185.1 🎓 醫學生版

185.1.0.1 📌 一頁重點

• 菌: Borrelia burgdorferi sensu lato group
  • B. burgdorferi sensu stricto (N. America)
  • B. afzelii, B. garinii, B. bavariensis (Europe / Asia)
• Vector: Ixodes hard tick (NOT Ornithodoros soft tick) — different from relapsing fever
  • I. scapularis (NE/Midwest USA)
  • I. pacificus (W coast USA)
  • I. ricinus (Europe)
  • I. persulcatus (Asia, Russia)
• Reservoir: 白足 mouse (Peromyscus) + deer (deer for tick lifecycle, not for transmission)
• Transmission: tick attached ≥ 36-48 hours to transmit (longer than other tick-borne diseases)
• 3 Stages:
  • Early Localized (Stage 1, 3-30d): erythema migrans (EM) at bite site — expanding red ring with central clearing or solid; ± constitutional sx (fever, headache, myalgia, LAP) — flu-like
  • Early Disseminated (Stage 2, weeks-months): multiple EM, carditis (3rd degree AVB), neuroborreliosis (cranial neuritis CN VII palsy, meningitis, radiculitis)
  • Late (Stage 3, months-years): Lyme arthritis (knee predominant, recurrent oligoarticular), encephalomyelitis (rare), peripheral neuropathy, acrodermatitis chronica atrophicans (Europe)
• Dx:
  • Clinical for EM alone (don’t need serology)
  • 2-tier serology (EIA + Western blot)
  • PCR / culture in selected cases
• Treatment:
  • Early: doxycycline 100 bid × 10-14d (or amox 500 tid)
  • Carditis: doxy / ceftriaxone IV × 14-21d (depending severity)
  • Neuroborreliosis: ceftriaxone 2 g IV qd × 14-21d (or PO doxy in select)
  • Arthritis: doxy 100 bid × 28d (or amox)
• Prophylaxis (post-bite): doxy 200 mg PO × 1 within 72 hr if Ixodes tick attached ≥ 36 hr in endemic
• PTLDS (Post-Treatment Lyme Disease Syndrome): persistent fatigue/pain/cognitive sx 6 mo+ after Tx; mechanism unclear; not active infection; supportive

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185.1.0.2 1️⃣ 細菌學 + Vector Biology

• B. burgdorferi sensu lato — spirochete, helical
• Outer membrane: OspA, OspC (key antigens)
• Cultivable BSK-II media (specialty lab)

185.1.0.2.1 Tick Lifecycle

• 2-yr lifecycle (eggs → larva → nymph → adult)
• Nymph (poppy seed size) — main human-biting stage (May-July)
• Larva (egg → larva): not infectious yet
• Adult bites — but more easily detected and removed
• Tick must attach ≥ 36-48 hr to transmit Borrelia (unlike RMSF 4-6 hr, Anaplasma 24 hr)

185.1.0.2.2 Reservoir

• White-footed mouse (Peromyscus leucopus) — main reservoir
• Deer (Odocoileus) — tick lifecycle host, not Borrelia reservoir
• Squirrels, birds, lizards (W coast — explains lower Lyme W vs E)

185.1.0.2.3 流行病學

• USA: ~ 480K cases/yr (CDC 2024 estimate)
• NE / Mid-Atlantic / Upper Midwest highest
• Europe: ~ 200K cases/yr
• Asia: emerging recognition
• Climate change → expanding range north + earlier season

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185.1.0.3 2️⃣ 臨床表現

185.1.0.3.1 Stage 1: Early Localized (3-30d post-bite)

185.1.0.3.1.1 Erythema Migrans (EM)

• ~ 70-80% of cases have EM
• Expanding erythema at tick bite site
• “Bull’s-eye” (central clearing) classic but only 20%; more often solid red
• Diameter ≥ 5 cm to be considered EM
• Painless, mildly warm
• Borreliae spread centrifugally → annular shape

185.1.0.3.1.2 Constitutional

• Mild flu-like: fever, headache, myalgia, fatigue, regional LAP
• Not severe

185.1.0.3.2 Stage 2: Early Disseminated (Weeks-Months)

185.1.0.3.2.1 Multiple EM

• Smaller annular lesions in distant sites
• Reflects bacteremic dissemination

185.1.0.3.2.2 Lyme Carditis

• 1-5% of untreated cases
• Variable AV block (commonly progresses up to 3rd degree)
• Myocarditis (mild)
• Pericarditis rare
• Reversible with antibiotic — pacemaker rarely permanent

185.1.0.3.2.3 Neuroborreliosis (Stage 2)

• 10-15% of untreated cases
• Cranial neuritis — most common, especially CN VII palsy (often bilateral)
• Lymphocytic meningitis — headache, photophobia
• Radiculitis — burning, shooting limb pain, often nocturnal
• Bannwarth syndrome (Europe) — painful radiculitis + meningitis + CN palsy

185.1.0.3.3 Stage 3: Late (Months-Years)

185.1.0.3.3.1 Lyme Arthritis

• USA more common (B. burgdorferi ss)
• Knee predominant (75%) — mono / oligoarticular
• Recurrent episodes (weeks-months)
• ~ 10% develop antibiotic-refractory arthritis (autoimmune, HLA-DR4 association)

185.1.0.3.3.2 Late Neuroborreliosis (rare)

• Encephalomyelitis
• Peripheral neuropathy
• Encephalopathy (memory, mood)

185.1.0.3.3.3 Acrodermatitis Chronica Atrophicans (ACA)

• Europe only (B. afzelii)
• Chronic skin atrophy on extremities — bluish, atrophic, easily bruised

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185.1.0.4 3️⃣ 診斷

185.1.0.4.1 EM Alone — Clinical Diagnosis

• Don’t need serology
• Treat empirically

185.1.0.4.2 2-Tier Serology

1. EIA / ELISA (1st tier) — screen
2. IgM + IgG Western blot (2nd tier) — confirm if + or equivocal

185.1.0.4.2.1 Serology Pitfalls

• IgM specific for early infection (don’t trust IgM in late infection — false +)
• 2-tier protocol reduces false +
• 2019 modified 2-tier: two EIAs (in lieu of EIA + Western blot) — equivalent + simpler
• False positives: syphilis, RA, SLE, mononucleosis, anaplasmosis

185.1.0.4.3 PCR

• Synovial fluid (arthritis) — high yield
• CSF (low yield ~ 30%)
• EM lesion biopsy

185.1.0.4.4 Culture

• Skin biopsy (high yield in EM)
• Specialty labs

185.1.0.4.5 CSF Studies (Neuroborreliosis)

• Lymphocytic pleocytosis (50-200 cells)
• Elevated protein
• CXCL13 (high in neuroborreliosis — promising biomarker)
• Intrathecal antibody (CSF/serum IgG index > 1.5 — diagnostic)

185.1.0.4.6 Arthritis

• Joint aspiration → high cell count (10K-50K) + PMN; PCR +; rule out crystal, septic
• MRI knee: effusion, synovitis

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185.1.0.5 4️⃣ 治療 (2020 IDSA/AAN/ACR Guidelines)

185.1.0.5.1 Early (Localized EM)

• Doxycycline 100 mg PO bid × 10-14d (preferred all ages > 8 yr)
• Amoxicillin 500 mg PO tid × 14d (pediatric / pregnant)
• Cefuroxime axetil 500 mg bid × 14d (alt)
• Azithromycin 500 qd × 7d (alt — inferior; avoid)

185.1.0.5.2 Early Disseminated — Multiple EM

• Doxycycline × 14d (same as early)

185.1.0.5.3 Carditis

• Mild (AVB 1° / 2° Type I, no sx): PO doxy × 14-21d
• Severe (3° AVB, sx, hospitalized): Ceftriaxone 2 g IV qd × 14-21d → PO doxy
• Temporary pacing if 3° AVB; usually reversible 1-2 wk

185.1.0.5.4 Neuroborreliosis

• Ceftriaxone 2 g IV qd × 14-21d (USA standard)
• 2020 IDSA: PO doxycycline non-inferior for non-CNS-severe (e.g., facial palsy alone) — but IV for clear meningitis / radiculitis
• Pediatric: ceftriaxone or doxy (PO acceptable if not severe meningitis)

185.1.0.5.5 Arthritis

• Doxycycline 100 bid × 28d (preferred)
• Amoxicillin 500 tid × 28d
• 失敗 — repeat doxycycline OR ceftriaxone × 28d
• “Antibiotic-refractory arthritis” (autoimmune) — DMARD, intra-articular steroid

185.1.0.5.6 Post-Bite Prophylaxis

• Doxycycline 200 mg PO × 1
• Conditions (all):
  • Endemic area
  • Ixodes scapularis identified
  • Attached ≥ 36 hr
  • Within 72 hr of removal

185.1.0.5.7 Pregnant / Pediatric

• Amoxicillin or cefuroxime (avoid doxy < 8 yr; doxy in pregnancy avoided but short course increasingly accepted IDSA)
• Ceftriaxone if IV needed

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185.1.0.6 5️⃣ Post-Treatment Lyme Disease Syndrome (PTLDS)

• 5-15% of treated patients
• Persistent fatigue + pain + cognitive sx > 6 mo
• Not active infection (multiple studies: prolonged antibiotic does NOT help)
• Mechanism unclear: residual inflammation, immune dysregulation, deconditioning, central sensitization
• Supportive: graded exercise, CBT, pain management, sleep hygiene
• NOT prolonged antibiotic (multiple RCTs show no benefit + risks)
• “Chronic Lyme disease” (non-evidence based diagnosis) — not endorsed by IDSA

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185.1.0.7 6️⃣ Vaccine + Prevention

185.1.0.7.1 Tick-Avoidance

• Long pants / sleeves in endemic
• Permethrin-treated clothing
• DEET / picaridin repellent
• Tick check after exposure (groin, axilla, neck, scalp)
• Remove tick with fine tweezers, pull straight up

185.1.0.7.2 Vaccine Development

• VLA15 (Valneva/Pfizer) — recombinant OspA 6-valent multi-species
• Phase 3 ongoing 2023-2025
• Pediatric + adult
• USA: Lyme vaccine LYMErix (1998-2002) withdrawn due autoimmunity concerns (not confirmed) + low uptake
• 期 FDA approval 2026+
• VLA15 uses OspA antigens — antibodies kill spirochetes in tick midgut before transmission

185.1.0.7.3 Tick Vaccine (Mice / Deer Targeting)

• Reservoir-targeted vaccines (mouse vaccination) — emerging research

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