From the Guidelines
Elevated Immunoglobulin E (IgE) levels above 1,000 are most commonly associated with Hyperimmunoglobulinemia E (Hyper-IgE) syndrome, a primary immunodeficiency disorder characterized by recurrent cutaneous and pulmonary infections, and elevated IgE levels. The causes of elevated IgE levels can be multifactorial, including:
- Primary immunodeficiency syndromes, such as Hyper-IgE syndrome (Job's syndrome) 1
- Allergic disorders, such as allergic asthma, atopic dermatitis, and food allergies 1
- Parasitic infections, such as strongyloidiasis due to Strongyloides stercoralis exposure 1
- Immunodeficiency syndromes associated with abnormal immunoglobulin levels, such as Omenn syndrome and Wiskott Aldrich syndrome 1
- Pulmonary eosinophilic diseases, such as allergic bronchopulmonary aspergillosis (ABPA) and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) 1 Key characteristics of Hyper-IgE syndrome include:
- Recurrent cutaneous and pulmonary infections
- Elevated IgE levels
- Coarse facial features
- Skeletal abnormalities, such as scoliosis and hyperextensible joints
- Dental abnormalities, such as delayed shedding of primary teeth Management of elevated IgE levels depends on identifying the underlying cause and may include:
- Antihistamines and corticosteroids for allergic disorders
- Antiparasitic medications for parasitic infections
- Immunomodulators and targeted biologics, such as omalizumab (Xolair), for primary immunodeficiency syndromes and pulmonary eosinophilic diseases Regular monitoring of IgE levels and comprehensive allergy management are essential for patients with persistently elevated IgE 1.
From the Research
Causes of Elevated Immunoglobulin E (IgE) Levels
Elevated IgE levels above 1,000, indicative of Hyperimmunoglobulinemia E (Hyper-IgE) syndrome, can be caused by various factors, including:
- Allergic diseases, such as bronchial asthma, allergic rhino-conjunctivitis, and atopic dermatitis 2, 3, 4, 5
- Primary immunodeficiencies (PID) 2, 3, 5
- Parasitosis, especially helminthiasis 3, 6
- Infections, such as recurrent skin abscesses and pneumonias 4, 6
- Malignancies 4
- Monogenic atopic disorders or inborn errors of immunity with an atopic phenotype 5, 6
Clinical Profile of Patients with Elevated IgE Levels
Studies have shown that:
- Atopic diseases are the most common cause of elevated IgE levels, accounting for 77% of cases 4
- Parasitic diseases, malignancy, and Hyper-IgE syndrome are less common causes of elevated IgE levels 4
- There is a statistically significant association between IgE levels and the severity of eczema 4
- Elevated IgE levels are not predictive of Hyper-IgE syndrome in the absence of typical clinical features 4
Diagnostic Approach
Pediatricians may use the Hyper-IgE syndrome scoring sheet to suspect a patient with PID and refer them to an immunologist for detailed immunologic tests if necessary 2. A comprehensive immunologic evaluation, including genetic testing, is required to identify the specific genetic abnormality and determine optimal therapy in cases of suspected inborn error of immunity 5, 6.