From the Guidelines
Intravenous immunoglobulin (IVIG) should be administered at a dose of 2 g/kg as a single infusion, usually given over 10 to 12 hours, to reduce the prevalence of coronary artery abnormalities in patients with Kawasaki disease. This recommendation is based on the most recent and highest quality study available, which demonstrated a conclusive decrease in new coronary artery abnormalities among IVIG-treated patients 1. The mechanism of action of IVIG in treating Kawasaki disease is unknown, but it appears to have a generalized anti-inflammatory effect, with possible mechanisms including modulation of cytokine production, neutralization of toxins or other pathogenic agents, and provision of anti-idiotypic antibodies.
The use of IVIG in Kawasaki disease has been well-established, with meta-analyses showing a dose-response effect, where higher doses given in a single infusion have the greatest efficacy 1. Peak adjusted serum immunoglobulin G levels are lower among patients who subsequently develop coronary artery abnormalities, and are inversely related to fever duration and laboratory indices of acute inflammation 1.
Key considerations when administering IVIG include:
- Patients should be treated with IVIG within the first 10 days of illness, and if possible, within 7 days of illness 1.
- IVIG should be administered together with aspirin 1.
- Measles, mumps, and varicella immunizations should be deferred for 11 months after receiving high-dose IVIG 1.
- Adverse effects of IVIG can vary considerably among products, and may include Coombs-positive hemolytic anemia, aseptic meningitis, and infusion reactions 1.
Overall, the use of IVIG in Kawasaki disease is a critical component of treatment, and administration of 2 g/kg as a single infusion is the recommended dose to reduce the risk of coronary artery abnormalities and improve outcomes 1.
From the Research
What is IVIG
- IVIG, or intravenous immune globulin, is a purified plasma product used for many immune-deficient conditions and autoimmune conditions 2, 3.
- It has been approved by the Food and Drug Administration (FDA) for use in 6 conditions: immune thrombocytopenic purpura (ITP), primary immunodeficiency, secondary immunodeficiency, pediatric HIV infection, Kawasaki disease, prevention of graft versus host disease (GVHD) and infection in bone marrow transplant recipients 2.
Usage and Indications
- IVIG is most commonly used in the treatment of chronic neuropathy, which includes chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy 2.
- Other common indications include the treatment of hypogammaglobulinemia, ITP, renal transplant rejection, myasthenia gravis, Guillain-Barre syndrome, necrotizing fasciitis, autoimmune hemolytic anemia, and Kawasaki disease 2.
- IVIG is also used in the treatment of Kawasaki disease, with the American Heart Association (AHA) recommending a single infusion of 2 g/kg preferably given during the first 10 days of illness 3.
Safety and Adverse Effects
- Most adverse effects of IVIG are mild and transient, including headaches, flushing, fever, chills, fatigue, nausea, diarrhea, blood pressure changes, and tachycardia 4.
- Late adverse events are rare and include acute renal failure and thromboembolic events, which can be prevented by slow infusion rate and good hydration 4.
- The occurrence of adverse effects was 24-36% after high-dose IVIG, most of which were mild and included headaches 4.
Mechanisms of Action
- The mechanisms of action of IVIG are diverse and include the reduction of activated IL-1β+ neutrophils in the circulation, which can be targeted by IVIG to ameliorate inflammation 5.
- IVIG can also activate neutrophil cell death via PI3K and NADPH oxidase, but independently of caspase activation 5.
- The varied mechanisms by which IVIG attains its beneficial effect are still being researched, with updates on its mechanisms of action and off-label use in autoimmune diseases 6.