I. Etiology

  1. Caused by Borrelia burgdorferi, a spirochete
  2. Transmitted to humans by the deer tick (Ixodes species)
  3. Transmission is more likely with prolonged tick attachment
  4. Usually acquired in NE United States between May & August

II. Clinical features

  1. Acute illness
  1. Erythema migrans (expanding bull's eye) in 60-80%, 3-30d after the tick bite
  2. Flu-like sx (fever, malaise, arthralgias, myalgias)
  1. Neurologic/cardiac manifestations can appear after 4-6wks if untreated (AV block, facial nn. palsy or other cranial or peripheral neuropathy; lymphocytic meningitis rarely, encephalitis)
  1. Arthritis is a late manifestation; occurs in 60% of untreated pts, anywhere from mild-mod. arthralgias to chronic destructive arthritis, most often in the knee
    1. In a series of 90 children (mean age 8.3y) dx'd with Lyme arthritis followed an average of 7y, arthritis had developed a mean of 4.3mos after earliest clinical signs of Lyme disease. 90% of pts had involvement of knees; 51% had only one episode of arthritis; only 2 developed chronic arthritis (Peds. 102:905, 1998--JW)
  1. In kids, us. present with single erythema migrans lesion; only 36% in one series had recognized a tick bite. Positive B. burgdorferi detected at presentation in 37% of one series of 201 kids (avg. age 7y) with one e. migrans lesion and in 89% of those with multiple lesions. At 2y f/u, 99.5% were asymptomatic (one pt had mild arthralgia) (NEJM 335:1270, 1996-JW)
  1. In a case-control study of 212 pts with Lyme disease studied median 4y after dx and 212 age-matched controls, there were no sig. differences in sx or self-rated disability in terms of ADL's and score on the SF-36 (JAMA 283:609, 2000--abst)

III. Diagnosis

  1. Dx usually made on Hx of tick bite & clinical presentation
  2. Erythema migrans can be considered pathognomonic in areas where Lyme disease is endemic
  3. Punch bx of erythema migrans lesions yields organisms in 60-80% of cases (Ann. Int. Med 12/97--ACP guidelines on Dx)
  4. Laboratory diagnosis
    1. No definitive early diagnostic test:
    2. ELISA & indirect fluorescent Ab pos. in 50% early on, pos. in most after 4-6wks
    3. Usually seropositive in late untreated Lyme disease; positive Elisa should be confirmed with western blot
    4. Borrelia burgdorferi-specific immune complexes--May be more sensitive and specific than serology (JAMA 282:1942, 1999--JW)
    5. Quantitative PCR of skin bx specimens (done from advancing border of erythema migrans rash) had sensitivity of 81% in one study of 47 pts with clinically diaganosed acute Lyme disease (Clin. Inf. Dis. 33:2023, 2001--AFP).  Other techniques had lower sensitivity:
      1. 2-step serologic testing (ELISA then immunoblot assay) had sensitivity 66%
      2. "Nested PCR" of blood had sensitivity 64%
      3. Large-volume (18cc) had sensitivity 45%
      4. Acute-phase serologic testing had sensitivity 41%

IV. Prevention

  1. Prompt removal of ticks is important b/c prolonged tick attachment sig. increases risk of transmission from the tick
  2. Lyme Vaccine (LYMErix)-3-dose series (0,1, and 12mos); may cause a flu-like illness 2-3d after the shot
  3. See "postexposure prophylaxis" below

V. Treatment of Lyme disease (per Med. Letter 42:37, 2000)--Continue x 2-4 weeks; shortens duration of rash & reduces risk of complications

  1. Acute treatment
    1. Doxyxycline 100mg BID (don't use in preg. women or kids < 9yo) is tx of choice
    2. Amox 500mg TID also effective
    3. Cefuroxime axetil 500mg TID also an option
    4. Azithromycin less effective than amoxicillin
    5. IV Rx (PCN 20-24MU/d, Ceftriaxone 2g QD, or Cefotaxime 2g Q8h) x 2-4wks often recc'd if pt has meningitis, periph. neuropathy, or cranial neuropathy other than isolated facial nn. palsy alone; also if has 1st degree AV block > 0.3 sec or more severe AV block); also for arthritis not responsive to 1mo of doxy or amox
    6. 180 pts > 16yo with lyme disease (erythema migrans > 5cm diameter) randomized to (Ceftriaxone 2g IV + doxycycline 100mg BID x 10d); (doxycycline 100mg BID x 10d), or (doxycycline 100mg BID x 20d).  No sig. diff. at 20d, 3mos, 12mos, and 30mos in incidence of complete response, partial response or tx failure (Ann. Int. Med. 138:697, 2003--JW)
  2. Treatment in special situations:
    1. Post-exposure prophylaxis-482 pts > 12yo with recent tick bite in areas with endemic Lyme ranodmized to Doxycycline 200mg PO x 1 vs. placebo. Sig. fewer (1 vs. 8) doxy recipients developed erythema migrans; no pts in either group had other clinial manifestations of Lyme disease or had asymptomatic seroconversion. (NEJM 345:79, 2001-JW)
    2. Acute disseminated Lyme: 140pts >8yo (had at least one of: erythema migrans lesion, heart block, neurol. abnormalities but not meningitis or encephalitis, or large-joint arthritis) randomized to 2wks of ceftriaxone IM or IV vs. 3wks of doxycycline PO. Only one pt in each group had evidence of Lyma at 9mo f/u visit. GI side f/x more common w/ ceftriaxone (NEJM 337:289, 1997-JW)
    3. Chronic Lyme encephalopathy--One unconctrolled trial of ceftriaxone 2g/d x 1mo showed symptomatic improvements in 18pts (J. Inf. Dis. 180:377, 1999--JW)
    4. Refractory knee arthritis unresponsive to IV abx--Arthroscopic synovectomy has been performed.
    5. Chronic sx in pts with past h/o confirmed Lyme--e.g. arthralgia, fatigue, memory loss
      1. 129 such pts with sx for mean 4.7y randomized to Ceftriaxone IV x 30d + Doxycycline PO x 60d vs. placebo. No sig. improvement in sx or quality of life at 30, 90, or 180d (NEJM 345:85, 2001--JW)
      2. In a follow-up report of the same cohort, there were no sig. diffs. at 90 or 180d in mean scores on neuropsychologic tests in the two groups (Neurol. 60:1916, 2003--JW)
      3. In a study of 55 pts with 6mos or more of persistent fatigue after initial tx for Lyme disease randomized to ceftriaxone IV x 28d vs. placebo; at 6mos, a sig. greater proportion of the active-tx group had improvement in fatigue scores (64% vs. 19%); no diffs. in neuropsychological testing findings ("STOP-LD" study; Neurol. 60:1923, 2003--JW)