Failure of intravenous immunoglobulin to prevent varicella-zoster infection.

Abstract

To The Editors: Varicella, typically a benign disease of childhood, can be severe in immunocompromised individuals. Active immunization is effective, and postexposure prophylaxis can be achieved with varicella-zoster immunoglobulin (VZIG). There are reports of successful postexposure prevention with intravenous immunoglobulin (IVIG), 1 and the most recent report of the American Academy of Pediatrics Committee on Infectious Diseases (Red Book) states that “Patients receiving monthly high-dose Immune Globulin Intravenous (400 mg/kg) are likely to be protected and probably do not require VZIG if the last dose of IVIG was given 3 weeks or less before exposure.”2 We report three immunodeficient patients who developed varicella despite regular IVIG therapy. Patient A was a 5-year-old boy with perinatally acquired HIV infection. He began receiving IVIG (500 mg/kg) at 2.5 years of age because of recurrent sinopulmonary infections and an inability to produce protective antibodies to tetanus toxoid and conjugated Haemophilus influenzae type b vaccine. His most recent CD4 T lymphocyte count was 758 cells/mm 3. A sibling developed chickenpox 14 days before the patient developed typical varicella lesions. He responded quickly to oral acyclovir. He had received his last dose of IVIG 7 days before the exposure and 21 days before the rash developed. Patient B was an 8-year-old boy with perinatally acquired HIV infection. He first received IVIG at 13 months of age for recurrent sinopulmonary infections and poor antibody responses to routine immunizations. Two months after beginning regular IVIG infusions, he developed typical varicella which was treated with intravenous acyclovir. He continued to receive monthly IVIG at 400 mg/kg for the next 7 years. At 8 years of age he experienced reactivation of varicella with vesicular lesions over numerous dermatomes, starting 9 days after his most recent IVIG infusion. This outbreak resolved with intravenous acyclovir treatment. His most recent CD4 lymphocyte count was 575 cells/mm 3. Patient C was a 20-year-old woman with common variable immunodeficiency and normal T lymphocyte subsets and in vitro functions. She had received IVIG (500 mg/kg) every 4 weeks for 6.5 years. Serum IgG was 1310 mg/dl before and 2030 mg/dl immediately after her latest infusion. She was exposed to varicella by her sister, and 10 days later developed the typical skin lesions of varicella. Oral acyclovir was begun, and the rash resolved uneventfully in 7 days. She had received IVIG 11 days before exposure, 21 days before eruption. Although the manufacturers of the IVIG products used in our patients do not regularly monitor or report varicella-zoster antibody titers in their preparations, both IVIG and VZIG are polyclonal immunoglobulin products which contain varicella-zoster antibodies and have achieved similar varicella-zoster antibody titers in at least one clinical study. 3 However, although IVIG appeared to have been protective when given to exposed children with leukemia, 1 breakthroughs have been reported after both VZIG 4 and IVIG. 5 The current cases demonstrate that IVIG may not protect against varicella even when given in a dosage and frequency that exceed the Red Book guidelines. That our patients did not experience severe varicella may be related to potential attenuation by IVIG, 6 the patients’ relatively intact CD4 lymphocyte counts or the early initiation of acyclovir therapy. IVIG-treated individuals with profound T cell deficiency or dysfunction may not respond as well and VZIG prophylaxis should be considered in these situations. Ronald M. Ferdman M.D. Joseph A. Church M.D.