Lyme Disease

Tickborne / Spirochete

Patient + scenario modifiers

Patient

Clinical scenario / source

Annotations only — chart still shows the full chemistry of each drug.

1. Clinical Syndrome

Multisystem infection caused by Borrelia burgdorferi (US) transmitted by Ixodes scapularis (east, north) or I. pacificus (west) nymphal ticks. Three clinical stages by tempo:

Early local (days–weeks): erythema migrans (EM, expanding annular rash >5 cm) ± flu-like symptoms. Single skin finding, no dissemination.
Early disseminated (weeks–months): multiple EM lesions, neuroborreliosis (Bell's palsy, lymphocytic meningitis, painful radiculitis — Bannwarth syndrome), carditis (AV block, sometimes high-degree), arthralgia.
Late (months–years): Lyme arthritis (monoarticular or oligoarticular, knee >> other large joints), late neuroborreliosis (encephalopathy, polyneuropathy — rare in US).

Excludes: STARI (Southern Tick-Associated Rash Illness — Amblyomma americanum, mimics EM serologically negative), Babesiosis (often co-infection — separate workflow with atovaquone + azithro or quinine + clinda), Anaplasmosis / Ehrlichiosis (often co-infection — doxycycline), Powassan virus encephalitis (rare but rising tickborne), post-treatment Lyme disease syndrome (subjective chronic symptoms — NOT chronic infection; supportive care).

2. Pathogens

Consider the patient: Geographic exposure (Northeast, Upper Midwest, Pacific NW US, Europe), tick exposure (deer, outdoor activity May–Sept peak), prior tick bite (even unrecognized).

Consider the case: Stage drives drug + duration. EM = treat empirically without serology (false-negative early). Disseminated / neuro / cardiac = serology + sometimes CSF / synovial fluid PCR. Co-infection screen (Babesia, Anaplasma) when febrile + severely ill or treatment-refractory.

Common

- Borrelia burgdorferi
  Sole cause of US Lyme disease. Spirochete; doesn't gram-stain; diagnosis via serology (two-tier ELISA → immunoblot) or PCR (synovial fluid for arthritis, CSF for neuroborreliosis).

3. Empiric Therapy

Tier	First choice	Alternatives	Duration	Comments
Outpatient	100 mg · PO BID · PO · 10 days (early local) or 14 days (early disseminated cranial neuropathy, isolated AV block, carditis-mild, mild arthritis)	500 mg · PO TID · PO · 14 days Preferred in pregnancy + children <8 y where doxy is relatively contraindicated. Equivalent efficacy. 500 mg · PO daily · PO · 7 days Reserved for true PCN + tetracycline allergy. Less effective; backup only.	10–14 days for early Lyme	Erythema migrans is a clinical diagnosis — treat empirically without serology (often false-negative in first weeks). Doxycycline preferred because it also covers Anaplasma / Ehrlichia co-infection. No follow-up serology needed; titers stay positive for years and don't reflect cure.
Outpatient — with comorbidities	100 mg · PO BID · PO · 28 days	500 mg · PO TID · PO · 28 days	28 days	Lyme arthritis (monoarticular knee swelling, late presentation). First course = oral. If recurrent / persistent synovitis after 28 d → second course oral or switch to IV ceftriaxone for 14–28 d. Persistent arthritis beyond that = post-infectious / antibiotic-refractory — DMARDs, not more antibiotics.
Admitted to ward	2 g · q24h · IV · 14–28 days	200 mg · PO BID · PO · 14–28 days Equally effective for neuroborreliosis per IDSA/AAN/ACR 2020 — high-dose PO doxycycline is non-inferior to IV ceftriaxone for most neurologic presentations (except severe parenchymal involvement).	14–28 days for neuroborreliosis, severe carditis, refractory arthritis	Neuroborreliosis (meningitis, encephalitis, painful radiculitis), high-degree AV block, severe carditis, refractory arthritis. IDSA 2020 increasingly supports oral high-dose doxycycline as non-inferior for most neuro presentations — but IV CTX remains the conventional choice and is preferred for parenchymal CNS disease or admitted patients.

4. Directed Therapy

Prophylaxis after high-risk tick bite: doxycycline 200 mg PO × 1 dose, when ALL met: (1) Ixodes scapularis (deer tick, not dog tick), (2) attached ≥36 hours OR engorged, (3) endemic region, (4) prophylaxis can be started within 72 hours of removal.

Stage-specific:

Early local (EM): doxy 100 BID × 10 d, or amox 500 TID × 14 d.
Multiple EM / mild disseminated / isolated facial palsy: doxy or amox × 14 d.
Lyme arthritis: doxy or amox × 28 d. Persistent → second course oral or IV CTX × 14–28 d.
Neuroborreliosis (meningitis, radiculitis, encephalitis): doxy 200 mg PO BID OR ceftriaxone 2 g IV daily × 14–28 d.
Carditis with AV block + hospitalization: ceftriaxone 2 g IV daily × 14–21 d, transition to oral when stable.
Late Lyme encephalopathy / polyneuropathy (rare): ceftriaxone × 28 d.

No role for:

Long-term / chronic antibiotic therapy ("chronic Lyme") — IDSA 2020 strong recommendation against. Multiple RCTs negative.
Routine retreatment for persistent symptoms (PTLDS).
Serologic monitoring of cure — titers stay positive for years.

Co-infection screening (Babesia, Anaplasma, Ehrlichia, Powassan): screen if febrile + severely ill, fail to improve on doxycycline, or hospitalized.

5. Monitoring

Resolution: EM fades within days–weeks (treat clinically, no follow-up serology needed). Arthritis swelling resolves over weeks–months. Neurologic deficits often resolve but Bell's palsy can persist briefly even after clearance.

Persistent symptoms: subjective fatigue, arthralgia, cognitive complaints after adequate tx = post-treatment Lyme disease syndrome (PTLDS) — supportive care only. NOT chronic infection.

Toxicity: doxycycline → photosensitivity (counsel sun avoidance esp summer), esophagitis (take with water + upright), tooth staining in <8 y (less concern for short course); ceftriaxone → biliary sludge with prolonged use, calcium-containing IV fluids interaction (precipitation).

Pearls

Erythema migrans → treat clinically, no serology. Two-tier serology (ELISA → immunoblot) for everything else; modified two-tier (two ELISAs) acceptable per CDC 2019. Doxycycline covers co-infections (Anaplasma, Ehrlichia) — amox doesn't. Carditis with AV block can be high-degree but is transient — temporary pacing only, no permanent. Lyme arthritis = monoarticular knee swelling weeks–months after exposure; PCR of synovial fluid most sensitive. No chronic Lyme — long-term antibiotics don't help PTLDS and cause harm. Prophylaxis after high-risk bite: doxy 200 mg × 1 within 72 h.