What are the causes of elevated Immunoglobulin E (IgE) levels and the appropriate workup?

From the Guidelines

Elevated IgE levels can result from various conditions, and the workup should begin with a thorough clinical history and physical examination, followed by laboratory testing, including complete blood count with differential, specific IgE testing, and stool examination for parasites, as recommended by the most recent guidelines 1. The causes of IgE elevation can be categorized into several groups, including:

• Allergic disorders, such as asthma, allergic rhinitis, atopic dermatitis, and food allergies
• Parasitic infections, particularly helminth infections
• Certain immunodeficiency syndromes, such as Hyper-IgE syndrome and Wiskott-Aldrich syndrome
• Malignancies, including IgE myeloma and Hodgkin's lymphoma
• Dermatological conditions, such as pemphigoid and dermatitis herpetiformis The workup for elevated IgE should include:
• Complete blood count with differential to look for eosinophilia
• Specific IgE testing or skin prick tests for suspected allergens
• Stool examination for parasites
• Genetic testing for primary immunodeficiencies in selected cases
• Additional testing, such as chest imaging, pulmonary function tests, or skin biopsy, depending on clinical presentation The management of elevated IgE depends on identifying and treating the underlying cause, and may include allergen avoidance, anti-inflammatory medications, antiparasitic drugs, or specific treatments for immunodeficiency syndromes, as recommended by the most recent guidelines 1. It is essential to interpret the results of IgE testing in the context of age-appropriate reference ranges, as the normal range for serum IgE varies by age, with higher levels typically seen in children and adolescents compared to adults 1. In cases of suspected food allergy, the diagnosis should be based on a combination of clinical history, skin prick testing, and serum specific IgE level determination, and should be confirmed by controlled food challenges or careful assessment of the effects of a food elimination diet 1.

From the Research

Causes of IgE Elevation

• Elevated IgE levels can be caused by various factors, including:
  • Allergies 2
  • Infections, such as parasitic infections like Toxocariasis 3
  • Immune conditions, including hyper-IgE syndrome (HIES) 2, 4, 5
  • Autoimmune conditions 6
• Other causes of elevated IgE levels include:
  • Atopic diseases, such as atopic dermatitis 2, 6
  • Malignancies 2, 6
  • Inborn errors of immunity 4, 6

Workup for IgE Elevation

• A diagnostic approach for patients with elevated IgE levels should include:
  • Clinical evaluation, including medical history and physical examination 3, 2
  • Laboratory tests, such as complete blood count (CBC) and serum IgE levels 3, 2
  • Imaging studies, such as abdominal ultrasound 3
  • Serological tests, such as tests for parasitic infections 3
• A list of conditions not related to atopic dermatitis that may present with elevated IgE levels and eosinophilia should be considered, including:
  • Inborn errors of immunity 4, 6
  • Inflammatory disorders 6
  • Lung disorders 6
  • Malignancies 2, 6
  • Infections/infestations 3, 6