Could an 11-year-old patient with elevated Immunoglobulin G (IgG) levels be reacting to other allergens?

Could an 11-Year-Old with Elevated IgG Be Reacting to Other Allergens?

Yes, an 11-year-old patient with elevated IgG levels can absolutely be reacting to other allergens, but IgG levels themselves do not indicate allergic reactions—you must evaluate for IgE-mediated sensitization to aeroallergens and foods, which are the true drivers of allergic disease in this age group. 1, 2

Understanding IgG vs. IgE in Allergic Disease

IgG Antibodies Are Not Diagnostic of Allergy

• IgG antibodies to foods indicate exposure, not allergy. The correlation between IgG levels and clinical improvement after immunotherapy has not been consistently demonstrated, and IgG testing should not be used to diagnose food allergies. 1
• While IgG levels increase during allergen immunotherapy (particularly IgG4), this represents a blocking antibody response that actually suppresses allergic reactions by preventing IgE-mediated activation of mast cells and basophils. 1, 3
• Research shows IgG to foods like egg white, wheat, rice, and orange may correlate with future development of IgE-mediated allergies, but elevated IgG alone does not cause current allergic symptoms. 4

IgE-Mediated Sensitization Is What Matters

• In pediatric patients with allergic disease, 71-93% show positive skin prick tests to aeroallergens, and 44-86% have serum IgE to outdoor, indoor, or both inhalant allergens. 1
• Aeroallergen sensitization includes outdoor allergens (grass, weeds, trees, molds at 64-93%) and indoor allergens (dog, cat, cockroach, dust mites at 16-69%), with polysensitization being extremely common. 1
• Food allergen sensitization occurs frequently alongside aeroallergen sensitization, with 32% of pediatric patients showing IgE to clusters including pollens, grains, soy, and nuts/peanuts. 1

Comprehensive Evaluation for Other Allergens

Specific Testing Required

• Perform skin prick testing or allergen-specific IgE testing for both aeroallergens and foods to identify true sensitization patterns, as these have >95% negative predictive value. 5, 2
• Test for outdoor aeroallergens (tree, grass, weed pollens, molds) and indoor aeroallergens (dust mites, cat, dog, cockroach) given the high prevalence in this age group. 1, 2
• Consider seasonal variability—tree and grass pollen levels directly correlate with new diagnoses of eosinophilic esophagitis, with decreased diagnoses in winter and increased in spring/summer/fall. 1

Complete Blood Count with Differential

• Obtain CBC with differential to assess for eosinophilia, which helps distinguish allergic, parasitic, and immunologic etiologies of elevated immunoglobulin levels. 2, 6
• Eosinophilia should be interpreted considering the patient's age, adherence to aeroallergen avoidance, pollen season, and control of comorbid allergic disease. 1

Rule Out Non-Allergic Causes

• If eosinophilia is present or there is travel history to endemic areas, perform stool examination for ova and parasites to exclude helminthic infections, particularly Strongyloides, which commonly elevate IgE. 2, 6
• Consider that elevated IgE (not IgG) occurs in 50-60% of patients with eosinophilic esophagitis, though total IgE levels are not predictive of therapeutic response. 1
• In children with recurrent infections and elevated immunoglobulin levels, consider underlying inborn errors of immunity, particularly if there is severe atopic dermatitis or extremely elevated IgE. 7, 8

Clinical Management Based on Findings

For Documented IgE-Mediated Allergies

• Implement strict allergen avoidance for any documented IgE-mediated allergies identified through testing. 1, 5
• Prescribe antihistamines for allergic rhinitis and urticaria (moderate-quality evidence). 5, 6
• If persistent allergic asthma is present, initiate inhaled corticosteroids (high-quality evidence). 5, 6
• Consider omalizumab (anti-IgE therapy) for moderate to severe persistent asthma inadequately controlled with inhaled corticosteroids in patients ≥12 years with documented IgE-mediated allergic asthma. 1, 5

For Aeroallergen Sensitization

• Recommend appropriate environmental avoidance measures for identified aeroallergen sensitivities, as aeroallergens have a complementary role in disease pathogenesis. 1
• Consider subcutaneous allergen immunotherapy for patients with allergic rhinitis or allergic asthma at steps 2-4 of treatment. 1
• When assessing esophageal biopsy results or other allergic manifestations, factor in the patient's aeroallergen sensitization profile and seasonality. 1

Critical Pitfalls to Avoid

• Do not use IgG testing to diagnose food allergies or guide dietary elimination—food triggers can only be identified by documenting disease remission after specific food elimination followed by recrudescence on reintroduction. 1
• Do not assume elevated IgG levels indicate current allergic reactions; they may simply reflect exposure or represent blocking antibodies from prior immunotherapy. 1
• For patients with positive skin tests to foods, appropriately evaluate for immediate hypersensitivity reactions and prescribe epinephrine if indicated, as loss of tolerance during food avoidance might result in significant reactions on reintroduction. 1
• Medically supervised food reintroduction is necessary for patients with previous allergic reactions or documented IgE-mediated sensitivity. 1