How do I diagnose and manage a patient with Selective Immunoglobulin A (IgA) Deficiency (SIGAD)?

Evaluation of Selective IgA Deficiency (SIGAD)

Diagnose SIGAD by measuring serum IgA levels (must be <0.07 g/L in patients >4 years old), confirming normal IgG and IgM levels, verifying normal vaccine responses, and excluding secondary causes of hypogammaglobulinemia. 1

Diagnostic Criteria

• Serum IgA must be less than 0.07 g/L in patients older than 4 years of age, with normal levels of IgG and IgM, and normal vaccine responses 1
• Exclude all secondary causes of hypogammaglobulinemia before confirming the diagnosis 1
• Partial IgA deficiency exists when serum IgA is higher than 0.07 g/L but two standard deviations below normal for age, which is quite common 1

Initial Evaluation Steps

Laboratory Assessment

• Measure serum immunoglobulin levels: IgA, IgG, IgM, and IgG subclasses to differentiate SIGAD from other immunodeficiencies 2
• Test specific antibody responses to pneumococcal polysaccharides, as these are impaired in many SIGAD patients 3
• Evaluate vaccine responses to confirm adequate IgG and IgM function 1

Medication Review (Critical First Step)

• Immediately investigate all current medications, as SIGAD can be drug-induced and potentially reversible 4
• Specific offending agents include antiepileptics, disease-modifying agents, NSAIDs, and antibiotics 4, 2
• Discontinuation of these medications may reverse the IgA deficiency in many cases 4

Clinical Phenotype Classification

• Categorize patients into one of five phenotypes: asymptomatic (75-90% of cases), minor infectious, allergic, autoimmune, or severe 1, 5
• This classification guides management intensity and monitoring frequency 5

Assessment for Complications

Infectious History

• Document recurrent sinopulmonary infections, particularly involving Haemophilus influenzae and Streptococcus pneumoniae 1
• Assess for gastrointestinal infections, especially Giardia lamblia 1, 2
• Evaluate frequency and severity of respiratory tract infections (sinusitis, otitis media) 4

Atopic Disease Evaluation

• Perform allergy skin testing or allergen-specific IgE testing to identify specific triggers - skin tests are preferred over serum IgE testing 6
• Recognize that allergic manifestations are IgE-mediated (not related to the IgA deficiency itself) and occur frequently in association with SIGAD 6
• Document presence of allergic rhinitis, asthma, or other atopic conditions requiring aggressive treatment 4

Autoimmune Disease Screening

• Screen for systemic lupus erythematosus, thyroid disorders (hyper- and hypothyroidism), Type 1 diabetes, and celiac disease 2
• For celiac disease screening in SIGAD patients, use IgG-based antibody tests (IgG anti-tissue transglutaminase or IgG anti-endomysial antibodies) rather than standard IgA-based tests 7
• Monitor for development of autoimmune manifestations over time 1

Differentiation from Other Immunodeficiencies

• Distinguish SIGAD from IgG2 or IgG4 deficiency, specific antibody deficiency, or early Common Variable Immunodeficiency (CVID) 2
• Some patients with SIGAD may progress to CVID, suggesting SIGAD can represent an evolving immunodeficiency 3
• Serial monitoring of immunoglobulin levels is necessary to detect progression 3

Blood Product Precautions Assessment

• Identify patients with complete IgA deficiency who may develop anti-IgA IgE antibodies, creating a rare risk of anaphylaxis with blood products containing IgA 4, 2
• Document this risk prominently in the medical record for future transfusion needs 4
• When blood transfusions are required, some centers transfuse products from IgA-deficient donors or wash cells before transfusion 4

Management Planning Based on Phenotype

Asymptomatic Patients

• No specific treatment required, but ensure vaccinations are up-to-date 1
• Educate patients about potential complications and need for monitoring 2

Symptomatic Patients with Infections

• Implement aggressive antimicrobial therapy for acute infections 4
• Consider prophylactic antibiotics for patients with recurrent infections 1, 2
• IVIG replacement therapy should be considered only in rare patients with recurrent infections negatively affecting quality of life and in whom aggressive antibiotic therapy and prophylaxis have failed or caused intolerable side effects 4
• The majority of SIGAD patients will have minimal clinical response to IVIG 4

Patients with Atopic Disease

• Aggressively treat atopic disease, as allergic inflammation predisposes patients to respiratory tract infections 4, 6
• Use intranasal corticosteroids as the most effective single agent for allergic rhinitis 6
• Add continuous second-generation antihistamines (levocetirizine or desloratadine) 6
• Incorporate leukotriene receptor antagonists (montelukast) for combination therapy 6
• Consider allergen immunotherapy (subcutaneous or sublingual) for patients with demonstrable specific IgE antibodies to clinically relevant allergens 6

Common Pitfalls to Avoid

• Never rely solely on IgA-based serological tests for celiac disease screening - always use IgG-based tests in SIGAD patients 7
• Do not overlook medication-induced SIGAD - always review and consider discontinuing potential offending agents first 4
• Avoid premature use of IVIG - reserve for truly refractory cases after exhausting other options 4
• Do not assume all SIGAD patients need treatment - 75-90% are asymptomatic and require only monitoring 1
• Remember that SIGAD can progress to CVID, requiring ongoing surveillance of immunoglobulin levels 3