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Infectious Diseases›Condition·Updated Jun 27, 2026·v1

Lyme Disease

Lyme disease is a multisystem spirochetal infection transmitted by Ixodes ticks, with a predictable clinical course from erythema migrans to disseminated disease. Diagnosis is clinical for classic EM; two-tier serology (or MTTT) is the gold standard for atypical presentations. First-line treatment is doxycycline (or amoxicillin in those with contraindications) for 10-28 days depending on stage. IV ceftriaxone is used for high-grade carditis and neuroborreliosis. Prolonged antibiotics are not indicated for PTLDS. Prevention includes single-dose doxycycline after high-risk tick bites and personal protective measures. Prognosis is excellent with appropriate therapy; fatal outcomes are exceptionally rare.

High Evidence210 references·10,125 words·41 min read·v1
Lyme diseaseBorrelia burgdorferierythema migranstick-borne diseaseneuroborreliosisLyme carditisLyme arthritisdoxycyclineceftriaxonetwo-tier serology

Quick Reference

RxDrug of choiceDoxycycline 100 mg PO BID (or 200 mg once daily) for 10-14 days for erythema migrans; IV ceftriaxone 2 g daily for 14-21 days for neuroborreliosis or high-grade carditis.
AltAlternativesAmoxicillin 500 mg PO TID or cefuroxime axetil 500 mg PO BID for 14-21 days for EM; azithromycin 500 mg PO daily for 7-10 days (second-line).
⊘AvoidNon-dihydropyridine CCBs (diltiazem, verapamil) in Lyme carditis; extended antibiotics (>28 days) for PTLDS; corticosteroids in early disease except for refractory AV block.
DxTest of choiceTwo-tier serology (EIA → Western blot) or modified two-tier testing (MTTT) for laboratory diagnosis; PCR of synovial fluid for Lyme arthritis; CSF antibody index for neuroborreliosis.
ScKey scoreModified two-tier testing (MTTT): C6-based EIA followed by whole-cell EIA, with higher sensitivity in early disease (36% vs 24% for standard algorithm) [126].
→When to referCardiology for high-grade AV block; neurology for encephalomyelitis or refractory neuroborreliosis; rheumatology for post-antibiotic Lyme arthritis; ophthalmology for ocular manifestations.
Treat early localized Lyme disease with 10-14 days of doxycycline or amoxicillin; disseminated disease (neuro, cardiac) requires IV ceftriaxone or extended oral therapy. Do NOT prescribe prolonged antibiotics for persistent symptoms after standard therapy.
Lyme disease, caused by spirochetes of the *Borrelia burgdorferi* sensu lato complex and transmitted by *Ixodes* ticks, is the most common vector-borne infection in the United States and Europe. Early recognition of erythema migrans and prompt treatment with doxycycline or amoxicillin prevent progression to disseminated disease. This page provides a comprehensive overview of the clinical stages, diagnostic testing, management, and prevention of Lyme disease, with evidence-based recommendations from the IDSA/AAN/ACR 2020 guideline.

Overview and Recommendations

Background

  • •Lyme disease is a multisystem bacterial infection caused by Borrelia burgdorferi sensu stricto (North America), B. garinii, and B. afzelii (Europe/Asia), transmitted through the bite of an infected Ixodes tick (primarily I. scapularis in the eastern U.S. and I. pacificus in the western U.S.) [1, 16].
  • •An estimated 476,000 cases are diagnosed and treated annually in the U.S., with incidence rising as Ixodes ticks expand their geographic range northward and into higher elevations due to climate change [9, 35, 41, 85].
  • •The infection typically follows a predictable temporal course: early localized disease (erythema migrans, days to weeks), early disseminated disease (multiple EM lesions, neurologic or cardiac involvement, weeks to months), and late disseminated disease (Lyme arthritis, late neuroborreliosis, months to years) [1].
  • •The spirochete lacks classical toxins; tissue damage results primarily from the host inflammatory response. Key virulence factors include VlsE lipoprotein (antigenic variation through gene conversion), adhesins (DbpA/B, BBK32, P66) that direct tissue tropism to collagen-rich sites, and outer surface proteins (OspA, OspC) that mediate transmission [31, 51, 58].
  • •Untreated, Lyme arthritis develops in ~60% of patients, neurologic manifestations in 10-15%, and carditis in ~1-5%. Fatal outcomes are exceptionally rare, with only one clinically consistent case among 114 death certificates listing Lyme disease [187, 194].
  • •Co-infections with other tick-borne pathogens (Anaplasma phagocytophilum, Babesia microti) occur in up to 28% of endemic ticks and can produce more severe or prolonged illness [11].

Evaluation

  • •Suspect Lyme disease in any patient with an expanding erythema migrans (EM) rash (≥5 cm diameter) who lives in or has recently visited an endemic area during May-August.
  • •Ask about tick exposure: recent outdoor activities, tick bites, and time spent in wooded or brushy habitats. The incubation period from tick detachment to EM is typically 7-14 days (range 3-30 days).
  • •Examine the entire skin surface for EM: classic 'bull's-eye' lesions occur in only 20-35%; most are uniformly erythematous. In darker skin types, EM may appear violaceous or hyperpigmented.
  • •Inquire about constitutional symptoms: fever, chills, fatigue, myalgia, headache. Male patients often report more severe early symptoms than females [75].
  • •For suspected disseminated disease, ask about: palpitations, syncope, or dyspnea (carditis); headache, photophobia, neck stiffness, radicular pain, or facial droop (neuroborreliosis); and joint swelling, especially of the knee (Lyme arthritis).
  • •Examine for bilateral facial nerve palsy, a key clue for Lyme neuroborreliosis, as bilateral involvement is rare in idiopathic Bell's palsy.
  • •Order a 12-lead ECG if carditis is suspected: look for first-degree AV block (PR prolongation), Mobitz II, or complete heart block. The classic clue is fluctuating AV block.
  • •For suspected neuroborreliosis, perform a lumbar puncture. CSF typically shows lymphocytic pleocytosis (100-1000 cells/µL), elevated protein, and normal glucose.
  • •Two-tier serology is the gold standard for laboratory diagnosis: first with an EIA, then a reflex Western blot (IgM or IgG) if the EIA is reactive. The modified two-tier test (MTTT), using a second EIA instead of a Western blot, has higher sensitivity in early disease (36% vs 24%) and is now an acceptable alternative [88, 126].
  • •Serology is NOT indicated for classic EM in an endemic area; it has only 30-40% sensitivity in the first 2 weeks [1, 104]. A negative test does not rule out early Lyme disease.
  • •IgM Western blot is only useful within 30 days of symptom onset; after 30 days, isolated IgM positivity is often a false positive [1, 110].
  • •For Lyme arthritis, synovial fluid PCR has 70-85% sensitivity before antibiotics and can confirm the diagnosis when serology is equivocal [8, 17].
  • •Consider alternative diagnoses: STARI (similar rash, but no Lyme), septic arthritis (acute pain, high fever), Bell's palsy (idiopathic, unilateral), viral meningitis, and tick-borne coinfections (anaplasmosis, babesiosis) in patients with high fever, thrombocytopenia, or hemolytic anemia.
  • •Perform a risk assessment: tick attachment ≥36 hours, outdoor occupation or activity in endemic area, and lack of prophylactic doxycycline are key risk factors for infection.

Management

  • •Initiate empiric treatment for early localized Lyme disease (erythema migrans) with doxycycline 100 mg orally twice daily (or 200 mg once daily) for 10-14 days. This regimen covers Borrelia burgdorferi and also treats co-infection with Anaplasma [1].
  • •For patients with contraindications to doxycycline (pregnancy, lactation, children <8 years, or allergy), use amoxicillin 500 mg orally three times daily for 14-21 days or cefuroxime axetil 500 mg orally twice daily for 14-21 days [1].
  • •For high-grade AV block (Mobitz II or complete heart block) from Lyme carditis, admit for telemetry and start IV ceftriaxone 2 g daily. Temporary pacing is needed in ~39% of complete heart block cases. Most patients recover conduction within 1-2 weeks [60, 111, 194].
  • •For mild carditis (asymptomatic first-degree block), oral doxycycline 100 mg twice daily for 14 days is sufficient [1].
  • •For Lyme meningitis or radiculoneuritis, administer IV ceftriaxone 2 g daily for 14-21 days. Oral doxycycline 100 mg twice daily for 14-21 days is an acceptable alternative for uncomplicated cases (e.g., isolated facial palsy without CSF pleocytosis) [1, 106].
  • •For Lyme arthritis, prescribe doxycycline 100 mg orally twice daily for 28 days (or amoxicillin 500 mg three times daily for 28 days). If arthritis persists after the first course, give a second 28-day oral course or switch to IV ceftriaxone 2 g daily for 14-28 days [1].
  • •For post-antibiotic Lyme arthritis (PALA), defined as persistent joint swelling ≥3 months after two courses of antibiotics despite negative synovial PCR, initiate NSAIDs (e.g., ibuprofen 600 mg TID) and consider referral to a rheumatologist for disease-modifying antirheumatic drugs (DMARDs) such as hydroxychloroquine or methotrexate.
  • •Administer a single dose of doxycycline 200 mg (orally) for post-exposure prophylaxis after a high-risk Ixodes tick bite: tick attached for ≥36 hours in an endemic area, given within 72 hours of removal. The NNT is approximately 50 [138, 160, 205].
  • •Monitor for clinical response: EM rash resolves within days, carditis improves within 1-2 weeks, and arthritis improves over 4-8 weeks. If no improvement, reconsider the diagnosis or assess for co-infection.
  • •Do NOT prescribe prolonged antibiotics (>28 days) for post-treatment Lyme disease syndrome (PTLDS). Randomized trials show no benefit and increased risks, including catheter-related infections and C. difficile colitis [1, 136].
  • •Refer to a cardiologist if high-grade AV block requires temporary pacing. Refer to a neurologist for encephalomyelitis or treatment-refractory neuroborreliosis. Refer to a rheumatologist for PALA or suspected autoimmune arthritis.
  • •Avoid non-dihydropyridine calcium-channel blockers (diltiazem, verapamil) in Lyme carditis, as they can worsen heart block. Avoid corticosteroids in early disease unless required for refractory high-grade AV block.
  • •In pregnant women with early Lyme disease, use amoxicillin 500 mg TID for 14-21 days or cefuroxime axetil 500 mg BID for 14-21 days. IV ceftriaxone 2 g daily is appropriate for disseminated disease. Doxycycline is avoided after the first trimester due to theoretical risk of fetal bone and tooth discoloration [80].
  • •For immunocompromised patients, consider PCR of blood, CSF, or synovial fluid for direct detection, as serology may be falsely negative. Do not delay empiric therapy; standard durations are generally adequate, but some experts extend to 21-28 days for disseminated disease [15].
  • •Discharge criteria: resolution of high-grade AV block (or stable PR interval <300 ms), neurologically stable with no meningeal signs, and ability to complete oral antibiotics at home for arthritis or EM.

Board Review — High Yield

  • •Erythema migrans, hallmark rash, expands ≥5 cm, non-pruritic, non-painful; 'bull's-eye' pattern in only 20-35%; most are uniformly erythematous.
  • •Bilateral facial nerve palsy, key clue for Lyme neuroborreliosis; idiopathic Bell's palsy is almost always unilateral.
  • •Fluctuating AV block, classic presentation of Lyme carditis; may fluctuate from first-degree to complete heart block within hours.
  • •VlsE antigenic variation, lipoproteins undergo gene conversion, generating millions of surface variants to evade antibody-mediated clearance; key virulence mechanism.
  • •Post-antibiotic Lyme arthritis (PALA), persistent joint swelling despite ≥2 courses of antibiotics; associated with HLA-DRB1*0404; treated with DMARDs.
  • •Post-treatment Lyme disease syndrome (PTLDS), subjective symptoms (fatigue, pain, cognitive complaints) ≥6 months after standard antibiotics; prolonged therapy is ineffective and not recommended.
  • •B. garinii, associated with neuroborreliosis (Bannwarth syndrome) in Europe; triad of radicular pain, cranial neuritis, lymphocytic meningitis.
  • •Modified two-tier testing (MTTT), replaces Western blot with a second EIA; higher sensitivity in early disease, reduced inter-laboratory variability, eliminates subjective band interpretation [126].
  • •Doxycycline prophylaxis, single 200 mg dose within 72 hours of high-risk Ixodes bite (attached ≥36 h in endemic area); NNT ~50.
  • •Ceftriaxone for Lyme carditis, IV 2 g daily for high-grade AV block; temporary pacing required in ~39% of complete heart block cases; conduction usually recovers within 1-2 weeks without a permanent pacemaker [60].

Deep Dive — Evidence Details

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