• Lyme disease is a tickborne infectious disease.

• Lyme disease was first recognized in 1975 after an investigation of a cluster of arthritis cases among children in Lyme, Connecticut.

• Prevalence
  • The most common tickborne infectious disease in the U.S.
  • 23,305 cases were reported to the Centers for Disease Control and Prevention in 2005.
• Geographic distribution
  • Lyme disease has been reported in almost every state.
    • 95% of all cases are concentrated in 11 states from 3 geographic regions.
      • The Northeast from Maine to Maryland
      • The Midwest in Wisconsin and Minnesota
      • The West in Northern California and Oregon
    • The occurrence of disease corresponds with the distribution of the tick vectors Ixodes scapularis in the East and Midwest and Ixodes pacificus in the West.

• In 1975, the black-legged deer tick I scapularis was implicated as the vector of this disease.
• In 1982, a spirochete, Borrelia burgdorferi, was detected in the midgut of the tick and identified as the etiologic agent.
• B burgdorferi live in mice, squirrels, and other small animals and are transmitted among these animals and to humans by the bite of the tick.
  • The tick lives for 2 years and has 3 stages: larvae, nymph, and adult.
  • A blood meal is required at each stage of development.
  • When the tick feeds on an infected animal, the spirochete is acquired; when the tick feeds again, the spirochete can be transmitted to a new host.
  • Although deer are important for maintaining the tick population, deer do not become infected by the spirochete.
• No causal relationship between maternal Lyme disease and congenital disease has been documented.
• No evidence exists to support transmission of B burgdorferi via human milk.

• Most cases of human Lyme disease are acquired in June, July, or August, when the nymphal stage is most active and human outdoor activity is greatest.

• The clinical manifestations of Lyme disease vary with the time that elapses after inoculation by the tick.
• The infection has thus been divided into:
  • Early localized phase
  • Early disseminated phase
  • Late-stage disease

Early localized phase

• Erythema migrans (EM) is the most common manifestation of early Lyme disease.
• Approximately 70–80% of patients exhibit or have a history of a skin lesion at the site of the tick bite.
• Macule gradually expands over several days to a large erythematous lesion that may increase in size to ≥5 cm, sometimes with central clearing.
• Early lesions may not have central clearing or the characteristic target-like appearance.
• Rash may be warm but is not painful.
• Influenza-like symptoms may accompany the skin lesion, including:
  • Malaise
  • Fatigue
  • Headache
  • Arthralgia
  • Myalgia
  • Fever
  • Regional lymphadenopathy
• Cough, rhinorrhea, vomiting, or diarrhea are not typical.
• Rash typically appears within 7–14 days (range, 3–30 days) of the tick bite and, if untreated, resolves within 3–4 weeks.

Early disseminated phase

• In the absence of antimicrobial therapy, spread of the spirochete may occur, producing the disseminated phase of early Lyme disease.
• Within days or weeks, in an untreated person, early disseminated disease may produce:
  • Multiple secondary EM lesions
  • Bell palsy
  • Lymphocytic meningitis
  • Conjunctivitis
• Common systemic symptoms include:
  • Arthralgia
  • Myalgia
  • Headache
  • Fatigue
• Serum antibody to B burgdorferi is usually not present during this phase, as antibody is not detectable until 3–4 weeks have passed.
• The spirochete is cultured from the skin more easily during early infection than at any other time in the illness.
• Approximately 60% of untreated patients will develop monoarticular or oligoarticular arthritis, which generally involves the knees.
• Approximately 5–10% of untreated patients will develop neurologic manifestations.
  • Nervous system involvement may include:
    • Cranial neuropathy (especially unilateral or bilateral facial palsy)
    • Radiculopathy
  • Central nervous system involvement may include lymphocytic meningitis.
  • Encephalopathy associated with late-stage Lyme disease consisting of mild abnormalities of memory and cognitive function is poorly understood and is a rare occurrence.
• < 5% of untreated patients will develop cardiac disease.
  • Cardiac involvement is characterized most commonly by varying degrees of atrioventricular block but may include myopericarditis.
  • Hospitalization is appropriate for patients with syncope, dyspnea, or chest pain.
  • Complete heart block is usually brief, and only temporary cardiac pacing is needed.
• In untreated persons, symptoms involving the joints, central nervous system, or heart reflecting spread of the spirochete to other parts of the body may occur months after the tick bite.

Late-stage disease

• Late-stage disease most commonly produces recurrent pauciarticular arthritis that involves the knees.
• Peripheral or central nervous system involvement is rare.
• Late-stage disease is uncommon in children who receive antimicrobial therapy early in the disease.

• The same tick that transmits B burgdorferi also can transmit Anaplasma phagocytophilum (the agent of ehrlichiosis) and Babesia microta (the agent of babesiosis), either as a mixed infection or as a single infection.
  • Ehrlichiosis or anaplasmosis should be suspected in the appropriate epidemiologic setting in a patient with:
    • Fever
    • Chills
    • Headache
    • Thrombocytopenia
    • Leukopenia
    • Increased liver enzyme levels
  • Babesiosis in symptomatic patients may produce:
    • Fever
    • Malaise
    • Chills
    • Sweating episodes
• Additional differential diagnosis
  • Pauciarticular juvenile arthritis
  • Septic arthritis
  • Acute rheumatic fever
  • Fibromyalgia syndrome
• Other considerations
  • Aseptic meningitis caused by enterovirus infection
  • Bell palsy
  • A peripheral neuropathy not caused by B burgdorferi
  • Multiple sclerosis

• Some patients with Lyme disease may offer no history of a tick bite and EM.

• During summer months in an endemic area, Lyme disease should be considered in a patient who has lymphocytic meningitis or arthritis involving the knee.
• EM can be diagnosed in a person who lives in or has traveled to an endemic area and generally is a sufficient basis for a clinical diagnosis without laboratory confirmation.

• Serologic testing in a person with typical EM is generally discouraged because of the lack of sensitivity at this early stage of disease.
  • As many as 60% of cases will have a false-negative test result at this stage.
  • However, not all patients with Lyme disease will develop EM, and many may not recall a tick bite.
• Serologic testing may be useful in the few patients in whom a diagnosis is uncertain, particularly when symptoms have been present for more than several weeks.
• A 2-tier approach to serologic testing for Lyme disease should be used with both acute- and convalescent-phase serum specimens.
  • Initial testing is conducted using an enzyme immunoassay.
  • If positive or equivocal results are obtained, then a standardized Western immunoblot for both Lyme-specific immunoglobulin M (IgM) and IgG should be performed, using the same serum specimen for tier 1 and tier 2 testing.
  • An IgM immunoblot is considered positive if 2 of 3 bands are present.
  • An IgG immunoblot is defined as positive if 5 of 10 bands are detected.
  • In endemic areas, a positive immunoblot result is not always due to an active B burgdorferi infection and may reflect previous infection.
  • 2-tier testing should be used because of the high sensitivity but low specificity of the commercial enzyme immunoassays used in the first step.
  • Testing by immunoblot should not be performed without first performing an enzyme immunoassay.
• Laboratory testing should not be performed for people who do not have symptoms of Lyme disease.
• Testing of individual ticks is not useful for deciding whether antibiotic therapy should be initiated after a tick bite.
• Other laboratory tests that should not be used include:
  • Urine antigen assays
  • Immunofluorescence staining for cell wall–deficient forms of B burgdorferi
  • Lymphocyte transformation assays

• The infection can be classified as:
  • Early localized phase
  • Early disseminated phase
  • Late-stage disease

Pharmacotherapy

• Patients with early localized or early disseminated disease who do not have neurologic or cardiac involvement should be treated for 14–21 days with doxycycline (for children ≥8 years of age)
  • Pregnant or lactating women should not be treated with doxycycline.
  • An advantage of doxycycline is efficacy against the agent of human granulocytic ehrlichiosis, which may be a coinfecting microbe.
• Amoxicillin should be used for children < 8 years of age and in pregnant women.
• Cefuroxime axetil is a third drug of choice for patients not able to take the above drugs.
• Clinical trials of patients with EM show resolution of symptoms in >90% of patients treated with doxycycline, amoxicillin, or cefuroxime axetil.
• Macrolide antibiotics are less effective than other antimicrobial agents and should be reserved for patients who cannot take preferred agents.
• Intravenous ceftriaxone is not superior to oral agents, except in patients with neurologic or cardiac involvement.
• Oral antimicrobial agents are effective for treating multiple EM and uncomplicated Lyme arthritis.
• Oral agents can be used to treat most people with facial nerve palsy.
• Central nervous system involvement, such as meningitis, should be treated with parenteral antibiotic therapy.
• Although first-degree atrioventricular block usually responds to oral therapy, higher-grade blocks are usually treated with parenteral ceftriaxone or penicillin.
• Persistent or recurrent arthritis should be treated with either parenteral ceftriaxone or penicillin.
• Specific dosages and durations are given in Table 292-1.

Vaccine

• In 1998, the U.S. Food and Drug Administration approved a vaccine against Lyme disease (LYMErix) for individuals 15–70 years of age.
• In 2002, the vaccine was withdrawn and is no longer available.

Prophylaxis after a tick bite

• Clinical practice guidelines for prevention of Lyme disease after a tick bite suggest that the following conditions be satisfied.
  • The biting tick is identified as I scapularis, with an estimated attachment time >36 hours based on the size of the engorged tick.
  • Prophylaxis can be started within 72 hours of tick removal.
  • Local rates of tick infection by B burgdorferi exceed 20%.
  • The use of doxycycline is not contraindicated.
    • Doxycycline is the only antibiotic shown to be effective for postexposure prophylaxis.
  • No data are available to support amoxicillin use in this setting.

• Cardiac involvement
• Meningitis or encephalopathy

• Cardiac involvement (heart block, pericarditis, myocarditis)
  • Neurologic involvement (except isolated facial palsy in patient with definite Lyme disease)
  • Nonspecific clinical history but positive or equivocal laboratory testing
  • Persistent arthritis

• Chronic pauciarticular arthritis
• Heart block
• Meningitis
• Cranial neuropathy
• Radiculopathy

• Ticks are most likely to be located in wooded and bushy areas with high grass.
• When walking in a tick-infested area, people should walk in the center of the path to avoid contact with grass and brush.
• Insect repellent containing N,N-diethyl-metatoluamide (DEET) should be applied to skin and clothing.
  • DEET-containing compounds can be used for children >2 months, should not be applied to the face or hands, and should be removed from skin with soap and water once the risk of exposure is over.
• Permethrin kills ticks on contact and can be applied to clothing but should not be applied directly to skin because it is inactivated by skin lipids.
• Long pants and sleeves will help keep ticks off skin.
• Light-colored clothing makes the task of spotting ticks easier.
• Daily tick checks should be performed.
• If a tick is attached for < 24 hours, the risk of acquiring Lyme disease is extremely small.
• Attached ticks should be removed as soon as possible using fine-tip forceps.
• Vaccine
  • In 1998, the U.S. Food and Drug Administration approved a vaccine against Lyme disease (LYMErix) for individuals 15–70 years of age
  • In 2002, the vaccine was withdrawn and is no longer available.

• Red Book: 2009 Report of the Committee on Infectious Diseases, 28th Edition (book), American Academy of Pediatrics.

• Steere AC. Lyme disease. N Engl J Med. 2001;345:115-125.  [PMID:11450660]
• 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;43:1089-1134.  [PMID:17029130]