— The current tools available for diagnosing food allergy include the clinical history, physical examination, trial elimination diets, diet diaries, prick/puncture skin testing, and in vitro food-specific IgE testing. Clinician-supervised oral food challenges are often required to confirm or rule out presence or resolution of a food allergy because of the limitations in the diagnostic accuracy of these methods.
Improved or new testing methodologies are needed for determining the presence and severity of a food allergy and the likelihood of resolution of an allergy . This topic reviews improvements in available diagnostic tools and new testing methods that are in development. Current diagnostic tools are discussed separately, as is the initial evaluation of a patient with suspected food allergy. (See “Diagnostic tools for food allergy” and see “History and physical examination in the patient with possible food allergy”).
An important concept regarding IgE-mediated food allergy is the distinction between sensitization and allergy. Sensitization refers to the presence of IgE capable of binding to a particular antigen. Production of specific IgE is necessary, but not sufficient, for clinical allergy. Individuals may have positive testing (skin or in vitro) and yet fully tolerate the antigen in the diet.
Beyond accurate diagnosis of food allergy, there are some closely related prognostic questions confronting food allergic patients, their families, and health care providers. Two of the most common questions are: “Who is at risk for anaphylaxis?” and, for children, ” Will the allergy be outgrown?”.
IgE epitopes — Food allergens must survive digestion and absorption from the gastrointestinal tract to induce systemic reactions. This fact has lead to the hypothesis that individuals who have IgE antibodies recognizing a greater number or a specific pattern of sequential epitopes (not easily destroyed by denaturation and partial digestion) are more likely to have clinical allergy rather than asymptomatic IgE sensitization .
- Steckelbroeck, S, Ballmer-Weber, BK, Vieths, S. Potential, pitfalls, and prospects of food allergy diagnostics with recombinant allergens or synthetic sequential epitopes. J Allergy Clin Immunol 2008; 121:1323.
- Sampson, HA. Improving in-vitro tests for the diagnosis of food hypersensitivity. Curr Opin Allergy Clin Immunol 2002; 2:257.
- Beyer, K, Ellman-Grunther, L, Jarvinen, KM, et al. Measurement of peptide-specific IgE as an additional tool in identifying patients with clinical reactivity to peanuts. J Allergy Clin Immunol 2003; 112:202.
- Matsuo, H, Morita, E, Tatham, AS, et al. Identification of the IgE-binding epitope in omega-5 gliadin, a major allergen in wheat-dependent exercise-induced anaphylaxis. J Biol Chem 2004; 279:12135.
- Matsuo, H, Kohno, K, Niihara, H, Morita, E. Specific IgE determination to epitope peptides of omega-5 gliadin and high molecular weight glutenin subunit is a useful tool for diagnosis of wheat-dependent exercise-induced anaphylaxis. J Immunol 2005; 175:8116.
- Lewis, SA, Grimshaw, KE, Warner, JO, Hourihane, JO. The promiscuity of immunoglobulin E binding to peanut allergens, as determined by Western blotting, correlates with the severity of clinical symptoms. Clin Exp Allergy 2005; 35:767.
- Flinterman, AE, Knol, EF, Lencer, DA, et al. Peanut epitopes for IgE and IgG4 in peanut-sensitized children in relation to severity of peanut allergy. J Allergy Clin Immunol 2008; 121:737.
- 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.
- Jarvinen, KM, Chatchatee, P, Bardina, L, et al. IgE and IgG binding epitopes on alpha-lactalbumin and beta-lactoglobulin in cow’s milk allergy. Int Arch Allergy Immunol 2001; 126:111.
- Chatchatee, P, Jarvinen, KM, Bardina, L, et al. Identification of IgE- and IgG-binding epitopes on alpha(s1)-casein: differences in patients with persistent and transient cow’s milk allergy. J Allergy Clin Immunol 2001; 107:379.
- Jarvinen, KM, Beyer, K, Vila, L, et al. Specificity of IgE antibodies to sequential epitopes of hen’s egg ovomucoid as a marker for persistence of egg allergy. Allergy 2007; 62:758.
- Beyer, K, Jarvinen, KM, Bardina, L, et al. IgE-binding peptides coupled to a commercial matrix as a diagnostic instrument for persistent cow’s milk allergy. J Allergy Clin Immunol 2005; 116:704.
- van der, Veen MJ, Mulder, M, Witteman, AM, et al. False-positive skin prick test responses to commercially available dog dander extracts caused by contamination with house dust mite (Dermatophagoides pteronyssinus) allergens. J Allergy Clin Immunol 1996; 98:1028.
- van der, Veen MJ, van Ree, R, Aalberse, RC, et al. Poor biologic activity of cross-reactive IgE directed to carbohydrate determinants of glycoproteins. J Allergy Clin Immunol 1997; 100:327.
- Astier, C, Morisset, M, Roitel, O, et al. Predictive value of skin prick tests using recombinant allergens for diagnosis of peanut allergy. J Allergy Clin Immunol 2006; 118:250.
- Lidholm, J, Ballmer-Weber, BK, Mari, A, Vieths, S. Component-resolved diagnostics in food allergy. Curr Opin Allergy Clin Immunol 2006; 6:234.
- Mothes, N, Valenta, R, Spitzauer, S. Allergy testing: the role of recombinant allergens. Clin Chem Lab Med 2006; 44:125.
- Sicherer, SH. Clinical implications of cross-reactive food allergens. J Allergy Clin Immunol 2001; 108:881.
- Breiteneder, H, Clare Mills, EN. Plant food allergens–structural and functional aspects of allergenicity. Biotechnol Adv 2005; 23:395.
- Asero, R, Mistrello, G, Roncarolo, D, et al. Lipid transfer protein: a pan-allergen in plant-derived foods that is highly resistant to pepsin digestion. Int Arch Allergy Immunol 2001; 124:67.
- Akkerdaas, JH, Wensing, M, Asero, R, et al. IgE binding to pepsin-digested food extracts. Int Arch Allergy Immunol 2005; 138:203.
- Shreffler, WG. Evaluation of basophil activation in food allergy: present and future applications. Curr Opin Allergy Clin Immunol 2006; 6:226.
- de Weck, AL, Sanz, ML, Gamboa, PM, et al. Diagnostic tests basedon human basophils: more potentials and perspectives than pitfalls. Int Arch Allergy Immunol 2008; 146:177.
- Moneret-Vautrin, DA, Sainte-Laudy, J, Kanny, G, Fremont, S. Human basophil activation measured by CD63 expression and LTC4 release in IgE-mediated food allergy. Ann Allergy Asthma Immunol 1999; 82:33.
- Erdmann, SM, Heussen, N, Moll-Slodowy, S, et al. CD63 expression on basophils as a tool for the diagnosis of pollen-associated food allergy: sensitivity and specificity. Clin Exp Allergy 2003; 33:607.
- Ebo, DG, Hagendorens, MM, Bridts, CH, et al. Flow cytometric analysis of in vitro activated basophils, specific IgE and skin tests in the diagnosis of pollen-associated food allergy. Cytometry B Clin Cytom 2005; 64:28.
- Erdmann, SM, Sachs, B, Schmidt, A, et al. In vitro analysis of birch-pollen-associated food allergy by use of recombinant allergens in the basophil activation test. Int Arch Allergy Immunol 2005; 136:230.
- Wallowitz, ML, Chen, RJ, Tzen, JT, Teuber, SS. Ses i 6, the sesame 11S globulin, can activate basophils and shows cross-reactivity with walnut in vitro. Clin Exp Allergy 2007; 37:929.
- Schwab, D, Raithel, M, Klein, P, et al. Immunoglobulin E and eosinophilic cationic protein in segmental lavage fluid of the small and large bowel identify patients with food allergy. Am J Gastroenterol 2001; 96:508.
- Saarinen, KM, Suomalainen, H, Savilahti, E. Diagnostic value of skin-prick and patch tests and serum eosinophil cationic protein and cow’s milk-specific IgE in infants with cow’s milk allergy. Clin Exp Allergy 2001; 31:423.
- Bacarese-Hamilton, T, Gray, J, Ardizzoni, A, Crisanti, A. Allergen microarrays. Methods Mol Med 2005; 114:195.
- Deinhofer, K, Sevcik, H, Balic, N, et al. Microarrayed allergens for IgE profiling. Methods 2004; 32:249.
- Harwanegg, C, Hiller, R. Protein microarrays for the diagnosis of allergic diseases: state-of-the-art and future development. Clin Chem Lab Med 2005; 43:1321.
- Hiller, R, Laffer, S, Harwanegg, C, et al. Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment. FASEB J 2002; 16:414.
- Jahn-Schmid, B, Harwanegg, C, Hiller, R, et al. Allergen microarray: comparison of microarray using recombinant allergens with conventional diagnostic methods to detect allergen-specific serum immunoglobulin E. Clin Exp Allergy 2003; 33:1443.
- Kim, TE, Park, SW, Cho, NY, et al. Quantitative measurement of serum allergen-specific IgE on protein chip. Exp Mol Med 2002; 34:152.
- Lebrun, SJ, Petchpud, WN, Hui, A, McLaughlin, CS. Development of a sensitive, colorometric microarray assay for allergen-responsive human IgE. J Immunol Methods 2005; 300:24.
- Wiltshire, S, O’Malley, S, Lambert, J, et al. Detection of multiple allergen-specific IgEs on microarrays by immunoassay with rolling circle amplification. Clin Chem 2000; 46:1990.
- Wohrl, S, Vigl, K, Zehetmayer, S, et al. The performance of a component-based allergen-microarray in clinical practice. Allergy 2006; 61:633.
- Shreffler, WG, Lencer, DA, Bardina, L, Sampson, HA. IgE and IgG4 epitope mapping by microarray immunoassay reveals the diversity of immune response to the peanut allergen, Ara h 2. J Allergy Clin Immunol 2005; 116:893.
- Alcocer, MJ, Murtagh, GJ, Wilson, PB, et al. The major human structural IgE epitope of the Brazil nut allergen Ber e 1: a chimaeric and protein microarray approach. J Mol Biol 2004; 343:759.
- Nowak-Wegrzyn, A, Sampson, HA, Wood, RA, Sicherer, SH. Food protein-induced enterocolitis syndrome caused by solid food proteins. Pediatrics 2003; 111:829.
- Niggemann, B, Reibel, S, Wahn, U. The atopy patch test (APT)– a useful tool for the diagnosis of food allergy in children with atopic dermatitis. Allergy 2000; 55:281.
- Stromberg, L. Diagnostic accuracy of the atopy patch test and the skin-prick test for the diagnosis of food allergy in young children with atopic eczema/dermatitis syndrome. Acta Paediatr 2002; 91:1044.
- Majamaa, H, Moisio, P, Holm, K, et al. Cow’s milk allergy: diagnostic accuracy of skin prick and patch tests and specific IgE. Allergy 1999; 54:346.
- Hansen, TK, Host, A, Bindslev-Jensen, C. An evaluation of the diagnostic value of different skin tests with egg in clinically egg-allergic children having atopic dermatitis.Pediatr Allergy Immunol 2004; 15:428.
- Giusti, F, Seidenari, S. Patch testing with egg represents a useful integration to diagnosis of egg allergy in children with atopic dermatitis. Pediatr Dermatol 2005; 22:109.
- Mehl, A, Rolinck-Weringhaus, C, Staden, U, et al. The atopy patch test in the diagnostic workup of suspected food-related symptomsin children. J Allergy Clin Immunol 2006; 118:923.
- Devillers, AC, de Waard-van, der Spek FB, Mulder, PG, Oranje, AP. Delayed- and immediate-type reactions in the atopy patch test with food allergens in young children with atopic dermatitis. Pediatr Allergy Immunol 2008; :.
- Isolauri, E, Turjamaa, K. J Allergy Clin Immunol 1996; 97:9.
- Canani, RB, Ruotolo, S, Auricchio, L, et al. Diagnostic accuracy of the atopy patch test in children with food allergy-related gastrointestinal symptoms. Allergy 2007; 62:738.
- De Boissieu, D, Waguet, JC, Dupont, C. The atopy patch tests for detection of cow’s milk allergy with digestive symptoms. J Pediatr 2003; 142:203.
- Spergel, JM, Andrews, T, Brown-Whitehorn, TF, et al. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann Allergy Asthma Immunol 2005; 95:336.
- Spergel, JM, Beausoleil, J, Brown-Whitehorn, T, Liacouras, CA. Authors’response to detection of causative foods by skin prick and atopy patch testsin patients with eosinophilic esophagitis: things are not what they seem. Ann Allergy Asthma Immunol 2006; 96:376.
- Assa’ad, A. Detection of causative foods by skin prick and atopy patch tests in patients with eosinophilic esophagitis: things are not what they seem. Ann Allergy Asthma Immunol 2005; 95:309.
- Spergel, JM, Brown-Whitehorn, T, Beausoleil, JL, et al. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis. J Allergy Clin Immunol 2007; 119:509.
- Furuta, GT, Liacouras, CA, Collins, MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007; 133:1342.
- Fogg, MI, Brown-Whitehorn, TA, Pawlowski, NA, Spergel, JM. Atopy patch test for the diagnosis of food protein-induced enterocolitis syndrome. Pediatr Allergy Immunol 2006; 17:351.
- Hill, DJ, Ball, G, Hosking, CS, Wood, PR. Gamma-interferon production in cow milk allergy. Allergy 1993; 48:75.
- Benlounes, N, Candalh, C, Matarazzo, P, et al. The time-course of milk antigen-induced TNF-alpha secretion differs according to the clinical symptoms in children with cow’s milk allergy. J Allergy Clin Immunol 1999; 104:863.
- Karlsson, MR, Rugtveit, J, Brandtzaeg, P. Allergen-responsive CD4+CD25+ regulatory T cells in children who have outgrown cow’s milk allergy. J Exp Med 2004; 199:1679.
- Provided by
DR WIDODO JUDARWANTO SpA
children’s ALLERGY CLINIC
JL TAMAN BENDUNGAN ASAHAN 5 JAKARTA PUSAT, JAKARTA INDONESIA 10210
PHONE : (021) 70081995 – 5703646
email : firstname.lastname@example.org\
Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.
Copyright © 2009, Children Allergy Clinic Information Education Network. All rights reserved.