Common Variable Immunodeficiency (CVID)

Epidemiology

  • Sex: M = F
  • Usually present initially during late childhood or early adulthood (may present earlier in some cases)
  • Persistent Enterovirus infection is less common in CVI than in Bruton’s Aggammaglobulinemia

Etiology

  • Autosomal recessive inheritance
    • Possibly localized to MHC on chromosome 6

Physiology

  • Possibly due to defective receptor for TH elaborated cytokines, intrinsic block of isotype switching, or autoAb against B or T-cells
  • Abnormal B-cell Differentiation (primary defect): B-cells are able to proliferate normally though
    • Normal total B-cell number
    • Hyperplastic lymphoid follicles
    • Normal mitogen response
    • Absence of plasma cells in lymphoid tissues and blood
  • TH Cytokine Production Dysregulation: possibly causes defect in cell-mediated immunity also
  • T-Cell Oversuppression: may play a role (since a case with HIV infection normalized Ig an resolved bacterial infctions)

Diagnosis

  • CXR/Chest CT Patterns
    • Bronchiectasis:
    • Pneumonia:
  • Total Serum IgG: decreased or absent
    • IgG subclasses: decreased
    • Note: during active infection, IgG levels may normalize (it is possible to have normal total IgG levels with a IgG subclass deficiency)
  • Serum IgA: variably decreased
  • Serum IgM: variably decreased

Clinical

(predisposed to infection with encapsulated bacteria)
(66% of cases are first symptomatic in adulthood)

Pulmonary Manifestations

  • Bronchiectasis (see [[Bronchiectasis]]): 40% of cases
  • Recurrent Pulmonary Infection (especially due to encapsulated bacteria, PCP, non-TB, mycobacteria, and fungi)
    • Bronchitis
    • Pneumonia (see [[Pneumonia]])
  • Pulmonary Lymphocytic Infiltration: few reported cases
  • Sarcoid-like Granulomas: few reported cases

Upper Airway Manifestations

  • Recurrent Sinusitis:
  • Recurrent Otitis Media:

GI Manifestations

  • Celiac Sprue-Like Syndrome: probably due to Giardia infection
  • Infectious Diarrheas: Campylobacter, Salmonella

Rheumatic Manifestations

  • Septic Arthitis:

Neurologic Manifestations

  • Meningitis:

Hematologic Manifestations

  • Acquired Thalassemia (see Thalassemia, [[Thalassemia]])

Associated Diseases

  • Autoimmune Diseases
    • Alopecia:
    • Autoimmune Thrombocyopenia: precedes diagnosis of CVI in 81% of cases
    • Autoimmune Hemolytic Anemia:
    • Vitiligo:
    • SLE: SLE has also been reported to precede CVI diagnosis in some cases
  • EBV Infection:
  • Malignancy: 10x increased risk of cancer
  • Lymphoma: females have an especially increased risk
  • Malignant Thymoma: 10% of malignant thymoma cases develop a CVI-like syndrome

Treatment

Treatment of Infections

  • As required

IVIG

  • Monthly administration
  • Improves daily symptoms of sinusitis and sputum production
  • Decreases need for antibiotics
  • Improves airway obstruction
  • Decreases frequency and severity of infections
  • May prevent bronchiectasis
  • Replacement in IgA-deficient CVI patients may cause anaphylaxis (due to IgE reaction against the infused IgA): use low IgA preparations
  • IVIG has no impact on autoimmune thrombocytopenia when it co-exists with CVI

Retinoic Acid Analogues

  • Promote B-cell differentiation

H2 -Blockers

  • Increases Ig production is some patients (due to modulation of T-cell inhibition)

IL-2

  • May be useful, but side effects limit use

Lung Transplant

  • One case (despite Ig replacement) still had T-cell defect associated respiratory infections

References

  • xx

Common Varable Immunodeficiency (CVID)

-Diagnosis:
1) Quant Immunoglbulins: best screening test for antibody deficiencies
-IgG: decreased (less than 400 mg/dl)
-IgM: decreased (less than 25 mg/dl) in over 80 percent of cases
-IgA: decreased (less than 10 mg/dl) in 70 percent of cases
-Clinical: mean age of onset in teens
1) Recurrent Upper and Lower Resp Tract Infxns/Bronchiectasis: encapsulated (H flu, Pneumococci), Mycoplasma, and PCP (rarely)
2) Joint/Bone Infxns:
3) GI Infections:
4) Autoimmune Disorders: ITP, RA, JRA, SLE, autoimmune hemolysis
5) Malignancy: gastric ca, NHL
6) BOOP:
7) LIP:
8) Follicular Bronchiolitis:
9) Granulomatous ILD: may be a type of sarcoid
10) Thymoma: CVID + Thymoma is called Good’s syndrome
-Treatment:
1) IVIG:
2) Steroids: for autoimmune hemolysis and ITP
3) CSA: may be useful for diffuse lung diseases