- Author: Robert Y Lin, MD; Chief Editor: Michael A Kaliner, MD more...
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. The standard treatment for hypogammaglobulinemia is IgG replacement, which may be given intravenously or subcutaneously.[9, 10, 20] IgG preparations are approved by the US Food and Drug Administration (FDA) for treatment of primary immunodeficiency disease (primary humoral immunodeficiency) and a few additional indications, but considerable amounts of intravenous immunoglobulins (IVIG) are used "off label" for other conditions.[9, 20]
As reviewed by the American Academy of Allergy, Asthma, and Immunology, the benefit of IgG treatment for these primary immune deficiencies is based on category IIb evidence (13). IVIG is approved for only 2 secondary immune deficiencies: B-cell chronic lymphocytic leukemia (B-CLL) and pediatric HIV. The use of IVIG for primary immune defects with normogammaglobulinemia and impaired specific antibody production is based on category III evidence only.
The usual IVIG dose is 0.4-0.6 g/kg every 3-4 weeks, titrating the dose and interval between infusions to achieve a trough IgG level greater than 500 mg/dL. Usual total monthly doses of subcutaneous IgG (SCIG) are in the same range, given as 100-200 mg/kg/wk. Some practitioners target trough levels 300 mg/dL higher than pretreatment levels, and trough levels >800 mg/dL may improve pulmonary outcomes. Some centers administer a loading dose of 1g/kg if the patient is agammaglobulinemic.[9, 10, 20]
Gammaglobulin may also be given intramuscularly or subcutaneously. The latter format is useful when allergic reactions limit the dose or rate, but it is becoming increasingly popular even when these problems are not present. SCIG can be given at home by parents or by patients themselves, usually requiring several hours of infusion. Intramuscular gammaglobulin injections were the standard of care before IVIG became readily available and are still useful in certain patients because of the simplicity of administration and fewer reactions. However, local injection site pain can be significant, and the doses that can be given this way are limited.
Up to 44% of patients report adverse reactions to IVIG. These most commonly respond to decreasing the rate of the Ig infusion. Usually, the IVIG-associated reactions are infusion-related and include back pain, abdominal aching, nausea, rhinitis, asthma, chills, low-grade fever, myalgias, and headaches. Renal failure is a less common but serious adverse reaction that was predominately caused by sucrose-containing lyophilized IgG preparations that are no longer available in the United States. Infusion rate reduction, systemic steroids, histamine blockers, and antipyretics or nonsteroidal anti-inflammatory drugs (NSAIDs) can help treat or prevent the reactions.
Although the incidence of reactions is highest during the first infusion, they may occur in repeat infusions of the same product. Although anti-IgA antibodies can be associated with increased reactions, most patients (regardless of anti-IgA antibody status) tolerate IVIG that is not depleted of IgA (low-IgA products should be selected for treatment in patients who cannot tolerate IVIG that is not depleted of IgA). Thrombosis, myocardial infarction, hemolytic anemia, hyperviscosity syndrome, and aseptic meningitis are uncommon but reported adverse events.
Improve clinical and immunologic aspects of the disease.
Immune globulin intravenous (Flebogamma, Gammagard, Gamunex, Privigen) and subcutaneous (Vivaglobin)
Results in elevated antiviral or antibacterial antibody titers for 1 mo.
Trough levels >500 mg/dL do not necessarily improve infection control except in certain long-standing infections but may significantly increase cost.
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