What is the recommended follow‑up and monitoring plan for an adult with common variable immunodeficiency (CVID)?

Follow-Up and Monitoring Plan for Adults with CVID

Adults with CVID require systematic surveillance every 3-6 months focusing on pulmonary function, liver enzymes, complete blood counts, and clinical assessment for autoimmune disease and malignancy, while maintaining adequate IgG replacement therapy with regular trough level monitoring.

Core Monitoring Components

Pulmonary Surveillance (Most Critical for Mortality)

• Perform pulmonary function tests and clinical respiratory assessment at every visit because infectious lung disease occurs in the majority of CVID patients and noninfectious chronic pulmonary disease directly reduces survival 1, 2.
• Obtain high-resolution chest CT at least every 2 years to detect progressive bronchiectasis, which develops in 10-20% of patients despite adequate IgG replacement and may progress silently without symptoms or PFT changes 1, 2, 3.
• Monitor specifically for granulomatous and lymphocytic interstitial lung disease (GLILD), which affects approximately 10% of patients and is associated with increased mortality, often accompanied by splenomegaly and diffuse adenopathy 1, 2.

Immunoglobulin Therapy Monitoring

• Measure serum IgG trough levels every 2-4 weeks initially, then every 3-6 months once stable to guide dose adjustments, recognizing that the target trough level varies widely between patients (5-17 g/L) 4, 5.
• Prioritize clinical response—reduction in infection frequency and severity—over achieving a specific trough IgG level when adjusting doses 4, 5.
• Patients with established bronchiectasis require higher IgG dosing, up to 0.6-1.2 g/kg/month, compared to those without lung damage 4, 5.

Gastrointestinal and Hepatic Monitoring

• Check liver function tests (especially alkaline phosphatase) every 3-6 months because approximately 40% of patients develop abnormalities, with nodular regenerative hyperplasia being the most common chronic liver disease leading to portal hypertension 1, 4.
• Evaluate for chronic diarrhea, malabsorption, and inflammatory bowel disease at each visit, testing for Giardia, Campylobacter jejuni, and chronic viral enteritis (CMV, norovirus, parechovirus) when symptoms arise 1, 4.
• Screen for chronic gastritis, villous atrophy, and lymphoid nodular hyperplasia, which affect 20-25% of patients and significantly impact quality of life 2, 4.

Autoimmune Disease Surveillance

• Obtain complete blood count with differential at every visit to detect autoimmune cytopenias (ITP, autoimmune hemolytic anemia), which occur in 11-12% of patients and represent the most common autoimmune manifestation 1, 4.
• Maintain vigilance for the broad spectrum of autoimmune diseases (overall prevalence ~20%), including thyroid disease, arthritis, and other organ-specific autoimmunity, through targeted history and examination 1, 4.

Malignancy Screening

• Perform systematic screening for lymphoproliferative disease and malignancy at each visit through physical examination (lymphadenopathy, splenomegaly) and appropriate imaging when clinically indicated 1, 4.
• Maintain heightened awareness for lymphomas and gastric carcinoma, which are the most frequently reported malignancies in CVID 6.

Infection Management During Follow-Up

Breakthrough Infection Protocol

• Add prophylactic antibiotics for any patient experiencing breakthrough infections despite adequate IgG replacement, continuing for months, years, or indefinitely based on clinical need 4.
• Patients with recurrent bronchitis and pneumonia—who are at greatest risk for developing bronchiectasis—derive the most benefit from long-term prophylaxis 4.
• Treat acute infections promptly and aggressively with appropriate antimicrobials, recognizing that common gastrointestinal pathogens include Giardia, Campylobacter jejuni, and Salmonella 4.

Advanced Complications Requiring Specialist Referral

Late-Onset Combined Immunodeficiency

• Monitor CD4 counts in patients developing new opportunistic infections, gastrointestinal disease, splenomegaly, or lymphomas, as approximately 9% of patients develop late-onset combined immunodeficiency with CD4 counts <200 cells/mL 1.

Consideration for Advanced Therapies

• Refer for stem cell transplantation evaluation in patients with malignancy or severe organ damage (e.g., severe GLILD), though experience is very limited with significant mortality risk 1, 2, 4.
• Consider lung transplantation referral for end-stage pulmonary disease, though this has been attempted in very few patients with limited success 2, 4.

Critical Pitfalls to Avoid

• Do not rely solely on clinical symptoms and PFTs to assess lung disease progression—HRCT can detect worsening bronchiectasis in asymptomatic patients with stable pulmonary function 3.
• Do not assume adequate IgG replacement prevents all complications—bronchiectasis prevalence increases from 47.3% to 54.7% over 5 years even with treatment, requiring ongoing surveillance 4.
• Do not delay dose escalation in patients with breakthrough infections—early aggressive management prevents irreversible organ damage and reduces mortality 2, 4, 7.
• Do not focus monitoring exclusively on infections—immune dysregulation (autoimmunity, lymphoproliferation, malignancy) affects >30% of patients and requires systematic surveillance 8.