What is the treatment for someone with Common Variable Immunodeficiency (CVID) with low Immunoglobulin A (IgA), low Immunoglobulin G (IgG), and low Immunoglobulin M (IgM) levels?

Treatment for CVID with Low IgA, IgG, and IgM

This patient requires immediate initiation of immunoglobulin replacement therapy, as IgG therapy is definitively indicated for all patients with CVID. 1

Immediate Treatment Initiation

Start immunoglobulin replacement therapy without delay to prevent serious bacterial infections, pneumonia, and irreversible organ damage such as bronchiectasis. 1, 2, 3

Route and Dosing Options

You have two primary routes to consider:

Intravenous Immunoglobulin (IVIG):

• Standard dose: 0.4-0.6 g/kg/month 1
• Higher dose (0.6 g/kg/month) if bronchiectasis is present or develops 1
• Doses up to 1.2 g/kg/month may be needed based on clinical response 1, 4

Subcutaneous Immunoglobulin (SCIG):

• For treatment-naïve patients: Loading dose of 150 mg/kg/day for 5 consecutive days, followed by weekly maintenance at 150 mg/kg/week starting Day 8 5
• If switching from IVIG: multiply monthly IVIG dose (in grams) by 1.37, then divide by number of weeks between IVIG doses 5
• Can be administered weekly, biweekly, or 2-7 times per week based on patient preference 5
• Offers home-based therapy option 1

Target Trough IgG Levels

Aim for trough IgG levels of 400-500 mg/dL minimum to prevent serious bacterial infections, though individual patients may require levels ranging from 500-1700 mg/dL to remain infection-free. 2, 3, 4 The goal is clinical improvement (reduction in infections), not achieving a specific laboratory value. 1, 2

Monitoring Requirements

Monitor IgG trough levels every 2 weeks during the first 8 weeks if treatment-naïve, then every 6-12 months once stable. 1, 2, 5

Additional monitoring should include:

• Complete blood counts (watch for hemolysis, cytopenias) 1, 6
• Serum chemistry including liver enzymes, creatinine, and blood urea nitrogen 1, 6
• Clinical assessment of infection frequency and severity 2, 3, 6

Multidisciplinary Care

Ensure joint care with both a clinical immunologist and respiratory specialist, as CVID patients are at high risk for developing bronchiectasis and other pulmonary complications. 1, 2

Adjunctive Therapies

Beyond immunoglobulin replacement:

• Prophylactic antibiotics may be needed for breakthrough infections despite adequate IgG replacement 1
• Keep antibiotics available to start immediately at onset of infections 6
• Screen for and manage complications including autoimmune diseases, lymphoproliferative disorders, and malignancy 2, 7

Critical Pitfalls to Avoid

Do not delay treatment while waiting for additional testing or specialist consultation—early initiation prevents irreversible lung damage and reduces mortality. 1, 2, 3

Do not focus solely on achieving a specific trough IgG level—the primary endpoint is clinical response (reduction in infection frequency and severity). 1, 2, 3, 6

Do not assume low IgA is a contraindication to immunoglobulin therapy—IgA deficiency with low IgG levels is an indication for treatment, and anaphylaxis to IVIG in IgA-deficient patients is extremely rare. 1

Do not use a one-size-fits-all dose—individual patients require doses ranging from 0.2 to 1.2 g/kg/month based on their clinical response, presence of bronchiectasis, and specific phenotype. 1, 4

Dose Adjustment Strategy

Increase the dose if:

• Breakthrough bacterial infections occur 2, 3, 4
• Bronchiectasis develops or is already present 1
• Trough IgG levels remain below 400-500 mg/dL 2, 3

The dose is adequate when:

• Infection frequency decreases significantly 2, 3, 6
• Patient can maintain normal daily activities without infection-related absences 1
• Hospitalizations for infections are prevented 1