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Lyme Disease: Diagnosis and Treatment


Lyme disease is a serious condition caused by six species of spirochetal bacteria, most commonly Borrelia burgdorferi in North America, following a deer tick bite that requires treatment. Clinical disease can occur within days to several months following a tick bite. Lyme disease is endemic to the northeastern states from Virginia to eastern Canada, the upper Midwest, particularly Wisconsin and 
Minnesota, and northern California. The following provides key points regarding diagnosis, treatment, prophylaxis and tick removal.


Early localized disease features:

  • Erythema migrans (EM)
    • 70 to 80% of infected individuals
    • At site of tick bite approximately day 7 to 14 days after bite (range 3 to 30 days) 
    • Expands slowly and develops central clearing  
    • May have multiple lesions indicating disseminated disease (not multiple tick bites) 
  • Fever, headache, and fatigue
  • Joint and muscle aches
  • Swollen lymph nodes

Ixodes tick and Erythema Migrans images courtesy 

Early disseminated disease features:  

  • Neurologic symptoms: lymphocytic meningitis | cranial nerve palsies |radiculopathy | mononeuropathy multiplex | peripheral neuropathy 
  • Carditis: palpitations | chest pain | light headedness | fainting | shortness of breath | and difficulty breathing with exertion 
  • Multiple EM lesions  
  • Conjunctivitis 

Late disease features (months to years after tick bite):

  • Large joing polyarthralgia
  • Confluent mononeuropathy multiplex
  • Encephalomyelitis


Note: The CDC has updated the Lyme laboratory screening algorithm

  • CDC still recommends the two step approach
    • Step 1: Serologic testing using a sensitive enzyme immunoassay (EIA) or immunofluorescence assay
    • Step 2: Follow step one with a western immunoblot assay for specimens yielding positive or equivocal results
  • Modified two-step approach
    • Two enzyme immunoassays (EIA) are run concurrently or sequentially
    • The CDC states that

When cleared by FDA for this purpose, serologic assays that utilize a second EIA in place of western immunoblot assay are acceptable alternatives for the serologic diagnosis of Lyme disease

Note: When EM is present and patient has been to a Lyme endemic area serologic testing is not recommended and treatment can be initiated following clinical diagnosis  


  • Two-tiered serologic testing is more sensitive the longer infection has been present
  • Myth that Lyme disease can become chronic and no longer detectable on lab testing
  • Testing can remain positive for years so can not be used to test for cure 


  • First line therapy for adults with early localized Lyme disease
    • Doxycycline: 100 mg twice per day for 10 days, or
    • Amoxicillin: 500 mg 3 times per day for 14 days, or
    • Cefuroxime axetil: (500 mg twice per day) for 14 days
  • Therapy for early disseminated Lyme disease with neurologic manifestations:
    • Doxycycline: 100 mg twice per day for 14 to 21 days, or
    • Ceftriaxone IV: 2 g daily for 14 to 21 days  
  • Therapy for early disseminated Lyme disease with mild carditis (1st degree AV block with PR interval ≤ 300 milliseconds):
    • Doxycycline: 100 mg twice per day for 14 to 21 days, or 
    • Amoxicillin: 500 mg three times per day for 14 to 21 days, or 
    • Cefuroxime: 500 mg twice per day orally for 14 to 21 days 
  • Therapy for early disseminated Lyme disease with severe carditis (symptomatic, 1st degree AV block with PR interval ≥ 300 milliseconds):
    • If severe carditis (symptomatic, 1st degree AV block with PR interval ≥300 milliseconds, 2nd or 3rd degree AV block) then patient should be admitted for telemetry monitoring and treated with Ceftriaxone IV 2 g daily for 14 to 21 days 
  • For treatment of late Lyme disease, including arthritis, the antibiotic course is extended to 28 days using the above antibiotics for early localized disease 
  • The CDC concurs with the following IDSA recommendation that advises strongly against the treatment of chronic Lyme disease (highest level of evidence ‘I’, based on randomized controlled trials) as overtreatment with unnecessary antibiotics may prove fatal (e.g. septic shock, C. difficile, paraspinal abscess and osteomyelitis): 

There is no convincing biologic evidence for the existence of symptomatic chronic B. burgdorferi infection among patients after receipt of recommended treatment regimens for Lyme disease. Antibiotic therapy has not proven to be useful and is not recommended for patients with chronic (⩾6 months) subjective symptoms after recommended treatment regimens for Lyme disease.

Prophylaxis: Management of asymptomatic individuals following a tick bite

  • Routine use of antimicrobial prophylaxis or serologic testing is not recommended
  • A single dose of doxycycline may be offered to adult patients (200 mg dose) when all the following are met:
    •  The attached tick can be reliably identified as an adult or nymphal I. scapularis deer tick that is estimated to have been attached for ⩾36 hours based on the degree of engorgement of the tick with blood or on certainty about the time of exposure to the tick
    • Prophylaxis can be started within 72 hours of the time that the tick was removed
    • Ecologic information indicates that the local rate of infection of these ticks with B. burgdorferi is ⩾20% (occurs in parts of New England, in parts of the mid-Atlantic States, and in parts of Minnesota and Wisconsin)
    • Doxycycline is not contraindicated

Tick Removal

  • The risk of getting a tick-borne disease is small if the tick is removed soon after it becomes attached
    • Deer ticks must remain attached one to two days to transmit Lyme disease, and about one day for other tick-borne diseases
  • Use tweezers to grasp the tick close to its mouth
  • Gently and slowly pull the tick straight outward
  • To avoid contact with the bacteria, if present, do not squeeze the ticks’ body
  • Wash the area and apply an antiseptic to the bite
  • Watch for early signs and symptoms of Lyme disease

Learn More – Primary Sources:

CDC MMWR: Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease — United States 

CDC: Lyme Disease Diagnosis, Treatment and Testing

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

Signs and Symptoms of Untreated Lyme Disease

Minnesota Department of Natural Resources: Deer Ticks

CDC: Lyme Disease Transmission

JAMA: Lyme Disease in 2018 – What Is New (and What Is Not)

FDA clears new indications for existing Lyme disease tests that may help streamline diagnoses

CDC: Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease

BMJ State-of-the-Art Review: Lyme borreliosis: diagnosis and management