Elevated IgE Levels—An Allergy or an Underlying Inborn Error of Immunity in Children with Recurrent Infections?

Abstract

Elevated immunoglobulin E (IgE) is a hallmark of allergic diseases. However, high IgE levels also occur in a number of other infectious and noninfectious diseases. In most cases, elevated IgE levels indicate allergy, eczema, or chronic skin infection. Very high IgE levels are not uncommon in patients with active eczema but more often indicate monogenic atopic disorder or inborn errors of immunity with an atopic phenotype. We conducted a retrospective study of 385 children with suspected immune deficiency referred to the clinic over a 9-year period. Measurement of IgE, IgG, IgA, IgM, and IgG subclasses in blood samples revealed that nearly one-third of the patients had elevated serum IgE levels. Most of the cases with elevated IgE were children with underlying atopy—mainly atopic dermatitis and, to a lesser extent, bronchial asthma—whereas 40.12% (37 children) had no atopy at all. In the most severe cases (with extremely elevated IgE or severe dermatitis), we confirmed genetic mutations for underlying immunodeficiency. Our results indicate that allergic phenotype should not be underestimated and that children with more severe allergic disease should be evaluated for an underlying inborn error of immunity. If inborn error of immunity (IEI) is suspected, a comprehensive immunologic evaluation is required. Genetic testing helps identify the specific genetic abnormality, which provides important insight into the immunopathogenesis of the disease and accurate determination of optimal therapy.

Elevated Immunoglobulin E Serum Levels: Possible Underlying Factors That Can Cause an Inborn Error of Immunity in the Pediatric Population with Recurrent Infections

“…Patients with medication allergies and atopic dermatitis had higher IgE levels, but patients with allergic rhinitis had lower or normal IgE levels. These results are similar to those in a study conducted among the pediatric population [36]. The second largest age group of patients was 10 to 15 years old.…”

“…Among the younger population, the average age at detection of the condition was 11.5 years [43]. According to the study outcomes, the first age group (1-5 years) contained the most patients, which is understandable given that the majority of infections emerge during the first years of life [23,36,44]. Patients with medication allergies and atopic dermatitis had higher IgE levels, but patients with allergic rhinitis had lower or normal IgE levels.…”

“…The development of the mutation that causes the body to produce IgE at an excessive rate might also be influenced by the environment [28,36]. Inner-city children differ in their allergen exposure and sensitivity based on geography [37].…”

Elevated Immunoglobulin E Serum Levels: Possible Underlying Factors That Can Cause an Inborn Error of Immunity in the Pediatric Population with Recurrent Infections

“…The development of the mutation that causes the body to produce IgE at an excessive rate might also be influenced by the environment [ 28 , 40 ]. Inner-city children differ in their allergen exposure and sensitivity based on geography [ 41 ].…”

“…Among the younger population, the average age at detection of the condition was 11.5 years [ 44 ]. According to the study outcomes, the first age group (1–5 years) contained the most patients, which is understandable given that the majority of infections emerge during the first years of life [ 23 , 40 , 45 ]. Patients with medication allergies and atopic dermatitis had higher IgE levels, but patients with allergic rhinitis had lower or normal IgE levels.…”