Confusable diagnoses · PANCE / PANRE

Syphilis vs Genital Herpes

Syphilis and Genital Herpes are easy to mix up on the boards. Here's a side-by-side comparison — presentation, workup, imaging, and first-line treatment — drawn from our full outlines.

Syphilis vs Genital Herpes at a glance

  • Syphilis: Spirochetal STI (Treponema pallidum) with characteristic primary chancre, secondary mucocutaneous disease, latent phase, and tertiary complications.
  • Genital Herpes: Recurrent painful genital vesicular ulcers caused by HSV-2 (and increasingly HSV-1) — managed with episodic or suppressive antiviral therapy.
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Side-by-side comparison

FeatureSyphilisGenital Herpes
At a glanceSpirochetal STI (Treponema pallidum) with characteristic primary chancre, secondary mucocutaneous disease, latent phase, and tertiary complications.Recurrent painful genital vesicular ulcers caused by HSV-2 (and increasingly HSV-1) — managed with episodic or suppressive antiviral therapy.
Classic presentationPainless genital ulcer that heals on its own → 6-8 weeks later, generalized rash including the palms and soles with mucous patches — classic primary and…Recurrent grouped painful vesicles/ulcers on the genitalia with prodromal tingling — classic HSV. Bilateral tender inguinal nodes with primary outbreak help…
Workup / key labsPositive serology with confirmation by reciprocal test; clinical staging based on examination, sexual history, and timing.; Two-step serology — order BOTH a…Positive HSV PCR from lesion (preferred) or type-specific serology in clinical context.; HSV PCR from lesion swab — most sensitive (deroof vesicle to…
ImagingEcho or CT chest if cardiovascular syphilis suspected; MRI brain/spine for neurosyphilis evaluation; Skeletal X-rays in congenital syphilis (metaphyseal…Not required for routine genital HSV; MRI brain and LP for suspected HSV encephalitis (HSV-1)
First-line treatmentPrimary, secondary, and early latent syphilis (<1 year duration):; • Benzathine penicillin G 2.4 million units IM × 1 dose; Late latent (≥1 year or unknown…First episode (treat all to reduce duration and severity):; • Acyclovir 400 mg PO TID × 7-10 days; • Valacyclovir 1 g PO BID × 7-10 days; • Famciclovir 250 mg…

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Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants.