Practice Essentials
Common variable immunodeficiency (CVID), one of the most prevalent primary immunodeficiency diseases, is a heterogeneous group of immunologic disorders of unknown etiology. CVID is characterized by marked reduction in serum levels of immunoglobulin G (IgG) and immunoglobulin A (IgA), as well as reduced immunoglobulin M (IgM) in about half of cases.
Signs and symptoms
Clinical manifestations of CVID include the following:
Recurrent infections
Autoimmune disease
Lymphoid hyperplasia
Granulomatous diseases
Malignancy
Recurrent infections may include the following:
Pyogenic sinopulmonary tract infection, especially after puberty
In some cases, infections with unusual organisms (eg, Pneumocystis jiroveci, mycobacteria, various fungi)
Mycoplasma pneumoniae infections in the urinary tract, joints, and deep abscesses
Persistent diarrhea and malabsorption caused by Giardia lamblia
Severe and recurrent infections with herpes simplex
Unusual enteroviral infections with a chronic meningoencephalitis and a dermatomyositis-like illness; presenting symptoms are either acute or insidious, with signs of encephalitis, seizures, headache, sensory motor disturbances, and personality changes
Autoimmune conditions in patients with CVID are as follows:
Idiopathic thrombocytopenic purpura (ITP)
Hemolytic anemia
More rarely, autoimmune neutropenia
Other solid organ–specific autoimmune diseases (eg, pernicious anemia, thyroid diseases, vitiligo)
Insulin-dependent diabetes
Psoriasis
Systemic lupus erythematosus
Rheumatoid arthritis
Juvenile rheumatoid arthritis
Uveitis
Severe gastroenteropathy with severe malabsorption, nodular lymphoid hyperplasia, and chronic inflammatory bowel disease (eg, ulcerative colitis, Crohn disease)
Physical examination findings may include the following:
Generalized lymphadenopathy and splenomegaly
Failure to thrive in young children, secondary to frequent infection and increased energy expenditure
See Clinical Presentation for more detail.
Diagnosis
The diagnosis of CVID is based on the following:
Defective functional antibody formation (eg, low IgG response to vaccination)
Decreased (not absent) serum immunoglobulin (Ig)G and IgA levels (usually)
Decreased serum IgM level (generally, but not invariably)
Exclusion of other known causes of antibody deficiency
See Workup for more detail.
Management
A major component of medical care is anti-infective and prevention of further infectious episodes by regular infusion of human immunoglobulin and antimicrobial therapy. Patients with autoimmune manifestations may require immunosuppressive therapy.
Immunoglobulin replacement is intravenously administered on a regular basis, as follows:
Tailor dose and frequency to the Ig trough levels and to clinical symptoms
Measure serum IgG level before each infusion, and accordingly adjust the dose of IVIG
Maintain trough serum IgG concentrations at 400–500 mg/dL in adults
For most patients, a dose of 400-600 mg/kg every 3–4 weeks suffices to reduce the frequency of infection
Some patients with chronic lung disease require up to 600–800 mg/kg per month
Once established on a regular regimen, IVIG can be administered at home
Subcutaneous infusion of Ig (SCIG) is an alternative method for patients with difficult venous access or for those who experience serious side effects from IVIG.
Anti-infective treatment is as follows:
Infections should be treated early with full doses of antimicrobial agents
Whenever possible, narrow-spectrum drugs should be used on the basis of microbial sensitivity testing
Prophylactic antibiotics should be avoided
Antiviral agents may be useful in some patients with persistent or severe viral infections
Some patients with a severe autoimmune process may require immunosuppressive therapy with one of the following:
Systemic corticosteroids
Cyclosporin A
Anti-CD20 monoclonal antibody (rituximab)
Anti-TNF monoclonal antibody (infliximab)
See Treatment and Medication for more detail.