Fellow's quick read · Infectious Diseases
Lyme disease
IDSA / AAN / ACR 2020 (Lantos et al, CID 2021;72(1):e1–e48) · reviewed 2026-07-07
Personal study digest for a new ID fellow. Recommendations are from the IDSA/AAN/ACR 2020 Lyme guideline. The “What’s changed since 2020” section is reviewer synthesis of newer evidence, each claim cited. Not a substitute for the full guideline.
In one line
Diagnose erythema migrans clinically (serology is often negative early) and treat almost everything by mouth: most Lyme — including neuroborreliosis — is now a course of oral doxycycline. IV ceftriaxone is reserved for parenchymal brain/cord disease and hospitalized carditis. Do not treat persistent post-treatment symptoms with more antibiotics.◆When to suspect / diagnose
- Erythema migrans = clinical diagnosis, no lab test, in an endemic exposure (strong). Serology is insensitive in the first weeks; a negative early test does not exclude it.
- Two-tier serology for later/disseminated disease (arthritis, carditis, neuroborreliosis) — and a modified two-tier (two-EIA) algorithm is now an accepted FDA-cleared alternative to EIA→Western blot.
- Stage-defining syndromes: EM → early disseminated (multiple EM, cranial neuritis esp. CN VII, meningitis, radiculoneuritis, AV block/carditis) → late (monoarticular knee arthritis).
- Diagnose neuroborreliosis and arthritis by serum antibody, not blood PCR/culture; in a seropositive arthritis patient, synovial-fluid PCR adds specificity (do NOT send synovial antibody).
- Co-infection with Anaplasma or Babesia shares the Ixodes vector — suspect it with high fever, cytopenias, or transaminitis.
◆Empiric & definitive therapy
| Manifestation | Drug / dose / route | Duration | Strength |
|---|---|---|---|
| Erythema migrans (early localized) | Doxycycline 100 mg PO BID (or 200 mg daily) | 10 d | strong / mod |
| EM — beta-lactam | Amoxicillin 500 mg PO TID or cefuroxime axetil 500 mg PO BID | 14 d | strong / mod |
| EM — 2nd line | Azithromycin 500 mg PO daily (lower efficacy) | 7 d (5–10) | — |
| Neuroborreliosis (non-parenchymal) | Oral doxycycline OR IV ceftriaxone 2 g daily (cefotaxime / penicillin G alt) | 14–21 d | strong / mod |
| Parenchymal CNS (brain / spinal cord) | IV ceftriaxone 2 g daily | 14–21 d | strong / mod |
| Carditis | Oral (outpatient); IV ceftriaxone → oral step-down if hospitalized | 14–21 d | weak / v.low |
| Arthritis (initial) | Oral doxycycline / amoxicillin / cefuroxime | 28 d | strong / mod |
| Post-exposure prophylaxis | Doxycycline 200 mg PO once (peds 4.4 mg/kg, max 200 mg) | single dose | strong / mod |
◆Key decisions a fellow owns
- Prophylaxis only for a high-risk bite — ALL three: (a) identified Ixodes vector, (b) highly endemic area, (c) attached ≥36 h — and give the single doxycycline dose within 72 h of removal. Equivocal/low-risk bite = watch and wait. Do NOT send the tick for PCR to decide.
- Route for neuro Lyme: oral doxycycline for meningitis, cranial neuritis (incl. facial palsy), and radiculoneuropathy; escalate to IV only for parenchymal brain/cord involvement.
- Carditis — who to admit: PR >300 ms, other arrhythmia, or myopericarditis → admit with continuous monitoring. If pacing is needed, use temporary pacing — the block resolves; do NOT implant a permanent pacemaker.
- ECG only if symptomatic — do not screen every early-Lyme patient.
- Persistent post-treatment symptoms: recommend AGAINST additional antibiotics without objective disease — the highest-yield place a fellow protects a patient from harm.
◆Special populations
- Children: short-course doxycycline (≤21 d) does NOT stain teeth — it is acceptable across all pediatric ages for Lyme (the old <8-year taboo came from older tetracyclines).
- Pregnancy / lactation: treat as non-pregnant except avoid doxycycline — use amoxicillin or cefuroxime; congenital Lyme has not been demonstrated with treatment.
- STARI (Lone Star tick, Amblyomma) mimics EM but is not Lyme — where ranges overlap and you cannot distinguish them, treat for Lyme.
◆Duration & stopping
- Most early and disseminated disease finishes in 10–21 days; arthritis is the outlier at 28 days. Complete response can lag the antibiotic course — symptom persistence alone is not treatment failure.
- Partial arthritis response → a second oral course or IV ceftriaxone; refractory synovitis is managed as immune-mediated (NSAIDs/DMARDs/synovectomy), not with more antibiotics.
What’s changed since 2020
Reviewer synthesis of newer evidence — not the guideline. Each claim cited; the guideline itself has not been superseded.
- A Lyme vaccine cleared Phase 3 — first since 2002. VLA15 / PF-07307405 (Pfizer–Valneva), a 6-valent OspA subunit vaccine, hit 73.2% efficacy from 28 d post-dose 4 (95% CI 15.8–93.5) and 74.8% from day 1 post-dose 4 (95% CI 21.7–93.9) in VALOR, ages ≥5. The pre-specified statistical bar (CI lower bound >20) was met only on the 2nd analysis (fewer cases than expected); regulatory submissions planned 2026. Pfizer/Valneva topline 23 Mar 2026; NCT05477524
- Lyme PrEP is a new category. A long-acting anti-OspA monoclonal (single seasonal SC dose) neutralizes Borrelia in the tick midgut: TNX-4800 (Tonix, ex-UMass Chan “2217LS”) passed Phase 1, with an adaptive Phase 2 field study planned for 2027. Moderna’s mRNA candidates (mRNA-1975/1982) are in Phase 1/2. IDSA Science Speaks, Jan 2026; UMass Chan/Tonix 2025–26
- No newer society guideline. The 2020 IDSA/AAN/ACR guideline was reaffirmed Oct 2023 and remains the operative US reference. idsociety.org practice-guideline/lyme-disease
- Rising, spreading burden. A 2022 surveillance-reporting change in high-incidence states raised counts (>89,000 reported in 2023; ~476,000 estimated diagnosed/treated per year), with continued geographic expansion — an epidemiologic shift, not a treatment change. CDC Lyme surveillance, 2025
◆Anki cards minted this run
- VLA15 / VALOR — first Phase 3 Lyme-vaccine efficacy readout (~73–75%).
- Oral doxycycline for non-parenchymal neuroborreliosis; IV reserved for brain/cord.
- Persistent post-treatment symptoms — against additional antibiotics.
- Doxycycline is acceptable in young children (short courses don’t stain teeth).
Held as already in deck: 10-day doxycycline for EM · single-dose doxycycline PEP (≥36 h, ≤72 h) · 28-day arthritis · carditis oral-vs-IV · persistent-arthritis DMARD ladder.
Sources: IDSA/AAN/ACR 2020 Lyme guideline (Lantos et al, Clin Infect Dis 2021;72(1):e1–e48; doi:10.1093/cid/ciaa1215; also Neurology 2021;96:262). VALOR topline (Pfizer/Valneva, 23 Mar 2026; NCT05477524). Lyme PrEP / TNX-4800 (IDSA Science Speaks blog, Jan 2026; UMass Chan/Tonix, 2025–26). Guideline reaffirmation Oct 2023 (idsociety.org). CDC Lyme surveillance (2025).