim of this study is to evaluate the extent to which cereals cross-react and to find the best substitute for wheat. Eighteen patients with definite diagnosis of type I hypersensitivity reactions to wheat enrolled in this study. Measurement of serum-specific IgE and skin prick test (SPT) for cereals flour (wheat, barley, oat, rye, rice and corn) and wheat bran was carried out. Also, open food challenge tests with available and conventional cereals in Iranian food culture (wheat, corn, rice and barley) were carried out. The SPTs were positive in 44.4% of patients for barley, 94.5% for wheat and 44-77% for other cereals. Positive serum-specific IgE was remarkable for wheat and barley and there was correlation between wheat and barley-specific IgE concentrations (r = 0.773 and p < 0.01). Corn serum-specific IgE was measured in 10 patients, which were positive in six of them. Of the patients, 55.5% had positive barley challenge tests, but all corn and rice challenge tests were negative. The best substitutes for wheat in wheat allergic patients are rice and corn. Regarding the correlation of wheat and barley serum-specific IgEs, there might be a high antigenic cross-reaction, therefore barley is not a good substitute for wheat and consuming barley needs a careful challenge test. Considering concordance of positive SPT to wheat flour and wheat bran, avoiding both of them is necessary in patients with wheat allergy.     

Diagnostic testing in the evaluation of food allergy

Food-related symptoms are frequent in childhood, and pediatricians are often requested to initiate a food allergy diagnostic workup. A careful history is the cornerstone for assessing whether tests are needed and which diagnostic procedures are most appropriate. Skin prick tests should be performed only according to standard procedures by a skilled health professional. Determining serum IgE levels (in vitro tests) are available for a wide range of foods. Of utmost importance is the need to correlate test results to the clinical picture. When a conclusion cannot be reached, oral food challenges should be performed for a definite diagnosis.     

Update on food allergy

Food allergy is a major public health issue with growing prevalence in the urbanized world and significant impact on the lives of allergic patients and their families. Research into the risk factors that have contributed to this increase and their underlying immune mechanisms could lead us to definitive ways for treatment and prevention of food allergy. For the time being, introduction of peanut and other allergenic foods in the diet at the time of weaning seems to be an effective way to prevent the development of food allergy. Improved diagnosis and appropriate management and support of food allergic patients are central to patient care with food immunotherapy and biologics making the transition to clinical practice. With the new available treatments, it is becoming increasingly important to include patients' and family preferences to provide a management plan tailored to their needs.     

New visions for food allergy: An iPAC summary and future trends

The spectrum of food allergy consists of a variety of different clinical pictures including immunoglobulin (Ig)E, and non-IgE food allergy as well as mixed, IgE and non-IgE disorders. In addition, eosinophilic diseases of the gastrointestinal (GI) tract with occasional IgE-type sensitization are increasingly recognized. As a consequence, the clinical picture of food allergy is pleomorphic and can range from chronic GI symptoms to severe anaphylaxis. The diagnosis of food allergy is mostly hampered by the lack of reliable in vitro tests for non-IgE-mediated diseases, and in most cases relies on a reoccurrence of symptoms upon re-exposure to the antigen; in general during a standardized food challenge. Currently, there is no safe and efficient treatment for food allergy and the treatment relies on avoidance diets. Priorities for research have been identified by iPAC (international Pediatric Allergy and Asthma Consortium) and outlined in this review. They include studies to better identify the pathogenesis of food allergy, including genetic aspects; studies to develop diagnostic and follow-up tests; studies for standardization of food challenges; as well as studies addressing a safe and efficient treatment of food allergy.