Lyme disease is the most common vector-borne infection in the northern hemisphere, caused by Borrelia burgdorferi and transmitted by Ixodes (blacklegged/deer) ticks. It presents in stages — early localized, early disseminated, and late disseminated — with erythema migrans as the hallmark finding in 70–80% of cases. [1-3]
1. History
- Tick exposure: Recent outdoor activity in endemic area (Northeast, upper Midwest, mid-Atlantic, northern California); known tick bite; duration of tick attachment (≥36 hours increases transmission risk significantly) [4]
- Rash: Expanding erythematous lesion at bite site, onset 3–30 days post-bite; may be homogeneous or "bull's-eye" pattern; ≥5 cm diameter; warm but rarely pruritic or painful [2-3]
- Constitutional symptoms: Fever, chills, fatigue, malaise, headache, myalgias, arthralgias [2]
- Timing/progression: Ask about symptom onset relative to tick bite; progression from localized to disseminated symptoms (multiple rashes, joint pain, facial weakness, palpitations, syncope) [2-3]
- Important negatives: No vesicles (unlike HSV), no purulence (unlike cellulitis), no scaling (unlike tinea); absence of rash does not exclude Lyme (20–30% lack EM) [3]
2. Alarm Features
- Lyme carditis: Syncope, presyncope, palpitations, exercise intolerance, dyspnea — suggests AV block; PR >300 ms or high-degree AVB requires admission [4-6]
- Neurologic dissemination: Bilateral facial palsy, meningismus, radiculopathy, encephalopathy [2]
- High-grade fever >1 day on antibiotics: Raises concern for coinfection with Anaplasma or Babesia [7]
- Sudden cardiac death: Rare but reported in Lyme carditis, particularly in young males [4][6]
3. Medications
- First-line treatment (IDSA/AAN/ACR 2020): [4-5]
- Doxycycline 100 mg PO BID × 10 days (erythema migrans) — preferred agent
- Amoxicillin 500 mg PO TID × 14 days
- Cefuroxime axetil 500 mg PO BID × 14 days
- IV therapy (meningitis, severe carditis): Ceftriaxone 2 g IV daily × 14–21 days [6][8]
- Second-line: Azithromycin (lower efficacy; reserve for doxycycline/beta-lactam intolerance) [2][4]
- Post-exposure prophylaxis: Doxycycline 200 mg × 1 dose within 72 hours of high-risk tick removal [2][4-5]
- Contraindicated: Prolonged antibiotic courses for post-treatment Lyme disease syndrome (no benefit, strong recommendation against) [4-5]
- Cautions: Doxycycline — photosensitivity, esophageal irritation; use with caution in pregnancy (discuss risks/benefits) [4]
4. Diet
- No specific dietary triggers or restrictions
- Adequate hydration during febrile illness
- Take doxycycline with food and a full glass of water; avoid lying down for 30 minutes after dosing to prevent esophageal ulceration
5. Review of Systems
- Dermatologic: Expanding rash(es), new skin lesions distant from bite site
- Neurologic: Facial weakness/droop (unilateral or bilateral), headache, neck stiffness, radicular pain, numbness/tingling, cognitive difficulties [2]
- Cardiac: Palpitations, chest pain, syncope, exercise intolerance [4][6]
- Musculoskeletal: Migratory joint pain/swelling (especially large joints, knees), myalgias [2-3]
- Ophthalmologic: Conjunctivitis, visual changes (uveitis, keratitis — rare) [8]
- Constitutional: Fever, fatigue, night sweats, weight loss
6. Collateral History and Family History
- Collateral: Travel history to endemic areas; outdoor activities (hiking, gardening, camping); pet exposure (dogs/cats may carry ticks into home); household members with similar symptoms [4][9]
- Family history: Not a hereditary condition, but shared environmental exposures in families are common
- Social context: Occupational exposure (forestry, landscaping, farming); recreational exposure in wooded/grassy areas [9]
7. Risk Factors
- Geographic: Residence in or travel to endemic areas (Northeast US from Virginia to Maine, upper Midwest, northern California) [2][4]
- Seasonal: Peak incidence late spring through summer (May–August), coinciding with nymphal tick activity [4]
- Behavioral: Outdoor activities in wooded/brushy areas, gardening near woodlands, failure to perform tick checks [9]
- Tick attachment duration: Transmission requires ≥36–48 hours of feeding [4]
- Demographics: Bimodal age distribution (children 5–15 and adults 45–55); Lyme carditis more common in young adult males [4][10]
8. Differential Diagnosis
- Erythema migrans mimics:
- Southern tick-associated rash illness (STARI) — clinically indistinguishable; caused by Amblyomma americanum bite; treat empirically in overlapping geographic areas [3][11]
- Cellulitis — tender, warm, often with clear borders; no central clearing
- Tinea corporis — scaling border, KOH positive
- Nummular eczema — pruritic, scaly, coin-shaped
- Fixed drug eruption, contact dermatitis, insect bite reaction [3]
- Disseminated Lyme mimics:
- Bell's palsy (idiopathic) — consider Lyme in endemic areas, especially if bilateral
- Viral meningitis — CSF profile may overlap; Lyme meningitis has lymphocytic pleocytosis
- Reactive arthritis, rheumatoid arthritis, septic arthritis — for joint presentations
- Myocarditis (viral, sarcoid, giant cell) — for cardiac presentations [12]
- Multiple sclerosis — for neurologic presentations [13]
- Conditions commonly misattributed to Lyme: Fibromyalgia, chronic fatigue syndrome, anxiety/depression, migraine, osteoarthritis [13]
9. Past Medical History
- Prior Lyme disease (antibodies remain elevated, complicating re-diagnosis) [7]
- History of immunosuppression (may alter serologic response)
- Pre-existing cardiac conduction disease (important to distinguish from Lyme carditis)
- Autoimmune conditions (may mimic or overlap with disseminated Lyme)
- Drug allergies (doxycycline, penicillin/beta-lactam allergy affects treatment choice)
10. Physical Exam
- Vital signs: Low-grade fever; bradycardia (if carditis with AV block); hypotension (rare, if hemodynamically significant block)
- Skin: Expanding erythematous patch ≥5 cm at bite site; may be homogeneous, target-shaped, or with central clearing; warm but not tender; check for multiple EM lesions (disseminated) [2-3]
- Neurologic: Cranial nerve exam (especially CN VII — facial droop, may be bilateral); meningeal signs; sensory/motor exam for radiculopathy [2]
- Cardiac: Irregular rhythm, bradycardia; assess for signs of heart failure [4]
- Musculoskeletal: Joint effusion (especially knee), limited ROM; Baker's cyst [2]
- Lymph nodes: Regional lymphadenopathy near bite site
11. Lab Studies
- Early localized EM: No lab testing needed — clinical diagnosis is sufficient in endemic areas with classic rash [7][14-15]
- Disseminated/late disease: Two-tiered serologic testing: [3][8]
- Step 1: ELISA (IgG/IgM)
- Step 2: Western blot (if ELISA positive/equivocal)
- Note: Serology often falsely negative in first 1–2 weeks (<40% sensitivity with EM) [3]
- If initially negative, repeat in 2–4 weeks if clinical suspicion remains [14]
- After 4 weeks of symptoms, only IgG Western blot is recommended [3]
- Lyme meningitis: LP showing lymphocytic pleocytosis, elevated protein, normal glucose [8]
- Coinfection workup (if high fever on antibiotics): CBC with differential (leukopenia, thrombocytopenia suggest anaplasmosis/babesiosis), peripheral smear for Babesia, LDH, indirect bilirubin [7]
- Carditis: Troponin, BNP, ESR/CRP [4][6]
- General: Elevated ESR, mildly elevated hepatic transaminases, microscopic hematuria/proteinuria may be seen [8]
12. Imaging
- Not routinely indicated for early localized disease
- Echocardiography: If carditis suspected — assess for ventricular dysfunction, pericardial effusion [6][16]
- MRI brain/spine: If neuroborreliosis suspected (meningitis, encephalitis, radiculopathy) — may show leptomeningeal enhancement, cranial nerve enhancement
- Joint imaging: Ultrasound or MRI for effusion/Baker's cyst if arthritis presentation; primarily to exclude septic arthritis
13. Special Tests
- Suspicious Index in Lyme Carditis (SILC) score: Risk stratifies patients with high-degree AVB for likelihood of Lyme carditis: [6]
- Erythema migrans (+4), tick bite (+3), constitutional symptoms (+2), outdoor activity/endemic area (+1), male sex (+1), age <50 (+1)
- Low risk: 0–2; Intermediate: 3–6; High: 7–12
- Rule of 7s (pediatric): Distinguishes Lyme meningitis from aseptic meningitis in children with CSF pleocytosis — headache ≥7 days, CSF mononuclear cells ≥70%, cranial nerve palsy
- Lumbar puncture: Required if meningitis suspected; send CSF for cell count, protein, glucose, Lyme antibody index
- Arthrocentesis: If septic arthritis is in the differential; Lyme arthritis shows inflammatory fluid but negative cultures; PCR for B. burgdorferi on synovial fluid can be helpful
14. ECG
- Obtain ECG in any patient with suspected disseminated Lyme disease, palpitations, syncope, or exercise intolerance [6][12]
- Findings in Lyme carditis: [6][16]
- First-degree AV block (PR prolongation) — may fluctuate rapidly
- Second-degree AV block (Mobitz type I/Wenckebach most common)
- Third-degree (complete) AV block — present in up to two-thirds of Lyme carditis cases
- PR interval can fluctuate from first-degree to complete block within minutes
- Less common: Bundle branch block, atrial/ventricular arrhythmias, ST-T wave changes
- Critical threshold: PR ≥300 ms warrants admission and continuous monitoring [4-5]
- Permanent pacemaker is NOT indicated — AV block is typically transient, resolving in 1–2 weeks with antibiotics [4][17]
15. Assessment
- Staging:
- Early localized (3–30 days): Solitary EM ± constitutional symptoms — excellent prognosis with treatment
- Early disseminated (days to months): Multiple EM, cranial neuropathy, meningitis, carditis — requires stage-specific treatment
- Late disseminated (months to years): Lyme arthritis (large joint oligoarthritis, especially knee) — most common late manifestation in North America [1][3]
- ~60% of untreated patients progress to disseminated disease [2]
- ~10% of treated patients experience post-treatment Lyme disease syndrome (fatigue, pain, cognitive symptoms) — usually self-limited; prolonged antibiotics not beneficial [4][18-19]
- Atypical presentations: Carditis may be the first/sole manifestation (only ~40% recall EM); bilateral facial palsy is highly suggestive of Lyme in endemic areas [4]
16. Treatment Plan
Post-exposure prophylaxis (high-risk bite: Ixodes tick, endemic area, attached ≥36 hours, within 72 hours of removal): [2][4]
Early localized (erythema migrans): [4-5]
- Doxycycline 100 mg PO BID × 10 days (preferred)
- Amoxicillin 500 mg PO TID × 14 days
- Cefuroxime axetil 500 mg PO BID × 14 days
Cranial nerve palsy without meningitis: [8]
Lyme meningitis: [3][8]
- Ceftriaxone 2 g IV daily × 14–21 days (preferred)
- Oral doxycycline 200 mg/day × 14–21 days may be considered for ambulatory patients [3]
Lyme carditis: [5-6]
- Serious (high-degree AVB, PR ≥300 ms): IV ceftriaxone 2 g daily × 10–14 days → transition to oral antibiotics for total 14–21 days; continuous telemetry; temporary pacing if symptomatic bradycardia
- Mild (first-degree AVB, PR <300 ms): Oral doxycycline 100 mg BID × 14–21 days; outpatient management may be appropriate
Lyme arthritis: [8]
- Oral doxycycline, amoxicillin, or cefuroxime × 28 days
- Refractory cases: IV ceftriaxone × 14–28 days
17. Disposition
- Discharge (majority of cases): Early localized EM — start oral antibiotics, PCP follow-up [2][14]
- Admission criteria: [4-5]
- PR interval ≥300 ms or high-degree AV block (second/third degree)
- Symptomatic bradycardia, syncope, hemodynamic instability
- Meningitis requiring IV antibiotics
- Myopericarditis with ventricular dysfunction or heart failure
- Observation: First-degree AV block with PR <300 ms — consider observation with serial ECGs; may be managed outpatient with close follow-up
- Specialist consultation triggers: Cardiology (any AV block or myocarditis), Infectious Disease (disseminated disease, treatment failure, coinfection), Neurology (meningitis, encephalitis, persistent neuropathy), Rheumatology (refractory Lyme arthritis)
The following figure illustrates a systematic approach to diagnosing and managing Lyme carditis with high-degree AV block, including the SILC score for risk stratification: [6]
18. Follow Up / Return Precautions
- Follow-up timing: PCP within 2–4 weeks for early localized disease; sooner if disseminated features
- Return precautions — seek immediate care for:
- New or worsening rash, multiple new skin lesions
- Facial weakness or droop
- Severe headache, neck stiffness, vision changes
- Palpitations, lightheadedness, syncope, chest pain
- New joint swelling or inability to bear weight
- Expected course: EM typically resolves within days to weeks of starting antibiotics; constitutional symptoms may take weeks to fully resolve [1-2]
- Counseling: Antibodies remain elevated after treatment — positive serology does not indicate active infection or treatment failure; tick prevention education (DEET, permethrin-treated clothing, daily tick checks, prompt removal) [4][7]
- Post-treatment Lyme disease syndrome: ~10% may have persistent fatigue, pain, or cognitive symptoms; these are self-limited in most cases; additional antibiotics are not recommended [4][18-19]
References
1. Lyme Borreliosis. — Strle F, Strle K, Marques A, et al. Nature Reviews. Disease Primers. 2026.
2. Tickborne Diseases of the United States: A Reference Manual for Healthcare Providers Sixth Edition. — Nancy Shadick MD MPH, Nancy Maher MPH, Dennis Hoak MD United States Centers for Disease Control and Prevention (2022). 2022.
3. Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A Review. — Sanchez E, Vannier E, Wormser GP, Hu LT. The Journal of the American Medical Association. 2016.
4. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. — Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2021.
5. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease. — Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Arthritis & Rheumatology. 2021.
6. Diagnosis and Treatment of Lyme Carditis: JACC Review Topic of the Week. — Yeung C, Baranchuk A. Journal of the American College of Cardiology. 2019.
7. Lyme Disease: Updated Recommendations From the IDSA, AAN, and ACR. — Williams AL, Bevan J, Arnold MJ. American Family Physician. 2021.
8. Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Management of Tick-Borne Illness in the United States. — Ho BM, Davis HE, Forrester JD, et al. Wilderness & Environmental Medicine. 2021.
9. Lyme Disease. — Shapiro ED. The New England Journal of Medicine. 2014.
10. Climate Change and Vectorborne Diseases. — Thomson MC, Stanberry LR. The New England Journal of Medicine. 2022.
11. Early Lyme Disease (Erythema Migrans) and Its Mimics (Southern Tick-Associated Rash Illness and Tick-Associated Rash Illness). — Strle F, Wormser GP. Infectious Disease Clinics of North America. 2022.
12. 2024 ACC Expert Consensus Decision Pathway on Strategies and Criteria for the Diagnosis and Management Of Myocarditis: A Report of the American College of Cardiology Solution Set Oversight Committee. — Drazner MH, Bozkurt B, Cooper LT, et al. Journal of the American College of Cardiology. 2025.
13. Mistaken Identity: Many Diagnoses Are Frequently Misattributed to Lyme Disease. — Kobayashi T, Higgins Y, Melia MT, Auwaerter PG. The American Journal of Medicine. 2022.
14. What Is Lyme Disease?. — Patel B, Malani PN. The Journal of the American Medical Association. 2025.
15. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). — Miller JM, Binnicker MJ, Campbell S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.
16. Lyme Carditis: From Pathophysiology to Clinical Management. — Radesich C, Del Mestre E, Medo K, et al. Pathogens. 2022.
17. 2018 ACC/AHA/HRS Guideline on The Evaluation and Management Of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. — Kusumoto FM, Schoenfeld MH, Barrett C, et al. Journal of the American College of Cardiology. 2019.
18. Lyme Borreliosis: Diagnosis and Management. — Kullberg BJ, Vrijmoeth HD, van de Schoor F, Hovius JW. BMJ. 2020.
19. Lyme Disease. — Smith RP. Annals of Internal Medicine. 2025.