Last updated March 16, 2022

Prevention, Diagnosis and Treatment of Lyme Disease

Management

I. Prevention

(A) Personal Protective Measures

Individuals at risk of exposure should implement personal protective measures to reduce the risk of tick exposure and infection with tick-borne pathogens. (G, )
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(B) Repellents to Prevent Tick Bites

For the prevention of tick bites, we recommend N, N-Diethylmeta-toluamide (DEET), picaridin, ethyl-3-(N-n-butyl-Nacetyl) aminopropionate (IR3535), oil of lemon eucalyptus (OLE), p-methane-3,8-diol (PMD), 2-undecanone, or permethrin. ( S , M)
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(C) Removal of Attached Ticks

We recommend promptly removing attached ticks by mechanical means using a clean fine-tipped tweezer (or a comparable device) inserted between the tick body and the skin (See Figure 5). (G, )
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We recommend against burning an attached tick (with a match or other heat device) or applying noxious chemicals or petroleum products to coax its detachment. (G, )
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II. Diagnostic Tick Testing

(A) Diagnostic Tick Testing

We recommend submitting the removed tick for species identification. (G, )
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We recommend against testing a removed Ixodes tick for B. burgdorferi. (, G)
Comment: The presence or absence of B. burgdorferi in an Ixodes tick removed from a person does not reliably predict the likelihood of clinical infection.
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(B) Diagnostic Testing of Asymptomatic Patients Following Tick Bites

We recommend submitting the removed tick for species identification. (G, )
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III. Antibiotic Prophylaxis

We recommend that prophylactic antibiotic therapy be given only to adults and children within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal risk or low risk. ( S , H)
Comment: If a tick bite cannot be classified with a high level of certainty as a high-risk bite, a wait-and-watch approach is recommended. A tick bite is considered to be high-risk only if it meets the following three criteria: the tick bite was from (a) an identified Ixodes spp. vector species, (b) it occurred in a highly endemic area, and (c) the tick was attached for ≥ 36 hours.
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IV. Antibiotic Regimen

For high-risk Ixodes spp. bites in all age groups, we recommend the administration of a single dose of oral doxycycline within 72 hours of tick removal over observation. ( S , M)
Comment: Doxycycline is given as a single oral dose, 200 mg for adults and 4.4 mg/kg (up to a maximum dose of 200 mg) for children.
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V. Erythema Migrans Testing

In patients with potential tick exposure in a Lyme disease endemic area who have 1 or more skin lesions compatible with erythema migrans, we recommend clinical diagnosis rather than laboratory testing. ( S , M)
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In patients with 1 or more skin lesions suggestive of, but atypical for erythema migrans, we suggest antibody testing performed on an acute-phase serum sample (followed by a convalescent-phase serum sample if the initial result is negative) rather than currently available direct detection methods such as polymerase chain reaction (PCR) or culture performed on blood or skin samples. ( W , L)
Comment: If needed, the convalescent-phase serum sample should be collected at least 2–3 weeks after collection of the acute-phase serum sample.
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VI. Erythema Migrans Antibiotic Regimens

For patients with erythema migrans, we recommend using oral antibiotic therapy with doxycycline, amoxicillin, or cefuroxime axetil. ( S , M)
Comment: For patients unable to take both doxycycline and beta-lactam antibiotics, the preferred second-line agent is azithromycin.
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VII. Erythema Migrans Antibiotic Duration

We recommend that patients with erythema migrans be treated with either a 10-day course of doxycycline or a 14-day course of amoxicillin or cefuroxime axetil rather than longer treatment courses. ( S , M)
Comment: If azithromycin is used, the indicated duration is 5–10 days, with a 7-day course preferred in the United States, since this duration of therapy was used in the largest clinical trial performed in the United States.
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VIII. The Southern Tick-associated Rash Illness (STARI)

In patients who develop an erythema migrans-like skin lesion following the bite of the lone star tick (Amblyomma americanum), an illness referred to as STARI, we make no recommendation for or against the use of antibiotics. (K, )
Comment: In certain geographic regions, both STARI and Lyme disease are endemic. Distinguishing single erythema migrans due to Lyme disease from STARI may not be possible clinically unless the responsible tick has been identified. When STARI cannot be distinguished from Lyme disease-associated erythema migrans in areas endemic for both conditions, antibiotic therapy directed toward Lyme disease is indicated.
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IX. Lyme Neuroborreliosis

When assessing patients for possible Lyme neuroborreliosis involving either the PNS or central nervous system (CNS), we recommend serum antibody testing rather than PCR or culture of either cerebrospinal fluid (CSF) or serum. ( S , M)
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If CSF testing is performed in patients with suspected Lyme neuroborreliosis involving the CNS, we (a) recommend obtaining simultaneous samples of CSF and serum for determination of the CSF:serum antibody index, carried out by a laboratory using validated methodology, (b) recommend against CSF serology without measurement of the CSF:serum antibody index, and (c) recommend against routine PCR or culture of CSF or serum. ( S , M)
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X. Neurological Presentations

In patients presenting with 1 or more of the following acute disorders: meningitis, painful radiculoneuritis, mononeuropathy multiplex including confluent mononeuropathy multiplex, acute cranial neuropathies (particularly VII, VIII, less commonly III, V, VI and others), or in patients with evidence of spinal cord (or rarely brain) inflammation, the former particularly in association with painful radiculitis involving related spinal cord segments, and with epidemiologically plausible exposure to ticks infected with B. burgdorferi, we recommend testing for Lyme disease. ( S , M)
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In patients with typical amyotrophic lateral sclerosis, relapsing-remitting multiple sclerosis, Parkinson’s disease, dementia or cognitive decline, or new-onset seizures, we recommend against routine testing for Lyme disease. ( S , L)
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In patients with neurological syndromes other than those listed above, in the absence of a history of other clinical or epidemiologic support for the diagnosis of Lyme disease, we recommend against screening for Lyme disease. ( S , L)
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In patients presenting with nonspecific magnetic resonance imaging (MRI) white matter abnormalities confined to the brain in the absence of a history of other clinical or epidemiologic support for the diagnosis of Lyme disease, we suggest against testing for Lyme disease. ( W , L)
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XI. Adult Psychiatric Illnesses

In patients with psychiatric illness, we recommend against routine testing for Lyme disease. ( S , L)
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XII. Childhood Psychiatric Illnesses

In children presenting with developmental, behavioral or psychiatric disorders, we suggest against routinely testing for Lyme disease. ( W , L)
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XIII. Acute Neurologic Manifestations

In patients with Lyme disease-associated meningitis, cranial neuropathy, radiculoneuropathy or with other peripheral nervous system (PNS) manifestations, we recommend using intravenous (IV) ceftriaxone, cefotaxime, penicillin G, or oral doxycycline over other antimicrobials. ( S , M)
Comment: Decisions about the choice of antibiotic among these, including the route of administration, should primarily be made based on individual factors such as side effect profile, ease of administration, ability to tolerate oral medication, concerns about compliance unrelated to effectiveness. Treatment route may be changed from IV to oral during treatment. The preferred antibiotic duration is 14–21 days.
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XIV. Brain or Spinal Cord

In patients with Lyme disease-associated parenchymal involvement of the brain or spinal cord, we recommend using IV over oral antibiotics. ( S , M)
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XV. Facial Nerve Palsy

In patients with Lyme disease-associated facial nerve palsy, we make no recommendation on the use of corticosteroids in addition to antibiotics. (K, )
Comment: In patients age 16 or older presenting with acute facial nerve palsy but without other objective clinical or serologic evidence of Lyme disease, corticosteroid treatment should be administered within 72 hours in accordance with current facial nerve palsy guideline recommendations.
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XVI. Lyme Carditis Screening

We suggest performing an electrocardiogram (ECG) only in patients with signs or symptoms consistent with Lyme carditis. ( W , L)
Comment: Symptoms and signs of cardiac involvement in Lyme disease include dyspnea, edema, palpitations, lightheadedness, chest pain, and syncope.
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XVII. Lyme Carditis Hospitalization

In patients with or at risk for severe cardiac complications of Lyme disease including those with significant PR prolongation (PR >300 milliseconds), other arrhythmias, or clinical manifestations of myopericarditis, we recommend hospital admission with continuous ECG monitoring. ( W , L)
Comment: Clinical manifestations of Lyme carditis include exercise intolerance, palpitations, presyncope, syncope, pericarditic pain, evidence of pericardial effusion, elevated biomarkers (such as troponin), edema, and shortness of breath.
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XVIII. Lyme Carditis Pacing

For patients with symptomatic bradycardia due to Lyme carditis that cannot be managed medically, we recommend temporary pacing modalities rather than implanting a permanent pacemaker. ( S , M)
Comment: Clinical manifestations of Lyme carditis include exercise intolerance, palpitations, presyncope, syncope, pericarditic pain, evidence of pericardial effusion, elevated biomarkers (such as troponin), edema, and shortness of breath.
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XIX. Lyme Carditis Antibiotics

In outpatients with Lyme carditis, we suggest oral antibiotics over IV antibiotics. ( W , VL)
Comment: Clinical manifestations of Lyme carditis include exercise intolerance, palpitations, presyncope, syncope, pericarditic pain, evidence of pericardial effusion, elevated biomarkers (such as troponin), edema, and shortness of breath.
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In the hospitalized patient with Lyme carditis, we suggest initially using IV ceftriaxone over oral antibiotics until there is evidence of clinical improvement, then switching to oral antibiotics to complete treatment. ( W , VL)
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For the treatment of Lyme carditis, we suggest 14–21 days of total antibiotic therapy over longer durations of treatment. ( W , VL)
Comment: Oral antibiotic choices for Lyme carditis are doxycycline, amoxicillin, cefuroxime axetil, and azithromycin.
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XX. Lyme Myocarditis/Pericarditis

In patients with acute myocarditis/pericarditis of unknown cause in an appropriate epidemiologic setting, we recommend testing for Lyme disease. ( S , L)
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In patients with chronic cardiomyopathy of unknown cause, we suggest against routine testing for Lyme disease. ( W , L)
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XXI. Lyme Arthritis Testing

When assessing possible Lyme arthritis, we recommend serum antibody testing over PCR or culture of blood or synovial fluid/tissue. ( S , M)
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In seropositive patients for whom the diagnosis of Lyme arthritis is being considered but treatment decisions require more definitive information, we recommend PCR applied to synovial fluid or tissue rather than Borrelia culture of those samples. ( S , M)
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XXII. Lyme Arthritis Initial Antibiotics

For patients with Lyme arthritis, we recommend using oral antibiotic therapy for 28 days. ( S , M)
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XXIII. Unresolved Lyme Arthritis

In patients with Lyme arthritis with partial response (mild residual joint swelling) after a first course of oral antibiotic, we make no recommendation for a second course of antibiotic versus observation. (K, )
Comment: Consideration should be given to exclusion of other causes of joint swelling than Lyme arthritis, medication adherence, duration of arthritis prior to initial treatment, degree of synovial proliferation versus joint swelling, patient preferences, and cost. A second course of oral antibiotics for up to 1 month may be a reasonable alternative for patients in whom synovial proliferation is modest compared to joint swelling and for those who prefer repeating a course of oral antibiotics before considering IV therapy.
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In patients with Lyme arthritis with no or minimal response (moderate to severe joint swelling with minimal reduction of the joint effusion) to an initial course of oral antibiotic, we suggest a 2–4 week course of IV ceftriaxone over a second course of oral antibiotics. ( W , L)
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XXIV. Post-antibiotic Arthritis

In patients who have failed one course of oral antibiotics and one course of IV antibiotics, we suggest a referral to a rheumatologist or other trained specialist for consideration of the use of disease modifying anti-rheumatic drugs (DMARDs), biologic agents, intraarticular steroids, or arthroscopic synovectomy. ( W , VL)
Comment: Antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit to patients with persistent arthritis if that treatment has included 1 course of IV therapy.
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XXV. Persistent Symptoms

For patients who have persistent or recurring nonspecific symptoms such as fatigue, pain, or cognitive impairment following recommended treatment for Lyme disease, but who lack objective evidence of reinfection or treatment failure, we recommend against additional antibiotic therapy. ( S , M)
Comment: Evidence of persistent infection or treatment failure would include objective signs of disease activity, such as arthritis, meningitis, or neuropathy.
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XXVI. Borrelial Lymphocytoma

In patients with borrelial lymphocytoma, we suggest oral antibiotic therapy for 14 days. ( W , L)
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XXVII. Acrodermatitis Chronica Atrophicans

In patients with acrodermatitis chronica atrophicans, we suggest oral antibiotic therapy for 21–28 days over shorter durations. ( W , L)
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XXVIII. Co-Infection with A. Phagocytophilum Or Microti?

In patients with Lyme disease who have a high-grade fever or characteristic laboratory abnormalities, clinicians should assess for possible coinfection with Anaplasma phagocytophilum and/or B. microti infection in geographic regions where these infections are endemic. (G, )
Comment: Coinfection should be investigated in patients who have a persistent fever for > 1 day while on antibiotic treatment for Lyme disease. If fever persists despite treatment with doxycycline, B. microti infection is an important consideration. Characteristic laboratory abnormalities found in both anaplasmosis and babesiosis include thrombocytopenia, leukopenia, neutropenia, and/or anemia. Evidence of hemolysis, such as elevated indirect bilirubin level, anemia, and elevated lactate dehydrogenase are particularly suggestive of babesiosis.
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Recommendation Grading

Overview

Title

Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease

Authoring Organizations

Publication Month/Year

January 1, 2021

Supplemental Implementation Tools

Quick-Reference Guide, Patient Information, Podcast

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adolescent, Adult, Child

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Social worker, physician

Scope

Assessment and screening, Diagnosis, Prevention, Treatment

Diseases/Conditions (MeSH)

D008193 - Lyme Disease

Keywords

Lyme Disease, ticks, babesiosis, tick-borne rickettsial infections

Supplemental Methodology Resources

Data Supplement