Common Variable Immunodeficiency

Key Features

Essentials of Diagnosis

• Frequent sinopulmonary infections secondary to humoral immune deficiency

• Low serum immunoglobulin levels and deficient functional antibody responses

• Primary defect may be with B cells or T cells

General Considerations

• Most common symptomatic primary immunodeficiency disorder

• Heterogeneous immunodeficiency disorder clinically characterized by an increased incidence of recurrent infections, autoimmune phenomena, and neoplastic diseases

Demographics

• Onset is generally in early adulthood but it can occur at any age

• The prevalence is about 1 in 25,000 in the United States

• Most cases are sporadic; about 10–20% are familial

Clinical Findings

• Increased susceptibility to infections, especially with encapsulated organisms

• Recurrent sinusitis

• Bronchitis

• Otitis

• Pharyngitis

• Pneumonia

• Gastrointestinal infections and dysfunction

• Autoimmune cytopenias

• Autoimmune endocrinopathies, seronegative rheumatic disease, and gastrointestinal disorders

• Lymph nodes may be enlarged in these patients, yet biopsies show marked reduction in plasma cells

Diagnosis

• Assess serum quantitative immunoglobulin levels

• Reduced serum levels of IgG, IgM, or IgA

• Diagnosis is made in patients who have reduced serum immunoglobulins and poor antibody response to vaccines, after exclusion of secondary causes, such as

  • Proteinuria

  • Protein-losing enteropathy

  • Drug effects (eg, rituximab, antiepileptics)

  • Chronic lymphocytic leukemia, lymphoma, and plasma cell myeloma

Treatment

• Should be treated aggressively with antibiotics at the first sign of infection; antibiotic therapy should cover encapsulated bacteria

• Infections with other microorganisms also can develop, including viruses, parasites, and extracellular gram-positive or gram-negative bacteria (such as Staphylococcus aureus or Pseudomonas aeruginosa)

Outcome

Complications

• Infections may be prolonged or associated with unusual complications such as meningitis or sepsis

Prevention

• Mainstay of preventive therapy

  • Subcutaneous or intravenous immunoglobulin replacement therapy, typically provided every 1–4 weeks, with a typical monthly dose of 300–600 mg/kg

  • Adjustment of the dosage or infusion interval is made primarily on the basis of clinical responses, in addition to serum IgG levels

  • Such therapy is essential for decreasing the incidence of potentially life-threatening infections, increasing quality of life, and reducing the progression of lung disease

When to Refer

• Refer patients with low serum immunoglobulins and history of recurrent or unusual infections, autoimmune disease, or family history of immunodeficiency

• The presence of bronchiectasis without a known underlying cause such as cystic fibrosis should raise the suspicion of a primary immunodeficiency; even when serum immunoglobulins are normal, the patient can have a specific antibody deficiency that would warrant further evaluation

References