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