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.     

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)     

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??Abstract??Objective To investigate the diagnostic value of mean diameter of SPT in food allergic infants. Methods Totally 91 infants suspected with food allergy ??median age 7.35±2.94 months?? were selected??and all patients received family history inquiry??skin prick test and open food challenge.The mean diameter of SPT was measured??and OFC was performed to confirm food allergy.Diagnostic value of skin prick test, including the sensitivity and specificity, was calculated.In addition??receiver operating characteristic curve??ROC?? was plotted and area under the curve??AUC??was calculated to quantify the accuracy of the parameter.The SPSS software package version 13.0 for windows was used for all statistical analysis. Results A total of 128 babies received food challenge test?? in which there were 109 times of OFC positive and 19 times negative??totally 79 infants were diagnosed with FA.The induced symptoms of food challenge test included skin symptoms??70.6%??, gastrointestinal symptoms??20.2%??, rest with crying?? coughing?? rubbing eyes??etc.??9.2%??.When the rash MD was ≥3 mm??the sensitivity of SPT diagnosis milk??egg white and protein allergy was 19%??60.6% and 60.5% respectively??the area under ROC curve of rash MD in the milk??egg white??protein was 0.718??0.604 and 0.716 respectively?? the rates of three food SPT test results complying with the OFC were 44.4%??53.7% and 65.9%??the rates being 62.5%?? 58.3% and 31.3% in positive family history??when family history was negative??the area under the ROC curve of rash MD was 0.793. In the cases with positive family history??the area of ROC curve was 0.533.When rash MD of milk??egg white and protein was ≥2.2??5.0??4.7 mm or the rash MD was ≥3.25mm in children with a negative family history??SPT FA diagnostic specificity could be up to 100%. Conclusion SPT has some value in the diagnosis of FA. By finding the critical value of SPT FA and comprehensive analysis of family history??doctors can improve the diagnostic rate of FA. SPT can prevent some suspicious FA infants from food challenge test. It is very important to obtain rapid clinical diagnosis and to reduce the risk and burden to their families.     

Bee-venom allergy in children: Long-term predictive value of standardized challenge tests

Venom immunotherapy (VIT) is able to protect insect venom-allergic patients against life-threatening sting reactions. Standardized sting challenges can be used as a diagnostic tool to check whether VIT is required. No data are available on the long-term predictive value of sting challenge tests. The purpose of this study was to investigate the long-term predictive value of sequential bee-sting challenges with respect to the ability to predict future sting reactions in bee-venom (BV) allergic children. Between 1988 and 1992, 92 BV-allergic children had been challenged with sequential bee stings at intervals of 2–6 weeks to determine the necessity of VIT. In 1996, all 92 families were followed-up using standardized telephone interviews. Until the follow-up, 61 children (66.3%) had experienced at least one natural bee sting. Based on the results of the initial challenge tests, 13 of the 61 patients had been started on VIT. Two of these 13 (15.4%) developed systemic reactions 1 year after VIT of 5 years, of which one was mild and one was severe. Among the 48 re-stung patients who were not treated with VIT, three children (6.3%) experienced mild systemic reactions, whereas 45 children reported no more than a local reaction. The long-term predictive value of sequential bee-sting challenge tests for systemic reactions in children not treated with VIT remained at a level of 93.8% (95% confidence interval: 82.8–98.7%) even over a period of more than 6 years. Based on this data, we conclude that sequential bee-sting challenges are a powerful tool to determine the necessity for VIT in BV-allergic children.     

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.     

Increasing specific immunoglobulin E levels correlate with the risk of anaphylaxis during an oral food challenge

Background

Oral food challenges (OFCs) are necessary to diagnose food allergies; however, these tests can cause anaphylaxis. Higher specific immunoglobulin E (sIgE) levels to causative food have been associated with a positive OFC. To date, no data have been found to indicate the factors associated with severe symptoms or anaphylaxis among challenge‐positive patients. This study aimed to clarify the association of sIgE with causative foods and anaphylaxis during OFC among the whole study population and challenge‐positive patients.

Methods

This cross‐sectional study collected symptom and severity data between June 2012 and December 2016 during an open OFC to diagnose food allergy or confirm tolerance acquisition. We analyzed the risk factors for anaphylaxis during OFC.

Results

A total of 2272 cases were analyzed (median age: 3.5 years; egg: 1166 cases; milk: 589 cases; wheat: 388 cases; and peanut: 129 cases). Among 979 challenge‐positive patients, anaphylactic reactions were observed in 334 cases. A statistically significant association was observed between anaphylaxis during OFC and higher sIgE levels to causative foods (odds ratio: 2.71, 95% confidence interval: 1.94‐3.78, for the third compared to the first tertile, P‐value for trend <.001). Only gastrointestinal, respiratory, cardiovascular, and neurological symptoms were also statistically significantly associated with higher sIgE levels to causative foods.

Conclusions

The risk of all symptoms, except skin symptoms, during OFCs increased with increasing sIgE levels, and this consequently increased anaphylaxis during OFCs. The mechanism of how sIgE affects the prevalence of gastrointestinal, respiratory, cardiovascular, and neurological symptoms or anaphylaxis is unknown; thus, further study is required.     

Follow‐up of patients with uncertain symptoms during an oral food challenge is useful for diagnosis

Background

Uncertain symptoms often emerge during an oral food challenge (OFC), and Open‐OFCs with those uncertain mild symptoms are ordinarily regarded as positive. Double‐blind placebo‐controlled food challenges should be conducted to determine these associations. Nevertheless, studies regarding the diagnosis of uncertain food allergy symptoms are lacking. We examined the diagnostic decision for a food allergy based on uncertain symptoms during an Open‐OFC.

Methods

We conducted an Open‐OFC between August 2005 and April 2012 with 2271 cases who suspected as allergic to hen's eggs, cow's milk, or wheat. For the primary diagnosis, Open‐OFCs with obvious symptoms were classified as “positive,” no symptoms as “negative,” and uncertain, indeterminate symptoms as “uncertain.” We encouraged the children in the uncertain group to consume the causative foods at home more than twice; if any definitive symptoms were induced, children were classified as “intolerant,” and children without any symptoms were classified as “tolerant,” for the final diagnosis.

Results

We analyzed 454 uncertain cases excluding 781 positive cases and 1036 negative cases. The symptoms that occurred for the uncertain cases included slight abdominal pain, localized skin rash, and an isolated cough. Of these cases, 362 (79.7%) were considered tolerant at the final diagnosis. Of the intolerant children at the final diagnosis, the induced symptoms at home were not serious.

Conclusions

Monitoring of recurring symptoms following consumption of causative foods at home by patients with uncertain symptoms improves the diagnostic accuracy of an Open‐OFC.     

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   

Addressing risk management difficulties in children with food allergies

Risk is a concept inherent in every medical procedure. It can be defined as the probability of an adverse event in a defined population over a specified period of time. In the frame of food allergy management, it might be related to a diagnostic procedure, a treatment, or the consumption of foods. The risk of an adverse event can also be augmented by individual factors. This rostrum article discusses various aspects faced by children with food allergies in the light of risk, and their practical implications. Identifying personal risks for severe reaction, such as unstable asthma, and correcting them whenever possible also contribute to a reduction of the risk inherent to food allergy. Among the facets discussed, oral food challenges (OFC) are the most common diagnostic procedures implying an inherent risk. The risk of OFCs can be minimized by correct indication and timing of the test, a safe setting, as well as by ensuring that the patient is otherwise well without potential stressor potentially increasing the risk of a more severe reaction. Oral immunotherapy (OIT) has been studied as a potential treatment for increasing the threshold dose for reaction, and thus reducing the risk of accidental reaction. Nevertheless, the procedure is not devoid of risk as the patients may and do often react during the course of the procedure. Ingestion of trace amounts in processed foods, mainly in community settings such as restaurants, schools, or day care, represents a potential risk of reactions, although for a minority of patients. Precautionary allergen labeling (PAL) is a widespread strategy to reduce the potential risk of reactions due to traces. However, PAL is currently inefficient due to inconsistent labeling, also not indicating a clear maximum amount possibly present in the manufactured food. Finally, cost-effectiveness needs to be considered in risk management, as many risk reduction procedures are clearly not cost-effective.     

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.     

Anaphylaxis management in Australian schools: Review of guidelines and adrenaline autoinjector use

Food allergy and anaphylaxis is increasing in Australian children, and anaphylaxis is relatively common in Australian schools. This review aims to provide an overview of current policies and practices for anaphylaxis management in Australian schools, including approaches to risk mitigation and anaphylaxis training. We reviewed literature related to anaphylaxis training in the school setting published between 2010 and 2018. Current anaphylaxis policies/guidelines were obtained from Australian education and health departments, and reports of suspected anaphylaxis and adrenaline autoinjector (AAI) use for 2016–2017 were obtained from education departments where available. Our review of policies/guidelines across Australian jurisdictions indicates inconsistent approaches to anaphylaxis management training. Almost half of Australian school anaphylaxis events required a general‐use AAI, administered to students not identified as at risk of anaphylaxis. Development of clear, evidence‐based, consistent guidelines related to anaphylaxis management and training in the school setting is imperative to minimise risk.     

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.     

Oral immunotherapy and tolerance induction in childhood

Prevalence rates of food allergy have increased rapidly in recent decades. Of concern, rates of increase are greatest among children under 5 yrs of age and for those food allergies that persist into adulthood such as peanut or tree nut allergy and shellfish allergy. Given these trends, the overall prevalence of food allergy will compound over time as the number of children affected by food allergy soars and a greater proportion of food‐allergic children are left with persistent disease into adulthood. It is therefore vital to identify novel curative treatment approaches for food allergy. Acquisition of oral tolerance to the diverse array of ingested food antigens and intestinal microbiota is an active immunologic process that is successfully established in the majority of individuals. In subjects who develop food allergy, there is a failure or loss of oral tolerance acquisition to a limited number of food allergens. Oral immunotherapy (OIT) offers a promising approach to induce specific oral tolerance to selected food allergens and represents a potential strategy for long‐term curative treatment of food allergy. This review will summarize the current understanding of oral tolerance and clinical trials of OIT for the treatment of food allergy.     

A new model for low-dose food challenge in children with allergy to milk or egg

Background: Atopic eczema and food allergy are common in early childhood. Children seem to gradually develop tolerance to milk and egg, and it is a relief for families when their child can tolerate small amounts of these basic foods, even if larger doses may still cause symptoms. Aim: To develop a model for low-dose oral food challenge, facilitating re-/introduction of milk or egg. Methods: In 39 children sensitized to milk and/or egg, we performed 52 challenges using a new standardized model for low-dose oral food challenge. The recipes were validated for blinding with sensorial tests. Results: Four children challenged to milk had a positive challenge outcome. There were no significant differences with respect to family history, associated atopic manifestations, nutritional supply, eczema severity, or skin-prick test compared with the non-reacting children, but total and specific IgE values were significantly higher. All but two of the non-reacting children were able to introduce milk and egg into their diet without problems.
Conclusion: We report recipes and a protocol to be used for standardized open and double-blind placebo-controlled low-dose food challenge in young children, enabling the introduction of small amounts of egg and milk into the diet during tolerance development.