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Lyme disease

Last updated: February 4, 2025

Summarytoggle arrow icon

Lyme disease (or borreliosis) is a tick-borne infection caused by certain species of the Borrelia genus (B. burgdorferi in the US; predominantly B. afzelii and B. garinii in Asia and Europe). There are three stages of Lyme disease. Stage I (early localized disease) is characterized by erythema migrans, an expanding circular red rash at the site of the tick bite, and may be associated with flu‑like symptoms. In stage II (early disseminated disease), patients may present with neurological symptoms (e.g., facial palsy), migratory arthralgia, and cardiac manifestations (e.g., AV block). Stage III (late disease) is characterized by chronic arthritis and neurological involvement (late neuroborreliosis) with possible progressive encephalomyelitis. In Asia and Europe, further skin manifestations may also occur in stage II (lymphadenitis cutis benigna) and stage III (acrodermatitis chronica atrophicans). Lyme disease is a clinical diagnosis in patients with erythema migrans. For all other patients, Lyme serology is recommended. Antibiotic treatment varies depending on the stage of Lyme disease and presentation. Options include oral doxycycline, amoxicillin, or cefuroxime axetil, and, in severe cases, intravenous ceftriaxone. Postexposure prophylaxis (PEP) for Lyme disease after a tick bite may be required in selected cases.

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Epidemiologytoggle arrow icon

  • Incidence: most commonly reported vector-borne disease in the US
  • Geographical distribution: primarily the Northeast and upper Midwest of the US

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

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Etiologytoggle arrow icon

  • Pathogen
  • Vector
    • Various tick species: mainly Ixodes scapularis (deer or black-legged tick) in the northeastern and upper midwestern US
      • Ixodes pacificus (western black-legged tick) in the northwestern US
      • Ixodes ricinus (castor bean tick) in Europe
    • Typically found in forests or fields on tall brush or grass
    • The incidence of Lyme disease is highest between April and October (especially from June to August).
    • Increased risk of disease for:
      • Outdoor workers (e.g., landscapers, farmers)
      • Outdoor enthusiasts (e.g., hikers, hunters)
  • Reservoir hosts
    • Deer, cattle
    • Peromyscus leucopus, the white‑footed mouse, is the primary reservoir of B. burgdorferi in the US.

References:[2]

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Clinical featurestoggle arrow icon

Stage I (early localized Lyme disease) [2][3][4]

Symptom onset occurs 7–14 days after a tick bite.

Stage II (early disseminated Lyme disease) [2][3][4]

Symptom onset occurs 3–10 weeks after a tick bite. [5]

Consider coinfection with other tick-borne pathogens (e.g., babesiosis or anaplasmosis) in patients with severe systemic symptoms (e.g., high-grade fever), clinical features of anemia, or persistent systemic symptoms after rash resolution.

Stage III (late disseminated Lyme disease) [2][3][4]

Symptom onset occurs months to years after the initial infection. [5]

To remember important symptoms of Lyme disease, think of someone making a FACE (Facial nerve palsy, Arthritis, Carditis, Erythema migrans) when biting into a lime.

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Diagnosistoggle arrow icon

Approach [5][6]

Lyme serology [5][6]

Indications

Possible tick exposure in Lyme-endemic regions, PLUS any of the following: [6][7]

Lyme serology can be deferred for patients with typically appearing erythema migrans and asymptomatic patients with a recent tick bite. [6]

Protocol [6][8]

Interpretation

Correlate results with clinical features and time from onset.

  • Negative result: no laboratory evidence of Lyme disease
    • False-negative results can occur.
    • Consider repeat testing after 2–4 weeks. [9]
  • Positive result [5][8]
    • IgM positive, IgG negative: consistent with acute or recent infection
    • IgG positive: consistent with recent or remote infection

Both IgM and IgG antibodies against B. burgdorferi can persist for years after a remote infection, even if it was treated. [6]

False-positive results can occur due to cross-reactivity, e.g., with syphilis, Rocky Mountain spotted fever, systemic lupus erythematosus, or rheumatoid arthritis. [5]

Further testing

Further testing may be considered depending on the clinical presentation.

Leukopenia, thrombocytopenia, significant anemia, and laboratory evidence of hemolysis are not typically seen in Lyme disease and should raise concern for coinfection with A. phagocytophilum and/or B. microti. [6]

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Differential diagnosestoggle arrow icon

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Treatmenttoggle arrow icon

Asymptomatic patients with tick bite

Tick removal [5][6][10]

  • Perform as soon as possible. [5]
  • Grasp the tick with forceps at the closest point of attachment to the skin. [6][10]
  • Gently pull the tick out and submit it for species identification. [6]
  • If parts of the tick remain attached: Apply local anesthesia and perform local excision. [10]

Do not use nail polish remover, adhesives, oils, or other similar substances to remove ticks.

Antibiotics [5][6]

Weigh the risks and benefits of doxycycline in pregnant, lactating, and young (< 8 years old) individuals under specialist guidance. Many experts consider short courses (e.g., < 14–21 days) safe for children, irrespective of age. [6][11][12]

Disposition [5][6]

  • Patients with indications for IV antibiotics: inpatient therapy with specialist consultation
  • Uncomplicated disease requiring oral antibiotics only: outpatient therapy with infectious disease follow-up
  • See “Disposition” in “Lyme carditis” and “Neuroborreliosis” for additional considerations.
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Subtypes and variantstoggle arrow icon

Overview

Overview of Lyme disease manifestations
Clinical features Diagnostics Management
Asymptomatic patients after endemic tick bite
  • Tick may still be attached.
  • No specific testing required

Erythema migrans

(early localized Lyme disease)

Neuroborreliosis

(disseminated Lyme disease)

Lyme carditis

(early disseminated Lyme disease)

Lyme arthritis

(late disseminated Lyme disease)

Borrelial lymphocytoma

(early disseminated Lyme disease)

  • Blue-red nodular lesion
  • Often on the earlobe, face, nipple

Acrodermatitis chronica atrophicans

(late disseminated Lyme disease)

  • Skin changes (atrophy, discoloration)
  • Typically on the extremities
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Erythema migranstoggle arrow icon

Description [2][3][4]

Clinical features [2][3][4]

  • Onset: 7–14 days after a tick bite
  • Usually a slowly expanding red ring around the tick bite site with central clearing (“bull's eye rash”)
  • Typically warm, painless; possibly pruritic
  • Often occurs in isolation
  • Self-limiting (typically subsides within 3–4 weeks)

Diagnosis [6]

Diagnostic testing is not required before treating typically-appearing erythema migrans. [6]

Differential diagnosis

See also “Overview of annular skin lesions.”

Treatment [6]

A small number of patients may experience Jarisch-Herxheimer reaction after starting treatment for early Lyme disease. [5][6]

Courses of oral doxycycline for ≤ 14 days are generally considered safe in all children; however, some specialists prefer amoxicillin or cefuroxime in children < 8 years of age. [6][14]

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Neuroborreliosistoggle arrow icon

Description [6][15]

  • A manifestation of disseminated Lyme disease
  • Can cause PNS or CNS dysfunction

Clinical features

There is no proven association between Lyme disease and specific neurodegenerative diseases (e.g., multiple sclerosis, Alzheimer disease, Parkinson disease) or psychiatric conditions (e.g., depression, anxiety, bipolar disorder). [6][15]

Diagnosis [6]

  • Lyme serology
  • Exclusion of other causes (see “Differential diagnosis”)

Lumbar puncture [5][6]

An elevated CSF/serum antibody index with normal protein levels and no pleocytosis may indicate a past infection; it does not confirm an ongoing infection. [6]

PCR and cultures have low sensitivity for detecting B. burgdorferi in CSF and are not recommended. [6]

Differential diagnosis

Treatment [6]

For Lyme-induced facial nerve palsy, oral doxycycline is the preferred treatment; consult a specialist regarding glucocorticoid use as the risk-benefit profile is unclear. [6][16]

Courses of oral doxycycline > 14 days should be used with caution in children < 8 years of age. [6]

Disposition [5][6]

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Lyme carditistoggle arrow icon

Description [5][6]

Clinical features [5][6]

Diagnosis [5][6]

Differential diagnoses

Treatment [6]

The choice of IV or oral antibiotics depends on symptoms; patients with severe manifestations (e.g., PR prolongation > 300 ms, high-degree AV block, arrhythmias, or features of perimyocarditis) require IV antibiotics.

Courses of oral doxycycline > 14 days should be used with caution in children < 8 years of age. [6]

Lyme-induced symptomatic bradycardia usually resolves within 3–7 days of initiating antibiotic therapy. [6]

Disposition [5][6]

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Lyme arthritistoggle arrow icon

Description [18]

  • Inflammation of the joint tissue due to Borrelia infection
  • Can be permanently disabling if untreated

Clinical features [18]

Diagnosis [6]

  • Lyme serology
  • Exclusion of other causes (see “Differential diagnosis”)

Arthrocentesis [5][6]

Arthrocentesis is usually conducted to rule out septic arthritis. Lyme arthritis is typically diagnosed based on clinical presentation and positive serology; PCR is not obligatory. [6]

Differential diagnosis

Treatment [6]

Courses of oral doxycycline > 14 days should be used with caution in children < 8 years of age. [6][14]

It may take weeks to months for patients with Lyme arthritis to respond to antibiotic therapy; most patients respond within 1–3 months. [5][6]

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Other cutaneous manifestationstoggle arrow icon

Borrelial lymphocytoma [6]

Acrodermatitis chronica atrophicans (Herxheimer disease) [6]

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Complicationstoggle arrow icon

Post-treatment Lyme disease syndrome (PTLDS)

After treatment for Lyme disease, avoid additional antibiotic therapy in patients with new or residual nonspecific symptoms if there is no evidence of treatment failure or reinfection. [6]

Many patients with PTLDS are ultimately diagnosed with fibromyalgia, chronic fatigue syndrome, or medically unexplained symptoms. [22]

We list the most important complications. The selection is not exhaustive.

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Preventiontoggle arrow icon

General prevention

  • There is no approved vaccine on the market for Lyme disease.
  • Avoid prime habitats in areas known for Lyme disease.
  • Tick bite prevention: Prevent and properly manage tick bites to avoid exposure.
    • Wear protective clothing: e.g., long-sleeved shirts, long pants, and light colors.
    • Use tick repellent and pesticides.
    • Check body for tick bites.
    • Remove ticks immediately; see “Tick removal.”
    • Observe the bite site for early detection of erythema migrans.

Postexposure prophylaxis for Lyme disease [6]

  • Consider prophylaxis for patients who fulfill all of the following criteria: [6]
    • The bite was from an identified Ixodes spp. tick.
    • The tick bite occurred in a highly endemic area. [23]
    • The tick was attached for ≥ 36 hours. [5]
    • Prophylaxis can be started within 72 hours of tick removal.
  • Prophylactic regimen: single dose of oral doxycycline (off-label) [6]

Consult infectious diseases about prophylaxis for pregnant or breastfeeding patients. [6]

Advise patients to monitor children < 12 years of age, even with postexposure prophylaxis, because of the limited data on doxycycline efficacy in this age group. [6]

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