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

Michal Yakubovsky,Alex Guri,Michael Giladi,Yoav Golan,Moshe Ephros,Daniel Glikman,Itzhak Levy

doi:10.3390/pathogens11020177

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.

Highlights

Cat scratch disease (CSD) is caused mostly by Bartonella henselae, a fastidious, gram negative bacillus found worldwide in bacteremic cats [1,2]
We report for the first time a mistaken diagnosis of typical and atypical CSD in patients with clinical presentations consistent with CSD due to false-positive serological testing following therapy with Intravenous immunoglobulin (IVIG) and present an approach to avoid an incorrect diagnosis
The following representative cases illustrate the clinical quandary about serodiagnosis of CSD following treatment with IVIG

Summary

Introduction

Cat scratch disease (CSD) is caused mostly by Bartonella henselae, a fastidious, gram negative bacillus found worldwide in bacteremic cats [1,2]. B. henselae culture from affected lymph nodes is rarely positive, and growth, if occurs, may require up to four weeks of incubation; Warthin Starry silver stain is of low sensitivity and inadequate specificity; cytology and histopathology are not specific; immunohistochemical assay is not available in routine diagnostic laboratories, and polymerase chain reaction (PCR), sensitive and specific, requires tissue or pus specimens from involved tissue, which are not commonly available [3]. Serological assays, both immunofluorescent antibody (IFA) test and enzyme immunoassay (EIA), for detection of anti-B. henselae antibodies have become the most commonly used diagnostic tests for CSD, both as in-house and commercial products

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