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

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Etiology

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

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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)

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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

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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

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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

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References

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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