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
| Feature | Syphilis | Genital Herpes |
|---|---|---|
| At a glance | Spirochetal 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 presentation | Painless genital ulcer that heals on its own → 6-8 weeks later, generalized rash including the palms and soles with mucous patches — classic primary and secondary syphilis.; Primary (3-90 days post-exposure): single painless indurated ulcer (chancre) with raised borders, clean base; heals spontaneously in 3-6 weeks; Secondary (4-10… | Recurrent grouped painful vesicles/ulcers on the genitalia with prodromal tingling — classic HSV. Bilateral tender inguinal nodes with primary outbreak help distinguish from syphilis (painless chancre, non-tender adenopathy).; Primary infection (often most severe): painful clustered vesicles → ulcers on genital mucosa, fever, malaise,… |
| Workup / key labs | Positive serology with confirmation by reciprocal test; clinical staging based on examination, sexual history, and timing.; Two-step serology — order BOTH a treponemal and non-treponemal test:; • Non-treponemal: RPR or VDRL (titers correlate with disease activity; used to monitor response). Can have false positives (pregnancy, HIV,… | Positive HSV PCR from lesion (preferred) or type-specific serology in clinical context.; HSV PCR from lesion swab — most sensitive (deroof vesicle to collect); Viral culture — historical, less sensitive than PCR; useful for typing if PCR unavailable; Type-specific serology (HSV-1 and HSV-2 IgG) — for confirming chronic infection or… |
| Imaging | Echo or CT chest if cardiovascular syphilis suspected; MRI brain/spine for neurosyphilis evaluation; Skeletal X-rays in congenital syphilis (metaphyseal lucencies, periostitis) | Not required for routine genital HSV; MRI brain and LP for suspected HSV encephalitis (HSV-1) |
| First-line treatment | Primary, secondary, and early latent syphilis (<1 year duration):; • Benzathine penicillin G 2.4 million units IM × 1 dose; Late latent (≥1 year or unknown duration) and tertiary syphilis without neurologic involvement:; • Benzathine penicillin G 2.4 million units IM weekly × 3 weeks (total 7.2 million units); Neurosyphilis, ocular… | 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 PO TID × 7-10 days; Episodic recurrent therapy (start at prodrome or within 24 hours of lesion onset):; • Acyclovir 800 mg PO BID × 5 days or 800 mg TID × 2 days; • Valacyclovir 1… |
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