Allergy Asthma Respir Dis AARD Allergy, Asthma & Respiratory Disease 2288-0402 2288-0410 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma, Allergy and Clinical Immunology 10.4168/aard.2015.3.1.22 Original Article Diagnostic utility of skin prick test to cooked egg in children with egg allergy Jhon Jin 1 Lee Kyung Eun 1 2 3 Kim Mi Na 1 2 3 Hong Jung Yeon 1 2 3 Kim Min Jung 1 2 3 Kim Yoon Hee 1 2 3 Park Hyun Bin 1 2 3 Han Yoon Ki 1 2 3 Lee Hee Seon 1 2 3 Kim Kyung Won 1 2 3 Sohn Myung Hyun 1 2 3 Park Jung-Won 2 3 4 Kim Kyu-Earn 1 2 3 Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea. Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. Correspondence to: Hee Seon Lee. Department of Pediatrics, Institute of Allergy, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea. Tel: +82-2-2228-2050, Fax: +82-2-393-9118, heeseon0701@naver.com 01 2015 31 01 2015 3 1 22 29 24 04 2014 20 10 2014 27 10 2014 © 2015 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma, Allergy and Clinical Immunology 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/). Purpose

Reliable predictors of tolerance to cooked egg in an egg allergic population are not established. We investigated the usefulness of the skin prick test to cooked egg in children with egg allergy.

 Methods

We studied 36 children with egg allergy. Skin prick tests (SPTs) for the uncooked or cooked form of egg white and egg yolk, whole egg, ovomucoid (OVM), and ovalbumin (OVA) were performed at diagnosis. The reagents of cooked egg for SPT were prepared by baking for 25 minutes in 200 degree oven. We also examined specific IgE levels to whole egg, egg white, egg yolk, OVM, and OVA.

 Results

Patients with history of allergic reaction to extensively heated egg showed significantly increased wheal size for cooked egg white (median [interquartile range]), 10.5 [7.0-14.6] vs. 4.2 [0.0-5.6], P<0.001) and OVM (9.6 [7.3-13.8] vs. 5.6 [0.0-7.8], P=0.001) than those without the history. The strongest positive correlation was found between wheal size for cooked egg white and OVM (r=0.788, P<0.001). SPT wheal size for cooked egg white were positively correlated with serum OVM-specific IgE levels (r=0.691, P<0.001). Cutoff value was 7.0 mm in SPT wheal size for cooked egg white, the sensitivity was 73.1% and specificity was 99.0%. SPT for cooked egg white showed significantly higher area under curve than serum egg white specific IgE.

 Conclusion

Our results suggest that SPT to cooked egg white may be useful predictor of allergic reaction to cooked egg. Further investigations will be needed.

 Egg hypersensitivity Skin tests Egg proteins Rona RJ Keil T Summers C Gislason D Zuidmeer L Sodergren E The prevalence of food allergy: a meta-analysis J Allergy Clin Immunol 2007 120 638 646 Heine RG Laske N Hill DJ The diagnosis and management of egg allergy Curr Allergy Asthma Rep 2006 6 145 152 Hong SJ Ahn KM Lee SY Kim KE The prevalences of asthma and allergic diseases in Korean children Korean J Pediatr 2008 51 343 350 Boyano Martinez T Garcia-Ara C Diaz-Pena JM Munoz FM Garcia Sanchez G Esteban MM Validity of specific IgE antibodies in children with egg allergy Clin Exp Allergy 2001 31 1464 1469 Colver AF Nevantaus H Macdougall CF Cant AJ Severe food-allergic reactions in children across the UK and Ireland, 1998-2000 Acta Paediatr 2005 94 689 695 Sampson HA Mendelson L Rosen JP Fatal and near-fatal anaphylactic reactions to food in children and adolescents N Engl J Med 1992 327 380 384 Hill DJ Hosking CS de Benedictis FM Oranje AP Diepgen TL Bauchau V Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: an international study Clin Exp Allergy 2008 38 161 168 Sampson HA Scanlon SM Natural history of food hypersensitivity in children with atopic dermatitis J Pediatr 1989 115 23 27 Langeland T A clinical and immunological study of allergy to hen's egg white. II. Antigens in hen's egg white studied by crossed immunoelectrophoresis (CIE) Allergy 1982 37 323 333 Caubet JC Kondo Y Urisu A Nowak-Wegrzyn A Molecular diagnosis of egg allergy Curr Opin Allergy Clin Immunol 2011 11 210 215 Deutsch HF Morton JI Immunochemical properties of heated ovomucoid Arch Biochem Biophys 1956 64 19 25 Kattan JD Wang J Allergen component testing for food allergy: ready for prime time? Curr Allergy Asthma Rep 2013 13 58 63 Alessandri C Zennaro D Scala E Ferrara R Bernardi ML Santoro M Ovomucoid (Gal d 1) specific IgE detected by microarray system predict tolerability to boiled hen's egg and an increased risk to progress to multiple environmental allergen sensitisation Clin Exp Allergy 2012 42 441 450 Ando H Moverare R Kondo Y Tsuge I Tanaka A Borres MP Utility of ovomucoid-specific IgE concentrations in predicting symptomatic egg allergy J Allergy Clin Immunol 2008 122 583 588 Lemon-Mule H Sampson HA Sicherer SH Shreffler WG Noone S Nowak-Wegrzyn A Immunologic changes in children with egg allergy ingesting extensively heated egg J Allergy Clin Immunol 2008 122 977 983.e1 Koplin JJ Osborne NJ Wake M Martin PE Gurrin LC Robinson MN Can early introduction of egg prevent egg allergy in infants? A population-based study J Allergy Clin Immunol 2010 126 807 813 Clark A Islam S King Y Deighton J Szun S Anagnostou K A longitudinal study of resolution of allergy to well-cooked and uncooked egg Clin Exp Allergy 2011 41 706 712 Martos G Lopez-Exposito I Bencharitiwong R Berin MC Nowak-Wegrzyn A Mechanisms underlying differential food allergy response to heated egg J Allergy Clin Immunol 2011 127 990 997.e1-2 Cortot CF Sheehan WJ Permaul P Friedlander JL Baxi SN Gaffin JM Role of specific IgE and skin-prick testing in predicting food challenge results to baked egg Allergy Asthma Proc 2012 33 275 281 Lieberman JA Huang FR Sampson HA Nowak-Wegrzyn A Outcomes of 100 consecutive open, baked-egg oral food challenges in the allergy office J Allergy Clin Immunol 2012 129 1682 1684.e2 Leonard SA Sampson HA Sicherer SH Noone S Moshier EL Godbold J Dietary baked egg accelerates resolution of egg allergy in children J Allergy Clin Immunol 2012 130 473 480.e1 Faraj Z Kim HL Skin prick testing with extensively heated milk or egg products helps predict the outcome of an oral food challenge: a retrospective analysis Allergy Asthma Clin Immunol 2012 8 5 Tan JW Campbell DE Turner PJ Kakakios A Wong M Mehr S Baked egg food challenges - clinical utility of skin test to baked egg and ovomucoid in children with egg allergy Clin Exp Allergy 2013 43 1189 1195 Hanifin JM Diagnostic criteria for atopic dermatitis: consider the context Arch Dermatol 1999 135 1551 Faeste CK Lovberg KE Lindvik H Egaas E Extractability, stability, and allergenicity of egg white proteins in differently heat-processed foods J AOAC Int 2007 90 427 436 Hill DJ Hosking CS Reyes-Benito LV Reducing the need for food allergen challenges in young children: a comparison of in vitro with in vivo tests Clin Exp Allergy 2001 31 1031 1035 Urisu A Ando H Morita Y Wada E Yasaki T Yamada K Allergenic activity of heated and ovomucoid-depleted egg white J Allergy Clin Immunol 1997 100 171 176 Lidholm J Ballmer-Weber BK Mari A Vieths S Component-resolved diagnostics in food allergy Curr Opin Allergy Clin Immunol 2006 6 234 240 Gruber P Becker WM Hofmann T Influence of the maillard reaction on the allergenicity of rAra h 2, a recombinant major allergen from peanut (Arachis hypogaea), its major epitopes, and peanut agglutinin J Agric Food Chem 2005 53 2289 2296 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 1540 1546 Correlation of skin prick test wheal size for raw egg white with OVA (A) and OVM (B), correlation of skin prick test wheal size for cooked egg white with OVA (C) and OVM (D). SPT, skin prick test; OVA, ovalbumin; OVM, ovomucoid. Correlation of skin prick test wheal size for raw egg white with serum OVA-sIgE (A) and OVM-sIgE (B), correlation of skin prick test wheal size for cooked egg white with OVA-sIgE (C) and OVM-sIgE (D). SPT, skin prick test; OVA, ovalbumin; OVM, ovomucoid. Comparison of receiver operating characteristic (ROC) curves among skin prick test to cooked egg white, serum specific IgE to egg white, egg yolk, ovalbumin, ovomucoid, and whole egg. The area under curve (AUC) of SPT to cooked egg white was 0.89 (95% confidence interval, 0.73-0.97). The AUC was 0.50 (0.33-0.68) for egg white-sIgE, 0.53 (0.36-0.70) for egg yolk-sIgE, 0.60 (0.42-0.76) for OVA-sIgE, 0.72 0.53-0.85) for OVM-sIgE, and 0.54 (0.36-0.71) for whole egg-sIgE. SPT to cooked egg white showed significantly higher AUC than egg white-sIgE (<italic>P</italic><0.001), egg yolk-sIgE (<italic>P</italic>=0.002), OVA-sIgE (<italic>P</italic>=0.035), and whole egg (<italic>P</italic>=0.016). SPT, skin prick test; OVA, ovalbumin; OVM, ovomucoid. Baseline characteristics of subjects
Characteristic Reaction to cooked egg (+) (n=26) Reaction to cooked egg (-) (n=10) P-value
Age 0.133
 Median (range), mo 20 (12-72) 18 (11-64)
 <2 yr 16 7 0.767
 2-5 yr 9 2 0.289
 >5 yr 1 1 0.928
Age at symptom onset (mo) 0.464
 Median (range) 12 (6-18) 13 (6-18)
Male sex 20 8 0.804
Onset time of symptoms to raw egg (min) 0.354
 Median (range) 10 (3-120) 5 (1-180)
Family history of allergic disease 17 6 0.767
Clinical diagnosis
 Urticaria 20 9 0.582
 Atopic dermatitis 19 9 0.518
 Bronchiolitis 4 2 0.868
 Asthma 3 1 0.645
 Allergic rhinitis 4 1 0.905
 Other food allergy 19 5 0.357
 Anaphylaxis 1 0 0.615
Symptoms
 Skin 22 7 0.601
 Ocular 12 2 0.289
 Upper respiratory 3 0 0.654
 Lower respiratory 3 0 0.654
 Oral 5 2 0.676
 Gastrointestinal 6 1 0.676
 Cardiovascular 1 0 0.615

Reaction to cooked egg positive or negative group included patients who had reacted or not reacted (respectively) to extensively heated egg by cooking in the patients' history.

 Comparison of skin prick test (SPT) and serum specific IgE between patients with and without history of allergic reaction to cooked egg
Allergen Reaction to cooked egg (+) (n=26) Reaction to cooked egg (-) (n=10) P-value
SPT wheal size (mm)
 Ovomucoid 9.6 (7.3-13.8) 5.6 (0.0-7.8) 0.001*
 Ovalbumin 9.1 (6.5-10.9) 5.6 (4.1-7.6) 0.063
 Raw egg white 12.1 (7.7-16.5) 6.1 (3.6-8.9) 0.001*
 Cooked egg white 10.5 (7.0-14.6) 4.2 (0.0-5.6) <0.001*
 Raw egg yolk 6.8 (3.7-8.7) 3.0 (0.0-4.4) 0.037*
 Cooked egg yolk 4.5 (2.6-6.0) 0.5 (0.0-2.9) 0.017*
 Raw whole egg 6.5 (4.5-8.1) 5.1 (2.6-5.8) 0.041*
 Total IgE 211.0 (110.0-671.0) 150.0 (28.2-206.0) 0.355
Serum sIgE (kUA/L)
 Ovomucoid 3.8 (2.2-9.6) 0.3 (0.1-8.5) 0.045*
 Ovalbumin 8.1 (2.1-31.7) 14.2 (9.9-48.2) 0.32
 Egg white 16.2 (5.8-46.1) 19.5 (7.9-47.3) 1
 Egg yolk 3.4 (1.5-6.3) 2.8 (1.3-5.5) 0.876
 Whole egg 11.7 (6.5-42.6) 19.3 (8.8-45.0) 0.76

Reaction to cooked egg positive or negative group included patients who had reacted or not reacted (respectively) to extensively heated egg by cooking in the patients' history.

Values are presented as median (interquartile range).

*P<0.05, statistically significant differences.

 Skin prick test wheal size in predicting response to cooked egg
Allergen AUC (95% CI) Cutoff value (mm) Sensitivity (%) Specificity (%) P-value
Cooked egg white 0.89 (0.73-0.97) 7 73.1 99 1
Raw egg white 0.83 (0.67-0.94) 9 73.1 90 0.284
Ovomucoid 0.84 (0.68-0.94) 7.8 69.2 90 0.466
Ovalbumin 0.70 (0.53-0.84) 5.8 88.5 60 0.137
Cooked egg yolk 0.76 (0.59-0.88) 2.9 69.2 80 0.08
Raw egg yolk 0.73 (0.56-0.86) 4.3 73.1 80 0.198
Raw whole egg 0.74 (0.56-0.87) 5.8 65.4 90 0.164

P-values were determined by pairwise comparison of receiver operating characteristic curves of cooked egg white with that of other allergens.

AUC, area under curve; CI, confidence interval.

 Serum specific IgE in predicting response to cooked egg
Allergen AUC (95% CI) Cutoff value (kUA/L) Sensitivity (%) Specificity (%) P-value
Ovomucoid 0.72 (0.53-0.85) 0.37 92.3 60 1
Ovalbumin 0.60 (0.42-0.76) 6.15 46.2 90 0.58
Egg white 0.50 (0.33-0.68) 5.78 73.1 10 0.016*
Egg yolk 0.53 (0.36-0.70) 3.62 50 70 0.076
Whole egg 0.54 (0.36-0.71) 12.6 56 60 0.418

P-values were determined by pairwise comparison of receiver operating characteristic curves of ovomucoid-sIgE with that of serum specific IgE to other allergens.

AUC, area under curve; CI, confidence interval.

*P<0.05, statistically significant differences.