What is the mechanism of action of Intravenous Immunoglobulin (IVIG) in the treatment of Kawasaki disease?

From the Guidelines

Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease, administered as a single infusion of 2 g/kg over 10-12 hours, and it works by having a generalized anti-inflammatory effect, although the exact mechanism of action is unknown. The treatment of Kawasaki disease with IVIG is well established to reduce the prevalence of coronary artery abnormalities, as shown in meta-analyses comparing IVIG with placebo 1. Possible mechanisms of action of IVIG in the treatment of KD include modulation of cytokine production, neutralization of toxins or other pathogenic agents, augmentation of regulatory T-cell activity, suppression of antibody synthesis, and provision of anti-idiotypic antibodies 1.

Some key points to consider when administering IVIG for Kawasaki disease include:

• The dose of IVIG should be 2 g/kg as a single infusion, usually given over 10 to 12 hours, together with ASA 1.
• A variety of dose regimens have been used in the past, but two meta-analyses have demonstrated a dose-response effect, with higher doses given in a single infusion having 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.
• Adverse effects of IVIG can vary considerably among products, and include Coombs-positive hemolytic anemia and aseptic meningitis 1.

It is also important to note that:

• Measles, mumps, and varicella immunizations should be deferred for 11 months after receiving high-dose IVIG 1.
• Even with high-dose IVIG regimens, 20% of children will develop transient coronary artery dilation, 5% will develop coronary artery aneurysms, and 1% will develop giant aneurysms 1.
• Additional therapies of potential benefit are being discussed, but optimal treatment awaits delineation of the specific agent(s)/trigger(s) and pathogenesis of KD 1.

From the Research

Mechanism of IVIG in Kawasaki Disease

• IVIG is widely used for the treatment of Kawasaki disease, with the primary goal of preventing coronary artery abnormalities (CAAs) 2, 3.
• The exact mechanism of IVIG in Kawasaki disease is not fully understood, but it is thought to modulate the immune system and reduce inflammation 2, 4.

Efficacy of IVIG in Preventing CAAs

• Studies have shown that IVIG can significantly reduce the incidence of CAAs in patients with Kawasaki disease 2, 4, 3.
• High-dose IVIG regimens have been found to be more effective in preventing CAAs compared to lower-dose regimens 2, 3.
• The addition of corticosteroids to IVIG therapy may also reduce the risk of CAAs, particularly in high-risk patients 4, 5.

Comparison of IVIG with Other Treatments

• IVIG has been compared to other treatments, including acetylsalicylic acid (ASA) and prednisolone, in the management of Kawasaki disease 2, 5.
• Studies have found that IVIG is more effective than ASA in preventing CAAs, and that the addition of corticosteroids to IVIG therapy may be beneficial in high-risk patients 2, 4, 5.

Safety and Adverse Effects of IVIG

• IVIG is generally well-tolerated, with few adverse effects reported in clinical trials 2, 4, 3.
• The risk of adverse effects is similar between IVIG and other treatments, including ASA and prednisolone 2, 5.

Clinical Guidelines and Recommendations

• Current clinical guidelines recommend the use of IVIG as the primary treatment for Kawasaki disease, with the goal of preventing CAAs 2, 6.
• High-dose IVIG regimens are recommended, particularly in high-risk patients, and the addition of corticosteroids may be considered in certain cases 2, 4, 6, 5.