ALLERGIC AND IMMUNOLOGIC CONDITIONS

Common Variable Immunodeficiency (CVID)

Classification: Heterogeneous primary antibody deficiency with impaired B-cell terminal differentiation and poor specific-antibody production (Kishiyama et al., 2019).

Key diagnostic discriminator: Recurrent sinopulmonary infection in an older child or adult, low IgG plus low IgA and/or IgM, poor vaccine response, and no secondary cause. B cells are often present (Kishiyama et al., 2019).

Clinical priority: Hemoptysis, progressive dyspnea, hypoxemia, or recurrent lower-respiratory infection may indicate bronchiectasis or interstitial lung disease (Kishiyama et al., 2019).

Etiology and risk factors

  • CVID is a heterogeneous syndrome with multiple genetic and immune-regulatory mechanisms; a single cause is not identified in many patients (Kishiyama et al., 2019).
  • Presentation may occur in childhood but commonly appears in adolescence or adulthood. Autoimmunity, lymphoproliferation, granulomatous disease, or family history can precede recognition (Kishiyama et al., 2019).

Pathophysiology

  • B cells usually reach the circulation but fail terminal differentiation into effective antibody-secreting plasma cells. Impaired class switching, T-cell help, cytokine signaling, or immune regulation may coexist (Kishiyama et al., 2019).
  • Reduced IgG and specific antibody impair opsonization and mucosal defense. Repeated infection drives chronic sinus disease, lung remodeling, and bronchiectasis; immune dysregulation contributes to autoimmunity and lymphoid complications (Kishiyama et al., 2019).

Clinical manifestations

  • Recurrent bacterial sinusitis, otitis, pneumonia, chronic cough, bronchiectasis, Giardia or other gastrointestinal infection, chronic diarrhea, or malabsorption (Kishiyama et al., 2019).
  • Autoimmune cytopenias, splenomegaly, lymphadenopathy, granulomatous disease, interstitial lung disease, inflammatory bowel-like disease, and increased lymphoma or gastric cancer risk may occur (Kishiyama et al., 2019).

Findings that argue against or redirect

  • Normal IgG and normal functional antibody responses argue against CVID. Isolated low IgA favors selective IgA deficiency (Kishiyama et al., 2019).
  • Markedly absent B cells in a male infant favors XLA. A medication, protein-losing state, nephrotic syndrome, hematologic malignancy, HIV, or other secondary cause must be excluded before labeling CVID (Kishiyama et al., 2019).

Diagnostic evaluation

  • Repeat quantitative IgG, IgA, and IgM and assess specific antibody responses after immunization when clinically appropriate. Lymphocyte subsets help distinguish CVID from defects with absent B cells or major T-cell loss (Kishiyama et al., 2019).
  • Exclude medication effects, protein loss, malignancy, HIV, and other secondary causes. Evaluate pulmonary and gastrointestinal complications when symptoms indicate organ damage (Kishiyama et al., 2019).

Expected diagnostic and laboratory findings

  • Low IgG with low IgA and/or IgM on repeated testing; impaired vaccine response; B cells normal or reduced; T-cell abnormalities may coexist (Kishiyama et al., 2019).
  • The diagnosis is syndromic and exclusionary rather than based on one confirmatory gene test. Some patients have an identifiable pathogenic variant (Kishiyama et al., 2019).

Differential diagnosis

  • XLA: male infancy, BTK defect, and almost absent B cells (Kishiyama et al., 2019).
  • Selective IgA deficiency: isolated IgA reduction with normal IgG and IgM (Kishiyama et al., 2019).
  • Secondary antibody deficiency: medication, protein loss, lymphoid malignancy, nephrotic syndrome, or HIV explains the laboratory pattern (Kishiyama et al., 2019).
  • SCID or another combined defect: severe T-cell abnormality and opportunistic infection accompany the antibody defect (Kishiyama et al., 2019).

Treatment and management

  • Regular intravenous or subcutaneous immunoglobulin replacement and prompt infection treatment are central. Selected patients need antimicrobial prophylaxis and airway-clearance or bronchiectasis management (Kishiyama et al., 2019; Norris, 2020).
  • Manage autoimmune, inflammatory, gastrointestinal, pulmonary, and malignant complications with immunology and organ-specific specialists. Do not assume that immunoglobulin replacement treats the noninfectious complications (Kishiyama et al., 2019; Norris, 2020).

Additional complications and red flags

  • Persistent lymphadenopathy, splenomegaly, weight loss, or cytopenias require evaluation for immune dysregulation and malignancy (Kishiyama et al., 2019).

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References

Kishiyama, J. L., Chang, J. J., & Donovan, S. M. (2019). Disorders of the immune system. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed.). McGraw-Hill Education.

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.