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Lyme Disease
Felix B. Chang, MD, DABMA, FAAMA
image BASICS
  • A multisystem infection caused by Borrelia spirochetes, transmitted primarily by ixodid ticks
    • Ixodes scapularis (deer ticks) in the New England and Great Lakes areas
    • Ixodes pacificus in the West (blacklegged ticks and Western blacklegged ticks)
    • Ixodes ricinus in Europe
    • Ixodes persuladas in Asia and Russia
  • Early localized Lyme disease includes a characteristic expanding skin rash (erythema migrans [EM]) (70%) and constitutional flulike symptoms.
  • Disseminated Lyme disease presents with involvement of ≥1 organ systems. Neurologic, cardiac, and pauciarticular arthritis are the most common.
  • Post-Lyme disease syndrome includes arthritis (50%) and chronic neurologic syndromes.
  • System(s) affected: hemic/lymphatic/immunologic; musculoskeletal; skin/exocrine; cardiac; neurologic
  • Synonym(s): Lyme arthritis; Lyme borreliosis
  • 96% of U.S. cases in 2011 were reported from 13 states: New England, New York, New Jersey, Delaware, Pennsylvania, Maryland, Minnesota, and Wisconsin (1).
  • In states where Lyme disease is endemic, the incidence is 0.5 per 1,000 but can be substantially higher in local areas.
  • Cases have been reported from all 50 states.
  • From 2003 to 2012, a total of 279,509 cases of Lyme disease were reported in the United States.
  • Currently the seventh most common reportable disease in the United States
  • The most reported vector-borne illness in the United States
  • Predominant age: most common in children ages 5 to 14 years and in adults aged 55 to 70 years of age
  • Predominant sex: male > female in the United States
  • Infection with spirochete Borrelia burgdorferi in the United States, or Borrelia afzelii or Borrelia garinii in Europe, transmitted by the bite of ixodid ticks (2)[A]
  • Approximately 90% of cases are transmitted during the nymph stage of the tick life cycle.
  • If a tick is infected, the chance of transmission increases with time attached: 12% at 48 hours, 79% at 72 hours, and 94% at 96 hours of attachment.
  • Primary animal reservoir is the white-footed mouse.
  • Spirochetes multiply and spread within dermis. Host response results in characteristic (EM) rash. Hematogenous dissemination results in disease within CNS, cardiovascular, or other organ systems.
  • Star ticks (Amblyomma americanum), the American dog tick (Dermacentor variabilis), the Rocky Mountain wood tick (Dermacentor andersoni), and the brown dog tick (Rhipicephalus sanguineus) are not known to transmit Lyme disease.
Human leukocyte antigen: Patients with haplotype DR4 or DR2 may be more susceptible to prolonged arthritis.
  • Exposure in tick-infested area, particularly from April to November
  • Those who reside or are employed in endemic areas where ixodid ticks are found are at increased risk.
  • Ixodid ticks are commonly found on deer. Hunters may be at an increased risk.
  • “Tick checks”: Examine skin after outdoor activities.
  • Remove ticks within 36 hours to limit transmission.
  • Wear clothing covering the ankles in endemic areas.
  • Use insect repellents containing DEET.
  • Apply permethrin to clothes, shoes, and tents.
  • Antibiotic prophylaxis is recommended for the prevention of Lyme disease in endemic areas following an Ixodes tick bite.
  • Prophylactic treatment with 1 dose of 200 mg of doxycycline within 72 hours of a tick bite in highly endemic areas is 87% effective. Contraindicated in pregnancy and in children; no prophylactic agent is approved for these groups (2)[A].
  • Coinfection with babesiosis has been reported. Suggested by high fever
  • Southern tick-associated rash illness may be mistaken for Lyme disease. It is seen in the Southeastern and South Central United States and is associated with the bite of the lone star tick, A. americanum.
  • Early Lyme disease
    • EM (4)[A]
  • Disseminated Lyme disease
    • Multiple EM
    • Facial palsies or other cranial neuropathies
    • Heart block—irregular pulse
    • Pericarditis—friction rub
    • Arthritis
    • Other focal neurologic findings
  • Other rickettsial disease (Rocky Mountain spotted fever [RMSF])
  • Juvenile rheumatoid arthritis; systemic lupus erythematosus (SLE); rheumatoid arthritis (RA)
  • Viral syndromes
  • Contact dermatitis; cellulitis; granuloma annulare (mimic EM)
  • Syphilis
  • AV block
Initial Tests (lab, imaging)
  • Testing and treatment not indicated if tick attached for <48 hours (3)
  • Diagnosis is based mainly on clinical findings in endemic areas (4).
  • Serology: enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig) M and IgG B. burgdorferi antibodies, followed by a Western blot test if positive or equivocal, or an indirect immunofluorescence assay
  • Culture of CSF for B. burgdorferi
  • Plasma polymerase chain reaction (PCR) testing is of little value (only exception is synovial fluid analysis).
  • No imaging routinely indicated.
Follow-Up Tests & Special Considerations
Disorders that may alter lab results: False-positive response has been seen with RMSF, syphilis, SLE, and RA.
  • Arthritis: Serology + PCR of synovial fluid is both sensitive and specific.
  • Neuroborreliosis: serology + CSF pleocytosis (PCR of CSF has a very low sensitivity)
  • Late-stage disease with negative serology may be seen in patients who received early antibiotic treatment.
  • After an infection, antibodies may persist for months to years. Serologic tests do not distinguish active from past infection.
  • Antibodies are not protective.

Diagnostic Procedures/Other
Lumbar puncture when neurologic findings are present, with ELISA of CSF for B. burgdorferi antibodies. Xenodiagnosis in humans (5)
Test Interpretation
Culture of B. burgdorferi from blood or skin biopsy has a very low yield.
Early and disseminated Lyme disease can usually be treated as an outpatient except when complicated by carditis or meningitis (requires parenteral antibiotics).
First Line
  • EM
    • Doxycycline (Vibramycin) 100 mg PO BID for 10 to 21 days (do not use in children <8 years old or in pregnant women) (2,6)[A]; or
    • Amoxicillin 500 mg PO TID for 14 to 21 days (pediatric dose 50 mg/kg/day); or
    • Cefuroxime axetil 500 mg PO BID for 14 to 21 days
      • Doxycycline has the advantage of covering other tick-borne infections such as ehrlichiosis, anaplasmosis, and RMSF.
      • Alternative: azithromycin 500 mg QD for 7 to 10 days or clarithromycin 500 mg BID for 14 to 21 days
  • Neurologic disease
    • Normal CSF, treat for 14 to 21 days (2)[A].
    • Doxycycline 100 mg PO BID or amoxicillin 500 mg PO TID
    • Abnormal CSF, treat for 4 weeks: ceftriaxone 2 g QD IV, cefotaxime 2 g q8h, or penicillin G 5 mIU q6h
    • Cardiac disease
      • Mild (first-degree AV block, PR <300 ms): doxycycline 100 mg PO BID or amoxicillin 500 mg PO TID for 14 to 21 days
      • More serious: ceftriaxone 2 g QD IV for 30 days
  • Arthritis without neurologic disease (2)[A]
    • Oral treatment for 28 days with doxycycline 100 mg BID or amoxicillin 500 mg TID
    • If oral treatment fails, repeat oral regimen for 28 days or begin IV treatment with ceftriaxone 2 g QD for 2 to 4 weeks.
  • Contraindications
    • Allergy to specific medication
    • Doxycycline is contraindicated in children and in women who are pregnant or breastfeeding.
  • Precautions
    • In ˜15% of patients treated with IV therapy, a Jarisch-Herxheimer-type reaction develops within 24 hours of initiation of therapy.
  • Significant possible interactions
    • Oral anticoagulants may require dose adjustments.
    • Oral contraceptives may be less effective.
Pediatric Considerations
  • Amoxicillin is the drug of choice in children.
  • Tetracyclines are contraindicated.
Pregnancy Considerations
  • Because B. burgdorferi can cross the placenta, pregnant patients with active disease should be treated with parenteral antibiotics.
  • Doxycycline should not be used in pregnancy.
Second Line
  • Azithromycin, 500 mg PO daily for 7 days, can be used for those allergic to &bgr;-lactams and unable to take tetracyclines but is less effective (2).
  • There is no evidence for meaningful clinical benefit from prolonged treatment or retreatment of patients with persistent unexplained symptoms despite previous antibiotic treatment of Lyme disease.
Admission Criteria/Initial Stabilization
  • Admission is recommended for patients with Lyme carditis and symptoms of chest pain, syncope, or dyspnea, and for those with second- or third-degree heart block or first-degree heart block of ≥300 ms.
  • Admission is also recommended for patients with symptoms of meningitis.
Patient Monitoring
Based on the severity of symptoms, patients with Lyme carditis, neurologic syndromes, or arthritis may require prolonged follow-up.
No restrictions
  • In endemic areas, patients should be advised to protect themselves against tick exposure.
  • https://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Lyme_Disease/
  • Prevention
    • Use repellents that contains 20-30% DEET (N,N-diethyl-meta-toluamide) on exposed skin and clothing for protection that last up to several hours.
    • Use 0.5% permethrin on clothing.
    • Bathe or shower as soon as possible after coming indoors (preferably within 2 hours) and perform tick check after outdoor activities.
  • Early treatment with antibiotics can shorten the duration of symptoms and prevent later disease.
  • Response of late-stage disease to treatment is variable. Symptoms may take weeks to resolve after beginning treatment.
1. Centers for Disease Control and Prevention. Statistics on Lyme disease. http://www.cdc.gov/lyme/stats/index.html. Accessed 2015.
2. Wright WF, Riedel DJ, Talwani R, et al. Diagnosis and management of Lyme disease. Am Fam Physician. 2012;85(11):1086-1093.
3. Duncan CJ, Carle G, Seaton RA. Tick bite and early Lyme borreliosis. BMJ. 2012;334:e3124.
4. Marques A, Telford SR III, Turk SP, et al. Xenodiagnosis to detect Borrelia burgdorferi infection: a first-in-human study. Clin Infect Dis. 2014;58(7):937-945. doi:10.1093/cid/cit939.
5. Klempner MS, Baker PJ, Shapiro ED, et al. Treatment trials for post-Lyme disease symptoms revisited. Am J Med. 2013;126(8):665-669.
6. Nadelman RB, Hanincová K, Mukherjee P, et al. Differentiation of reinfection from relapse in recurrent Lyme disease. N Engl J Med. 2012;367(20):1883-1890.
7. Marques A. Chronic Lyme disease: a review. Infect Dis Clin North Am. 2008;22(2):341-360.
8. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-1134.
Additional Reading
Tickborne Diseases of the United States. A Reference Manual for Health Care Providers. Third edition, 2015. www.cdc.gov/lyme/resources/tickbornediseases.pdf
  • A69.20 Lyme disease, unspecified
  • A69.23 Arthritis due to Lyme disease
  • A69.21 Meningitis due to Lyme disease
Clinical Pearls
  • The presence of EM following a tick bite in an endemic area is an indication for empiric treatment for Lyme disease.
  • Repeat episodes of EM in appropriately treated patients are due to reinfection and not relapse.
  • Lyme disease during pregnancy may lead to infection of the placenta and possible stillbirth. Amoxicillin is the preferred treatment during pregnancy.
  • Ticks must be attached for at least 24 hours or more to transmit Lyme disease.
  • There is no evidence that Lyme disease can be transmitted by breastfeeding or close personal contact.
  • Vaccines for Lyme disease is no longer available.