Lyme Disease

Background

• Lyme disease is a tick-borne illness caused by spirochetes of the Borrelia burgdorferi sensu lato species complex.
  • Commonly found in North America and Europe.
  • Hard-bodied ticks of the Ixodes genus are the main vectors.
  • Infecting bacterial genospecies vary with the specific tick vector and geography.
    • B. burgdorferi sensu stricto is endemic in the United States.
      • Most disease is acquired in the Northeast and upper Midwest.
      • Disease also occurs along the Pacific coast.
    • Borrelia garinii and Borrelia afzelii are the two primary endemic genospecies in Europe and Asia, B. burgdorferi sensu stricto also circulates but comprises a minority of isolates in some parts of Europe.
  • Most cases are reported between April and September.

Evaluation

• Be aware of the different clinical presentations associated with Lyme.
  • Erythema migrans (EM), a localized skin infection, is the most common manifestation of Lyme disease.
    • EM lesions are characterized as an area of expanding erythema arising approximately 7 to 14 days after the tick detaches.
    • Lesions are often > 5 cm, may be flat or raised, and may be homogenous or have an area of central clearing (classic target lesion).
  • Other manifestations may arise from hematogenous spread, such as:
    • multiple EM skin lesions
    • higher frequency of systemic symptoms including fevers and chills
    • carditis: typically atrioventricular conduction disturbances
    • neurologic Lyme disease: such as seventh cranial nerve palsy, radiculoneuritis, or meningitis
    • arthritis: often involving the large joints, especially the knee
    • lymphocytoma: rare cutaneous solitary bluish-red plaque, papule, or nodule up to a few centimeters in size, mainly caused by B. afzelii in Europe
    • acrodermatitis chronic atrophicans: fibrosing skin lesions primarily seen with disease acquired in Europe due to B. afzelii
• In patients with typical EM, diagnosis is based on the appearance of the EM lesion in an endemic area, as serologic testing is insensitive at this stage and typically not needed in patients with compatible exposure histories.
• Perform standard 2-tiered serologic testing (STTT) for diagnosis in patients with atypical EM or non-EM presentations.
  • Standard 2-tiered serologic testing:
    • Tier 1 is a screening immunoassay - if negative, no further testing is needed.
    • Tier 2 is an immunoblot and is performed if positive or equivocal results are obtained at tier 1.
  • A modified 2-tiered testing (MTTT) approach using 2 different enzyme immunoassays concurrently or in tandem has also been approved by the FDA. MTTT offers a quicker turnaround time and may diagnose earlier infection better than STTT.
• Testing for intrathecal production of cerebral spinal fluid (CSF) Borrelia antibodies for determining CSF:serum antibody index (Lyme central nervous system [CNS] antibody index [AI]) may be needed for neurologic disease.

Management

• Prescribe oral antibiotics for the treatment of erythema migrans (Strong recommendation).
• Preferred oral options with normal renal function include
  • doxycycline
    • adults, 100 mg orally twice daily or 200 mg orally once daily for 10 days
    • children, 4.4 mg/kg/day (maximum 200 mg/day) orally in 2 divided doses for children for 10 days
  • amoxicillin
    • adults, 500 mg orally 3 times daily for 14 days
    • children, 50 mg/kg/day orally in 3 divided doses (maximum 500 mg per dose) for 14 days
  • cefuroxime
    • adults, 500 mg orally twice daily for 14 days
    • children, 30 mg/kg/day orally in 2 divided doses (maximum 500 mg per dose) for 14 days
• Azithromycin is an alternative option for persons with erythema migrans not able to take any of the above antibiotics
  • adults, 500 mg orally once daily for 7 days
  • children, 10 mg/kg (maximum 500 mg) orally once daily for 7 days
• The same preferred oral options are recommended for uncomplicated Lyme arthritis, but the duration of therapy should be 28 days (Strong recommendation). A second course of oral therapy or a course of IV antibiotics may be required in some cases.
• Recommendations for Lyme carditis:
  • Hospitalize patients with symptoms or high-degree atrioventricular block (Strong recommendation):
    • Use temporary pacing modalities for patients with symptomatic Lyme carditis-associated bradycardia that cannot be managed medically (Strong recommendation).
    • Consider ceftriaxone 2 g IV once daily initially, then complete a 14-21 day course with oral therapy as above once patient is stable (Weak recommendation).
  • For patients who do not need hospitalization, use the same oral regimens as for erythema migrans and treat for 14-21 days (Weak recommendation).
• Recommendations for neurologic Lyme disease vary by the degree of neurologic involvement.
  • For neurologic manifestations without parenchymal involvement of the brain or spinal cord, use one of ceftriaxone 2 g IV daily, cefotaxime 2 g IV 3 times daily, penicillin G 18-24 million IV daily, divided every 4 hours, or doxycycline 100 mg orally twice daily, for 14-21 days (Strong recommendation).
  • For neurologic manifestations with parenchymal involvement of the brain or spinal cord, IV regimens for 14-21 days are preferred (Strong recommendation).
  • For seventh cranial nerve palsy, in the absence of other evidence of CNS involvement, consider treatment with doxycycline orally for 14-21 days (Weak recommendation).
• For borrelial lymphocytoma consider the same oral treatment as EM for 14 days (Weak recommendation).
• For acrodermatitis chronic atrophicans consider the same oral regimen as EM for 21-28 days (Weak recommendation).
• Some patients report persistent symptoms following treatment for Lyme disease, but there is no convincing biological evidence that ongoing symptoms are due to persistent Borrelia infection.
  • Retreatment is not shown to be effective.
  • Consider co-infection or misdiagnosis for patients with symptoms that persist or progress after treatment of early Lyme disease.
• Do not retest patients to determine whether antibody titers have declined after treatment as both IgM and IgG seroreactivity often persists for years after sufficient treatment of infection.
• Do not prescribe antibiotic therapy for patients with persistent or recurring nonspecific subjective symptoms after recommended treatment regimens for Lyme disease (posttreatment Lyme disease syndromes) (Strong recommendation).

Prevention

• Urge patients in endemic areas to avoid exposure to vector ticks by using appropriate insect repellant on skin and clothes and by inspecting themselves, children, and pets after possible exposure.
• Instruct patients to promptly but carefully remove attached ticks with tweezers, pulling straight up with even steady pressure and then cleanse the area with soap and water.
• Do not routinely prescribe antibiotic prophylaxis following a tick bite, but consider single-dose doxycycline 200 mg orally (4.4 mg/kg [maximum 200 mg] for children of all ages) for patients in highly endemic areas if tick is identified as Ixodes species, adherent for at least 36 hours, and doxycycline can be given within 72 hours of tick removal (Strong recommendation).