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Guidelines for Lyme Disease Are Updated

      The Infectious Diseases Society of America (IDSA) published a comprehensive guideline on Lyme disease in 2020.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      For the first time, the 2020 Lyme disease guideline was a joint effort of the IDSA, the American Academy of Neurology, and the American College of Rheumatology.
      An estimated 476,000 Lyme disease cases are treated annually in the United States.
      • Kugeler KJ
      • Schwartz AM
      • Delorey MJ
      • Mead PS
      • Hinckley AF.
      Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018.
      The majority of cases occur in New England, the mid-Atlantic, and north-central regions of the country. In the United States, the vast majority of Lyme disease cases are acquired from the bite of Ixodes scapularis ticks, commonly called “deer ticks.” Lyme disease can also be transmitted by the bite of an infected western black-legged tick, Ixodes pacificus, which accounts for cases of Lyme disease occurring in the states of California, Oregon, and Washington. These states, however, account for less than 1% of the total number of reported cases of Lyme disease in the United States.

      Centers for Disease Control and Prevention (CDC). Reported cases of Lyme disease by state or locality, 2009-2018. Updated November 22, 2019. Available at:https://www.cdc.gov/lyme/stats/tables.html. Accessed May 13, 2021.

      Because there are no available vaccines for humans, prevention of Lyme disease largely depends on preventing I. scapularis bites. Or if bites have occurred, measures that reduce organism transmission or development of clinical disease. Potentially useful measures include covering up the skin as much as possible, using tick repellents on exposed skin, permethrin applied to clothing, and regular tick checks over the entire skin surface after outdoor activities (Table). Promptly removing attached ticks can prevent infection because at least 36 hours of tick attachment is needed for transmission of Borrelia burgdorferi.
      • des Vignes F
      • Piesman J
      • Heffernan R
      • et al.
      Effect of tick removal on transmission of Borrelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis nymphs.
      ,
      • Sood SK
      • Salzman MB
      • Johnson BJ
      • et al.
      Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic.
      For persons of any age, a single dose of oral doxycycline to prevent Lyme disease may be considered within 72 hours of tick removal for tick bites deemed high risk.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      High risk means the tick was identified as an Ixodes vector species, the bite occurred in a highly endemic area for Lyme disease, and the tick was likely attached for at least 36 hours. Removed ticks should not be tested for pathogens because this information is a poor predictor of human infection.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      TablePrevention and Initial Treatment of Lyme Disease in the United States (modified from the 2020 guideline
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      )
      Prevention of tick bites
      Use of an EPA-approved repellent or insecticide, as per the manufacturer's instructions.

      A single agent should be used for topical applications on skin.
      N,N-Diethyl-meta-toluamide (DEET)

      Picaridin

      IR3535

      Oil of lemon eucalyptus (OLE)

      p-methane-3,8-diol (PMD)

      2-undecanone

      Permethrin (for application to clothing  and gear only)
      Personal prevention measuresAvoid risky habitats

      Wear light-colored clothing

      Wear long sleeves and pants

      Tuck pants into socks or footwear

      Wear permethrin-treated clothing

      Perform tick checks after outdoor activities
      Treatment
      Disease ManifestationRouteMedication
      Further details regarding adult and pediatric dosing can be found in the 2020 Guideline.1
      Duration (days)
      Ranges are given if available studies are insufficient to determine the optimal duration.
      Lyme disease
       Erythema migransOralDoxycycline or

      Amoxicillin or

      Cefuroxime axetil
      10

      14

      14
       Meningitis/radiculopathyOral

      IV
      Cefotaxime and penicillin G are alternative IV options.
      Doxycycline

      Ceftriaxone
      14-21

      14-21
       Cranial nerve palsyOralDoxycycline14-21
       EncephalomyelitisIV
      Cefotaxime and penicillin G are alternative IV options.
      Ceftriaxone14-28
       CarditisOral IV
      Parenteral therapy is used for hospitalized patients, who, with improvement, may transition to oral antibiotics to complete the treatment course.
      Doxycycline or

      Amoxicillin or

      Cefuroxime axetil

      Ceftriaxone
      14-21

      14-21
       ArthritisOralDoxycycline or

      Amoxicillin or

      Cefuroxime axetil
      28
      EPA = Environmental Protection Agency; IV = intravenous.
      low asterisk Further details regarding adult and pediatric dosing can be found in the 2020 Guideline.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      Ranges are given if available studies are insufficient to determine the optimal duration.
      Cefotaxime and penicillin G are alternative IV options.
      § Parenteral therapy is used for hospitalized patients, who, with improvement, may transition to oral antibiotics to complete the treatment course.
      Early Lyme disease with the characteristic skin lesion, erythema migrans, is diagnosed clinically because standard 2-tier antibody testing is too insensitive, with positivity rates of just 20%-40%, although higher rates of seropositivity may occur in patients with multiple skin lesions or if the skin lesion has been present for several weeks.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      Seropositivity is, however, essential for diagnosing later clinical manifestations, including neurologic manifestations, carditis, and arthritis. Lumbar puncture is not routinely required for presentations such as facial palsy in patients with a positive serology.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      However, if cerebrospinal fluid (CSF) is obtained for antibody testing, such as for a patient with lymphocytic meningitis suspected to be from Lyme disease, only the CSF Lyme antibody index should be performed by a qualified laboratory to assess intrathecal production of antibodies to B. burgdorferi. The index requires the simultaneous collection and testing of serum and CSF samples to ensure that CSF seroreactivity is not simply due to the passive transfer of antibody from serum.
      • Theel ES
      • Aguero-Rosenfeld ME
      • Pritt B
      • Adem PV
      • Wormser GP.
      Limitations and confusing aspects of diagnostic testing for neurologic Lyme disease in the United States.
      Serologic testing for Lyme disease is not recommended for asymptomatic patients after a tick bite.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      It is important to be aware that background seropositivity rates of the general population in Lyme disease endemic areas in the United States may exceed 5%, potentially resulting in misdiagnoses, if serologic testing is done without consideration of the pretest probability of the person having active Lyme disease. Regardless of geographic location in the United States, routine serologic testing for Lyme disease is also not recommended for patients with cognitive decline or dementia, those with nonspecific white matter abnormalities confined to the brain on magnetic resonance imaging, patients with psychiatric disorders, children with developmental or behavioral disorders, and patients with chronic cardiomyopathy.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      Culture is not a routinely recommended diagnostic test due to the time involved to detect growth and low test sensitivity. Polymerase chain reaction (PCR) testing for detection of nucleic acids of B. burgdorferi is insensitive in CSF (<20%).
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      The main use for PCR clinically is to test synovial fluid samples, particularly if the diagnosis of Lyme arthritis is uncertain;
      • Marques AR.
      Laboratory diagnosis of Lyme disease: advances and challenges.
      reported sensitivity rates of PCR on synovial fluid of Lyme arthritis patients range from 71% to 100%.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      Seropositive patients with the characteristic knee joint effusions of Lyme arthritis may not require arthrocentesis if other explanations appear unlikely, such as septic arthritis or microcrystalline disorders.
      Standard 2-tier serologic testing, incorporating an enzyme immunoassay (EIA) or an immunofluorescence assay that, if positive, reflexes to immunoglobulin (Ig)M and IgG immunoblots, has been the primary diagnostic testing strategy since 1995. In 2019, the US Food and Drug Administration approved a modified 2-tier test (MTTT) strategy using 2 particular enzyme immunoassays.
      • Mead P
      • Petersen J
      • Hinckley A.
      Updated CDC recommendation for serologic diagnosis of Lyme disease.
      The MTTT dispenses with immunoblots, potentially offering quicker test results, as well as improved sensitivity for diagnosing early Lyme disease.
      • Branda JA
      • Strle K
      • Nigrovic LE
      • et al.
      Evaluation of modified 2-tiered serodiagnostic testing algorithms for early Lyme disease.
      A limitation of MTTT is that it cannot define which antigens antibodies are directed to, an important consideration for the diagnosis of Lyme arthritis, a late clinical manifestation with characteristic IgG seropositivity to at least 5 of 10 particular antigens.
      Based on two clinical trials, 10 days of doxycycline, rather than longer treatment courses, is now recommended for treating patients with erythema migrans.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      ,
      • Wormser GP
      • Ramanathan R
      • Nowakowski J
      • et al.
      Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial.
      ,
      • Stupica D
      • Lusa L
      • Ruzic-Sabljic E
      • Cerar T
      • Strle F.
      Treatment of erythema migrans with doxycycline for 10 days versus 15 days.
      Other first-line therapies include 14-day courses of amoxicillin or cefuroxime axetil (Table). Based on multiple European trials, oral doxycycline is now recommended as a first-line treatment option for Lyme meningitis and other neurologic manifestations of Lyme disease, except for encephalomyelitis. This recommendation also pertains to children younger than 8 years of age because several studies have found a lack of dental staining following short courses of this tetracycline. Doxycycline was not recommended for treatment of patients with Lyme disease with encephalomyelitis, not because of proven lack of efficacy but instead because of the limited data available on the use of oral doxycycline for this rare, late clinical manifestation. Treatment recommendations for the other clinical manifestations of Lyme disease are shown in the Table.
      More studies are needed to determine the minimum effective duration of antimicrobial therapy for the various clinical manifestations of Lyme disease. Further research to develop sensitive and accurate laboratory tests for patients with erythema migrans would help clinicians in the evaluation of atypical skin lesions and differentiate patients with a similar skin lesion occurring in Southern Tick Associated Rash Illness (STARI). Southern Tick Associated Rash Illness, which is associated with the bite of the Amblyomma americanum (Lone star) tick, is emerging in certain Lyme disease-endemic areas.
      • Raghavan RK
      • Peterson AT
      • Cobos ME
      • Ganta R
      • Foley D.
      Current and future distribution of the Lone Star tick, Amblyomma americanum (L.) (Acari: Ixodidae) in North America.
      The 2020 Lyme disease guideline is consistent with prior guidelines in not recommending antibiotic treatment for Post-Lyme Disease Syndrome/Symptoms (PTLDS) in the absence of a concomitant objective clinical manifestation of Lyme disease.
      • Lantos PM
      • Rumbaugh J
      • Bockenstedt LK
      • et al.
      Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.
      Further research is needed to understand better the pathogenesis and management of Post-Lyme Disease Syndrome/Symptoms and to develop an objective diagnostic test for this condition.

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        • Delorey MJ
        • Mead PS
        • Hinckley AF.
        Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018.
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