DOI: 10.12890/2026_007473

Should the traditional algorithm for syphilis screening be abandoned? Neurosyphilis presenting as limbic encephalitis: a prozone false-negative RPR missed by an RPR-only initial screen

Authors

  • Hidenori Sanayama Division of General Medicine, Department of Comprehensive Medicine 1, Jichi Medical University Saitama Medical Center, Saitama, Japan
  • Yuka Hayashi Division of Neurology, Department of Comprehensive Medicine 1, Jichi Medical University Saitama Medical Center, Saitama, Japan 0009-0007-8021-121X
  • Takahiko Fykuchi Division of General Medicine, Department of Comprehensive Medicine 1, Jichi Medical University Saitama Medical Center, Saitama, Japan

sanayama@jichi.ac.jp

Keywords

Neurosyphilis, prozone phenomenon, limbic encephalitis, rapid plasma reagin, syphilis serology

Abstract

Introduction: Neurosyphilis is a treatable mimic of viral and autoimmune limbic encephalitis. The prozone phenomenon—antibody excess preventing the antigen–antibody lattice—can render an undiluted non-treponemal test such as the rapid plasma reagin (RPR) test falsely negative, with reactivity restored on dilution.
Case description: A 37-year-old man presented with seizures and rapidly progressive limbic encephalitis; Brain magnetic resonance imaging (MRI) with fluid-attenuated inversion recovery sequences showed hyperintensities in the amygdalae, periventricular regions, left insula and left putamen. On admission, the possibility of a sexually transmitted infection was considered, but only an RPR was requested, and it was negative. When the encephalitis failed to respond to empirical antiviral, antibacterial and corticosteroid therapy, a Treponema pallidum haemagglutination assay was added; it was positive, and serially diluted serum yielded a reactive RPR (endpoint titre 1:32), revealing a prozone false negative. Cerebrospinal fluid studies confirmed neurosyphilis, and the patient recovered fully after penicillin.
Discussion: With an RPR-only screen, the non-treponemal/treponemal discordance that typically signals a prozone never arose, so the false negative was accepted at face value; the delay reflected the prozone compounded by the initial testing strategy. Because empirical ceftriaxone active against T. pallidum had been started on admission, effective treatment was not delayed.
Conclusion: When syphilis is suspected, a negative undiluted RPR does not exclude it; pairing a treponemal test with the RPR—or adopting a treponemal-first screening strategy—guards against prozone-related false negatives.

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References

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Published

2026-09-28

Issue

Vol. 13 No. 10 (2026)

Categories

How to Cite

1.
Sanayama H, Hayashi Y, Fykuchi T. Should the traditional algorithm for syphilis screening be abandoned? Neurosyphilis presenting as limbic encephalitis: a prozone false-negative RPR missed by an RPR-only initial screen. EJCRIM [Internet]. 2026 Sep. 28 [cited 2026 Nov. 3];13(10). Available from: https://ejcrim.com/index.php/ejcrim/article/view/7473