Lyme Disease

Introduction

• Lyme disease is a condition caused by the introduction of Borrelia burgdorferi into the body following a tick bite from the Ixodes species.
• The disease progresses through 3 classic stages, each with its own possible clinical manifestations.
• A challenging aspect of Lyme disease diagnosis is the broad range of symptoms.

Epidemiology

• In 2013, the CDC reported over 25,000 confirmed cases and nearly 10,000 more suspected cases (1).
• However, the incidence of Lyme disease varies greatly across the United States, with the Midwest and Northeast reporting the highest disease rates.
• The incidence of Lyme disease in Illinois has increased significantly over the past decade, with rates rising from 0.7 cases per 1000 people in 2004 to 2.6 per 1000 in 2013.
• Examine the graphs below to see the increase in Lyme disease in northern Illinois.
  • Recent research demonstrated that many Ixodes ticks in Chicago and surrounding suburbs are now infected with Borrelia burgdorferi – a dramatic change from the past (2).

http://www.cdc.gov/lyme/stats/index.html

Borrelia Transmission

• The spirochete is transmitted into the human bloodstream via bites from the Ixodes scapularis (deer) tick.
• Ticks progress through defined life cycles, and the risk of disease transmission varies by life stage.

Shapiro ED. Lyme Disease. Pediatrics in Review 2014

• Adults lay eggs in the spring, which take a full year to become ‘nymph’ ticks – the kind most likely to transmit Lyme disease.
  • Nymphs are extremely small (less than 2 mm), and may bite humans for days while remaining unnoticed.
  • The CDC shows the following picture to demonstrate the relative sizes of deer ticks compared to a dime:

http://www.cdc.gov/lyme/transmission/index.html

• Ticks generally must be attached for 1-2 days to transmit Lyme disease.

Clinical Disease and Manifestations

• Lyme disease has 3 distinct clinical stages, with different clinical manifestations (3, 4) :

1. Early Localized
2. Early Disseminated
3. Late Disseminated

• The early localized stage is marked by the characteristic erythema migrans rash.
  • Erythema migrans is a rash at the site of the tick bite that appears usually within 1-2 weeks after the bite.
    • This rash is  frequently located around the head, neck, arms, legs and back areas in children.
    • The lesions are annular, flat without scaling,  and rarely painful.
• Of note, the rash does not have to be the “bulls eye” rash so commonly associated with Lyme disease.
  • Greater than 50% of the time, the rash is uniformly erythematous (4).
• Erythema migrans occurs in approximately 90% of patients with Lyme disease (5).
  • Patients may display multiple smaller erythema migrans rashes.

"Bullseye Lyme Disease Rash" by Hannah Garrison, Wikimedia

Early Disseminated Disease

• The manifestations of early disseminated disease are broad and may include (4,6):

1. Multiple erythema migrans (most common sign of early disseminated disease)
2. CN VII Facial nerve palsy, unilateral or bilateral
3. Neurologic involvement (15% of untreated patients)
   1. Meningitis, encephalitis, optic neuritis, cerebellar ataxia
4. Cardiac involvement (5% of untreated patients)
   1. Heart block (may be 3°/complete heart block with A-V dissociation)
5. Systemic Symptoms (fever)
    

Late Disseminated Disease

• If untreated, Lyme disease may progress to a late-stage disease with variable effects.
• Arthritis (painful swelling of the joints) is the most common manifestation.
• Unlike in adults, however, children rarely progress to have a chronic, life-long arthritis (7).
  • One study of 46 children with Lyme disease studied the progression of arthritis.
  • The first episode of arthritis began an average of 3.4 months after infection, with the knee as the most common site of involvement.
  • Arthritis resolved quickly in almost all patients.
  • However, one patient continued to suffer from arthritis 7 years after infection.
• Long-term neurologic sequelae are possible but rare events in children with Lyme disease (7).
• Approximately 5% of children developed symptoms of memory loss and headache greater than 10 years after infection.
  • CSF analysis demonstrated high Borrelia titers.

Diagnosis of Lyme Disease

• The diagnosis of Lyme disease may be challenging and different strategies are necessary during different stages of disease.
• The official guidelines from the CDC recommend “two-tiered testing” in their approach to diagnosis.
• All patients with symptoms consistent with Lyme disease are recommended to receive either an enzyme immunoassay or immunofluorescence assay, even with symptoms lasting < 30 days.

http://www.cdc.gov/lyme/healthcare/clinician_twotier.html

• However, most experts do not recommend testing a patient in an endemic area with a rash consistent with erythema migrans (4,8) due to the low sensitivity.
• The diagnosis of Lyme disease in the early localized stage is generally a clinical diagnosis.
  • The erythema migrans rash in an endemic area (or with recent travel to an endemic area) is sufficient for diagnosis, as most patients will not have positive antibody titers (4,8).
  • These experts recommend serologic testing for early disseminated or late disseminated disease.
• Serologic testing involves initial use of ELISA or IFA.
  • If positive, IgM (for symptoms < 30 days) or IgG and IgM (symptoms > 30 days) western blot should be performed.
  • If positive, the patient has confirmed Lyme disease. If negative, the patient is considered not to have Lyme disease.

Differential

• Southern tick-associated rash illness (STARI) is associated with a rash indistinguishable from erythema migrans.
  • However, it is transmitted by the Amblyomma americanum tick and is found primarily in the southeast and south central regions of the U.S.
• Fibromyalgia is a common chronic disorder characterized by musculoskeletal pain that may involve areas near the joints and fatigue.
  • However, while Lyme disease is an inflammatory disorder, fibromyalgia is not.

Treatment

• For most cases of Lyme disease, oral therapy with Doxycycline, amoxicillin or cefuroxime axetil may be used (4).
  • Doxycycline is first line for children > 8 years old.
  • Amoxicillin is preferred in children younger than 8.
  • Intravenous ceftriaxone is recommended for Lyme meningitis.

Shapiro ED. Lyme Disease. Pediatrics in Review 2014

References

1. http://www.cdc.gov/lyme/stats/chartstables/casesbyyear.html
2. Jobe DA, JA Nelson, MD Adam et al. Lyme Disease in Urban Areas, Chicago. Emerging Infectious Diseases 2007. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375794/pdf/07-0801_finalL.pdf
3. Shapiro ED. Lyme disease: Clinical Manifestations in Children. UpToDate. January 30, 2014.
4. Shapiro ED. Lyme Disease. Pediatrics in Review 2014 (35): 500-509.    
5. Gerber MA, ED Shapiro, GS Burke et al. Lyme disease in children in southeastern Connecticut. New England Journal of Medicine 1996: 1270-1274.
6. Steere AC. Lyme Disease. New England Journal of Medicine 2001 (345.2): 115-125.
7. Szer IS, E Taylor, AC Steere. The long-term course of lyme arthritis in children. New England Journal of Medicine 1991 (325): 159-163.
8. Hu L. Diagnosis of Lyme Disease. UpToDate. March 20, 2015.

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