Common Variable Immunodeficiency |
Common Variable Immunodeficiency, also called Hypogammaglobulinemia, is a relatively common primary immune deficiency and affects males and females in equal numbers. The exact incidence is unknown but is about 1 in 50,000.
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Common Variable Immunodeficiency is characterized by a lack of antibody producing B-cells or plasma cells, low levels of most or all immunoglobulin classes, and recurrent bacterial infections. Its name is derived from the fact that it is a relatively common form of immune disorder and that the degree and type of deficiency, as well as its clinical signs and symptoms, vary among patients. In most patients there is a reduced amount of IgG, IgA, and IgM in the blood. However, in some patients just the IgG and IgA classes of immunoglobulins are reduced. Some degree of T-lymphocyte dysfunction is present in up to 50% of the patients. The disorder first presents as recurrent bacterial infection in infancy and early childhood, during puberty, or even in the third, fourth, or later decades of life. Common Variable Immunodeficiency is also known by other names, often Hypogammaglobulinemia, or sometimes Adult Onset Hypogammaglobulinemia. Another name previously used was Acquired Agammaglobulinemia, but use of this term is discouraged because of Acquired Immunodeficiency Syndrome or AIDS. This name was usually applied to persons who developed the immunodeficiency in their late 20's through their 50's so is more appropriately termed "late onset". Because of the variable manifestation of this disorder, no clear pattern of inheritance has been observed. In most cases, there is no family history of immunodeficiency. However, in instances where more than one family member is affected, an autosomal recessive (two abnormal genes, one from each parent) mode of inheritance is suggested. In about 5% of the cases, one or more of the family members can be found to be IgA deficient.
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Frequent presenting features of this disorder are recurrent infections of the ears, sinuses, bronchi, and lungs. If these infections are sever and occur repeatedly, permanent damage to the bronchi may occur resulting in bronchiectasis (widening and scarring of the bronchial tubes). Common bacteria that often cause infection in Hypogammaglobulinemia include Hemophilus influenzae, pneumococci, and staphylococci. Another common infection agent is mycoplasma pneumonia. Some patients may have regular morning cough that produces yellow or green sputum suggestive of a chronic infection or bronchiectasis (widening and scarring of the bronchi). Other patients who may not receive adequate gammaglobulin replacement may develop painful inflammation of the knee, ankle, elbow, or wrist joints. These inflammatory symptoms may disappear with the administration of gammaglobulin therapy. Gastrointestinal complaints occur more frequently, and may include abdominal pain, bloating, nausea, vomiting, diarrhea or weight loss. These symptoms may be indicative of malabsorption of fat or certain sugars or may indicate the presence of the Giardia lambia parasite. Major gastrointestinal manifestations include: nodular lymphoid hyperplasia (excessive lymphatic tissue) giardiasis (protozoan disease), a sprue-like (gastrointestinal) disorder, pernicious anemia, atrophic (tissue wasting) gastritis, aphthous stomatitis (ulcerous mouth inflammation), inflammatory bowel disease and malignancy. Some patients with Common Variable Immunodeficiency develop autoantibodies (antibodies to their own tissue) which can attack and destroy red cells, white cells, or platelets in the blood. Other autoimmune processes can cause other problems. Unless patients have developed complications, they do not have physical abnormalities. When physical disease appears, the presence of enlarged spleen and lymph nodes is fairly common. Patients with chronic lung disease may have decreased vital capacity. Gastrointestinal problems may impair normal growth and induce weight loss.
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Diagnostic criteria include significantly decreased serum IgG and IgA levels not always associated with decreased serum IgM levels. However, antibody production is abnormal. In most patients, circulating B-lymphocytes is varied and may include the following:
In some patients whose B-cells fail to develop normally, large numbers of B-cells may accumulate in lymph tissue which has been stimulated by bacteria or other foreign cells. This causes marked peripheral lymph node disease and spleen enlargement which sometimes suggestive of malignancy. Other patients develop overgrowth of intestinal lymphoid tissues, and, rarely, lymphoma or other malignancies. Various inheritance patterns have been noted, but sporadic cases with no apparent inheritance factors are most common. Family members of persons with Common Variable Immunodeficiency have a higher than usual incidence of IgA and IgG subclass deficiency; autoimmune disorders (immune system mistakenly attacks the body's own tissues); and autoantibodies (antibodies to their own tissue). These autoimmune disorders may include pernicious anemia, hemolytic anemia, idiopathic thrombocytopenic purpura, endocrinopathies, rheumatoid arthritis, systemic lupus erthematosus and dermatomyositis. There is also a high frequency of similar autoimmune disorders among first degree relatives of these patients. Aside from measuring serum immunoglobulins, a patient's ability to make protective amounts of antibodies after a vaccination is an excellent means of further evaluating B-cell function.
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Treatment is similar to other severe B-cell defects. Immunoglobulin concentrates are the treatment of choice and almost always provide clinical improvement. Intravenous gammaglobulin in doses of 300mg/kg every three weeks or 400mg/kg every four weeks (two common dosage systems) is usually needed to restore normal antibody levels. However, because gammaglobulin contains little IgA or IgM, the total antibody deficiency is not replaced. Patients with chronic sinusitis or lung disease may need long term treatment with broad spectrum antibiotics like ampicillin, tetracycline, cephalosporin and trimethoprim/sulfmethoxazole (brand names: Bactrim/Septra), and Ciprofloxacin (brand name: Cipro) or others. Physical therapy and daily postural draining of secretions and pus from lungs and bronchi may be necessary for those who have developed bronchiectasis. For those patients suffering gastrointestinal problems or malabsorption problems, evaluation for Giardia lamblia, rotavirus, or other infections should be undertaken. In most patients with immunodeficiency and arthritis who have never received immunoglobulin, adequate treatment with immunoglobulin usually provides symptom relief. Unless lung damage has occurred, most patients will not develop pneumonia after gammaglobulin treatment has started.
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The major factor in assessing prognosis of these patients is dependent on the extent of damage to lungs and other organs, and how successfully future infections can be prevented.
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Inheritance patterns vary among patients and are not present in most patients, making this disorder impossible to prevent. Back to
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