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COMMON VARIABLE IMMUNODEFICIENCY (CVID)

DEFINITION:

A heterogeneous group of B-cell disorders characterized by hypogammaglobulinemia resulting in the late onset of recurrent sino-pulmonary and gastrointestinal infections.

EPIDEMIOLOGY:

incidence: ?
age of onset:
- 2nd and 3rd decades; rarely before 6 years of age
risk factors:
- familial - autosomal recessive and dominant forms
  - chrom.#: ?
  - gene: ?
- M = F

PATHOGENESIS:

1. Etiology

1. Hereditary Predisposition

autosomal recessive and dominant forms
increased incidence of hypogammaglobulinemia, Selective IgA Deficiency, autoimmune disease, and neoplasms among first degree relatives

2. Acquired

may also be acquired forms

2. Defect

hypothesized that a variety of factors (hereditary and acquired) result in the failure of B cells to undergo terminal plasma cell differentiation and/or to secrete immunoglobulins -> humoral-me-iated immunodeficiency -> persistent infections by encapsulated bacteria (H. flu, pneumococcus, staphylococcus), mycoplasma, or ureaplasma
the differentiation of B-cells into antibody-secreting cells may be blocked at any number of sites
may represent a heterogeneous group of disorders where the B cells fail to receive or respond to normal maturational signals as B-cells from patients with CVID have the capacity to differen-tiate into plasma cells when exposed to an appropriate set of stimuli in vitro
apart from a later onset, the clinical manifestations of CVID may be indistinguishable from those of Bruton Disease

CLINICAL FEATURES:

1. Immunodeficiency Manifestations

1. Respiratory

1. Sinopulmonary Infections (90%)

may be chronic and recurrent
paranasal sinusitis, bronchitis, chronic cough
chronic otitis media (30%)

2. Serious Pulmonary Involvement

30-40% progress to develop serious pulmonary involvement
pneumonia
interstitial fibrosis
panlobular emphysema
chronic lung disease
chronic progressive bronchiectasis

2. Gastrointestinal

1. Chronic Diarrhea (60%) +/-

malabsorption (vitamin B12) +/- steatorrhea
protein-loosing enteropathy
giardiasis (35-65%)
clostridium difficle (24%)

2. Others

bacterial overgrowth, disaccharidase deficiency, jejunal villous atrophy, lactose intolerance, Nodular
Lymphoid Hyperplasia

2. Complications

1. Autoimmune Disorders

hemolytic anemia, pernicious anemia (5%), autoimmune neutro-penia
Rheumatoid Arthritis, SLE, ITP, Dermatomyositis, Scleroder-ma, Chronic Active Hepatitis

2. Neoplasms

present in the 5th to 6th decades
reticuloendothelial tumors (lymphomas)
stomach cancer

3. Infectious

noncaseating granulomas of the lungs, spleen, liver, skin
vaccine-associated poliomyelitis
infectious mononucleosis
echovirus meningoencephalitis and dermatomyositis

4. Others

nondeforming polyarthritis and/or polyarthralgias
Amyloidosis
Hemolytic Uremic Syndrome
cutaneous anergy (in up to 50% of cases)

INVESTIGATIONS:

1. Serum

1. Humoral-Mediated

variable number of circulating B-cells from decreased to increased (there are only a few circulating immature B-cells in Bruton Disease)
proliferating B-cells may cause splenomegaly, hepatomegaly, and hypertrophy of lymph nodes & intestinal lymphoid tissue - absence of plasma cells in some lymphoid tissues (lymph nodes, bone marrow, tonsils, spleen)
reduced levels of IgG, IgA, and IgM (IgM tends to be less affected)
diverse expression of surface immunoglobulins on B-cells
increased incidence of autoantibodies (rheumatoid factor, anti-RBC antibodies, antibodies to T- or B-cells)
markedly reduced antibody response on challenge with a variety of antigens

2. Cell-Mediated

normal number and function of T cells, i.e., initially there is normal cell-mediated immunity
normal CD4+ T Helper Cell number and function
normal or increased CD8+ T Suppressor Cell number
as patients age, significant T-cell abnormalities may develop

3. CBC

pancytopenia - anemia (40%), leukopenia, lymphopenia
anemia may be due to folate or Vitamin B12 malabsorption

MANAGEMENT:

1. Supportive

antibiotics for specific infections
flagyl for giardiasis
corticosteroids for noncaseating granulomas
follow for the development of autoimmune disorders or other complications and treat any that develop

2. Immunosuppression

1. Intravenous Immunoglobulin (IV IgG)

0.1-0.6 g/kg/month
indications:
- severe sinopulmonary infections
- echovirus-induced meningoencephalitis and dermatomyo-sitis
- polyarthritis and/or polyarthralgia

2. Cimetidine

may reverse T Suppressor activity and subsequently increase serum IgG levels

3. Prognosis

increased mortality especially from late-onset malignancies

Pediatric Database - COMMON VARIABLE IMMUNODEFICIENCY (CVID)

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