Misleading Positive Serology for Cat Scratch Disease following Administration of Intravenous Immunoglobulin

Abstract

Cat scratch disease (CSD), caused by Bartonella henselae, usually presents as regional lymphadenopathy/lymphadenitis, known as typical CSD or as atypical CSD, which includes, among others, neurological manifestations. Serology for anti-B. henselae IgG antibodies is the most commonly used diagnostic tests for CSD. Intravenous immunoglobulin (IVIG) is given for an increasing number of medical conditions and may cause interference with serological testing. We report six patients with neurological manifestations and two patients with Kawasaki disease mimicking typical CSD, mistakenly diagnosed as CSD due to false-positive serology following IVIG therapy. Bartonella IgG serology was positive one to six days after IVIG administration and reverted to negative in seven of eight patients or significantly decreased (1 patient) ≤30 days later. In patients with CSD, IgG titers remained essentially unchanged 15-78 days after the positive serum sample. An additional eight patients treated with IVIG for various conditions were evaluated prospectively. All were seronegative one day pre-IVIG infusion, five patients demonstrated an increase in the IgG titers one to three days after IVIG administration, one interpreted as positive and four as intermediate, whereas three patients remained seronegative, suggesting that false seropositivity after IVIG therapy may not occur in all patients. Treatment with IVIG can result in false-positive serology for B. henselae. Increased awareness to the misleading impact of IVIG is warranted to avoid misinterpretation. Repeat testing can distinguish between true and false serology. Preserving serum samples prior to IVIG administration is suggested.

Keywords: Bartonella henselae; cat scratch disease; enzyme immunoassay; false positive results; intravenous immunoglobulin; serology.

Figure 1

Kinetics of anti-B. henselae IgG antibodies determined by enzyme immunoassay in 2 representative cases with false-positive cat scratch disease (CSD) serology and in a control group of 24 CSD patients. Serum specimens were diluted 1:100. Anti-B. henselae IgG expressed in ELISA units (EU). Bold solid horizontal line represents cutoff point for a positive test results (60 EU). False-positive CSD serology. Blue circles—A patient with encephalitis. First serum (day 0) was tested negative 2 days prior to IVIG administration with sharp increase of IgG titers on day 6. A third specimens taken on day 30 tested negative. Red circles—A patient with atypical Kawasaki disease considered initially to have typical CSD. First serum specimen was taken 1 day after IVIG administration and was tested positive. Serum specimens from days 12 and 30 tested negative. Control group (scatter plot). Each dot represents one serum sample of a CSD patient tested for anti-B. henselae IgG. Each patient had 2 serum samples obtained 15–78 days apart. Yellow dots represent first serum samples. Lilac dots represent second serum samples.