Syphilis

Symptoms

• 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 weeks after chancre): diffuse maculopapular rash including palms and soles, mucous patches, condyloma lata (moist gray-white papules in intertriginous areas), patchy 'moth-eaten' alopecia, generalized lymphadenopathy, low-grade fever, headache, hepatitis, glomerulonephritis
• Latent: asymptomatic but seropositive — early latent (<1 year) versus late latent (≥1 year or unknown duration)
• Tertiary (years-decades): cardiovascular syphilis (aortitis, aortic aneurysm), gummatous lesions (granulomas of skin/bone/viscera), neurosyphilis at any stage (meningitis, meningovascular, general paresis, tabes dorsalis, Argyll Robertson pupils)

Signs / physical exam

• Painless genital, anal, or oral ulcer with raised indurated borders
• Palmar/plantar maculopapular rash (highly characteristic in secondary)
• Generalized lymphadenopathy
• Late: ascending aortic aneurysm, dorsal column dysfunction with sensory ataxia and lancinating pains, dementia, small accommodating but non-reactive pupils (Argyll Robertson — 'prostitute's pupil')
• Congenital: snuffles, saddle nose, Hutchinson teeth, mulberry molars, saber shins, interstitial keratitis, sensorineural deafness

Classic findings

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.

Diagnostic criteria

Positive serology with confirmation by reciprocal test; clinical staging based on examination, sexual history, and timing.

Labs

• 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, autoimmune disease, IV drug use, viral infections)
• • Treponemal: FTA-ABS, TP-PA, or EIA (positive for life; cannot use to monitor treatment)
• • Traditional algorithm: non-treponemal screen → treponemal confirm. Reverse algorithm: treponemal screen → non-treponemal confirm
• Dark-field microscopy of chancre fluid (specialty labs only)
• Direct PCR available in some centers
• Lumbar puncture for neurosyphilis: CSF VDRL specific but insensitive; reactive CSF treponemal sensitive but nonspecific; CSF pleocytosis and elevated protein suggest disease
• HIV testing in all syphilis cases; screen for other STIs

Imaging

• Echo or CT chest if cardiovascular syphilis suspected
• MRI brain/spine for neurosyphilis evaluation
• Skeletal X-rays in congenital syphilis (metaphyseal lucencies, periostitis)

First-line

• 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 syphilis, otosyphilis:
• • Aqueous crystalline penicillin G 18-24 million units/day IV × 10-14 days (3-4 million units q4h or continuous infusion)
• • Alternative: procaine penicillin G 2.4 million units IM daily + probenecid 500 mg PO QID × 10-14 days
• Congenital syphilis: aqueous crystalline penicillin G 50,000 units/kg IV q12h (first 7 days of life) then q8h × 10 days total

Second-line / adjunct

• Penicillin allergy: doxycycline 100 mg PO BID × 14 days (early) or 28 days (late) — NOT for pregnancy or neurosyphilis
• Ceftriaxone 1-2 g IM/IV daily × 10-14 days — alternative in penicillin allergy or neurosyphilis if desensitization not feasible
• Pregnancy: penicillin is the ONLY recommended therapy. Desensitize if allergic (doxycycline is teratogenic; tetracyclines and erythromycin do not adequately treat fetus)
• Jarisch-Herxheimer reaction (fever, chills, headache, myalgia within hours of first penicillin dose) — common in secondary syphilis; supportive care; counsel patients in advance