Common Variable Immunodeficiency

Introduction

Essentials of Diagnosis

• Defect in terminal differentiation of B cells, with absent plasma cells and deficient synthesis of secreted antibody.
  
• Frequent sinopulmonary infections secondary to humoral immune deficiency.
  
• Confirmation by evaluation of serum immunoglobulin levels and deficient functional antibody responses.

General Considerations

The most common cause of panhypogammaglobulinemia in adults is common variable immunodeficiency, a heterogeneous immunodeficiency disorder clinically characterized by an increased incidence of recurrent infections, autoimmune phenomena, and neoplastic diseases. The onset generally is during adolescence or early adulthood but can occur at any age. The prevalence of common variable immunodeficiency is about 1:80,000 in the United States.

Clinical Findings

A. Symptoms and Signs
The pattern of immunoglobulin isotype deficiency is variable. Most patients present with significantly depressed IgG levels, but over time all antibody classes (IgG, IgA, and IgM) may be affected. Increased susceptibility to pyogenic infections is the hallmark of the disease. Virtually all patients suffer from recurrent sinusitis, with bronchitis, otitis, pharyngitis, and pneumonia also being common infections. Infections may be of prolonged duration or associated with unusual complications such as meningitis or sepsis.

Gastrointestinal disorders are commonly associated, and patients may develop a sprue-like syndrome, with diarrhea, steatorrhea, malabsorption, protein-losing enteropathy, and hepatosplenomegaly. Paradoxically, there is an increased incidence of autoimmune disease (20%), though patients may not display the usual serologic markers. Autoimmune cytopenias are most common, but also commonly seen are autoimmune endocrinopathies, seronegative rheumatic disease, and gastrointestinal disorders. Lymph nodes may be enlarged in these patients, yet biopsies show marked reduction in plasma cells. Noncaseating granulomas are frequently found in the spleen, liver, lungs, or skin. There is an increased propensity for the development of B cell neoplasms (50- to 400-fold increase risk of lymphoma), gastric carcinomas, and skin cancers.

B. Laboratory Findings
Diagnosis is confirmed in patients with recurrent infections by demonstration of functional or quantitative defects in antibody production. Serum IgG levels are usually less than 250 mg/dL; serum IgA and IgM levels are also subnormal. Decreased to absent functional antibody responses to protein antigen immunizations establish the diagnosis.