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.     

Proposal for a standardized interpretation of the atopy patch test in children with atopic dermatitis and suspected food allergy

The interpretation of the atopy patch test (APT) to foods is not standardized. This study aimed to validate the reading of the APT in terms of the diagnostic accuracy of individual skin signs. Eighty-seven children (mean age 2.4 +/- 2.5 yr, range 0.5-13.5; 57 male) with atopic dermatitis (AD) and suspected food allergies underwent APT to cow's milk, hen's egg, wheat and soy. Twelve-millimetre Finn chambers were applied for 48 h, and results were read after 48 and 72 h. Skin changes were graded for erythema, induration, papule formation and 'crescendo' phenomenon (increase of skin sign severity from 48 to 72 h). Food allergy was assessed by double blind, placebo-controlled food challenges (DBPCFC). Sensitivity, specificity and predictive values were calculated for each skin signs in relation to challenge outcome. Of 165 DBPCFC children, 75 (45%) were positive. The combination of any skin induration plus papules (seven or more), or of moderate erythema plus any induration plus seven or more papules had a positive predictive value (PPV) and specificity for the challenge outcome of 100%; however, the sensitivity was low (8% and 15%). The best diagnostic accuracy for single signs was found for induration beyond the Finn chamber margin (PPV 88%, specificity 99%, sensitivity 9%) and presence of at least seven papules (PPV 80%, specificity 96% sensitivity 21%). Presence of both induration and of at least seven papules at 72 h were the APT skin signs with the greatest diagnostic accuracy for food allergy in children with AD.     

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)     

What is the optimal occlusion time for the atopy patch test in the diagnosis of food allergies in children with atopic dermatitis?

The atopy patch test (APT) is a valuable additional tool in the diagnosis of food allergies in children with atopic dermatitis (AD). Nevertheless, this technique needs to be standardized, and this is particularly true for the occlusion time. We compared the results obtained after a 24-h occlusion period with those obtained after a 48-h occlusion period, the usual occlusion time used in contact allergy. We performed 64 open oral food challenges in 48 children (30 boys and 18 girls), aged between 3 and 29 months (median 14 months). The sensitivity, positive predictive value and negative predictive value were all better for the 48-h occlusion time than for the 24-h occlusion time. Therefore, the recommended occlusion time for the APT with foods should be 48 h, as for contact allergens.     

上海地区720例特应质儿童食物过敏临床分析

目的 探讨上海地区特应质儿童中食物过敏的发病情况和临床特点,以及食物过敏与其他过敏性疾病的关系.方法 采用国际上经典的食物过敏诊断方法 进行研究,对2007年7月-2008年7月因过敏症状在上海儿童医学中心过敏/免疫专科就诊的720例2个月～17岁特应质儿童,进行病史收集、皮肤点刺试验、排除性饮食试验和开放式食物激发试验.结果 最后确诊食物过敏59例(发生率8.19%).初次发生食物过敏的平均年龄为(0.40±0.33)岁.引起过敏的主要食物为鸡蛋(5.83%)、牛奶(2.78%),虾(1.67%)、鱼(1.25%);3岁以下儿童对鸡蛋过敏多见,≥3岁对虾过敏多见(P<0.01);94.92%的儿童对一种或二种食物过敏.食物过敏100%可引起皮肤症状,25%的特应质儿童因食物过敏引起湿疹;消化道症状发生率为3.39%;呼吸道症状发生率为1.69%;过敏性休克发生率为1.69%.≥3岁仍食物过敏的儿童吸入性过敏原阳性、患哮喘和过敏性鼻炎/结膜炎的人数均显著多于3岁以下的食物过敏儿童(P<0.01).结论 上海地区的特应质儿童中,食物过敏的发生率高,发生年龄小.对有皮肤过敏症状的儿童,应首先考虑食物过敏可能.早期诊断并阻断食物过敏,可预防其他严重过敏性疾病的发生.     

An evaluation of the diagnostic value of different skin tests with egg in clinically egg-allergic children having atopic dermatitis

Skin testing is a common diagnostic procedure in food allergy, but the final diagnosis of food allergy is based on the clinical response to food challenge. We studied the value of the skin prick-prick test (SPT), skin application food test (SAFT) and atopy patch test (APT) with fresh egg extract in diagnosing egg allergy. Ten clinically egg-allergic children with atopic dermatitis (AD; age 10 months to 8.4 yr, mean 3.4 yr) and 10 egg-tolerant children with and 10 without AD (age 2.4-11 yr, mean 5.5 yr) participated. In SAFT several false-negative reactions were seen, whereas all clinically egg-allergic children were positive in SPT and 40-60% in APT. In APT and in SPT false-positive reactions to egg were observed. In this study comprising a small number of patients including control subjects, neither SAFT nor APT with fresh whole egg extract were able to increase the diagnostic accuracy in detecting egg-allergic children with AD compared with SPT.     

Prevalence of food allergy among preschool children in northern Thailand

Background: The epidemiology and clinical spectrum of food allergies (FA) confirmed by oral food challenge tests (OFC) in the Southeast Asian countries are limited. The aim of the present study was to examine the prevalence and characteristics of FA among preschool children in northern Thailand. Methods: Five hundred and forty‐six children aged 3–7 years living in Chiang Mai, Thailand participated in this study. A cross‐sectional parent questionnaire survey was conducted. Families with children reporting FA were invited to undergo further investigations with skin prick testing, serum specific IgE, and OFC. Results: A total of 452 out of 546 questionnaires (82.8%) were returned. Forty‐two children (9.3%) were reported to have FA. The five leading allergic foods reported were shrimp, cow's milk, fish, chicken eggs, and ant eggs. The most commonly reported symptom was a skin rash (78.0%), followed by abdominal pain and vomiting (31.1%). Anaphylaxis was found in two children (3.4%), from ant eggs allergy. Eighteen children underwent OFC; five of them were positive to shrimp, fish, and crab. Either skin prick test or serum‐specific IgE was positive in these children. Factors associated with parent‐reported FA included personal and family history of atopic dermatitis. Conclusions: The prevalence of IgE‐mediated FA confirmed on OFC was ≥1.11% (95% confidence interval: 0.41–2.98%). The most common causative food was shrimp. Ant eggs were a unique food allergen causing severe reactions in preschool children in northern Thailand.     

Fish and shellfish allergy in children: Review of a persistent food allergy

The increased consumption of fish and shellfish has resulted in more frequent reports of adverse reactions to seafood, emphasizing the need for more specific diagnosis and treatment of this condition and exploring reasons for the persistence of this allergy. This review discusses interesting and new findings in the area of fish and shellfish allergy. New allergens and important potential cross‐reacting allergens have been identified within the fish family and between shellfish, arachnids, and insects. The diagnostic approach may require prick to‐prick tests using crude extracts of both raw and cooked forms of seafood for screening seafood sensitization before a food challenge or where food challenge is not feasible. Allergen‐specific immunotherapy can be important; mutated less allergenic seafood proteins have been developed for this purpose. The persistence of allergy because of seafood proteins’ resistance after rigorous treatment like cooking and extreme pH is well documented. Additionally, IgE antibodies from individuals with persistent allergy may be directed against different epitopes than those in patients with transient allergy. For a topic as important as this one, new areas of technological developments will likely have a significant impact, to provide more accurate methods of diagnosing useful information to patients about the likely course of their seafood allergy over the course of their childhood and beyond.     

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.     

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.     

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.     

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   

Delayed- and immediate-type reactions in the atopy patch test with food allergens in young children with atopic dermatitis

In recent years, the atopy patch test (APT) has been suggested as an addition in the allergological work‐up of children with atopic dermatitis (AD) and suspected food allergy. We initiated a prospective clinical study in children with AD younger than 3 yr, to evaluate the additional clinical value of the APT next to our own standardized allergological work‐up in case of a suspected food allergy. One hundred and thirty‐five children were included in the study. They were tested using the skin application food test (SAFT), the APT and measurement of specific IgE. The allergens used in the skin tests were freshly prepared food stuffs and included commercially available cow’s milk (CM), the egg white of a hard boiled hen’s egg and mashed peanuts in a saline solution. Allergy was defined using a flowchart incorporating the results from the SAFT, oral challenges (OCs) and elimination and (re)introduction periods. To determine the additional value of the APT next to the SAFT, we analyzed the SAFT negative patients per allergen and used an exact binary logistic analysis to evaluate the simultaneous effects of the APT and measurement of specific IgE, calculating mutually adjusted odds ratios (ORs) for positive APTs and specific IgE levels above 0.70 U/l. We found clinically relevant food allergies in 23% (egg white) to 28% (CM and peanut) of our study population. Positive SAFT reactions were observed in 14% (peanut), 16% (egg white) and 21% (CM) of our patient population. Next to the SAFT, we did not observe a significant additional value of the APT for the diagnosis of CM or egg white allergy, but we did find a significant additional value for the diagnosis of peanut allergy (OR = 11.56; p < 0.005, 2‐sided). In clinical practice this statistically significant value does not exclude the need for OC and controlled elimination and (re)introduction periods due to the presence of false‐negative as well as false‐positive results in the APT. In conclusion, we could not find enough support for the current addition of the APT to our standardized allergological work‐up in young children below the age of 3 yr with AD and suspected food allergy. At the moment the additional value of the classical delayed‐type APT next to the SAFT seems to be very limited at best in this study population and does not justify the time‐consuming nature of the skin test.