Medical Care
The goals of therapy in patients with immunoglobulin G (IgG) deficiency are 3-fold. [29] First, treat the acute infection with antibiotics. Because agammaglobulinemia may lead to failure of opsonization in serum, acute infections require aggressive and longer courses of antibiotic treatment than is required in normal patients. Emphasis must be placed on encapsulated organisms such as S pneumonia and H influenzae. Second, institute prophylaxis with IgG replacement. Third, prevent or treat pulmonary disease secondary to repeated bouts of bronchitis and pneumonia. This is necessary because structural lesions in the lungs escalate the lung infection rate and the possibility of cor pulmonale. Do not underestimate the likelihood of death in these patients secondary to pulmonary disease. Physiotherapy with drainage may be helpful to clear respiratory secretions. [30]
Historically, IgG was given subcutaneously or intramuscularly because the IgG preparations contained aggregated IgG and impurities that often caused serious reactions when administered intravenously. However, presently, intravenous immunoglobulin (IVIG) replacement therapy is generally accepted as the treatment of choice for selected patients with IgG subclass deficiency and persons with other immunodeficiencies including primary immune deficiencies. [30, 31] The aim of treatment is to prevent or greatly reduce the frequency and severity of acute serious bacterial infections. In recent years, home infusions of IgG administered subcutaneously (IGSC) have become increasingly popular. This mode of therapy has been shown to result in higher health-related quality of life as compared to hospital- or office-based intravenous therapy. [32]
Although the deficiency in any given patient may be just in an individual subclass or a range of specific antibodies (ie, against polysaccharides), IgG replacement doses and regimens are similar in all immunodeficiencies because individual IgG subclass components have not yet been developed. Current IgG preparations are 95-99% IgG with minimal quantities of IgA, IgM, IgD, and IgE and have a half-life of 20 days. However, prior to immunoglobulin treatment, repeated measurements of IgG level, specific antibody, or subclass are necessary for documentation of selective deficiencies. [8, 9, 10]
Immunoglobulin preparations for replacement therapy are prepared from large pools of plasma obtained from thousands of donors. These pools are subsequently fractionated by cold ethanol fractionation and additional chromatography steps. All donors are screened for potential infectious disease agents, including HIV and hepatitis B and C viruses. Following treatment with physical and chemical viral inactivating regimens, as well as nanofiltration, these preparations are remarkably free of transmissible infectious agents. However, because they are blood products, the risk of transmitting infectious agents is always present.
Currently, the accepted therapy for IgG deficiency is the intravenous administration of 300-600 mg/kg of IgG once every 3-4 weeks, or 100-200 mg/kg/wk subcutaneously. [33] Higher doses have been shown to be more effective in reducing infections in patients with histories of chronic or recurrent sinopulmonary infections. [33] Monitoring trough immunoglobulin levels may help define the optimal time between doses because immunoglobulin clearance varies from patient to patient. Consensus guidelines suggest that IgG trough levels (drawn just before the next infusion) should be at least 500 mg/dL. However, patients with chronic sinopulmonary disease often do better with higher trough levels.
Although the benefits of IgG replacement therapy are unquestionable in appropriate patients, IVIG may be associated with infusion-related adverse effects. [34] IGSC is often associated with local infusion site reactions but is widely regarded as being much freer from systemic reactions than intravenous therapy. Of treated patients, 3-12% develop headache, myalgia, chills, fever, and mild nausea upon infusion. These symptoms are more common when IgG therapy is newly initiated and may decrease with subsequent infusions. To minimize serious reactions, intravenous infusions should be started no faster than 0.01 mL/kg/min. Patients should be closely monitored until their tolerance of particular regimens is established, and infusions should be temporarily stopped or slowed down if symptoms occur. Adverse effects of IVIG infusions can be minimized with antihistamines, antipyretics, hydrocortisone, or a combination thereof. [30]
Antibiotics also may be useful for patients who have poor responses to bacterial vaccines; when used, microbicidal agents are preferable.
Vaccination is important in patients who do not have antibodies to Pneumococcus and Haemophilus polysaccharides, regardless of whether they have an absolute deficiency of IgG2. If they do not respond to vaccination with Pneumococcus and Haemophilus polysaccharide vaccines, revaccination with protein-conjugated Pneumococcus and Haemophilus polysaccharide vaccines is indicated. Such vaccination may result in the production of protective antibodies in the IgG1 or IgG3 subclasses. [9]
Surgical Care
Pulmonary lobectomyor functional endoscopic sinus surgery may be useful to remove structurally abnormal, chronically infected tissues that can serve as foci of infection, which then reseed other areas, causing recurrent infections in areas that have not yet been permanently damaged.
Consultations
ENT and pulmonary consultations are frequently advisable. Other specialists may be needed for specific problems in individual cases.
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Immunoglobulin G deficiency. Schematic representation of an immunoglobulin G molecule. CH indicates constant region of heavy chain; CL, constant region of light chain; VH, variable region of heavy chain; and VL, variable region of light chain.
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Immunoglobulin G deficiency. Human immunoglobulin G subclasses.
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Immunoglobulin G deficiency. Changes in serum immunoglobulin G concentrations during infancy and childhood.
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Immunoglobulin G deficiency. Schematic representation of the molecular interaction of CD40 on B cells, with CD40L on T cells involved in the switch from immunoglobulin M to immunoglobulin G.
