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Common Variable Immunodeficiency (CVID)

Common variable immunodeficiency (CVID) is the most common form of severe antibody deficiency affecting both children and adults. It is a disorder characterized by a low level of certain immunoglobulins in the blood that results in an impaired ability of the immune system to produce antibodies after exposure to bacteria and viruses.

Patients with CVID are increasingly susceptible to frequent, chronic, severe and often unusual infections of the respiratory (nose, sinuses, bronchi, lungs) and digestive tracts. The age of onset is usually in the 20s or 30s; however, certain patients can develop CVID at much older age such as 40s and 50s.

In some cases, a variety of genetic mutations and familial inheritance contribute to a failure to generate antibodies against antigens and a poor response to vaccines. However, the exact causes of CVID are mainly unclear in most cases.

Both males and females seem to be equally affected. It’s the most common primary immunodeficiency in adults. The clinical course and the immunoglobulin's level of deficiency vary widely depending on the individual.

Bacteria such as H. influenzae, Streptococcus pneumoniae and Staphylococcus aureus are the most common causes of infections because they naturally colonize human nasopharynx and have the ability to migrate to other parts of the human body to cause various diseases of the upper respiratory tract such as pneumonia, otitis media, and bronchitis.

Digestive problems include chronic diarrhea or constipation, nausea resulted in vomiting, a failure to absorb nutrients from foods, weight loss, and abdominal pain. Infections could also occur in other organs, such as the eyes, skin, liver, or lymph nodes. Many of these infections respond to antibiotics but will occur again after antibiotic treatment is completed.

Once the immune system becomes unbalanced, a domino effect occurs where the people with CVID in addition to infections potentially could develop autoimmune disorders, a condition in which the body attacks its healthy cells.

Common conditions are thrombocytopenic purpura, anemia, psoriasis, vitiligo, rheumatoid arthritis, atrophic gastritis, inflammatory bowel disease, and other disorders. Patients with CVID are also at higher risk of blood and stomach cancers (lymphoid and gastrointestinal cancers.)

The diagnosis of common variable immunodeficiency (CVID) can be assigned to a patient over age four who demonstrates all of the following characteristics:

  • Significantly reduced total serum concentrations of immunoglobulin G (IgG)

  • Low immunoglobulin A (IgA) and/or immunoglobulin M (IgM)

  • Poor or absent response to immunization

  • The absence of any other defined immunodeficiency state (ie, CVID is a diagnosis of exclusion)

Most patients present with recurrent sinopulmonary infections. Serum immunoglobulin levels are markedly abnormal in patients with CVID. Serum immunoglobulin G (IgG) should be below the lower limit of normal and generally under 400 mg/dL.

In addition, immunoglobulin A (IgA) and/or low immunoglobulin M (IgM) should be below the lower limit of normal. One-half of patients have no detectable immunoglobulin. Once low immunoglobulin levels have been demonstrated, the patient's ability to respond to vaccines should be assessed.

IgG antibodies to tetanus and diphtheria, which provide an estimate of the patient's response to protein-based vaccines. A panel of IgG antibodies to 14 or 23 serotypes of the polysaccharides in the polysaccharide pneumococcal vaccine, which provide an estimate of the patient's response to polysaccharide-based vaccines.

Treatment consists of immunoglobulin replacement therapy, which refills certain immunoglobulins that a patient lacks to a healthy level. These Ig infusions are administered at established intervals for life and could cure the most symptoms. Treatment may also involve administration of immunosuppressants, high dose steroids, and antibiotics.

In addition to recurrent infections, patients with CVID have evidence of immune dysregulation leading to autoimmunity, a variety of inflammatory disorders, and malignant disease.

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