Translate this page into:
Allergen-specific immunoglobulin E in Vietnamese children with atopic dermatitis
Corresponding author: Dr. Hien Thi Thu Do, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; Hanoi Medical University, Hanoi, Vietnam; Vietnam National University, Hanoi, University of Medicine and Pharmacy. hienphuonglinh@yahoo.com
-
Received: ,
Accepted: ,
How to cite this article: Do HTT, Luong TTM, Ziersch A, Doanh LH. Allergen-specific immunoglobulin E in Vietnamese children with atopic dermatitis. Indian J Dermatol Venereol Leprol. doi: 10.25259/IJDVL_570_2025
Abstract
Background
In atopic dermatitis (AD), allergen-specific IgE (sIgE) antibodies is considered to play an important role in the disease’s pathogenesis and could be used to identify triggers. However, the association between sIgE and clinical and sub-clinical characteristics of AD varies according to different allergens and different countries.
Aim
This study aims to assess sIgE antibodies and their association with clinical and sub-clinical characteristics of Vietnamese children with AD.
Methods
This descriptive cross-sectional study was conducted among 160 children aged 2 to 12 years old, diagnosed with AD based on Hanifin and Rajka’s criteria. sIgE antibodies were measured by the EUROLINE Immunoblot test.
Results
sIgE positivity to at least one allergen was detected in 119 out of 160 (74.4%) children. The top two positive allergens were food allergens (88/160, 55%), and house dust mite allergens (64/160, 40%). sIgE antibodies were more often positive in children with a high tIgE level (p=<0.001), children with a family history of atopic diseases (p=<0.001), and children with moderate and severe AD (p=0.037). sIgE positivity to food allergens was more common in children in the younger age group than children in the middle and oldest age groups (p=<0.001), while sIgE positivity to house dust mite allergens was more common in children in the older age group (p=0.025). Food allergens were more often positive with moderate and severe AD (p=0.01).
Limitations
The participants did not represent all children with AD attending the National Hospital of Dermatology and Venereology, as we used a convenience sample and excluded those whose parents/guardians declined to participate. In addition, some information, such as medical history, was only obtained from the parent/guardian report. This information may lack reliability.
Conclusions
Given the high incidence of sIgE antibody positivity and its association with family history of atopic diseases, age, disease severity, and tIgE in Vietnamese children with AD, it would be worthwhile to assess allergen-specific IgE antibodies when there is clinical suspicion of an allergen trigger to advise on allergen avoidance for preventing the exacerbation of AD.
Keywords
Allergen-specific IgE
atopic dermatitis
Vietnamese children
Introduction
Atopic dermatitis (AD) is a recurrent, chronic inflammatory skin disease, most common in children and affecting 15% to 25% of children worldwide.1,2 Patients with AD often suffer from other atopic diseases such as food allergies, allergic rhinitis, and asthma.1,2 The pathogenesis of the disease includes defects in skin barrier function, disturbances in cell-mediated immune response, and disturbances of IgE immune response. In AD, Th2 activation of B-cells leads to an increase in IgE production, which mediates subsequent hypersensitivity reactions upon antigen exposure.3,4 However, total serum IgE (tIgE) only indicates that the patient is having an allergic reaction without identifying the specific allergen. Many AD patients have low levels of IgE. This emphasises the importance of considering specific IgE (sIgE) rather than total IgE, despite the positive correlation between them.5
While many studies have demonstrated an association between tIgE level and the severity of AD,5,6 the association between sIgE and clinical and sub-clinical characteristics of AD varies according to different allergens and different countries. For example, a significantly higher prevalence of food sensitisation was observed in children with moderate to severe AD than in children with mild AD in a study by Moghtaderi, involving 90 children with AD aged from 2 to 48 months in Iran. Schäfer’s study of 2,201 schoolchildren aged from 5 to 14 years in Eastern Germany demonstrated a significant correlation between sIgE positivity to house dust mite and cat allergens and AD severity score.7,8 Mavroudi et al. conducted a study in Greece, involving 88 children with AD, aged 3 months to 7 years, and reported a prevalence of 26.13% and 80% for food sensitisation detected by Oral Food Challenges (OFCs) and by high sIgE levels, respectively.9 High sIgE levels have not been found to be more prevalent among children with severe AD, nor among those with food sensitisation detected by OFCs.9 Another study by Yu and Li, including 154 AD patients of all ages in China from 2019 to 2021, found that infants and children with AD showed significantly higher frequencies of positive sIgE to food allergens; however, adolescents and adults showed significantly higher frequencies of positive sIgE to inhaled allergens.6
In Vietnam, so far, there has been no research investigating this issue in children with AD. Therefore, this study aimed to assess positivity to sIgE antibodies and their association with clinical and sub-clinical characteristics of Vietnamese children with AD.
Methods
Study design and population
The study design was a descriptive cross-sectional study. Every parent/guardian of each child with AD at the Examination Department of the National Hospital of Dermatology and Venereology from September 2022 to August 2023 was asked to participate in the study by answering the questionnaire and agreeing to do the sIgE test. Approximately 90% of them agreed to join the study. The final study population included 160 children aged 2 to 12 years old, diagnosed with AD based on the 1980 Hanifin and Rajka’s criteria, and with parental /guardian consent for participation.
Questionnaire and dermatological examination
The study’s set of questionnaires was answered by parents/guardians and included: demographic characteristics, medical history, atopic history (allergic rhinitis and asthma), allergy history, and family history. The children also received a dermatological examination. AD severity was assessed using the Scoring Atopic Dermatitis (SCORAD) tool, graded as follows: mild AD (SCORAD <25); moderate AD (25 ≤ SCORAD <50); and severe AD (SCORAD ≥50).10
Laboratory tests
A blood sample was taken for IgE testing by the EUROLINE Immunoblot test of 53 allergens. We selected 28 common allergens in Vietnam to analyse the results and divided them into five subgroups. The food allergen group included 17 allergens: egg white, egg yolk, shrimp, soybeans, corn, peanuts, cow’s milk, chocolate, tomatoes, lemons, oranges, strawberries, apples, pineapples, pork, beef, and chicken. The house dust mite allergen group included three allergens: Dermatophagoides pter, Dermatophagoides farinae, and Blomia tropicalis. The insect allergen group included three allergens: fire ants, mosquitoes, and cockroaches. The next group only included cats and dogs. The remaining allergen group included thrree allergens: rubber resin, C. albicans, and chicken feathers. A test value above 0.35 kUA/L was interpreted as positive.
Total IgE was quantified by Roche-Cobas E411 tester, based on the electrochemical principle of luminescence ECLIA (COBAS Esystem format). tIgE level varies according to age and is considered elevated when it is ≥ 60 IU/mL (2-5 years old), ≥ 90 IU/mL (6-9 years old), ≥ 200 IU/mL (10-12 years old).
Statistical analysis
The data were analysed using SPSS 22.0. Descriptive statistics were applied based on data type. Categorical variables, including age group, disease severity, family history of atopic diseases, allergy history, sIgE, and tIgE level, were summarised using frequencies and percentages. Associations between variables were evaluated using Pearson’s chi-square or Fisher’s exact test. Parametric (Student t-test or ANOVA) and nonparametric tests (Mann-Whitney U test or Kruskal-Wallis) were performed after testing for normality using the Kolmogorov-Smirnov test. The threshold of statistical significance was set at P < 0.05.
The study was approved by the National Hospital of Dermatology and Venereology. Written informed consent was obtained from parents or legal guardians of all participants.
Results
Clinical features of patients
The patient characteristics have been described in Table 1, and AD severity by age group has been described in Table 2.
| Patient characteristics | n | % | |
|---|---|---|---|
| Age Group (years) | 2-5 | 71 | 44.4 |
| 6-9 | 58 | 36.3 | |
| 10-12 | 31 | 19.3 | |
| Severity of disease (SCORAD) | Mild | 46 | 28.7 |
| Moderate to severe | 114 | 71.3 | |
| Allergy history | No | 140 | 87.5 |
| Yes | 20 | 12.5 | |
| Family history of atopic diseases | No | 83 | 51.9 |
| Yes | 77 | 48.1 | |
|
AD severity Age group |
2-5 years | 6-9 years | 10-12 years | |||
|---|---|---|---|---|---|---|
| n | % | n | % | n | % | |
| Mild | 12 | 16.9 | 23 | 39.7 | 11 | 35.5 |
| Moderate to severe | 59 | 83.1 | 35 | 60.3 | 20 | 64.5 |
| Total | 71 | 100 | 58 | 100 | 31 | 100 |
In our study, 77 out of 160 children (48.1%) reported a family history of atopic diseases, including asthma, allergic rhinitis, or AD. As reported by parents/guardians, 140 children (87.5%) had no history of allergies, and 20 (12.5%) had a history of allergies. Food allergy was reported in 11 (6.9%), followed by house dust mite allergy in 8 (5%) and antibiotic allergy in 1 (0.6%). Four types of allergic reactions were reported by parents/guardians of children. This history included itching (13/20, 65%), eczema reaction (10/20, 50%), urticaria (7/20, 35%), and angioedema (1/20, 5%).
sIgE antibodies in children with AD
In terms of testing antibodies, 119/160 children (74.4%) were positive to at least one allergen. Food sensitivity was discovered in 88/160 children (55.0%), followed by dust mite sensitivity (64/160 children, 40%), insect sensitivity (30/160 children, 18.8%), dog and cat sensitivity (16/160 children, 10%), and the remaining allergens (4, 4%).
Five individual allergens with the highest specific IgE positive rate were D. farinae (58/160, 36.3%), followed by D. pter (53/160, 33.1%), egg whites (52/160, 32.5%), cow’s milk (36/160, 22.5%), and B. tropicalis (31/160, 19.4%).
The association between sIgE positivity and clinical, sub-clinical characteristics of children with AD
There was a significant relationship between age group and IgE positivity to food allergens, with the youngest group having a higher proportion than children in the middle and oldest age groups (χ2=17.215, df=2, p=<.001) [Figure 1].
- Relationship between positivity to food allergens and the age group of children with AD.
There was a higher proportion of children in the older age group with IgE positivity to house dust mite allergens than children in the middle and youngest age groups (χ2=7.339, df=2, p=0.025) [Figure 2].
- Relationship between house dust mite allergen positivity and the age group of children with AD.
Children with a family history of atopic diseases showed 1.3 times higher IgE positivity to at least one allergen than those without a family history of atopic diseases (χ2=10.014, df=1, p=0.002) [Table 3].
| Family history of atopic diseases | sIgE to at least one allergen | Total n (%) | |
|---|---|---|---|
| Negative n (%) | Positive n (%) | ||
| No | 30 (36,1) | 53 (63,9) | 83 (100) |
| Yes | 11 (14,3) | 66 (85,7) | 77 (100) |
| p | 0.002 | ||
Among 20 patients with reported history of allergies, the EUROLINE Immunoblot test discovered only nine who were positive to one or more allergens. Seven of them were positive to dust mites, one was positive to shrimp, and one was positive to pineapple.
Children with moderate and severe AD had 1.3 times higher IgE positivity to at least one allergen than children with mild AD (χ2=4.350, df=1, p=0.037) [Table 4]. Children with moderate and severe AD had a proportion of IgE positivity to food allergens 1.6 times higher than children with mild AD (χ2=6.569, df=1, p=0.01). We found no significant association between IgE positivity to other groups of allergens, such as house dust mite allergen, and the severity of the disease (p>0.05).
| IgE positivity to at least one allergen | Severity of disease (SCORAD) | p | ||
|---|---|---|---|---|
| Mild n (%) | Moderate/severe n (%) | |||
| sIgE to at least one allergen | Negative n (%) | 17 (37) | 24 (21.1) | 0.037* |
| Positive n (%) | 29 (63) | 90 (78.9) | ||
| Total n (%) | 46 (100) | 114 (100) | ||
| sIgE to food allergens | Negative n (%) | 28 (60.9) | 44 (38.6) | 0.010* |
| Positive n (%) | 18 (39.1) | 70 (61.4) | ||
| Total n (%) | 46 (100) | 114 (100) | ||
| sIgE to house dust mite allergens | Negative n (%) | 29 (63) | 67 (58.8) | 0.618 |
| Positive n (%) | 17 (37) | 47 (41.2) | ||
| Total n (%) | 46 (100) | 114 (100) | ||
p<0.05; chi-square test.
There were more than 1.6 times as many children with high total IgE levels who had IgE positivity to at least one allergen than children with normal total IgE levels, and this difference was statistically significant (χ2=13.593, df=1, p<0.001) [Table 5].
| tIgE | sIgE | Total | |
|---|---|---|---|
| Negative n (%) | Positive n (%) | ||
| Normal | 16 (45.7) | 19 (54.3) | 35 (100) |
| High | 16 (15.4) | 88 (84.6) | 104 (100) |
| p | <0.001* | ||
p<0.05; chi-square test.
Discussion
In our study, 74.4% of children had IgE positivity with at least one allergen. However, only 12.5% were reported with an allergy history by parents/guardians. Similarly, a study by Yu and Li found that only 12% patients reported definite correlation of clinical food allergy with food IgE positivity; and while the most common food allergens detected by elevated sIgE levels were egg, cow milk, and wheat, the most common food allergens reported by AD patients was seafood, including crab, shrimp, and fish.6 In addition, Mavroudi et al. found food sensitisation in only 26.13% of children with AD when detected by OFCs, whereas the prevalence detected by high sIgE levels was almost 80%.9 Food sensitisation detected by sIgE levels was almost 3 or 6 times higher than that detected by OFCs or by reported allergy history, respectively. This may be explained by the fact that a later type of allergy reaction, such as the onset of AD exacerbations 6 to 48 hours after exposure to allergens, may be quite difficult for parents/guardians to recognise.
The literature showed differences between sensitivity (ranging from 60-95%) and specificity (ranging from 30-95%) of the specific IgE test, depending upon the type of allergen and the age of the patient.11 The 74.4% IgE positivity to any allergen in our study is lower than the 90.6% positivity rate reported in Bonyadi’s study, which was conducted in Iran, where the mean age of the participants was 30.2 ± 14.7 years.12 This discrepancy may be due to differences in race/ethnicity and patients’ age range, which in our study was limited to children aged 2-12 years, as well as differences in the test kit used.
The two allergen groups more often positive in our study were food allergens (55%) and house dust mite allergens (40%). Among these, the five allergens with the highest positivity rates were D. farinae, D. pter, egg white, cow’s milk, and B. tropicalis. A study by Yu and Li found that the most common food allergens with elevated sIgE levels were egg (71%), cow milk (39%), and wheat (32%).6 In addition, studies by Emran et al (2019) and Beltrani (2003) found similar positive rates in patients of all ages with AD for these three types of house dust mites.13,14 Although the literature shows a variety of specific food allergen positivity in patients with AD across countries, egg whites and cow’s milk were the two most common food allergens.9,15,16
In our study, children in the younger age group had a higher proportion of IgE positivity to food allergens than children in the middle and oldest age groups, and children in the older age group had a higher proportion of IgE positivity to the house dust mite allergens than children in the middle and youngest age groups. This finding is consistent with studies by Bonyadi and Guillet, which suggests that as children age, they tend to show a gradual decrease in susceptibility to food allergens and an increase in susceptibility to aeroallergens.12,17
Our study recorded no patients with asthma or allergic rhinitis based on medical history reported by parents/guardians. This is in contrast to Lee’s study, conducted among children with AD in elementary schools in South Korea, using a questionnaire filled in by paediatricians, which found that children with AD over the age of 6 were at higher risk for asthma and allergic rhinitis.18 This difference could be attributed to a limitation of our study in relying on the reports by parents/guardians.
A family history of atopic diseases was reported in 48.1% of children with AD in our study, and this rate ranged from 46% to 70% in other studies.4,19 We also found that children with a history of atopic diseases were more often positive to any allergen than those without. This finding aligns with the study’s result by Fang et al.20 The literature found that the most important risk factors for AD include mutations in the FLG gene and a family history of atopic diseases, such as AD, allergic rhinitis, and asthma.21 Although these are distinct diseases, they share a number of regulatory genes, referred to as the “multi-directional” effect, such as 29 common genes between asthma and AD, 27 shared genes between allergic rhinitis and AD, and 22 identical genes between food allergies and AD.22 The risk of children developing AD is 2 to 3 times higher if one parent has an atopic disease, and 3 to 5 times higher if both parents have atopic diseases.21
Our study found that children with moderate and severe AD had the proportion of IgE positivity to any allergen 1.3 times higher and IgE positivity to food allergen 1.6 times higher than that proportion of children with mild AD, which is consistent with findings by Guillet and Kiiski.17,23 We observed no significant association between IgE positivity to other groups of allergens and the severity of the disease. This does not align with studies by Čelakovská’s and Mitterman, who found the association between IgE positivity to aeroallergens and disease severity in adult patients with AD.24,25 The difference could be explained by the variations in patients’ age range, which in our study was limited to children aged 2-12 years old. On the other hand, Mavroudi et al. reported no association between food sensitisation, whether detected by OFCs or specific IgE levels, and AD severity.9 Therefore, although sIgE positivity in AD is a marker of atopic sensitisation and broadly indicates an IgE-mediated immune response, the relationship between sIgE levels and AD severity remains inconsistent across studies and requires careful clinical interpretation.
Children with high total IgE levels in our study had a higher proportion of IgE positivity to any allergen than children with normal total IgE levels. This is consistent with literature by Ohman and Wong.26,27
This is the first study in Vietnam to consider the relationship between specific allergen IgE and the clinical and subclinical characteristics of children with AD. A limitation of our study is that the participants did not represent all children with AD attending the NHDV, as we used a convenience sample and excluded those whose parents/guardians declined participation. In addition, some information, such as medical history, atopic history, allergy history, and family history, was only obtained from the parent/guardian reports, which may lack reliability.
Limitations
The participants did not represent all children with AD attending the National Hospital of Dermatology and Venereology, as we used a convenience sample and excluded those whose parents/guardians declined to participate. In addition, some information, such as medical history, was only obtained from the parent/guardian report. This information may lack reliability.
Conclusion
Given the high incidence of specific IgE antibody positivity and its association with family history of atopic diseases, age, disease severity, and tIgE in Vietnamese children with AD, it would be worthwhile to assess sIgE antibodies when there is clinical suspicion of an allergen trigger, and subsequently to advise patients to avoid the allergen for preventing the exacerbation of AD.
Ethical approval
The research/study was approved by the Institutional Review Board at Vietnam National Hospital of Dermatology & Venereology, number 71/HDDD-BVDLTW, dated 01/09/2022.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
References
- The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. J Allergy Clin Immunol. 2004;113:925-31.
- [CrossRef] [PubMed] [Google Scholar]
- Natural history and risk factors of atopic dermatitis in children. Allergy Asthma Immunol Res. 2015;7:101-5.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Atopic dermatitis; Etio-pathogenesis, an overview. Indian J Dermatol. 2015;60:327-31.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Role of IgE in atopic dermatitis. Curr Opin Immunol. 1993;5:956-62.
- [CrossRef] [PubMed] [Google Scholar]
- Targeting immunoglobulin E in atopic dermatitis: A review of the existing evidence. World Allergy Organ J. 2021;14:100519.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- A Multi-centre analysis of serum IgE levels in atopic dermatitis. Indian J Dermatol. 2024;69:486.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Specific IgE to common food allergens in children with atopic dermatitis. Iran J Immunol. 2012;9:32-8.
- [PubMed] [Google Scholar]
- Association between severity of atopic eczema and degree of sensitization to aeroallergens in school children. J Allergy Clin Immunol. 1999;104:1280-4.
- [CrossRef] [PubMed] [Google Scholar]
- Assessment of IgE-mediated food allergies in children with atopic dermatitis. Allergol Immunopathol (Madr). 2017;45:77-81.
- [CrossRef] [PubMed] [Google Scholar]
- Practical issues on interpretation of scoring atopic dermatitis: SCORAD Index, objective SCORAD, patient-oriented SCORAD and three-item severity score. Curr Probl Dermatol. 2011;41:149-55.
- [CrossRef] [PubMed] [Google Scholar]
- Allergy blood testing: A practical guide for clinicians. Cleve Clin J Med. 2011;78:585-92.
- [CrossRef] [PubMed] [Google Scholar]
- Assessment of allergen-specific IgE by immunoblotting method in atopic dermatitis. Eur Ann Allergy Clin Immunol. 2017;49:213-9.
- [CrossRef] [PubMed] [Google Scholar]
- House dust mite sensitisation and association with atopic dermatitis in Brunei. Clin Transl Allergy. 2019;9:65.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- The role of house dust mites and other aeroallergens in atopic dermatitis. Clin Dermatol. 2003;21:177-82.
- [CrossRef] [PubMed] [Google Scholar]
- The allergic sensitization in infants with atopic eczema from different countries. Allergy. 2009;64:295-303.
- [CrossRef] [PubMed] [Google Scholar]
- IgE antibody responses in young children with atopic dermatitis. Pediatr Allergy Immunol. 2008;19:332-6.
- [CrossRef] [PubMed] [Google Scholar]
- Natural history of sensitizations in atopic dermatitis A 3-year follow-up in 250 children: Food allergy and high risk of respiratory symptoms. Arch Dermatol. 1992;128:187-92.
- [CrossRef] [PubMed] [Google Scholar]
- Comparison of prevalence and risk factors of atopic dermatitis by physical examination and questionnaire survey in elementary school children. Pediatr Allergy Respir Dis. 2011;21:186.
- [CrossRef] [Google Scholar]
- Guidelines of care for the management of atopic dermatitis. J Am Acad Dermatol. 2014;70:338-51.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Trends in the contributions of atopic family history to pediatric food sensitization and allergy. Front Pediatr. 2022;10
- [CrossRef] [Google Scholar]
- Resolving the etiology of atopic disorders by genetic analysis of racial ancestry. J Allergy Clin Immunol. 2016;138:676-99.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- High serum total IgE predicts poor long-term outcome in atopic dermatitis. Acta Derm Venerol. 2015;95:943-7.
- [CrossRef] [PubMed] [Google Scholar]
- Severity of atopic dermatitis in relation to food and inhalant allergy in adults and adolescents. Food Agric Immunol. 2017;28:121-33.
- [Google Scholar]
- IgE Sensitization profiles differ between adult patients with severe and moderate atopic dermatitis. PLoS ONE. 2016;11:e0156077.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Allergen-specific IgE in atopic dermatitis. Acta Derm Venereol. 1974;54:283-90.
- [CrossRef] [PubMed] [Google Scholar]
- Longitudinal analysis of total serum IgE levels with allergen sensitization and atopic diseases in early childhood. Sci Rep. 2020;10:21278.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]