Spirochetal STI (Treponema pallidum) with characteristic primary chancre, secondary mucocutaneous disease, latent phase, and tertiary complications.
Also known as: syphilis, Treponema pallidum, lues, neurosyphilis, congenital syphilis
Overview
Systemic infection caused by Treponema pallidum subspecies pallidum, a microaerophilic spiral bacterium transmitted by sexual contact, vertical transmission, and rarely transfusion. Disease progresses through primary, secondary, latent, and tertiary stages over years if untreated.
Epidemiology
US rates have risen sharply over the past decade — 207,000 cases of all stages in 2022 (CDC), highest since 1950s. Disproportionate increase in MSM, women of reproductive age, and congenital syphilis (alarming resurgence; >3,700 congenital cases in 2022). HIV coinfection common (~50% in MSM with syphilis).
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Question 1Infectious DiseaseMedium
A 28-year-old man presents with a diffuse maculopapular rash involving his palms and soles, along with mucous patches in his mouth and condylomata lata in the perianal region. He had a painless genital ulcer six weeks ago that resolved on its own. RPR is reactive at 1:64 and confirmatory treponemal testing is positive. Which of the following is the most likely long-term complication if he remains untreated?
AAcute glomerulonephritis
BMyocardial infarction
CTabes dorsalis
DHemolytic anemia
Reveal answer & full explanation
Correct answer: C — Tabes dorsalis
AAcute glomerulonephritis
BMyocardial infarction
CTabes dorsalis✓
DHemolytic anemia
Why Tabes dorsalis is correct
This presentation is secondary syphilis, characterized by a palmar/plantar maculopapular rash, mucous patches, and condylomata lata, occurring 4-10 weeks after the primary chancre.
Without treatment, roughly one-third of patients progress to tertiary syphilis years to decades later.
Tertiary manifestations include neurosyphilis (tabes dorsalis, general paresis, Argyll Robertson pupils), cardiovascular syphilis (ascending aortic aneurysm), and gummatous disease.
Tabes dorsalis results from demyelination of the dorsal columns and dorsal roots and is among the most recognizable late complications.
Why the others are wrong
Acute glomerulonephritis — a rare immune-complex phenomenon seen only during secondary syphilis, not a long-term sequela.
Myocardial infarction — not a recognized syphilitic complication; cardiovascular syphilis instead causes thoracic aortic aneurysm and aortic regurgitation.
Hemolytic anemia — not a feature of any stage of syphilis.
Additional high-yield points
Penicillin G remains the treatment of choice across all stages of syphilis.
Question 2Infectious DiseaseEasy
A 35-year-old man presents with a painless, indurated genital ulcer and non-tender bilateral inguinal lymphadenopathy. Rapid plasma reagin (RPR) is positive at 1:64 and is confirmed by fluorescent treponemal antibody absorption (FTA-ABS). Which of the following is the most likely diagnosis?
AGenital herpes
BLymphogranuloma venereum
CChancroid
DPrimary syphilis
Reveal answer & full explanation
Correct answer: D — Primary syphilis
AGenital herpes
BLymphogranuloma venereum
CChancroid
DPrimary syphilis✓
Why Primary syphilis is correct
Primary syphilis presents with a painless indurated chancre and non-tender regional lymphadenopathy
Diagnosis is confirmed by a positive RPR at 1:64 confirmed by fluorescent treponemal antibody absorption (FTA-ABS)
Why the others are wrong
Genital herpes — causes painful grouped vesicles and shallow ulcers, not a single painless indurated chancre, and is not RPR/FTA-ABS positive
Lymphogranuloma venereum — produces a transient painless ulcer followed by painful suppurative inguinal buboes and is caused by Chlamydia trachomatis L serovars, not Treponema
Chancroid — causes painful, soft, ragged ulcers with tender suppurative adenopathy (Haemophilus ducreyi), the opposite of the painless indurated chancre
Additional high-yield points
Treatment is benzathine penicillin G 2.4 million units IM x 1
Non-pregnant penicillin-allergic patients can receive doxycycline x 14 days
Repeat RPR at 6 and 12 months to confirm treatment response
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T. pallidum penetrates intact mucous membranes or microabrasions, replicates locally, then disseminates hematogenously and lymphatically within hours. Cannot be cultured in vitro. Tissue damage results from intense host inflammatory response. CNS invasion occurs early; clinical neurosyphilis can present at any stage.
Clinical presentation
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')
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.
Drug eruption — Recent drug exposure; eosinophilia
Lichen planus — Pruritic violaceous polygonal papules with Wickham striae
Diagnostic workup
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)
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)
CDC 2021 syphilis treatment by stage (penicillin-based regimens).
Treatment
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
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