Abstract
Food allergy is becoming an increasingly common diagnosis. Because of this increase in prevalence, it is imperative that physicians evaluating patients with possible adverse reactions to foods understand the currently available assays and how they should best be used to accurately diagnose the disease. Simple tests such as skin prick testing (SPT) and serum food-specific IgE testing are the most commonly used diagnostic tests to evaluate for IgE-mediated food reactions. However, these tests, which measure sensitization and not clinical allergy, are not without pitfalls, and their utility must be appreciated to avoid over- and underdiagnosis. Although the physician-supervised oral food challenge remains the gold standard for food allergy diagnosis, a careful medical history paired with SPT and serum food-specific IgE testing often can provide a reliable diagnosis. In this review, we examine the usefulness and pitfalls of SPT and serum food-specific IgE levels, as well as examine atopy patch testing and other emerging tests, such as component-resolved diagnostics and the basophil activation test. Finally, we describe the use of the double-blind, placebo-controlled oral food challenge as the current gold standard for food allergy diagnosis.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Sicherer SH, Muñoz-Furlong A, Godbold JH, Sampson HA: US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. J Allergy Clin Immunol 2010, 125:1322–1326.
Rona RJ, Keil T, Summers C, et al.: The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol 2007, 120:638–646.
Branum AM, Lukacs SL: Food allergy among children in the United States. Pediatrics 2009, 124:1549–1555.
•• Schneider Chafen JJ, Newberry SJ, Riedl MA, et al.: Diagnosing and managing common food allergies: a systematic review. JAMA 2010, 303:1848–1856. This was a large systematic review of studies on food allergy epidemiology and diagnosis.
Sicherer SH, Sampson HA: Food allergy. J Allergy Clin Immunol 2010, 125:S116–S125.
May CD: Objective clinical and laboratory studies of immediate hypersensitivity reaction to foods in asthmatic children. J Allergy Clin Immunol 1976, 58:500–515.
Atkins FM, Steinberg SS, Metcalfe DD: Evaluation of immediate adverse reactions to foods in adult patients. J Allergy Clin Immunol 1985, 75:348–355.
Sampson HA: Comparative study of commercial food antigen extracts for the diagnosis of food hypersensitivity. J Allergy Clin Immunol 1988, 82:718–726.
Eigenmann PA, Sampson HA: Interpreting skin prick tests in the evaluation of food allergy in children. Pediatr Allergy Immunol l998, 9:186–191.
Sporik R, Hill DJ, Hosking CS: Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children. Clin Exp Allergy 2000, 30:1541–1546.
Hill DJ, Hosking CS, Reyes-Benito LV: Reducing the need for food allergen challenges in young children: a comparison of in vitro and in vivo tests. Clin Exp Allergy 2001, 31:1031–1035.
Roberts G, Lack G: Diagnosing peanut allergy with skin prick and specific IgE testing. J Allergy Clin Immunol 2005, 115:1291–1296.
Knight AK, Shreffler WG, Sampson HA, et al.: Skin prick test to egg white provides additional diagnostic utility to serum egg white-specific IgE antibody concentration in children. J Allergy Clin Immunol 2006, 117:842–847.
Tripodi S, Businco AD, Alessandri C: Predicting the outcome of oral food challenges with hen’s egg through skin test end-point titration. Clin Exp Allergy 2010, 39:1225–1233.
Hefle SL, Helm RN, Burks AW, et al.: Comparison of commercial peanut skin extracts. J Allergy Clin Immunol 1995, 95:837–842.
Ortolani C, Ispano M, Pastorello EA, et al.: Comparison of results of skin prick tests (with fresh foods and commercial food extracts) and RAST in 100 patients with oral allergy syndrome. J Allergy Clin Immunol 1989, 83:683–690.
Rance F, Juchet A, Bremont F. et al.: Correlations of skin prick tests using commercial extracts and fresh foods, specific IgE, and food challenges. Allergy 1997, 52:1031–1035.
Verstege A, Mehl A, Rolinck-Werninghaus C: The predictive value of skin prick test wheal size for the outcome of oral food challenges. Clin Exp Allergy 2005, 35:1220–1226.
• Bernstein IL, Li JT, Bernstein DI, et al.: Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol 2008, 100(Suppl 3):S1–S148. These are the practice parameters developed by the American Academy of Allergy Asthma and Immunology and American College of Allergy, Asthma and Immunology Joint Task Force. This is an exceptional guide for practicing clinicians on appropriate testing.
Sampson HA, Ho DG: Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents. J Alleryg Clin Immunol 1997, 100:444–451.
Sampson HA: Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 2001, 107:891–896.
Garcia-Ara C, Boyano-Martinez T, Diaz-Pena JM, et al.: Specific IgE levels in the diagnosis of immediate hypersensitivity to cow’s milk protein in the infant. J Allergy Clin Immunol 2001, 107:185–190.
Osterballe M, Bindslev-Jensen C: Threshold levels in food challenge and specific IgE in patients with egg allergy: is there a relationship? J Allergy Clin Immunol 2003, 112:196–201.
Clark AT, Ewan PW: Interpretation of tests for nut allergy in one thousand patients, in relation to allergy or tolerance. Clin Exp Allergy 2003, 33:1041–1045.
Perry TT, Matsui EC, Conover-Walker KM, et al.: The relationship of allergy-specific IgE levels and oral food challenge outcome. J Allergy Clin Immunol 2004, 114:144–149.
Celik-Bilgili S, Mehl A, Verstage A, et al.: The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges. Clin Exp Allergy 2005, 35:268–273.
Komata T, Sodersrom L, Borres MP, et al.: The predictive relationship of food-specific serum IgE concentrations to challenge outcomes for egg and milk varies by patient age. J Allergy Clin Immunol 2007, 119:1272–1274.
Van der Gugten AC, den Otter M, Meijer Y, et al.: Usefulness of specific IgE levels in predicting cow’s milk allergy. J Allergy Clin Immunol 2008, 121:531–533.
• Wainstein BK, Studdert J, Ziegler M, et al.: Prediction of anaphylaxis during peanut food challenge: usefulness of the peanut skin prick test (SPT) and specific IgE level. Pediatr Allergy Immunol 2010, 21:603–611. This was the first large-scale study evaluating the relationship between IgE levels and severity of reactions. The investigators continued challenges with the goal of eliciting more serious reactions so as to be able to show what was thought to be true, which is that increasing IgE is correlated with more severe reactions.
Wood RA, Segal N, Ahlstedt S: Accuracy of IgE antibody laboratory results. Ann Allergy Asthma Immunol 2007, 99:34–41.
Wang J, Godbold JH, Sampson HA: Correlation of serum allergy (IgE) test performed by different assay systems. J Allergy Clin Immunol 2008, 121:1219–1224.
• Cox L, Williams B, Sicherer SH, et al.: Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma, and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Task Force. Ann Allergy Asthma Immunol 2008, 101:580–592. This publication provides a more in-depth look at IgE testing and what the clinician should take into account when using IgE testing to diagnose allergy.
Isolauri E, Turjanmaa K: Combined skin prick and patch testing enhances identification of food allergy in infants with atopic dermatitis. J Allergy Clin Immunol 1996, 97:9–15.
Roehr CC, Reibel S, Ziegert M, et al.: Atopy patch tests, together with determination of specific IgE levels, reduce the need for oral food challenges in children with atopic dermatitis. J Allergy Clin Immunol 2001, 107:548–553.
Mehl A, Rolinck-Werninghaus C, Staden U, et al.: The atopy patch test in the diagnostic workup of suspected food-related symptoms in children. J Allergy Clin Immunol 2006, 118:923–929.
Fogg MI, Brown-Whitehorn TA, Pawlowski NA, et al.: Atopy patch test for the diagnosis of food protein-induced enterocolitis syndrome. Pediatr Allergy Immunol 2006, 17:351–355.
Vanto T, Juntunen-Backman K, Kalimo K, et al.: The patch test, skin prick test, and serum milk-specific IgE as diagnostic tools in cow’s milk allergy in infants. Allergy 1999, 54:837–842.
Osterballe M, Andersen KE, Bindslev-Jensen C: The diagnostic accuracy of the atopy patch test in diagnosing hypersensitivity to cow’s milk and hen’s egg in unselected children with and without atopic dermatitis. J Am Acad Dermatol 2004, 51:556–562.
• Nicolaou N, Poorafshar M, Murray C, et al.: Allergy or tolerance in children sensitized to peanut: prevalence and differentiation using component-resolved diagnostics. J Allergy Clin Immunol 2010,125:191–197. This well-designed study furthers the possible role of CRD in determining sensitization versus clinical allergy. This study showed the importance of IgE binding to Ara h 2 in differentiating allergy from sensitization.
Mittag D, Akkerdaas J, Ballmer-Weber BK, et al.: Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy. J Allergy Clin Immunol 2004, 114:1410–1417.
Hansen KS, Poulsen LK: Component resolved testing for allergic sensitization. Curr Allergy Asthma Rep 2010, 10:340–348.
Shreffler WG, Beyer K, Chu TH, et al.: Microarray immunoassay: association of clinical history, in vitro IgE function, and heterogeneity of allergenic peanut epitopes. J Allergy Clin Immunol 2004, 113:776–782.
• Wang J, Lin J, Bardina L, et al.: Correlation of IgE/IgG4 milk epitopes and affinity of milk-specific IgE antibodies with different phenotypes of clinical milk allergy. J Allergy Clin Immunol 2010, 125:695–702. This study further defined the role of epitope binding and tolerance.
Wanich N, Nowak-Wegrzyn A, Sampson HA, et al.: Allergen-specific basophil suppression associated with clinical tolerance in patients with milk allergy. J Allergy Clin Immunol 2009, 123:789–794.
Ocmant A, Muller S, Hanssens L, et al.: Basophil activation tests for the diagnosis of food allergy in children. Clin Exp Allergy 2009, 39:1234–1245.
Stapel SO, Asero R, Ballmer-Weber BK, et al.: Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force report. Allergy 2008, 63:793–796.
Bernstein M, Day JH, Welsh A: Double-blind food challenges in the diagnosis of food sensitivity in the adult. J Allergy Clin Immunol 1982, 70:205–210.
• Nowak-Wegrzyn A, Assa’ad AH, Bahna SL, et al.: Work group report: oral food challenge testing. J Allergy Clin Immunol 2009, 123(Suppl):S365–S383. This is the most up-to-date guide on how and when to perform OFC testing.
Huijbers GB, Colen AA, Jansen JJ, et al.: Masking foods for food challenge: practical aspects of masking foods for a double-blind, placebo-controlled food challenge. J Am Diet Assoc 1994, 94:645–649.
Caffarelli C, Petroccione T: False-negative food challenges in children with suspected food allergy. Lancet 2001, 358:1871–1872.
Acknowledgment
Dr. Sicherer is supported in part by grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases.
Disclosure
Dr. Sicherer has served as a consultant for the Food Allergy Initiative and has received honoraria from Quest Diagnostics. Dr. Lieberman reported no potential conflicts of interest relevant to this article.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lieberman, J.A., Sicherer, S.H. Diagnosis of Food Allergy: Epicutaneous Skin Tests, In Vitro Tests, and Oral Food Challenge. Curr Allergy Asthma Rep 11, 58–64 (2011). https://doi.org/10.1007/s11882-010-0149-4
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11882-010-0149-4