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.
Try two board-style questions on Syphilis vs Genital Herpes
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1NeurologyMedium
A 58-year-old man presents with progressive difficulty walking and sharp, lightning-like pains in his legs over the past year. He reports urinary incontinence and a history of an untreated genital ulcer 20 years ago. On exam, he has a wide-based gait, absent patellar and Achilles reflexes, loss of vibratory and position sense in the lower extremities, and small irregular pupils that constrict to accommodation but not to light. Romberg sign is positive. Which of the following is the most likely diagnosis?
ATabes dorsalis
BDiabetic sensory polyneuropathy
CSubacute combined degeneration
DMultiple sclerosis
Reveal answer & full explanation
Correct answer: A — Tabes dorsalis
ATabes dorsalis✓
BDiabetic sensory polyneuropathy
CSubacute combined degeneration
DMultiple sclerosis
Why tabes dorsalis is correct
Tabes dorsalis is a late manifestation of tertiary neurosyphilis, with Treponema pallidum damaging the dorsal columns and dorsal roots, typically 15-25 years after an untreated primary infection (the remote genital ulcer).
Dorsal column degeneration produces loss of vibratory and position sense, sensory ataxia with a wide-based gait and a positive Romberg, and absent lower-extremity reflexes; lancinating "lightning" pains are characteristic.
Argyll Robertson pupils — small, irregular pupils that accommodate but do not react to light — are essentially pathognomonic.
Confirm with serum treponemal testing and treat neurosyphilis with IV penicillin G.
Why the others are wrong
Diabetic sensory polyneuropathy — a length-dependent neuropathy that can blunt vibratory and position sense, abolish ankle reflexes, and cause lancinating pain, but nothing in this history suggests diabetes and it does not account for the small irregular pupils with light-near dissociation or the remote untreated chancre (confused-with another cause of sensory ataxia).
Subacute combined degeneration — vitamin B12 deficiency damages the dorsal columns AND lateral corticospinal tracts, producing hyperreflexia and upgoing toes, not the areflexia here, and never Argyll Robertson pupils (confused-with another dorsal-column disease).
Multiple sclerosis — affects younger patients with relapsing-remitting CNS lesions and causes optic neuritis or internuclear ophthalmoplegia, not Argyll Robertson pupils or this syphilis history (premature closure on the common demyelinating diagnosis).
Question 2Infectious DiseaseMedium
A 29-year-old woman with a 4-year history of recurrent genital herpes (HSV-2 confirmed by PCR) presents with her third episode of severe headache, neck stiffness, and photophobia in the past 18 months. Each episode resolves spontaneously over several days without antiviral therapy. Lumbar puncture today shows a lymphocytic pleocytosis, normal glucose, and a mildly elevated protein; CSF bacterial cultures are negative. Which of the following is most likely responsible for this recurrent presentation?
AHerpes simplex encephalitis
BMollaret aseptic meningitis
CDisseminated herpes infection
DElsberg syndrome radiculopathy
Reveal answer & full explanation
Correct answer: B — Mollaret aseptic meningitis
AHerpes simplex encephalitis
BMollaret aseptic meningitis✓
CDisseminated herpes infection
DElsberg syndrome radiculopathy
Why Mollaret aseptic meningitis is correct
HSV-2 is the classic cause of Mollaret meningitis: recurrent, self-limited episodes of aseptic (lymphocytic) meningitis that resolve spontaneously over days.
The CSF profile here (lymphocytic pleocytosis, normal glucose, mildly elevated protein, negative bacterial cultures) is the expected aseptic/viral pattern, and the recurrent self-resolving course in a patient with established HSV-2 is the signature of this entity.
HSV-2 reactivation in the sacral ganglia can seed the meninges, producing repeated benign episodes; CSF HSV-2 PCR confirms the diagnosis.
Why the others are wrong
Herpes simplex encephalitis is a fulminant, sporadic infection caused almost always by HSV-1, presenting with fever, altered mentation, focal deficits, and seizures (often temporal-lobe), not benign recurrent self-resolving meningitis.
Elsberg syndrome radiculopathy is the sacral radiculitis complication of genital HSV, presenting with sacral sensory loss and bladder dysfunction (urinary retention), not headache, neck stiffness, and CSF pleocytosis.
Disseminated herpes infection causes multiorgan spread (hepatitis, pneumonitis) in immunocompromised or neonatal hosts and is severe and non-recurring, not a benign self-limited course in an otherwise healthy adult.
🔒 Free preview limit reached
Keep comparing — start your free trial
You've used your 2 free previews. Create your free account to see the full Syphilis vs Genital Herpes comparison — plus all 514 diagnosis outlines, 7,200+ board-style questions, and an AI tutor. Your 7-day free trial includes everything, no credit card required.
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 (median ~3 weeks, range 10-90 days after exposure): single painless indurated ulcer (chancre) with raised borders, clean base; heals spontaneously in 3-6…
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…
Drill Syphilis vs Genital Herpes questions on FirstPassPA
Turn this comparison into retention. 7,200+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
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 or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.