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ORIGINAL ARTICLE
Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial
Hospital at Linkuo, Chang Gung University, Taoyuan, Taiwan
Received 7 April 2013; received in revised form 10 September 2013; accepted 28 October 2013
Available online 22 March 2014
KEYWORDS Background: Immunoglobulin E (IgE)-mediated food allergy, such as egg white allergy, is com-
Allergen component; mon in young children (<3 years old), but not all young children sensitive to egg white present
Egg white; with allergic symptoms. This study investigated the relationship between sensitization to egg
Sensitization white component allergens and clinical manifestations of allergic diseases in young children.
Methods: From March to December 2010, 2256 children with physician-diagnosed allergic
diseases were tested for serum levels of egg white, ovalbumin, and ovomucoid-specific
IgE in the Pediatric Allergy and Asthma Center of Chang Gung Memorial Hospital. Serum
was analyzed for specific IgE antibodies to egg white, ovalbumin, and ovomucoid by Immu-
noCAP (Phadia, Uppsala, Sweden). Allergen-specific IgE levels 0.35 kUA/L were defined as
positive.
Results: There was a significantly higher sensitization rate to egg white and its components
in children aged 2e4 years old. The sensitization rate to egg white, ovalbumin, and ovomu-
coid in this age group was 53.5%, 48.3%, and 37.2%, respectively, and the trend of the sensi-
tization decreased with age (p < 0.001). After adjusting for age, sensitization to egg white
and ovalbumin was associated with children with dermatitis [egg white: odds ratio
(OR) Z 1.28, 95% confidence intervals (CI) Z 1.03 e1.58, p < 0.05; ovalbumin:
OR Z 1.30, 95% CI Z 1.04e1.62, p < 0.05]. Children with ovomucoid sensitization had
no statistically significant risk among different groups in the current study.
Conclusion: Children aged 2e4 years old have higher sensitivity to egg white, ovalbumin,
and ovomucoid. Children with egg white and ovalbumin sensitization have a higher risk
for atopic dermatitis, and ovalbumin has a more important contribution. Furthermore,
* Corresponding author. Division of Pediatric Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital
at Linkuo and Chang Gung University, 5 Fu-Hsin Street, Taoyuan, Taiwan.
E-mail address: kwyeh@adm.cgmh.org.tw (K.-W. Yeh).
1684-1182/$36 Copyright 2014, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
http://dx.doi.org/10.1016/j.jmii.2014.01.002
Allergy to egg white components 113
we suggested that in children with atopic dermatitis, if they are aged 2e4 years old and are
having egg white and ovalbumin sensitization, avoiding eating raw or slightly heated eggs
might have a beneficial effect.
Copyright 2014, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is
an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).
Table 1 Distribution of different allergic diseases by sex, age, and sensitization to egg white allergens
Groups A B C D E F G All Any AS Any AR Any AD
Total 133 496 58 1077 37 270 185 2256 1432 2028 550
Male 78 303 35 656 20 152 106 1350 860 1217 313
(%) (58.6) (61.1) (60.3) (60.9) (54.1) (56.3) (57.3) (59.8) (60.1) (60) (56.9)
Female 55 193 23 421 17 118 79 906 572 811 237
(%) (41.4) (38.9) (39.7) (39.1) (45.9) (43.7) (42.7) (40.2) (39.9) (40) (43.1)
Age (y)
0e2 33 51 30 42 14 73 16 259 105 182 133
(%) (24.8) (10.3) (51.7) (3.9) (37.8) (27.0) (8.6) (11.5) (7.3) (9.0) (24.2)
2e4 44 154 16 340 19 89 73 734 475 655 197
(%) (33.1) (31.0) (27.6) (31.6) (51.4) (33.0) (39.5) (32.5) (33.2) (32.3) (35.8)
4e6 35 111 3 382 3 44 47 624 466 583 97
(%) (26.3) (22.4) (5.2) (35.5) (8.1) (16.3) (25.4) (27.6) (32.5) (28.7) (17.6)
6e9 15 71 3 201 1 33 20 345 238 326 57
(%) (11.3) (14.3) (5.2) (18.7) (2.7) (12.2) (10.8) (15.3) (16.6) (16.1) (10.4)
9e12 5 69 5 84 0 16 20 200 110 190 41
(%) (3.8) (13.9) (8.6) (7.8) (5.9) (10.8) (8.9) (7.7) (9.4) (7.5)
12e18 1 40 1 28 0 15 9 94 38 92 25
(%) (0.8) (8.1) (1.7) (2.6) (5.6) (4.9) (4.2) (2.7) (4.5) (4.5)
Allergen sensitization
Egg white 47 150 20 368 19 108 76 788 510 702 223
(%) (35.3) (30.2) (34.5) (34.2) (51.4) (40.0) (41.1) (34.9) (35.6) (34.6) (40.5)
Ovalbumin 43 137 17 298 18 96 67 676 426 598 198
(%) (32.3) (27.6) (29.3) (27.7) (48.6) (35.6) (36.2) (30) (29.7) (29.5) (36.0)
Ovomucoid 35 105 12 267 12 63 55 549 369 490 142
(%) (26.3) (21.2) (20.7) (24.8) (32.4) (23.3) (29.7) (24.3) (25.8) (24.2) (25.8)
Group A Z patients with asthma (AS) only; Group B Z patients with allergic rhinitis (AR) only; Group C Z patients with atopic dermatitis
(AD) only; Group D Z patients with both asthma and allergic rhinitis; Group E Z patients with both asthma and atopic dermatitis; Group
F Z patients with both atopic dermatitis and allergic rhinitis; Group G Z patients with asthma, atopic dermatitis, and allergic rhinitis
simultaneously.
diseases. Also most cases of allergic diseases were found in the mid-age range. These results are similar to those of
children aged 2e4 years. Moreover, children with atopic previous studies.8,18
dermatitis are most likely to be among the younger age Although it is a common allergen in infancy and chil-
group and those with allergic rhinitis are most likely to be dren, egg white sensitization decreased with age.19,20 Wan
among the older age group, while those with asthma are in et al 21 demonstrated that the prevalence of egg white
Table 2 Logistic regression analysis of the association of allergic diseases with sex, age, and sensitization to allergens
Groups A B C D E F G Any AS Any AR Any AD
Sex
Female 1.05 0.93 0.98 0.92 1.27 1.18 1.12 0.97 0.93 1.17
Age (y)
0e2 Ref. Ref. Ref. Ref. Ref. Ref. Ref. Ref. Ref. Ref.
2e4 0.47* 1.77 0.18* 4.72* 0.50 0.38* 1.79* 2.91* 3.75* 0.40*
4e6 0.44* 0.96 0.04* 8.70* 0.05* 0.21* 1.33 4.74* 6.55* 0.20*
6e9 0.34* 1.15 0.07* 7.71* 0.09* 0.30* 1.01 3.54* 7.14* 0.22*
9e12 0.19* 2.35* 0.21* 4.07* e 0.25* 1.83 1.98* 7.99* 0.29*
12e18 0.08* 3.07* 0.09* 2.25* e 0.51* 1.66 1.05 7.22* 0.38*
Allergen sensitization
Egg white 1.02 0.76* 0.98 0.94 1.99* 1.28 1.33 1.08 0.89 1.37*
Ovalbumin 1.13 0.87 0.97 0.82* 2.25* 1.34* 1.37 0.98 0.86 1.45*
Ovomucoid 1.11 0.79 0.80 1.03 1.49 0.93 1.34 1.21 0.88 1.10
*p < 0.05, by logistic regression.
Note: Group E had no individuals aged 9e18 years of age.
AD Z atopic dermatitis; AR Z allergic rhinitis; AS Z asthma.
116 Y.-T. Lin et al.
Table 3 Multivariate analysis of egg white component allergens and their association with allergic diseases
Groups A B C D E F G Any AS Any AR Any AD
Egg white OR 1.02 0.76* 0.98 0.94 1.99* 1.28 1.33 1.08 0.89 1.37*
Adjusted OR 0.87 0.86 0.87 0.95 1.34 1.23 1.30 1.03 1.05 1.28*
Ovalbumin OR 1.13 0.87 0.97 0.82* 2.25* 1.34* 1.37 0.98 0.86 1.45*
Adjusted OR 0.94 1.01 0.77 0.85 1.41 1.25 1.34 0.94 1.09 1.30*
Ovomucoid OR 1.11 0.79 0.80 1.03 1.49 0.93 1.34 1.21 0.88 1.10
Adjusted OR 1.05 0.87 0.88 0.97 1.23 0.95 1.29 1.10 0.88 1.09
*p < 0.05, by logistic regression.
AD Z atopic dermatitis; AR Z allergic rhinitis; AS Z asthma; OR Z odds ratio.
Allergy to egg white components 117
years of age had higher egg-specific IgE levels and egg- 2. Boyano Martinez T, Garcia-Ara C, Diaz-Pena JM, Munoz FM,
IgE/ovalbumin-IgG4. Furthermore, with any food allergy, Garcia Sanchez G, Esteban MM. Validity of specific IgE anti-
ovalbumin-IgG4 levels and ovalbumin-IgG4/egg-IgE are bodies in children with egg allergy. Clin Exp Allergy 2001;31:
lower than those of nonallergic, nonatopic individuals. 1464e9.
3. Hill DJ, Sporik R, Thorburn J, Hosking CS. The association of
IgG4 antibody is a marker of development of food toler-
atopic dermatitis in infancy with immunoglobulin E food
ance and IgG4 antibodies have been proposed to act as sensitization. J Pediatr 2000;137:475e9.
blocking antibodies by competing with IgE for allergen 4. Niggermann B, Sielaff B, Beyer K, Binder C, Wahn U. Outcome of
binding to IgE receptor expressing cells.24 By contrast, IL- double-blind, placebo-controlled food challenge tests in 107
10 secreted by inducible T regulatory cells increases IgG4 children with atopic dermatitis. Clin Exp Allergy 1999;29:91e9.
production but inhibits IgE production.25 It is proposed 5. Sampson HA, Scanlon SM. Natural history of food hypersensi-
that the titer of ovalbumin-IgG4 antibodies decreases but tivity in children with atopic dermatitis. J Pediatr 1989;115:
that of ovalbumin-IgE antibodies increases in atopic or 23e7.
allergic diseases. This hypothesis supports the results of 6. Uguz A, Lack G, Pumphrey R, Ewan P, Warner J, Dick J, et al.
the present study, that in children with atopic dermatitis, Allergic reactions in the community: a questionnaire survey of
members of the anaphylaxis campaign. Clin Exp Allergy 2005;
serum egg-white and ovalbumin-specific IgE levels are
35:746e50.
high. Tomicic et al26 also report that sensitized, eczem- 7. Kewalramani A, Bollinger ME. The impact of food allergy on
atous infants with high ratios of IgG4/IgE to ovalbumin at asthma. J Asthma Allergy 2010;3:65e74.
an early age are more likely to tolerate egg at 4.5 years 8. Ker J, Hartert TV. The atopic march: whats the evidence? Ann
than infants with low ratios. They also reveal that the Allergy Clin Immunol 2009;103:282e9.
ovalbumin-IgG4-to-IgE ratio can be used to predict the 9. Nickel R, Kulig M, Forster J, Bergmann R, Bauer CP, Lau S, et al.
development of egg tolerance later in life. Caubet et al27 Sensitization to hens egg at the age of twelve months in
also found that the combination of specific IgE and IgG4 is predictive for allergic sensitization to common indoor and
better than specific IgE alone in predicting reactivity to outdoor allergens at the age of three years. J Allergy Clin
baked egg. Immunol 1997;99:613e7.
10. Ricci G, Patrizi A, Baldi E, Menna G, Tabanelli M, Masi M. Long-
The heat and acid-stable characteristics of ovomucoid
term follow-up of atopic dermatitis: retrospective analysis of
can be used to predict the persistence of egg and/or baked related risk factors and association with concomitant allergic
egg allergies.13,14 However, the role of ovomucoid-specific diseases. J Am Acad Dermatol 2006;55:765e71.
IgE in atopic or allergic diseases is not fully known at pre- 11. Heine RG, Laske N, Hill DJ. The diagnosis and management of
sent. The results here show that ovomucoid sensitization egg allergy. Curr Allergy Asthma Rep 2006;6:145e52.
does not affect the possibility of having allergic diseases, 12. Cooke SK, Sampson HA. Allergenic properties of ovomucoid in
but implies that the association of egg sensitization with man. J Immunol 1997;159:2026e32.
atopic dermatitis is mainly due to ovalbumin, not 13. Jarvinen KM, Beyer K, Vila L, Bardina L, Mishoe M, Sampson HA.
ovomucoid. Specificity of IgE antibodies to sequential epitopes of hens egg
In children with allergic diseases in Taiwan, the positive ovomucoid as a marker for persistence of egg allergy. Allergy
2007;62:758e65.
rates of egg white, ovalbumin, and ovomucoid sensitization
14. Ando H, Moverare R, Kondo Y, Tsuge I, Tanaka A, Borres MP,
are highest in those aged 2e4 years. Children with egg et al. Utility of ovomucoid-specific IgE concentrations in pre-
white sensitization also have a high risk of having asthma dicting symptomatic egg allergy. J Allergy Clin Immunol 2008;
with atopic dermatitis, but not allergic rhinitis alone. 122:583e8.
Furthermore, children sensitized to ovalbumin are more 15. Joo K, Kato Y. Assessment of allergenic activity of a heat-
likely to have asthma with atopic dermatitis, atopic coagulated ovalbumin after in vivo digestion. Biosci Bio-
dermatitis with allergic rhinitis, or atopic dermatitis, but technol Biochem 2006;70:591e7.
are less likely to have asthma with allergic rhinitis. After 16. Perez-Calderon R, Gonzalo-Garijo MA, Lamilla-Yerga A, Man-
controlling for confounding factors, children with egg white gas-Santos R, Moreno-Gasto n I. Recurrent angioedema due to
and ovalbumin sensitization are still more likely to have lysozyme allergy. J Investig Allergol Clin Immunol 2007;17:
264e6.
atopic dermatitis. Children with ovomucoid sensitization
17. Everberg H, Brostedt P, Oman H, Bohman S, Move rare R. Af-
had no statistically significant risk among different allergic finity purification of egg-white allergens for improved
disease groups. Furthermore, we suggested that in children component-resolved diagnostics. Int Arch Allergy Immunol
with atopic dermatitis, if they are aged 2e4 years old and 2011;154:33e41.
are having egg white and ovalbumin sensitization, avoiding 18. Zheng T, Yu J, Oh MH, Zhu Z. The atopic march: progression
eating raw or slightly heated egg might have a beneficial from atopic dermatitis to allergic rhinitis and asthma. Allergy
effect. Asthma Immunol Res 2011;3:67e73.
19. Soderstro
m L, Lilja G, Borres MP, Nilsson C. An explorative
study of low levels of allergen-specific IgE and clinical allergy
Conflicts of interest symptoms during early childhood. Allergy 2011;66:1058e64.
20. Wahn U, Warner J, Simons FE, de Benedictis FM, Diepgen TL,
All authors declare no conflicts of interest in this study. Naspitz CK, et al. IgE antibody responses in young children with
atopic dermatitis. Pediatric Allergy Immunol 2008;19:332e6.
21. Wan KS, Yang W, Wu WF. A survey of serum specific-lgE to
References common allergens in primary school children of Taipei City.
Asian Pac J Allergy Immunol 2010;28:1e6.
1. Eggesbo M, Botten G, Halvorsen R, Magnus P. The prevalence of 22. Gaffin JM, Sheehan WJ, Morrill J, Cinar M, Borras Coughlin IM,
allergy to egg: a population-based study in young children. Sawicki GS, et al. Tree nut allergy, egg allergy, and asthma in
Allergy 2001;56:403e11. children. Clin Pediatr (Phila) 2011;50:133e9.
118 Y.-T. Lin et al.
23. Kukkonen AK, Savilahti EM, Haahtela T, Savilahti E, Kuitunen M. 26. Tomicic S, Norrman G, Fa lth-Magnusson K, Jenmalm MC,
Ovalbumin-specific immunoglobulins A and G levels at age 2 Devenney I, Bottcher MF. High levels of IgG4 antibodies to
years are associated with the occurrence of atopic disorders. foods during infancy are associated with tolerance to corre-
Clin Exp Allergy 2011;41:1414e21. sponding foods later in life. Pediatr Allergy Immunol 2009;20:
24. Uermo si C, Beerli RR, Bauer M, Manolova V, Dietmeier K, 35e41.
Buser RB, et al. Mechanisms of allergen-specific desensitiza- 27. Caubet JC, Bencharitiwong R, Moshier E, Godbold JH,
tion. J Allergy Clin Immunol 2010;126:375e83. Sampson HA, Nowak-We grzyn A. Significance of ovomucoid-
25. Till SJ, Francis JN, Nouri-Aria K, Durham SR. Mechanisms of and ovalbumin-specific IgE/IgG(4) ratios in egg allergy. J Al-
immunotherapy. J Allergy Clin Immunol 2004;113:1025e34. lergy Clin Immunol 2012;129:739e47.