eMedicine Specialties > Allergy and Immunology > Immunodeficiencies
Immunoglobulin G Deficiency: Treatment & Medication
Updated: Jul 9, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
The goals of therapy in patients with immunoglobulin G (IgG) deficiency are 3-fold.18 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.19
- 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.19 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.20
- 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.4,5,6
- 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.21 Higher doses have been shown to be more effective in reducing infections in patients with histories of chronic or recurrent sinopulmonary infections.21 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.22 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.19
- 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.5
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.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. In the modern era, this includes not only preventing acute, severe, life-threatening infections but also preventing morbidity from the slow development of end organ damage due to subclinical chronic infection. Since most of these patients require life-long immunoglobulin replacement, an additional goal is to provide optimal therapy without compromising the patient’s quality of life.21
Immune globulins (human)
Accepted medical therapy for patients with IgG deficiency. Purified human IgG may be given intravenously (IVIG) or subcutaneously (IGSC). Intramuscular IgG and plasma are rarely employed for chronic use in the current era. IVIG and IGSC for use in the United States are derived from human plasma obtained from carefully screened and tested US donors. All preparations available in the United States contain all 4 IgG subclasses, with an antibody distribution approximately the same as human serum. The traditional methods of preparation of different commercial products consist of cold ethanol fractionation followed by further purification, usually employing additional precipitations and one or more steps of chromatography, followed by specific steps to remove or inactivate potential viral pathogens.
Although many physicians use different IVIG preparations interchangeably and with similar overall efficacy, the individual products differ from each other in final purification steps, IgA content, and excipients. Different products may be tolerated differently by different patients. Thus, a patient on established therapy with one particular product may have increased adverse effects if given a different product. Most products in the US market are labeled for use in primary immune deficiency and immune thrombocytopenic purpura (ITP), but other uses are common, and an evidence-based review of the multiple on- and off-label uses of IgG has recently been published.23 Immune globulin preparations may have individual differences, and more detailed descriptions may be obtained from other sources, including the Physicians' Desk Reference.
Although generally safe, IVIG has been associated with some adverse reactions in certain patient populations. For example, IVIG should not be given to patients with isolated IgA deficiency. Use of this product in these patients has been associated with severe complications, including anaphylactic shock and death. However, this problem is rare. Most patients have some IgA or no antibody production at all, so production of IgE antibodies against IgA is not common.
In patients with preexisting risk factors for coronary artery disease and atherosclerosis, the administration of IVIG has been associated with thromboembolic events. Reports of myocardial infarction, transient ischemic attacks, and stroke, although rare, have been described in the literature.22 Infusion of IVIG may affect the cardiovascular system by different, possibly synergistic, mechanisms. A recent comprehensive review covers many aspects of IVIG therapy.21
IVIG regimens usually are given in the form of infusions of 300-600 mg/kg every 3-4 weeks, since the half-life of IgG in the circulation is approximately 21 days. Higher doses are often preferred in patients with chronic lung or sinus infections. High doses may lead to increased plasma and blood viscosity, leading to decreased myocardial perfusion; preparations containing higher sodium concentrations may contribute to fluid overload; and some preparations may contain activated clotting factors. Furthermore, some preparations may contain leukoagglutinins, antibodies which can lead to microaggregation of white blood cells, causing transfusion-related acute lung injury.22 Acute renal failure, positive Coombs tests and frank hemolysis have also been reported following IVIG infusions.22 IVIG infusions are frequently accompanied by rate-related adverse effects such as headache, chills fever, myalgia, nausea, or vomiting.
Usually, infusions are started at a slow rate (0.01 mg/kg/min), which is increased in a stepwise manner, as tolerated by the patient. If symptoms of an infusion reaction begin, these can usually be controlled by slowing or temporarily stopping the infusion. Often, however, medications such as nonsteroid anti-inflammatory drugs (NSAIDs), other antipyretics, or antihistamines may be helpful. Some immunologists may pretreat patients with these medications, corticosteroids, or both to prevent or ameliorate symptoms of infusion reaction. In addition to headaches that accompany infusions, many patients develop headaches as much as 48-72 hours after the infusion is completed. These headaches may range in severity and may include features of migraine, which may respond to triptans. Severe headaches with meningeal signs and aseptic meningitis have also been reported.22
IgG is also frequently administered subcutaneously, usually using small battery-powered ambulatory infusion pumps. In general, one fourth of the monthly IgG dose is administered weekly into 2 or more subcutaneous sites using small (ie, 25-27 gauge) needles over approximately 2 hours.24,25 These infusions rarely induce systemic adverse effects, although local redness, swelling, or other injection site reactions may occur.
Many patients report relief from headaches or other reactions associated with IVIG infusions when they switch to IGSC. Because of this freedom from systemic adverse reactions, and since intravenous access is not required, home therapy independent from nurses or other medical professionals is possible and has been reported to result in better health-related quality of life.24,20 With IGSC regimens, the IgG is slowly absorbed into the bloodstream, peaking at 48-72 hours, so adverse effects associated with the high peaks achieved with intravenous therapy are obviated. Because additional doses are usually given within a week, before the IgG level drops very much, low troughs and wear-off effects reported by many patients on monthly intravenous infusions are also obviated.24
Immune globulin, subcutaneous (Vivaglobin)
16% human immune serum globulin, pasteurized
Adult
100-200 mg/kg/wk, or 1.37 X weekly equivalent of IVIG dose, divided by 4
Pediatric
Not established; suggested dosing is as in adults
Globulin preparation may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)
Documented hypersensitivity to human plasma products, selective IgA deficiency with known antibody against IgA
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not for IV administration
Immune globulin, intravenous, 5-10% liquids (Flebogamma, Gammagard, Gamunex, Privigen, Octagam, Carimune)
Immune globulin purified from human plasma, usually supplied as 5% or 10% liquid
Adult
200-800 mg/kg IV every 3-4 wk
Pediatric
Administer as in adults
Globulin preparations may interfere with immune response to attenuated live virus vaccines (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)
Documented hypersensitivity to human immune globulin products; different individual preparations contain different excipients such as glycine, maltose, proline, or sorbitol, which may be specifically contraindicated in certain patients
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
See FDA black box warning in prescribing information for all products
Check serum IgA (use an IgA-depleted product if patient is IgA-deficient with sensitivity); may increase serum viscosity or may cause thromboembolic events, including MI or stroke; may increase risk of migraine, aseptic meningitis (10%), urticaria, pruritus, and petechiae (2-5 d postinfusion to 30 d); increases risk of renal tubular necrosis in elderly patients and patients with diabetes, volume depletion, and preexisting kidney disease; be sure patients are adequately hydrated before administering; associated laboratory result changes may include elevated antiviral or antibacterial antibody titers for 1 mo, positive direct antiglobulin (Coombs test), and apparent hyponatremia; be sure product is at room temperature before infusing but do not heat; infuse through separate line without mixing with other IV fluids or medications; if administered through indwelling catheter, flush it with D5W before and after infusion; do not perform a skin test to check for sensitivity (local irritation may be interpreted as a positive reaction)
For technical information, consult prescribing information for individual product, the manufacturer, or Physician's Desk Reference
More on Immunoglobulin G Deficiency |
| Overview: Immunoglobulin G Deficiency |
| Differential Diagnoses & Workup: Immunoglobulin G Deficiency |
 Treatment & Medication: Immunoglobulin G Deficiency |
| Follow-up: Immunoglobulin G Deficiency |
| Multimedia: Immunoglobulin G Deficiency |
| References |
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Further Reading
Keywords
immune deficiency, immune globulin deficiency, IgG deficiency, IgG subclass deficiency, insufficient antibody production, gammaglobulin deficiency, hypogammaglobulinemia, immune deficiency, immunity, immunology, immune function, immunologic system interaction, autoimmune disorders, T-cell disease, B-cell dysfunction, complement deficiency, immunological disturbances, white blood cell diseases, WBC diseases, immunotherapy, intravenous immune globulin treatment, IVIG treatment, IV immunoglobulin treatment, common variable immunodeficiency, CVI, CVID, ataxia-telangiectasia, Sjogren syndrome, Sjogren's syndrome, X-linked agammaglobulinemia, X-LA, XLA, congenital agammaglobulinemia, transient hypogammaglobulinemia of infancy, Bruton’s, sinusitis, chronic sinusitis, recurrent sinusitis, tympanic membrane, effusion of middle ear, middle ear effusion
