Immunology · Year 2 · from Immunology
Case 2: Common Variable Immunodeficiency (CVID)
Patient Demographics
- Age: 32 years old
- Sex: Female
- Ethnicity: Caucasian
Chief Complaint
Recurrent sinusitis and pneumonia
History of Present Illness
A 32-year-old woman is referred for evaluation of recurrent respiratory infections. Over the past 5 years, she has had 8-10 episodes of sinusitis requiring antibiotics annually and 3 episodes of pneumonia requiring hospitalization. She also reports chronic diarrhea and has been diagnosed with "IBS." She had childhood chickenpox and recovered normally from measles vaccine. Review of records shows progressively worsening pulmonary function tests.
Past Medical History
- Recurrent sinusitis (8-10 episodes/year for 5 years)
- Three hospitalizations for bacterial pneumonia (Streptococcus pneumoniae, Haemophilus influenzae)
- Chronic diarrhea (5 years)
- Autoimmune thyroiditis (on levothyroxine)
- Idiopathic thrombocytopenic purpura (ITP) at age 28
Family History
- Brother with "immune problems"
- No consanguinity
Physical Examination
- General: Well-appearing woman
- Vital Signs: Normal
- HEENT: Mucosal inflammation of nasal turbinates, no tonsillar tissue visible
- Lungs: Scattered crackles at bases bilaterally
- Abdomen: Mild hepatomegaly, spleen not palpable
- Extremities: No clubbing
- Lymphatics: Small palpable lymph nodes in cervical chain
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| IgG | 180 mg/dL | 700-1600 mg/dL |
| IgA | <5 mg/dL | 70-400 mg/dL |
| IgM | 25 mg/dL | 40-230 mg/dL |
| CD19+ B cells | 8% (normal) | 5-20% |
| CD4+ T cells | Normal | -- |
| CD8+ T cells | Normal | -- |
| Tetanus antibody (post-vaccine) | <0.1 IU/mL | >0.5 IU/mL |
| Pneumococcal antibodies (post-Pneumovax) | 0/14 serotypes protective | >70% protective |
| HIV | Negative | -- |
| CT chest | Bronchiectasis lower lobes | -- |
Clinical Image
Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Bronchiectasis_HRCT.jpg). Licensed under CC BY-SA 4.0.
Diagnosis
Common Variable Immunodeficiency (CVID) with secondary bronchiectasis and autoimmune complications.
Discussion
CVID is the most common symptomatic primary immunodeficiency in adults, characterized by hypogammaglobulinemia with impaired vaccine responses but preserved B cell numbers. The pathophysiology is heterogeneous, with identified genetic causes (ICOS, TACI, BAFFR, CD19 mutations) in only 10-15% of patients.
Key diagnostic criteria:
- Low IgG plus low IgA and/or IgM
- Impaired vaccine responses (tested with both protein and polysaccharide antigens)
- Exclusion of other causes (HIV, medications, protein-losing states)
- Age >4 years (to exclude transient hypogammaglobulinemia of infancy)
CVID complications beyond infections:
- Autoimmunity (ITP, AIHA, autoimmune thyroiditis) - present in 20-25%
- Granulomatous disease (lungs, liver, spleen)
- GI disease (IBD-like, nodular lymphoid hyperplasia, malabsorption)
- Lymphoma (10-fold increased risk)
- Bronchiectasis (from recurrent infections)
Treatment
- Immunoglobulin replacement: IVIG or subcutaneous Ig (SCIG) - lifelong, targeting trough IgG >500 mg/dL (higher for those with chronic lung disease)
- Treat established bronchiectasis: Airway clearance, surveillance for infections
- Monitor for complications: Annual screening for autoimmunity, lymphoproliferation
- Vaccination: Inactivated vaccines can be given (may have suboptimal response); avoid live vaccines