What are the causes and treatments of elevated Immunoglobulin E (IgE) levels in adults?

Causes of Raised IgE Levels in Adults

Elevated IgE levels in adults are most commonly caused by allergic/atopic diseases (asthma, allergic rhinitis, atopic dermatitis), followed by parasitic infections, eosinophilic disorders, and less commonly by primary immunodeficiencies—particularly when IgE exceeds 1000 kU/L. 1, 2

Primary Allergic/Atopic Causes

Allergic diseases represent the most frequent etiology of elevated serum IgE, with levels >114 kU/L found in 50-60% of patients with eosinophilic esophagitis and 55% of the general U.S. population 1. The predominant conditions include:

• Atopic dermatitis, allergic rhinitis, and asthma are the most common atopic conditions, though approximately 20% of confirmed atopic dermatitis patients have normal IgE levels 1, 3
• Aeroallergen sensitization occurs in 44-86% of patients with elevated IgE, with polysensitization common in both adults (86%) and children (71-93%) 4, 1
• Eosinophilic esophagitis shows elevated IgE in 50-60% of cases, with higher levels in allergen-sensitized versus nonsensitized patients 4

Parasitic Infections

Parasitic infections, particularly helminths (Strongyloides and other intestinal parasites), must be excluded through stool examination for ova and parasites, especially with travel history to endemic areas or unexplained eosinophilia 1, 2, 3. This is critical as parasitic infections are a common non-allergic cause of elevated IgE 5.

Eosinophilic Disorders

Eosinophilic disorders show strong association with very high IgE levels across all age groups 6. Specific conditions include:

• Allergic bronchopulmonary aspergillosis (ABPA) presents with characteristic findings of Aspergillus-specific IgE and elevated total IgE 1, 2
• Eosinophilic esophagitis demonstrates peripheral eosinophilia in 40-50% of cases (>300-350 per mm³) 4

Primary Immunodeficiencies

When IgE exceeds 1000 kU/L, primary immunodeficiencies should be considered, particularly hyper-IgE syndromes caused by mutations in STAT3, DOCK8, and PGM3 2, 5. These monogenic disorders present with:

• High IgE, eczema, and recurrent infections 5
• Recurrent pneumonias leading to bronchiectasis 5
• Increased risk across all age groups, with borderline association in ages 18-30 (hazard ratio = 1.802) 6

Other Significant Associations

Very high IgE levels (≥1000 IU/mL) are associated with increased cardiovascular disease risk in adults aged 31-64 years (hazard ratio = 1.249; 95% CI, 1.054-1.481) 6. Additional causes include:

• Malignancy and immune dysregulation 5
• Autoimmune diseases show higher prevalence (46% versus 15%) in IgE-deficient patients, though this represents the opposite end of the spectrum 7

Critical Diagnostic Approach

Complete blood count with differential should be performed to assess for eosinophilia, which helps distinguish between allergic, parasitic, and immunologic etiologies 1, 2, 3. The systematic evaluation should include:

• Specific IgE testing or skin prick testing to identify suspected allergens, with >95% negative predictive value 2, 3
• Stool examination for ova and parasites if travel history to endemic areas, high-risk populations, or unexplained eosinophilia present 1, 2
• Comprehensive metabolic panel with liver function tests, lactate dehydrogenase, and uric acid to evaluate for underlying conditions 1

Important Clinical Pitfalls

Do not diagnose atopic dermatitis based solely on elevated IgE and pruritus—primary eczematous lesions with characteristic distribution are mandatory, as 20% of confirmed cases have normal IgE 1, 2. Additional caveats:

• Total IgE measurement cannot diagnose food allergy in eosinophilic esophagitis, as levels do not predict therapeutic response 4, 1, 2
• IgE elevation is nonspecific, found in 55% of the general U.S. population and in numerous non-atopic conditions 1, 2
• Total IgE levels remain elevated for up to 1 year after omalizumab treatment, so re-testing during treatment cannot guide dose determination 3, 8
• Peripheral eosinophil counts should be interpreted with consideration for age, adherence to aeroallergen avoidance, pollen season, and control of comorbid allergic disease 4

Management Based on Underlying Etiology

Strict allergen avoidance should be implemented for documented IgE-mediated allergies 1, 2, 3. Specific treatments include:

• Inhaled corticosteroids for persistent allergic asthma (high-quality evidence) 1, 2, 3
• Antihistamines for allergic rhinitis and urticaria (moderate-quality evidence) 1, 2, 3
• Omalizumab (anti-IgE therapy) for moderate to severe persistent asthma inadequately controlled with inhaled corticosteroids 1, 2, 3, 8
• Oral itraconazole with therapeutic drug monitoring for symptomatic asthmatic patients with ABPA despite corticosteroid therapy 2
• Appropriate antiparasitic treatment based on stool examination results and geographic exposure patterns 2