IVIG

You are administering intravenous immune globulin (IVIG) to a child who has Kawasaki disease. Shortly after beginning the infusion, he experiences wheezing and hypotension.

The child described in the vignette has Kawasaki disease and is receiving intravenous immune globulin (IVIG). Like any biologic agent, IVIG is associated with a certain number of risks. Because biologic agents are usually proteins, they are antigenic. Adverse reactions commonly are allergic (immunoglobulin E-mediated) or immunologic.

The immunologic reactions are characterized by a constellation of symptoms ranging from bone pain and hypotension to fevers and chills.

IVIG is comprised primarily of IgG, which is the most abundant antibody type in the body. Its primary function is to bind to antigens and facilitate their clearance from the body. There is a small amount of IgA in virtually all the commercial IVIG preparations. In an IgA-deficient patient, the small quantity of IgA in IVIG can trigger an anaphylactic reaction. Approximately 1 in 500 people has a serum IgA deficiency. A proportion of these people has secretory IgA in saliva and other secretions and, therefore, will not react to IgA in biologic preparations such as IVIG.

An IgA-deficient patient also can react to other blood products, such as packed red blood cells, which contain a small amount of serum containing IgA.

The patient described in the vignette presumably is experiencing an anaphylactic reaction because he is IgA-deficient and has received IVIG that contains some IgA. The reaction is not a drug allergy because the agent being administered is primarily IgG and the reaction is to the IgA, an unavoidable contaminate that cannot be removed during IVIG processing. The clinical findings are consistent with a latex allergy, but it would be very unusual for a child's initial exposure to latex to occur during an intravenous infusion. Therefore, this is not the most likely cause.

A type II hypersensitivity reaction is an antibody-antigen reaction. A good example is Rh incompatibility. These reactions are not IgE-mediated; they are mediated by IgG binding to a protein. IgG reactions do not cause wheezing and hypotension, which are the symptoms described for the child in the vignette. The child's symptoms are most compatible with a type I IgE-mediated reaction.

Finally, although cardiac signs and symptoms are common in anaphylaxis, cardiac arrhythmias do not produce wheezing.

• note: live virus vaccines (MMR, varicella) should be delayed 11 months after IVIG dosing for Kawasaki dz
• Suggested intervals between administration of some immune globulin preparations and live virus vaccines (see Red Book for complete listing):
• Synagis ………………..…………...none
• Hepatitis B prophylaxis…………….3 mo
• Varicella prophylaxis………………5 mo
• pRBCtransfusion………………..... 5 mo (none for washed RBC)
• Plasma or platelet transfusion………7 mo
• IGIV replacement………….…….…8 mo
• IGIV, Kawasaki disease…….……...11 mo (Need 11 months after IVIG for live vaccines to “take” (can give the vaccines in less than 11 months, but should repeat it again after that time to ensure immunity)
  
   

References:
Ballow M. Mechanisms of action of intravenous immune serum globulin therapy. Pediatr Infect Dis J. 1994;13:806-811

Buckley RH, Schiff RI. The use of intravenous immune globulin in immunodeficiency diseases. N Engl J Med. 1991;325:110-117

Kumar S, Williams K. Latex allergy. Pediatr Rev. 1999;20:35
Full text is available online for subscription or fee.

Leung DYM. Allergy and the immunologic basis of atopic disease. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 17th ed. Philadelphia, Pa: WB Saunders Co; 2004:743-747

Ramesh S, Schwartz SA. Therapeutic uses of intravenous immunoglobulin (IVIG) in children. Pediatr Rev. 1995;16:403-410