Lyme Disease

Background

  • Primarily caused by Borrelia burgdorferi in the US
  • Carried by the Ixodes scapularis (blacklegged tick or deer tick) on the East coast and the Ixodes pacificus (Western blacklegged tick) on the West coast
    • Ixodes may also carry Ehrlichia phagocytophila or Babesia microti, so watch out for co-infection
  • Ticks in the nymphal life phase are the most likely to spread infection
  • The tick must attach and feed for 36-72 hours to transmit disease

ixodeswcms.jpg

Source: https://www.cdc.gov/lyme/transmission/index.html

Epidemiology

  • Most common vector-borne illness in the US
  • 329,000 cases in the US annually
  • Located largely in the Northeast and Midwest
    • 96% of confirmed Lyme disease cases were from 14 states (Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, and Wisconsin)
  • Peaks in the summer months and early fall
  • 20-50% of Ixodes ticks in the Northeast are infected
  • Overall risk of Lyme disease after tick bite in endemic area is 1-3%
  • Children are twice as likely to be infected as adults are
Screen-shot-2012-02-01-at-11.05.30-AM.png
Source: http://commonhealth.legacy.wbur.org/2012/02/ultimate-lyme-disease-map

Clinical Manifestation

  • 3-20 day asymptomatic incubation period (median length of 12 days)
  • Symptoms are likely related to host immune response
    • Early localized (3-30 days after bite):
      • Systemic symptoms such as fever, chills, muscle and joint aches, and fatigue
      • Single site of erythema migrans at the site of the original bite (annular, flat lesion with or without central clearning)--90% of cases
        • May be puritic but generally not painful
        • Commonly occurs in the axillae, groin, back, abdomen, and popliteal fossae; may be on the head and neck of younger children
        • 20% or more of patients do not have erythema migrans

erythema-migrans-leg-boy_0.jpg

Source: http://www.lymeneteurope.org/info/erythema-migrans
  • Early disseminated (3-5 weeks after bite):
    • May be a more generalized erythema migrans rash with multiple lesions
    • Cranial nerve palsy (especially CN VIII)
    • Meningitis
    • 15% of patients left untreated may develop neurological symptoms (facial nerve palsy, meningitis, mononeuropathy multiplex, or acute radiculopathy)
    • 0.5% of untreated children have cardiac complications such as AV block or myopericarditis
  • Late (weeks to months after bite):
    • Can be mono- or poly-articular, intermittent or chronic, with or without swelling
    • Knee is the most commonly affected joint (90% of cases)
    • Neurological disease the a less common late presentation, affecting 5% of untreated adult patient
      • Most likely to manifest as chronic axonal polyneuropathy
  • Atypical presentations:
    • Rarely presents with a lymphocytoma
  • Chronic Lyme Disease Syndrome:
    • Marked by extreme fatigue, depression, or neurological symptoms months to years after treatment
    • Controversial entity without current clinical basis

Differential

Rash

  • Southern Tick-associated Rash Illness (STARI)
  • Nummular eczema
  • Granuloma annulare
  • Other insect or spider bite
  • Tick bite hypersensitivity
  • Tinea corporis (ring worm)
  • Cellulitis

Neurological

  • Viral induced Bell's palsy, meningitis, or encephalitis
  • Other bacterial meningitis or encephalitis

Carditis

  • Viral carditis
  • Digitalis toxicity
  • Hyperkalemia
  • Congenital defect

Arthiritis

  • Septic arthritis
  • Juvenile Rheumatic Arthritis

​Diagnosis

  • May be made clinically if erythema migrans is present and history is consistent with disease
  • If disease is suspected but erythema migrans is absent, perform 2-tier testing:
    • Syphilis, autoimmune disease and infectious mononucleosis can give false positives, test only if pretest probability is high:
      • Patient has visited or lives in an endemic area, was exposed to ticks, and has consistent symptoms
    • ELISA (sensitive and quantitative):
      • Required to make diagnosis
      • Likely negative serology early in the disease course
    • Western blot (specific and qualitative):
      • Insufficient to make diagnosis without ELISA
    • Lumbar puncture indicated if CN palsy or meningeal signs are present

Rule of 7's (for rule out Lyme meningitis)

  • 96% sensitivity
  • Lyme meningitis is unlikely if:
    • Headache duration is less than 7 days
    • CSF contains less than 70% mononuclear cells (generally WBC count of around 25,000, rarely exceeding 100,000, and no orgnanism seen on stain)
    • There is no CN VII palsy

​Treatment

  • Depends on the presenting symptoms:
  • Erythema migrans is present:
    • Doxycycline 4 mg/kg divided into two divided doses, up to 100mg/dose, by mouth for 14 days (for children age 8 and older)
    • Amoxicillin 50mg/kg/day divided into three daily doses, up to 500mg/dose, for 14 days
    • Cefuroximine axetil 30mg/kg divided into two daily doses, up to 500mg/dose for 14 days
    • Macrolide may be considered if patient is intolerant of all of the above
  • Early neurological involvement/CN palsy:
    • Ceftriaxone 50-75mg/kg, up to 2g, IV once daily for 14 days
  • Arthritis:
    • Doxycycline 4mg/kg divided into two daily doses, up to 100mg/dose, by mouth for 28 days (for children age 8 and older)
    • Amoxicillin 50mg/kg/day divided into three daily doses, up to 500mg/dose for 28 days
  • Late neurologic involvement or arthritis with neurological involvement:
    • Ceftiraxone 50-75mg/kg, up to 2g, IV once daily for 2-4 weeks
    • Alternates: penicillin G, cefotaxime, or high dose doxycycline
  • Lyme carditis:
    • Ceftriaxone 50-75mg/kg/day for 14 days
    • Alternates: penicillin G, cefotaxime, or high dose doxycycline
    • Consider admitting for cardiac monitoring and pacemaker placement

​Prevention/Prophylaxis:

Avoid tick bites: stay out of woods and brush in endemic areas, use bug spray, and wear long sleeved clothing.

Bathe within 2 hours of possible tick exposure.

Remove ticks with tweezers using appropriate technique. (https://www.cdc.gov/lyme/removal/index.html)

Source: Youtube

The Infectious Disease Society of America does not recommend routine antibiotic prophylaxis following bites unless the tick is attached for over 36 hours, the bite occurs in an endemic area, and prophylaxis is available within 72 hours. If given, prophylaxis consists of one dose of doxycycline 4mg/kg, up to 200 mg, for children over 8.

No vaccine currently available. 

References

Berende A, ter Hofstede HJM, Vos FJ, et al. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. New England Journal of Medicine. 2016;374(13):1209–1220. doi:10.1056/nejmoa1505425.

Bratton RL, Whiteside JW, Hovan MJ, Engle RL, Edwards FD. Diagnosis and treatment of Lyme disease. Mayo Clinic Proceedings. 2008;83(5):566–571. doi:10.4065/83.5.566.

CDC. Data and statistics. http://www.cdc.gov/lyme/stats/index.html. Accessed September 17, 2016.

Cohn KA, Thompson AD, Shah SS, et al. Validation of a clinical prediction rule to distinguish Lyme Meningitis from aseptic Meningitis. PEDIATRICS. 2011;129(1):e46–e53. doi:10.1542/peds.2011-1215.

Connally NP, Durante AJ, Yousey-Hindes KM, Meek JI, Nelson RS, Heimer R. Peridomestic Lyme disease prevention. American Journal of Preventive Medicine. 2009;37(3):201–206. doi:10.1016/j.amepre.2009.04.026. 

Diagnosis and Management of Lyme Disease - American Family Physician. http://www.aafp.org/afp/2012/0601/p1086.html. Accessed May 9, 2016. http://www.aafp.org/afp/2012/0601/p1086.html

Gerber MA, Shapiro ED, Burke GS, Parcells VJ, Bell GL. Lyme disease in children in southeastern Connecticut. New England Journal of Medicine. 1996;335(17):1270–1274.  

Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. New England Journal of Medicine. 2001;345(2):85–92. doi:10.1056/nejm200107123450202. 

Lyme Disease. http://www.idph.state.il.us/public/hb/hblyme.htm. Accessed May 9, 2016. http://www.idph.state.il.us/public/hb/hblyme.htm

Nelson CA, Saha S, Kugeler KJ, et al. Incidence of clinician-diagnosed Lyme disease, United States, 2005–2010. Emerging Infectious Diseases. 2015;21(9):1625–1631. doi:10.3201/eid2109.150417. 

OADC/DNEM. Lyme Disease Rashes and Look-alikes | Lyme Disease | CDC. http://www.cdc.gov/lyme/signs_symptoms/rashes.html. Accessed May 9, 2016.

Richardson M, Elliman D, Maguire H, Simpson J, Nicoll A. Evidence base of incubation periods, periods of infectiousness and exclusion policies for the control of communicable diseases in schools and preschools. The Pediatric Infectious Disease Journal. 2001;20(4):380–391. doi:10.1097/00006454-200104000-00004. 

Seltzer EG. Long-term outcomes of persons with Lyme disease. JAMA. 2000;283(5):609. doi:10.1001/jama.283.5.609.

Shapiro ED. Borrelia burgdorferi (Lyme Disease). Pediatr Rev. 2014;35(12):500-509. doi:10.1542/pir.35-12-500.

Skogman BH, Glimaker K, Nordwall M, Vrethem M, Odkvist L, Forsberg P. Long-term clinical outcome after Lyme Neuroborreliosis in childhood. PEDIATRICS. 2012;130(2):262–269. doi:10.1542/peds.2011-3719. 

Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. The Lancet. 2012;379(9814):461–473. doi:10.1016/s0140-6736(11)60103-7. 

Steere AC, Sikand VK. The presenting manifestations of Lyme disease and the outcomes of treatment. New England Journal of Medicine. 2003;348(24):2472–2474.

 Wilhelmsson P, Lindgren PE. Detection of a novel Lyme borreliosis pathogen. The Lancet Infectious Diseases. 2016;16(5):511–512. doi:10.1016/s1473-3099(15)00483-1.

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. Clinical Infectious Diseases. 2006;43(9):1089–1134. doi:10.1086/508667.

Wormser GP. Early Lyme disease. New England Journal of Medicine. 2006;354(26):2794–2801. doi:10.1056/nejmcp061181.

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