Food-related hypersensitivity reactions in children are commonly classified into true food allergies, which are immune-mediated (often IgE-dependent), and pseudoallergic reactions, which occur without immune sensitization and are frequently related to histamine intolerance or enzymatic deficiencies. Clinically, both conditions may present with similar symptoms such as urticaria, gastrointestinal discomfort, and respiratory manifestations, complicating differential diagnosis. Eosinophil cationic protein reflects eosinophilic inflammation and is associated with allergic immune responses, whereas diamine oxidase plays a critical role in metabolizing exogenous histamine. Understanding the comparative diagnostic roles of these markers is essential for improving clinical decision-making and avoiding unnecessary dietary restrictions.
The objective of this study was to evaluate and compare the clinical utility of eosinophil cationic protein and diamine oxidase levels in distinguishing true food allergy from pseudoallergic reactions in children, as well as to determine their sensitivity and specificity as diagnostic biomarkers.
Materials and Methods
The study included 80 children aged 4–14 years presenting with suspected food hypersensitivity. Based on clinical history, IgE testing, and elimination-provocation tests, patients were divided into two groups: true food allergy (n=40) and pseudoallergic reactions (n=40). Serum ECP levels were measured using enzyme-linked immunosorbent assay (ELISA), and DAO activity was assessed via enzymatic assay. Additional parameters included total IgE levels, eosinophil count, and clinical severity scoring. Statistical analysis involved comparison of mean values between groups and receiver operating characteristic (ROC) curve analysis to assess diagnostic performance.
Children with true food allergy showed significantly elevated ECP levels (mean 42 ± 12 ng/mL) compared to those with pseudoallergic reactions (18 ± 7 ng/mL; p<0.001). In contrast, DAO activity was markedly reduced in the pseudoallergy group (6.5 ± 2.1 U/mL) compared to the true allergy group (14.8 ± 3.6 U/mL; p<0.001). ECP demonstrated higher sensitivity for detecting immune-mediated allergic reactions, while DAO showed greater specificity for identifying pseudoallergic conditions related to histamine intolerance. Combined analysis of both markers improved diagnostic accuracy up to 87%. A negative correlation was observed between ECP levels and DAO activity (r = -0.58; p<0.01).
The findings highlight distinct pathophysiological mechanisms underlying true food allergy and pseudoallergic reactions. Elevated ECP levels reflect eosinophil-driven inflammation typical of IgE-mediated responses, whereas decreased DAO activity suggests impaired histamine metabolism, leading to pseudoallergic symptoms. The use of both biomarkers provides complementary information and enhances diagnostic precision. This approach may reduce misdiagnosis and prevent unnecessary elimination diets, which can negatively impact nutritional status in children. Limitations of the study include a relatively small sample size and the need for standardization of DAO measurement techniques.
Eosinophil cationic protein and diamine oxidase are valuable biomarkers in differentiating true food allergy from pseudoallergic reactions in pediatric patients. ECP is more indicative of immune-mediated allergic inflammation, while DAO deficiency is associated with histamine-related pseudoallergic responses. The combined assessment of these markers offers improved diagnostic accuracy and supports more personalized management strategies in children with food hypersensitivity.
1. Sicherer S.H., Sampson H.A. Food allergy: epidemiology and pathogenesis. J Allergy Clin Immunol. 2014;133:291–307.
2. Maintz L., Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007;85:1185–1196.
3. Koller D.Y., et al. Eosinophil cationic protein in allergic diseases. Pediatrics. 1997;99:227–231.
4. Schwelberger H.G. Diamine oxidase (DAO) enzyme and histamine metabolism. Inflamm Res. 2010;59:S219–S221.
5. Rothenberg M.E. Eosinophilia in allergic disorders. N Engl J Med. 1998;338:1592–1600.
6. Reese I., et al. Diagnostic approach to histamine intolerance. Allergo J Int. 2017;26:72–79.
7. Brown S.G.A. Mechanisms of anaphylaxis. J Allergy Clin Immunol. 2016;137:17–28.
8. Weller P.F., et al. Eosinophil biology in health and disease. J Allergy Clin Immunol. 2016;137:1349–1358.
9. Ogbogu P.U., et al. Hypereosinophilic syndromes. Blood. 2009;114:3736–3741.
10. med1.uz — educational resources on pediatric allergy and diagnostics.