181.1 🎓 醫學生版

181.1.0.1 📌 一頁重點

• 菌: Treponema pallidum subsp. pallidum — spirochete (corkscrew), 不可常規 culture
• 傳播: 性接觸 (oral, anal, vaginal), vertical (congenital), 偶 blood / transplant
• Stages:
  • Primary: chancre (painless ulcer + indurated edge), 3 wk after exposure, heals 3-6 wk; ± painless inguinal LAP
  • Secondary: 4-10 wk later — generalized 紅疹 (palms/soles), condyloma lata (mucocutaneous), mucous patches, generalized LAP, mild systemic
  • Latent: serology + but no sx (early latent < 1 yr, late latent > 1 yr or unknown duration)
  • Tertiary: gummas (skin/bone), CV (aortitis), late neurosyphilis (tabes, paresis)
  • Neurosyphilis ANY stage: meningitis, meningovascular, parenchymal (tabes dorsalis, general paresis), otic, ocular (uveitis, optic neuritis)
• Congenital: stillbirth, neonatal: snuffles, rash, osteochondritis, hepatosplenomegaly; late: Hutchinson teeth, mulberry molars, saber shins, deafness
• Dx:
  • Direct: dark-field microscopy of chancre (rare lab now), PCR
  • Serology:
    • Non-treponemal (VDRL, RPR) — titer (4-fold drop = response); false + (autoimmune, pregnancy, HIV, age)
    • Treponemal (FTA-ABS, TP-PA, EIA, CIA) — confirmation, stays + lifelong
  • Reverse algorithm (treponemal EIA first → if + then RPR/VDRL) — increasingly used
• Treatment:
  • Primary / secondary / early latent: Benzathine PCN G 2.4M U IM × 1
  • Late latent / tertiary: Benzathine PCN G 2.4M U IM weekly × 3
  • Neurosyphilis / ocular / otic: Aqueous PCN G 18-24M U IV daily × 10-14d
  • Pregnant: PCN G (only; desensitize if allergic — no alternative)
  • Doxycycline 100 bid × 14d (early) or 28d (late) — alternative non-pregnant non-neuro
• Jarisch-Herxheimer reaction: 6-24 hr after first dose — fever, chills, myalgia, ↑ rash; supportive; 不停藥
• Follow-up: RPR titer at 6, 12, 24 mo; 4-fold drop = response

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181.1.0.2 1️⃣ 細菌學

• T. pallidum — spirochete, helical, motile (axial filament)
• Cannot 培養 standard
• Microaerophilic
• Dark-field microscopy of fresh chancre exudate — historical
• PCR + (mucosal lesions, CSF, blood — newer)
• Generation time slow (30+ hr) — why long abx duration

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181.1.0.3 2️⃣ Stages — Clinical

181.1.0.3.1 Primary

• 潛伏 10-90d (mean 21d)
• Chancre: single, painless, indurated, clean base ulcer at site of inoculation (genitalia, anus, mouth, lip)
• ± painless regional LAP (rubbery)
• Heals 3-6 wk untreated → progress to 2°
• 鑑別: HSV (painful, multiple, vesicular), chancroid (painful, soft, multiple, suppurative LAP), LGV (painless ulcer + tender groove sign LAP)

181.1.0.3.2 Secondary

• 4-10 wk after 1°
• Generalized constitutional (fever, malaise, LAP)
• Rash: 紅斑 → maculopapular, involves palms + soles (classic), trunk + extremities
• Condyloma lata (mucocutaneous, broad warts in moist areas — vs HPV condyloma acuminata)
• Mucous patches (oral, vulvar — slate-gray, highly infectious)
• Patchy alopecia (“moth-eaten”)
• Hepatitis, glomerulonephritis, uveitis, meningitis (10% have CSF involvement at this stage)

181.1.0.3.3 Latent

• Asymptomatic, serology +
• Early latent: < 1 yr (CDC) — still infectious sexual + vertical
• Late latent: > 1 yr or unknown duration — less sexually transmitted, but vertical risk

181.1.0.3.4 Tertiary (Late)

• Gummatous: granulomatous lesions skin, bone, viscera; rare today
• Cardiovascular: aortitis → aortic aneurysm (ascending), AR — 15-30 yr after
• Late Neurosyphilis (10-30+ yr):
  • Tabes dorsalis: posterior column degeneration — wide-based ataxia, lightning pains, Argyll-Robertson pupil, loss of position/vibration sense, Charcot joint
  • General paresis: dementia, personality change, psychosis
  • Meningovascular: stroke in young patient

181.1.0.3.5 Neurosyphilis (Any Stage)

• Can occur at any time after primary
• Early: meningitis (1° / 2°)
• Meningovascular (months-years)
• Parenchymal (years-decades): tabes, paresis
• Ocular: anterior/posterior uveitis, optic neuritis — emergency
• Otic: SNHL, vertigo, tinnitus
• HIV + late presentation accelerated (faster progression)

181.1.0.3.6 Congenital

• Vertical transmission risk 60-100% in untreated early; declines in late
• Early congenital (< 2 yr): snuffles (mucopurulent rhinitis), rash (palmar/plantar), hepatosplenomegaly, osteochondritis, anemia, jaundice, hydrops fetalis (severe in utero)
• Late congenital (> 2 yr): Hutchinson teeth (notched incisors), mulberry molars, saber shins, frontal bossing, saddle nose, deafness (CN VIII), interstitial keratitis, intellectual disability

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181.1.0.4 3️⃣ 診斷

181.1.0.4.1 Direct Detection

• Dark-field microscopy of chancre / wet lesion exudate — gold standard but lab capability declining
• PCR of lesion, CSF, blood — emerging
• DFA-TP (direct fluorescent Ab) — less common

181.1.0.4.2 Serology

181.1.0.4.2.1 Non-treponemal (NTT): VDRL, RPR

• Measures Ab to cardiolipin-lecithin-cholesterol (host-derived)
• Titer correlates with disease activity — 4-fold drop = response
• Becomes + 1-2 wk after chancre
• Declines after treatment (may persist low titer = “serofast”)
• False +: autoimmune (SLE, APS), pregnancy, HIV, advanced age, IV drug use, malaria, hepatitis C, leprosy

181.1.0.4.2.2 Treponemal (TT): FTA-ABS, TP-PA, EIA, CIA

• Detects Ab to T. pallidum antigens
• Stays + lifelong even after treatment (most)
• Confirmatory test

181.1.0.4.2.3 Traditional vs Reverse Algorithm

Approach	Step 1	Step 2
Traditional	NTT (RPR/VDRL) screen	TT confirm if +
Reverse	TT (EIA/CIA) screen	NTT (RPR) titer for activity

Reverse algorithm preferred increasingly (high throughput); discordant results → TP-PA tiebreaker

181.1.0.4.3 CSF Studies (Neurosyphilis Workup)

• CSF VDRL — specific but low sensitivity (30-70%)
• CSF protein, cells — pleocytosis, ↑ protein
• CSF FTA-ABS — high sens, low spec (R/O if neg)

181.1.0.4.4 Indications for LP

• Neurologic / ocular / otic signs
• Tertiary syphilis
• HIV + late latent / unknown duration (controversial — IDSA 2024: not routine if asymptomatic + RPR < 1:32 + CD4 > 350)
• Treatment failure (titer not declining)

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181.1.0.5 4️⃣ Treatment (2024 CDC + IDSA)

181.1.0.5.1 Primary / Secondary / Early Latent

• Benzathine PCN G 2.4 M U IM × 1

181.1.0.5.2 Late Latent / Tertiary (no Neuro)

• Benzathine PCN G 2.4 M U IM weekly × 3 (total 7.2 M U)

181.1.0.5.3 Neurosyphilis / Ocular / Otic

• Aqueous Crystalline PCN G 18-24 M U/day IV (continuous infusion or 3-4M q4h) × 10-14 days
• Alt: Procaine PCN G 2.4 M U IM daily + Probenecid 500 mg PO qid × 10-14d
• Follow with Benzathine PCN G 2.4M IM weekly × 3 after IV course
• LP repeat at 6 mo (CSF normalization expected)

181.1.0.5.4 Pregnant

• PCN G ONLY — desensitize if allergic, no alternative effective
• Doxycycline contraindicated, ceftriaxone limited data

181.1.0.5.5 Doxycycline (Non-pregnant, Non-neuro, PCN-allergy)

• Early syphilis: doxy 100 mg PO bid × 14d
• Late: doxy 100 PO bid × 28d
• Less data, monitor closely
• Doxy-PEP (200 mg post-sex) — CDC 2024 — reduces syphilis incidence in MSM (added to N. gonorrhoeae)

181.1.0.5.6 Ceftriaxone

• Some data; not first-line
• Ceftriaxone 1 g IM/IV qd × 10-14d (early, neurosyphilis some advocates)

181.1.0.5.7 Jarisch-Herxheimer Reaction

• 6-24 hr after first PCN dose
• Fever, chills, myalgia, headache, ↑ rash
• Spirochete killing → endotoxin-like release
• Common in 1° / 2° (50% +)
• Supportive — antipyretic + fluids
• Do not stop antibiotic
• Pregnant patient — Herxheimer can cause uterine contractions / fetal distress — admit + monitor

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181.1.0.6 5️⃣ Follow-up + Test of Cure

181.1.0.6.1 RPR Titer Monitoring

• 6, 12, 24 months post-treatment
• 4-fold drop = success (e.g. 1:32 → 1:8)
• No drop or rise: re-treat (may indicate failure or re-infection)
• Serofast (stable low titer): no re-treat if asymptomatic + no exposure

181.1.0.6.2 LP Re-do

• Neurosyphilis: CSF normalization expected 6 mo
• VDRL → undetectable, pleocytosis resolution

181.1.0.6.3 HIV Co-testing

• All syphilis patients → HIV test
• PrEP discussion in MSM / high-risk
• All partner tracking

181.1.0.6.4 Partner Notification

• Public Health partner services
• All sexual partners within 90 days of presumed exposure (1° / 2°) or longer (late)

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181.1.0.7 6️⃣ 流行病學 + 2024 Resurgence

• 2014-2024 USA cases 5× increase, global syphilis 8M new/yr
• Congenital syphilis surge — USA cases 10× increase 2014-2024 (Texas + Mississippi worst)
• Drivers: MSM HIV-PrEP era (less condom use), opioid epidemic, social determinants
• WHO global goal: 50% reduction congenital syphilis by 2030
• 通報 mandatory

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