The distribution patterns and clinical significance of serum immunoglobulin E in children with chalazion in Hubei, China
Highlight box
Key findings
• Children with high level of total immunoglobulin E (IgE) and more positive allergens-specific IgE associate with more severe stage of chalazia.
What is known and what is new?
• According to previous studies, bacterial and/or demodex infection is a risk factor for chalazia.
• High level of IgE maybe a risk factor for chalazia.
What is the implication, and what should change now?
• Reducing allergen exposure and anti-allergic treatment may be helpful for children with chalazion.
Introduction
Chalazion is a chronic inflammation of eyelid and palpebral conjunctiva associated with blockage and swelling of meibomian gland, which can develop limited, painless, red and swollen mass (1). Chalazion is common in children with incidence rate of 1.7% to 4.3% (2), and can be cosmetically disfiguring. Severe cases can lead to ptosis and astigmatism. According to a previous study, bacterial and/or demodex infection is a risk factor for chalazia (3), which can also lead to allergic reaction or immune cross-reaction. Meanwhile, it is well-known that allergic ocular disease is associated with immunoglobulin E (IgE)-mediated conjunctival or eyelid inflammation or chalazia (4). The ophthalmic manifestations of the hyper-IgE syndrome also include recurrent chalazia. A previous study showed that history of allergies was associated with chalazion risk (5). The serum total IgE (T-IgE) level and specific IgE (sIgE) test are common allergic indicators. To investigate the potential correlation between chalazion and allergic inflammation, we compared the distribution patterns of allergens-sIgE between chalazia and allergic conjunctivitis (AC) (seasonal or perennial AC). Moreover, the correlation between serum T-IgE, allergens-sIgE, and stages of chalazia was analyzed. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2024-565/rc).
Methods
Subjects
A total of 224 children with chalazia from June 2020 to December 2021 at Wuhan Children’s Hospital were enrolled in the retrospective cross-sectional study. Data of the serum food and inhaled allergens-sIgE antibody of 157 children with AC (seasonal or perennial AC) during the same period were collected. Patients who had been treated with corticosteroids, immunosuppressants, or antihistamines within 1 week were excluded (6). Of the 224 chalazia children, 98 (43.8%) were males. The average age was 3.5±2.0 years (range, 0.5 to 11.2 years). All the participants were divided into two groups, including preschool children (<6 years) and school children (6–12 years). This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and was approved by the Institutional Ethics Committee of Wuhan Children’s Hospital (No. 2021R162). Informed consent was obtained from the patients’ legal guardians or parents.
Study methods
All the participants underwent blood tests including serum T-IgE, serum sIgE. According to the clinical symptoms and signs, children with chalazion were classified into four stages (7). Stage I (early of the disease) was defined as painless, soft, single mass in eyelid with conjunctival congestion. Stage II (granulomatous phase) was defined that conjunctival polypus or hard, multiple mass in eyelid developed. Pus points or pressing pain occurred in stage III (concurrent infection). In stage IV (late of the disease), the red and swollen mass of the skin spontaneously burst with pus overflowed.
The serum T-IgE and serum sIgE was quantitative detected by enzyme-linked immunosorbent assays (allergen-sIgE antibody reagent kit from HOB Biotech Group, Suzhou, China). There were 10 food allergens (peanut, soy, milk, crab, shrimp, egg, beef, codfish, wheat flour, and mutton) and 10 inhaled allergens (Dermatophagoides pteronyssinus, Dermatophagoides farina, epithelial materials of cats, epithelial materials of dogs, house dust, cockroach, Alternaria alternate, willow, ragweed, and mugwort). The range of the serum T-IgE was 0 to 60 IU/mL. It was considered negative if serum T-IgE was less than 60 IU/mL. The lower limits of detection were 0.35 IU/mL for serum allergen-sIgE. Any type of allergen-sIgE (<0.35 IU/mL) was considered negative. Moreover, according to the value of serum allergen-sIgE, any single food or inhaled allergens were classified to seven grades (grade 0, <0.35 IU/mL; grade 1, 0.35–0.70 IU/mL; grade 2, 0.71–3.50 IU/mL; grade 3, 3.51–17.50 IU/mL; grade 4, 17.51–50.0 IU/mL; grade 5, 50.01–100.0 IU/mL; grade 6, >100.0 IU/mL). The degree of allergic reaction increased with grade of the allergens.
Statistical analysis
All statistical data were analyzed using SPSS software, version 20.0 (SPSS Inc.). The continuous variables were expressed as means and ranges if the data were normally distributed. Categorical data were represented by percentages and counts which were compared by Chi-squared (χ2) test or Fisher’s exact test. Spearman test was used for correlation analysis between two rank statistical variables. A two-tailed P<0.05 was considered statistically significant.
Results
The characteristics of distribution patterns of serum sIgE between chalazion and AC in children
The data of distribution features of serum food and inhaled allergens between chalazion and IgE-mediated AC during the same period on the same baseline in children are summarized in Table 1. As shown in Table 1, the most common allergens-sIgE in children with chalazia were milk [118 (52.7%)], egg [85 (37.9%)], and Dermatophagoides farina [24 (10.7%)]. None of the children was sensitive to soy and mutton. Compared to AC, the positive rate of nine kinds of allergens-sIgE was lower in pediatric patients with chalazion, including soy (0.0% vs. 5.7%, P=0.001), crab (0.9% vs. 6.4%, P=0.007), shrimp (0.4% vs. 6.4%, P=0.002), codfish (0.4% vs. 3.8%, P=0.04), wheat flour (6.7% vs. 13.4%, P=0.03), Dermatophagoides pteronyssinus (9.8% vs. 24.2%, P<0.001), Dermatophagoides farina (10.7% vs. 36.3%, P<0.001), house dust (8.0% vs. 28.7%, P=0.005), and Alternaria alternate (2.2% vs. 15.9%, P<0.001). However, the positive rate of epithelial materials of dogs was higher in chalazia children than that of children with AC (9.4% vs. 0.6%, P=0.001). As for other allergens, there was no statistically difference.
Table 1
| Variables¶ | Chalazion (n=224) | Seasonal or perennial AC (n=157) | t/χ2 value | P value |
|---|---|---|---|---|
| Age (years) | 3.5±2.0 | 3.7±1.1 | −1.238 | 0.22† |
| Male | 98 (43.8) | 78 (49.7) | 1.307 | 0.25‡ |
| Food allergen | ||||
| Peanut | 1 (0.4) | 4 (2.5) | 1.734 | 0.19‡ |
| Soy | 0 | 9 (5.7) | – | 0.001§* |
| Milk | 118 (52.7) | 92 (58.6) | 1.308 | 0.25‡ |
| Crab | 2 (0.9) | 10 (6.4) | 7.369 | 0.007‡* |
| Shrimp | 1 (0.4) | 10 (6.4) | 9.534 | 0.002‡* |
| Eggs | 85 (37.9) | 67 (42.7) | 0.861 | 0.35‡ |
| Beef | 1 (0.4) | 1 (0.6) | 0.063 | 0.80‡ |
| Codfish | 1 (0.4) | 6 (3.8) | 4.109 | 0.04‡* |
| Wheat flour | 15 (6.7) | 21 (13.4) | 4.813 | 0.03‡* |
| Mutton | 0 | 0 | – | – |
| Inhaled allergen | ||||
| Dermatophagoides pteronyssinus | 22 (9.8) | 38 (24.2) | 14.391 | <0.001‡* |
| Dermatophagoides farinae | 24 (10.7) | 57 (36.3) | 36.112 | <0.001‡* |
| Epithelial materials of cats | 1 (0.4) | 4 (2.5) | 1.734 | 0.19‡ |
| Epithelial materials of dogs | 21 (9.4) | 1 (0.6) | 11.397 | 0.001‡* |
| House dust | 18 (8.0) | 45 (28.7) | 28.455 | 0.005‡* |
| Cockroach | 4 (1.8) | 1 (0.6) | 0.263 | 0.61‡ |
| Alternaria alternate | 5 (2.2) | 25 (15.9) | 23.853 | <0.001‡* |
| Willow | 3 (1.3) | 1 (0.6) | 0.023 | 0.88‡ |
| Ragweed | 2 (0.9) | 2 (1.3) | <0.01 | >0.99‡ |
| Mugwort | 12 (5.4) | 2 (1.3) | 3.271 | 0.07‡ |
Data are presented as mean ± standard deviation or n (%). †, independent-sample t-test (the data of both groups were in accordance with the normal distribution). ‡, Chi-squared test. §, Fisher exact probability test. ¶, the lower limits of detection were 0.35 IU/mL for serum allergen-sIgE. Any type of allergen-sIgE (≥0.35 IU/mL) was considered positive. *, P<0.05. AC, allergic conjunctivitis; sIgE, specific immunoglobulin E.
The characteristics of positive rate of food or inhaled allergens in different age groups in chalazia children
The comparison on positive rate of food or inhaled allergens between preschool age group and school age group in chalazia children is analyzed in Table 2. In Table 2, it was obvious that the positive rate of food allergens in preschool children (71.4%) was higher than that in school children (50.0%) (P=0.008). However, there was no statistically difference between the two groups on the positive rate of inhaled allergens.
Table 2
| The serum food and inhaled allergens | Preschool age (<6 years) (n=182) | School age (6–12 years) (n=42) | χ2 value | P value |
|---|---|---|---|---|
| The positive rate of food allergens | 130 (71.4) | 21 (50.0) | 7.133 | 0.008†* |
| The positive rate of inhaled allergens | 54 (29.7) | 13 (31.0) | 0.027 | 0.87† |
Data are presented as n (%). †, Chi-squared test. *, P<0.05. sIgE, specific immunoglobulin E.
The correlation between serum T-IgE level, sIgE, and the stages of disease in chalazia children
The correlation between serum T-IgE level, sIgE, and the stages of chalazion among pediatric patients is analyzed in Table 3 and Figure 1. Table 3 showed that the numbers of positive allergens and the grade of allergens had a positively correlation with the stages of disease in children, respectively (R=0.269, 0.245, P<0.001). Furthermore, there was also a positive correlation between the value of serum T-IgE and the stages of chalazion in children (R=0.238, P=0.001) (as in Figure 1).
Table 3
| The serum specific food and inhaled allergens | Stage I (n=33) | Stage II (n=97) | Stage III (n=73) | Stage IV (n=21) | R value | P value |
|---|---|---|---|---|---|---|
| The number of positive food and inhaled allergens | 0.269 | <0.001†* | ||||
| T ≤1 (n=137) | 26 (78.8) | 63 (64.9) | 42 (57.5) | 6 (28.6) | ||
| 1< T ≤3 (n=59) | 7 (21.2) | 27 (27.8) | 18 (24.7) | 7 (33.3) | ||
| T >3 (n=28) | 0 | 7 (7.2) | 13 (17.8) | 8 (38.1) | ||
| The number of highest allergen grade‡ | 0.245 | <0.001†* | ||||
| G ≤2 (n=178) | 30 (90.9) | 83 (85.6) | 54 (74.0) | 11 (52.4) | ||
| 2< G ≤4 (n=42) | 2 (6.1) | 14 (14.4) | 18 (24.7) | 8 (38.1) | ||
| G >4 (n=4) | 1 (3.0) | 0 | 1 (1.4) | 2 (9.5) | ||
Data are presented as n (%). †, Spearman-test. ‡, according to the value of serum allergen-sIgE, any single food or inhaled allergen were classified to seven grades (grade 0, <0.35 IU/mL; grade 1, 0.35–0.70 IU/mL; grade 2, 0.71–3.50 IU/mL; grade 3, 3.51–17.50 IU/mL; grade 4, 17.51–50.0 IU/mL; grade 5, 50.01–100.0 IU/mL; grade 6, >100.0 IU/mL). *, P<0.05. T, the number of positive food and inhaled allergens; G, the number of highest allergen grade. sIgE, specific immunoglobulin E.
Discussion
Chalazion usually arises in children and severe cases disfigures cosmetic. Allergic ocular disease is associated with IgE, and the ophthalmic manifestations of the hyper-IgE syndrome also include allergic responses and recurrent chalazia (8). This research investigates the distribution patterns of serum T-IgE and sIgE levels in children with chalazia.
In this study, the dominant positive allergens to children in both chalazion and AC were milk, egg, and Dermatophagoides farina. Consistent with previous studies (9,10), milk and egg are the most common allergens in children (11), while peanut and seafood are more common in adults. Nevertheless, milk is the main food source for children in the early stage of life. It is one of the commonest food protein allergies with an estimated prevalence of 0.5% to 3% at 1 year of life (12). Many recent reports describe the natural history of milk or egg allergens in children. The age at which nearly half of children develop acquisition of tolerance to milk allergen vary in Finland (13) (2 years old), Israeli (14) (2 years old), Portugal (15) (5 years old), and the United States (16) (8 years old). Consistent with milk allergen, the egg allergen has similar history of natural tolerance. In a cohort study of Spanish, half of children obtain tolerance to egg allergen at the age of 3 years old (17).
There were statistically differences on allergens distribution between chalazion and AC in children. In our study, the positive rate of allergen-sIgE to soy, crab, shrimp, codfish, wheat flour, Dermatophagoides pteronyssinus, Dermatophagoides farinae, house dust, and Alternaria alternate in the AC group was significantly higher than that in the chalazia group (P<0.05). According to previous reports, the Dermatophagoides pteronyssinus, Dermatophagoides farina, and house dust were the most common allergens in various allergic diseases such as allergic rhinitis, asthma, or atopic dermatitis (18,19). However, the positive rate of these three allergens was not high in chalazia children. In the study, the positive rate of epithelial materials of dogs was higher in the chalazia group than the AC group (P=0.001), which is not consistent with the previous researches. Reports showed that the positive rate of animal hairs in AC was 30.8–35.3% (18,20), which was higher than that in our study. One explanation was that detection sensitivity was different by different test methods and countries or regions had their certain kinds of animal hairs. Meanwhile, there could be cross-immune responses between various allergens (18,21), Another reason was that various factors (21,22), such as race, seasonal and regional variations, environment temperature and humidity, or life habits were contributed to allergen patterns or distributions. Race and ethnicity showed some important associations with chalazion (2).
In our study, compared to younger children, older had lower positive rate of specific-food allergens (50.0% vs. 71.4%, P=0.008). The hypothesis was that with continuous exposure to specific food allergens in small doses, older children developed acquisition of tolerance. Based on previous investigations, milk or egg allergy had been considered a transient condition, and children could obtain tolerance at certain age (23,24). Kim et al. (11) found that 50% of the children outgrew milk allergy at a median age of 8.7 years old. However, some food allergens, for example peanut or seafood, were always allergic to children or adults.
Children with higher serum T-IgE level, more numbers of positive allergens, or higher grade of allergens were more likely to develop more severe stage of chalazion (P<0.001), suggesting that more attention should be paid on chalazia children with allergic reaction. A previous report showed that bacterial and/or demodex infection (25), the use of makeup and inflammation of eyelid margin (26) contribute to the development of chalazia. Some studies found that patients with chalazion had lower serum vitamin B12 and low serum vitamin A than healthy participants (27,28). The allergic mediators or immune stimulation response might cause swollen meibomian glands to become inflammatory in children with chalazion, leading to blepharitis or eyelid skin infection. Moreover, the meibomian gland ducts in children are thinner which can lead more easily to obstruction (26). Therefore, children with chalazion need to avoid exposure to allergens, and combined anti-allergic treatment might help to improve the ocular symptoms.
There are many limitations in this study. Firstly, due to the lack of prospective data, it was impossible to analyze the differences in food or inhaled allergens between healthy participants and chalazia children. Secondly, children in this study came from Hubei only, which leading to geographical limitation. Thirdly, some children had diseases such as rhinitis or eczema, which could be a confounding factor, especially in the correlation analysis between the serum T-IgE level, allergens, and the stages of chalazia. We will further explore the changes in IgE before and after treatment with antiallergic drugs in children with chalazia. Nevertheless, the present study is clinically significant for the distribution patterns of food and inhaled allergens in chalazia children, as well as the correlation between T-IgE level, allergens and the stages of chalazia in children.
Conclusions
Chalazia children were more sensitive to the epithelial materials of dogs than children with AC in Hubei province. Furthermore, the serum T-IgE level, the numbers or grades of allergens might have positive correlation with the severity of chalazion in children.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2024-565/rc
Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2024-565/dss
Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2024-565/prf
Funding: This study was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2024-565/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and was approved by the Institutional Ethics Committee of Wuhan Children’s Hospital (No. 2021R162). Informed consent was obtained from the patients’ legal guardians or parents.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
References
- Tesluk GC. Eyelid lesions: incidence and comparison of benign and malignant lesions. Ann Ophthalmol 1985;17:704-7.
- Evans J, Vo KBH, Schmitt M. Chalazion: racial risk factors for formation, recurrence, and surgical intervention. Can J Ophthalmol 2022;57:242-6. [Crossref] [PubMed]
- Zhu D, Gupta RR, Stein RL, et al. Randomized Prospective Evaluation of Microblepharoexfoliation BlephEx as Adjunctive Therapy in the Treatment of Chalazia. Cornea 2023;42:172-5. [Crossref] [PubMed]
- Kim ES, Afshin EE, Elahi E. The lowly chalazion. Surv Ophthalmol 2023;68:784-93. [Crossref] [PubMed]
- Patel S, Tohme N, Gorrin E, et al. Prevalence and risk factors for chalazion in an older veteran population. Br J Ophthalmol 2022;106:1200-5. [Crossref] [PubMed]
- Alimuddin S, Rengganis I, Rumende CM, et al. Comparison of Specific Immunoglobulin E with the Skin Prick Test in the Diagnosis of House Dust Mites and Cockroach Sensitization in Patients with Asthma and/or Allergic Rhinitis. Acta Med Indones 2018;50:125-31.
- Lin P, Liu YF, Wu ZQ. Analysis on the risk factors for children's multiple chalazion. International Eye Science 2018;18:751-3.
- AlYafie R, Velayutham D, van Panhuys N, et al. The genetics of hyper IgE syndromes. Front Immunol 2025;16:1516068. [Crossref] [PubMed]
- Giannetti A, Toschi Vespasiani G, Ricci G, et al. Cow's Milk Protein Allergy as a Model of Food Allergies. Nutrients 2021;13:1525. [Crossref] [PubMed]
- Anagnostou A. Optimizing Patient Care in Egg Allergy Diagnosis and Treatment. J Asthma Allergy 2021;14:621-8. [Crossref] [PubMed]
- Kim M, Lee JY, Yang HK, et al. The Natural Course of Immediate-Type Cow's Milk and Egg Allergies in Children. Int Arch Allergy Immunol 2020;181:103-10. [Crossref] [PubMed]
- Malik R, Kaul S. Cow's Milk Protein Allergy. Indian J Pediatr 2024;91:499-506. [Crossref] [PubMed]
- Saarinen KM, Pelkonen AS, Mäkelä MJ, et al. Clinical course and prognosis of cow's milk allergy are dependent on milk-specific IgE status. J Allergy Clin Immunol 2005;116:869-75. [Crossref] [PubMed]
- Elizur A, Rajuan N, Goldberg MR, et al. Natural course and risk factors for persistence of IgE-mediated cow's milk allergy. J Pediatr 2012;161:482-487.e1. [Crossref] [PubMed]
- Santos A, Dias A, Pinheiro JA. Predictive factors for the persistence of cow's milk allergy. Pediatr Allergy Immunol 2010;21:1127-34. [Crossref] [PubMed]
- Skripak JM, Matsui EC, Mudd K, et al. The natural history of IgE-mediated cow's milk allergy. J Allergy Clin Immunol 2007;120:1172-7. [Crossref] [PubMed]
- Boyano-Martínez T, García-Ara C, Díaz-Pena JM, et al. Prediction of tolerance on the basis of quantification of egg white-specific IgE antibodies in children with egg allergy. J Allergy Clin Immunol 2002;110:304-9. [Crossref] [PubMed]
- Wang W, Du X, Ye L, et al. Distribution of serum specific IgE in children with allergic conjunctivitis and analysis of its concomitant allergic diseases. Transl Pediatr 2020;9:636-44. [Crossref] [PubMed]
- Leonardi A, Quintieri L, Presa IJ, et al. Allergic Conjunctivitis Management: Update on Ophthalmic Solutions. Curr Allergy Asthma Rep 2024;24:347-60. [Crossref] [PubMed]
- Bignardi D, Comite P, Mori I, et al. Allergen-specific IgE: comparison between skin prick test and serum assay in real life. Allergol Select 2019;3:9-14. [Crossref] [PubMed]
- Lei DK, Grammer LC. An overview of allergens. Allergy Asthma Proc 2019;40:362-5. [Crossref] [PubMed]
- Minami T, Fukutomi Y, Inada R, et al. Regional differences in the prevalence of sensitization to environmental allergens: Analysis on IgE antibody testing conducted at major clinical testing laboratories throughout Japan from 2002 to 2011. Allergol Int 2019;68:440-9. [Crossref] [PubMed]
- van Neerven RJJ, Savelkoul HFJ. The Two Faces of Cow's Milk and Allergy: Induction of Cow's Milk Allergy vs. Prevention of Asthma. Nutrients 2019;11:1945. [Crossref] [PubMed]
- Flom JD, Sicherer SH. Epidemiology of Cow's Milk Allergy. Nutrients 2019;11:1051. [Crossref] [PubMed]
- Tarkowski W, Owczyńska M, Błaszczyk-Tyszka A, et al. Demodex mites as potential etiological factor in chalazion - a study in Poland. Acta Parasitol 2015;60:777-83. [Crossref] [PubMed]
- Chen L, Chen X, Xiang Q, et al. Prevalence of low serum vitamin a levels in young children with chalazia in southwest china. Am J Ophthalmol 2014;157:1103-1108.e2. [Crossref] [PubMed]
- Ilhan C. Serum Levels of Thyroid Hormone, Vitamin B12, Vitamin D3, Folic Acid, and Ferritin in Chalazion. Ocul Immunol Inflamm 2022;30:776-80. [Crossref] [PubMed]
- Tashbayev B, Chen X, Utheim TP. Chalazion Treatment: A Concise Review of Clinical Trials. Curr Eye Res 2024;49:109-18. [Crossref] [PubMed]
