Last updated: November 4, 2014
Synonyms: Common variable immunodeficiency; severe combined immun- odeficiency; X-linked immunodeficiency.
ICD-9 Codes: Immunodeficiency, 279.3; common variable, 279.06; severe combined, 279.2.
Definition: Immunodeficiency diseases are a diverse group of disorders that result from quantitative or qualitative defects in specific parts of the immune system. They may be categorized as primary or secondary (Table 18).
Etiology: Primary immunodeficiencies often relate to focal defects in enzyme systems, cell surface molecules, or other factors critical to development or function of immunocompetent cells. Secondary immunodeficiencies represent impairments in the immune response related to use of immunosuppressive medications, systemic infections, and other conditions.
Demographics: The incidence of primary immunodeficiencies ranges from one in 10,000 to one in 100,000 population. They typically arise in children, and approximately 85% of cases are found in persons 15 years of age or younger. Because many of the primary immunodeficiencies are X-linked, boys substantially outnumber girls. Secondary immunodeficiencies are much more common than primary; in addition, they occur most commonly among older adults.
Cardinal Findings: The clinical hallmark of immunodeficiency is increased susceptibility to infection. However, some immunodeficiencies are associated with a variety of autoimmune and musculoskeletal manifestations. This is particularly true for antibody or immunoglobulin-deficiency syndromes, which have been associated with an increased incidence of arthritis, SLE, immune thrombocytopenia, autoimmune hemolytic anemia, myositis, and vasculitis. The most common musculoskeletal manifestation is arthritis, which may occur in 35% of untreated patients with immunoglobulin deficiency. The arthritis is usually oligoarticular and affects the larger joints such as the knee. However, some patients have joint involvement resembling that of RA. In some patients, the arthritis may be related to infection with Mycoplasma. The presumed infectious etiology of the arthritis in these patients is supported by a decreased incidence among patients receiving therapy with ϒ-globulin.
|Table 18: Immunodeficiency Diseases|
|Selected primary immunodeficiencies|
|B cell (antibody/immunoglobulin) defects|
|X-linked (Bruton) agammaglobulinemia|
|Common variable immunodeficiency|
|Combined B cell and T cell defects|
|Severe combined immunodeficiency|
|T cell defects|
|Chronic granulomatous disease|
|Selected causes of secondary immunodeficiency|
|Systemic inflammatory diseases|
|Systemic lupus erythematosus|
HIV, human immunodeficiency virus.
Diagnostic Tests: The diagnosis of an immunodeficiency is established by demonstrating defects in particular components of the immune response. For immunoglobulin deficiencies, one should initially determine the serum immunoglobulin (IgG, IgA, IgM) levels. In rare cases, more elaborate testing may be required.
Keys to Diagnosis: Key to the diagnosis of an underlying immunodeficiency is a high degree of clinical suspicion. Patients typically have a history of recurrent infections that may also be excessively severe, respond poorly to therapy, or be caused by unusual organisms.
Therapy: Therapy of antibody deficiency syndromes consists of gammaglobulin, typically administered intravenously at 4-week intervals. This has almost entirely replaced such older forms of therapy as intramuscular gamma- globulin or prophylactic antibiotics.
Prognosis: With appropriate treatment, the prognosis of those with antibody deficiency diseases improves substantially and approaches normal.
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Rosen FS, Cooper MD, Wedgwood JP. The primary immunodeficiencies. N Engl J Med 1995;333:431–440. PMID:7616993