01Approach to the Critical Patient/attcp38

Cardiac emergency recognition

›High-degree AV block identification

›Complete heart block with hemodynamic compromise

›Syncope or presyncope in endemic area exposure

›Bradycardia with hypotension

›Rapid fluctuation from first to third degree block within minutes

›PR interval threshold for admission

›PR interval >300 ms requires continuous telemetry and hospitalization

›Second-degree or third-degree block warrants IV antibiotics

›Immediate interventions for symptomatic high-degree block

›Atropine 0.5 mg IV for hemodynamic compromise

›Transcutaneous pacing as bridge if atropine fails

›Avoid permanent pacemaker placement — block resolves with antibiotics

›Escalation triggers

›Cardiology consultation for any new conduction abnormality

›AV block at any degree in appropriate clinical context

›Ventricular arrhythmia

›ICU-level care triggers

›Hemodynamic instability with high-degree block

›Myopericarditis with ventricular dysfunction

Neurologic emergency recognition

›Lyme meningitis red flags

›Severe headache with neck stiffness in tick-endemic region

›Lymphocytic pleocytosis on LP distinguishes from bacterial meningitis

›Normal glucose differentiates from bacterial meningitis

›Bilateral facial palsy

›Bilateral CN VII palsy is highly suggestive of Lyme neuroborreliosis

›Isolated unilateral facial palsy also requires Lyme serology in endemic area

02History/hx55

Exposure history

›Tick exposure context

›Outdoor activities in endemic areas — Northeast, Upper Midwest, mid-Atlantic US

›95% of US cases from CT, DE, ME, MD, MA, MN, NH, NJ, NY, PA, RI, VT, VA, WI

›Peak nymphal tick activity May through September

›Known tick bite with duration of attachment

›Transmission typically requires at least 36 hours of tick attachment

›Only approximately 40% of Lyme carditis patients recall an EM rash

›Occupational and recreational exposures

›Forestry, landscaping, outdoor recreation, camping, gardening

›Pet ownership — dogs can carry ticks indoors

Symptom characterization

›Dermatologic history

›Prior single erythema migrans lesion that was untreated or unnoticed

›Original bite site rash may have resolved before systemic spread

›New rashes at sites distant from original bite

›Multiple EM lesions are the hallmark of early disseminated disease

›Cardiac symptoms

›Palpitations, chest pain, dyspnea on exertion

›Syncope or presyncope — highest urgency

›Exercise intolerance

›Pericarditic chest pain — pleuritic in quality

›Neurologic symptoms

›Facial droop or weakness — unilateral or bilateral

›Bilateral facial palsy is highly suggestive of Lyme neuroborreliosis

›Headache with neck stiffness or photophobia

›Suggests Lyme meningitis

›Radicular pain, paresthesias, limb weakness

03Physical Exam/exam54

Vital signs

›Hemodynamic assessment

›Heart rate — bradycardia in Lyme carditis

›Rate below 50 beats/min with symptoms requires immediate intervention

›Pulsus paradoxus if pericardial effusion

›Blood pressure — hypotension with high-degree block

›MAP <65 mmHg triggers urgent cardiac intervention

›Temperature — fever common in early disseminated disease

›Hypothermia may indicate severe systemic illness

›Oxygen saturation — reduced with myopericarditis and heart failure

Skin examination

›Multiple erythema migrans lesions

›Annular erythematous lesions at sites distant from original bite

›Most lesions are uniformly erythematous — not classic bull's-eye

›Bull's-eye or target appearance represents minority of EM presentations

›Lesion size and distribution

›Multiple lesions at varying stages

›Expanding borders with central clearing when classic

Neurologic examination

›Cranial nerve examination

›CN VII — facial nerve

›Bilateral facial palsy highly suggestive of Lyme neuroborreliosis

›Inability to close eye, forehead involvement distinguishes peripheral from central

›Other cranial nerves — CN VI, CN VIII, CN IX, CN X

›Diplopia from CN VI palsy

›Vertigo or hearing loss from CN VIII involvement

›Meningeal signs

›Kernig sign and Brudzinski sign

04Differential Diagnosis/ddx57

Dermatologic mimics

›Multiple EM differential

›Erythema multiforme

›ICD-10 L51.9

›Target lesions but involves palms and soles; no tick exposure

›Viral exanthem

›Concurrent viral prodrome

›Non-expanding lesions

›Southern Tick-Associated Rash Illness (STARI)

›Caused by Amblyomma americanum tick; lone star tick

›Clinically indistinguishable but responds to doxycycline

›Tinea corporis

›KOH preparation positive

›Non-expanding, scaly border

›Granuloma annulare

›Dermal papules without central clearing

›No constitutional symptoms

Facial palsy differential

›Causes of facial nerve palsy

›Idiopathic Bell palsy

›ICD-10 G51.0

›Unilateral; bilateral palsy strongly favors Lyme

›Ramsay Hunt syndrome

›Zoster vesicles in ear canal

›Otalgia preceding palsy

›Stroke

›Central pattern — forehead sparing

›Associated upper motor neuron signs

05Laboratory Tests/lt42

Serologic testing

›Two-tiered Lyme serology — primary diagnostic test for disseminated disease

›First tier — enzyme immunoassay screen

›High sensitivity; moderate specificity

›False positives in EBV, autoimmune disease, syphilis

›Second tier — Western blot IgM and IgG

›IgM Western blot interpretable only if symptoms present less than 30 days

›IgG Western blot used for symptoms over 30 days

›Sensitivity for early disseminated disease approximately 70–90%

›Modified two-tiered testing — MTTTA

›Replaces Western blot with second EIA

›Improved early sensitivity — 74% versus 41% with standard algorithm

›FDA cleared; increasingly accepted per IDSA/AAN/ACR 2020 guidelines

Hematology and chemistry

›Complete blood count interpretation

›Generally normal in isolated Lyme disease

›Leukopenia or thrombocytopenia suggests co-infection with Anaplasmosis or Babesiosis

›Hemolytic anemia suggests Babesiosis co-infection

›Blood smear if co-infection suspected

›Morulae for Anaplasmosis

›Ring forms or Maltese cross for Babesiosis

›Metabolic panel and hepatic function

›Mildly elevated transaminases may be present in Lyme disease

›Markedly elevated AST/ALT suggests Anaplasmosis co-infection

›Renal function for antibiotic dosing adjustment

Inflammatory markers

›Acute phase reactants

›ESR and CRP typically elevated in disseminated disease

06Diagnostic Tests/dt57

Scoring Systems

›Lyme carditis severity stratification

›Mild carditis — first-degree AV block PR <300 ms

›Outpatient management with oral antibiotics if asymptomatic

›Daily ECG follow-up until resolution

›Moderate carditis — PR >300 ms or second-degree AV block

›Hospital admission with continuous telemetry

›IV antibiotics with transition to oral when PR <300 ms

›Severe carditis — third-degree complete heart block

›Immediate hospitalization and IV antibiotics

›Transcutaneous pacing if hemodynamically compromised

›Avoid permanent pacemaker — conduction typically resolves with antibiotics

›Neuroborreliosis clinical severity

›Isolated cranial nerve palsy without meningitis

›Oral antibiotics; outpatient management

›Lyme meningitis or encephalitis

›IV ceftriaxone; hospitalization

›Radiculoneuritis with confirmed meningitis

›IV antibiotics required

MRI

›Brain MRI with gadolinium contrast

›Indications for CNS imaging

›Suspected Lyme encephalitis or myelitis

›Focal neurologic deficits beyond cranial neuropathy

›Altered mental status or cognitive dysfunction

›Expected findings in neuroborreliosis

›Meningeal enhancement pattern

›White matter T2 hyperintensities — rare in Stage 2

07Disposition/dispo40

Admission indications

›Mandatory hospitalization criteria

›Cardiac involvement requiring telemetry

›PR interval >300 ms

›Second-degree or third-degree AV block

›Symptomatic bradycardia, syncope, or presyncope

›Myopericarditis with ventricular dysfunction or pericardial effusion

›Neurologic involvement requiring IV antibiotics

›Confirmed Lyme meningitis

›Encephalitis or myelitis

›Radiculoneuritis with confirmed CNS involvement

›Inability to tolerate oral antibiotics

›Severe nausea, vomiting, or GI intolerance

Discharge criteria

›Safe for outpatient management

›Multiple EM without cardiac or neurologic involvement

›Oral doxycycline initiated

›Follow-up arranged within 1–2 weeks

›Isolated facial palsy without meningitis

›LP performed or clinical decision not to perform LP

›Outpatient oral antibiotics with neurology follow-up

›First-degree AV block with PR <300 ms and asymptomatic

›Cardiology follow-up within 48–72 hours arranged

›Return precautions given for palpitations, syncope, presyncope

Observation indications

›Borderline presentations requiring monitoring

›PR prolongation approaching 300 ms

›Telemetry monitoring with serial ECGs

08Treatment/t74

Multiple erythema migrans — oral regimens

›First-line oral therapy — doxycycline

›Doxycycline 100 mg PO twice daily for 10 days

›Preferred for multiple EM without neurologic or cardiac involvement

›Also active against Anaplasmosis co-infection

›Take with food and water to reduce GI side effects

›Avoid dairy within 2 hours of dose

›IDSA/AAN/ACR 2020 guideline recommendation

›Strong recommendation; moderate quality evidence

›Alternative oral options — penicillin class

›Amoxicillin 500 mg PO three times daily for 14 days

›Preferred in pregnancy and children under 8 years

›Not active against Anaplasmosis

›Cefuroxime axetil 500 mg PO twice daily for 14 days

›Alternative when amoxicillin not tolerated

›Not active against Anaplasmosis

›Second-line — azithromycin

›Azithromycin 500 mg PO daily for 7 days

›Only for cutaneous manifestations; not extracutaneous disease

›Lower efficacy than doxycycline or amoxicillin

›Reserve for penicillin allergy when doxycycline contraindicated

Cranial nerve palsy without meningitis

›Oral antibiotics — equivalent to IV for isolated CN palsy

›Doxycycline 100 mg PO twice daily for 14 to 21 days

›LP should be performed or clinically decided not to perform before oral-only treatment

›If LP shows pleocytosis — treat as Lyme meningitis with IV antibiotics

›Amoxicillin 500 mg PO three times daily for 14 to 21 days

›Alternative for pregnant patients and children under 8 years

›Supportive care for facial palsy

›Ophthalmologic protection — lubricating eye drops and taping eye closed at night

›Prevents corneal exposure keratitis from incomplete eye closure

›Corticosteroids not routinely recommended for Lyme-associated facial palsy

Lyme meningitis and CNS disease

›IV antibiotics for CNS involvement

›Ceftriaxone 2 g IV once daily for 14 to 21 days

›Preferred agent for Lyme meningitis — strong CNS penetration

›IDSA/AAN/ACR 2020 — strong recommendation

›Monitor for biliary sludge with prolonged courses

›Alternative — oral doxycycline for ambulatory patients

›Doxycycline 200 mg PO daily in two divided doses for 14 to 21 days

›Achieves CSF levels adequate for Lyme meningitis

›Only for patients able to take oral medications reliably

›Alternative IV — penicillin G

›Penicillin G 18–24 million units IV daily in divided doses every 4 hours

›For 14 to 21 days

›Use when ceftriaxone not available or tolerated

Lyme carditis

›IV antibiotics — hospitalized patients

›Ceftriaxone 2 g IV once daily as initial therapy

›Continue until PR interval normalizes below 300 ms and symptoms resolve

›Transition to oral doxycycline 100 mg twice daily to complete 14 to 21 days total

›Total treatment duration 14 to 21 days including IV and oral

›Oral therapy — mild outpatient carditis

›Doxycycline 100 mg PO twice daily for 14 to 21 days

›Only for PR <300 ms and asymptomatic first-degree block

›Temporary pacing

›Transcutaneous pacing as bridge for hemodynamic compromise

›Avoid permanent pacemaker — AV block typically resolves with antibiotics

›Temporary transvenous pacing if transcutaneous fails

›Atropine 0.5 mg IV as immediate pharmacologic bridge

›Repeat up to total 3 mg for symptomatic bradycardia

›Short-acting — not a substitute for pacing or antibiotics

›Monitoring during carditis treatment

›Continuous cardiac telemetry until PR interval consistently below 300 ms

›Repeat 12-lead ECG every 4 to 6 hours during acute phase

›Repeat ECG 1 to 2 weeks post-discharge to confirm resolution

Antibiotic contraindications and adjustments

›Doxycycline contraindications

›Pregnancy — avoid due to fetal bone and tooth development effects

›Use amoxicillin 500 mg PO TID or ceftriaxone IV depending on manifestation

›Children under 8 years of age

›Dental staining and enamel hypoplasia risk

›Use amoxicillin weight-based dosing

›Photosensitivity — counsel all patients on sun avoidance during treatment

›Post-treatment Lyme disease syndrome

›Approximately 10% of treated patients experience persistent fatigue, pain, or cognitive symptoms

›Termed post-treatment Lyme disease syndrome (PTLDS)

›Prolonged antibiotic courses are not beneficial — Class I contraindication

›Symptoms typically improve gradually over time

09Special Populations/sp49

Pregnancy

›Antibiotic selection in pregnancy

›Doxycycline is contraindicated in pregnancy

›Risk of fetal dental staining and bone growth interference

›Avoid in all trimesters

›Safe alternatives for multiple EM

›Amoxicillin 500 mg PO three times daily for 14 days

›Cefuroxime axetil 500 mg PO twice daily for 14 days

›CNS or cardiac involvement in pregnancy

›Ceftriaxone 2 g IV once daily for 14 to 21 days

›Consultation with maternal-fetal medicine recommended

›Maternal and fetal outcomes

›B. burgdorferi can cross the placenta — rare reports of adverse fetal outcomes

›Prompt treatment minimizes fetal risk

›Neonatal Lyme disease is rare when mother adequately treated

›Serologic testing interpretation unchanged in pregnancy

›Two-tiered testing algorithm applies

Geriatric

›Clinical presentation differences in older adults

›AV block may be attributed to age-related conduction disease

›Lyme serology required in endemic area with new-onset AV block

›Preexisting conduction disease complicates baseline comparison

›Atypical neurologic presentations more common

›Cognitive changes may be attributed to dementia

›Lower threshold for LP in elderly with altered mentation

›Medication considerations in older adults

›Renal function — ceftriaxone dose adjustment rarely required

›Doxycycline does not require renal dose adjustment

10Background/b84

Epidemiology

›Incidence and distribution

›Lyme disease is the most common vector-borne disease in the United States

›Approximately 476,000 cases diagnosed annually in the US

›True incidence substantially higher due to underdiagnosis and underreporting

›Geographic distribution

›95% of reported cases from 14 northeastern and upper midwestern states

›Endemic regions include northeastern US, Upper Midwest, and mid-Atlantic

›European cases caused by Borrelia afzelii and B. garinii — broader neurologic spectrum

›Stage 2 — early disseminated prevalence

›Approximately 60% of untreated early localized Lyme disease disseminates

›Multiple EM is most common Stage 2 manifestation

›Neurologic involvement in 10–15% of untreated patients

›Cardiac involvement in 1–2% of untreated patients

›Lyme carditis demographics

›Peak incidence in young adult and middle-aged men

›Male predominance approximately 3:1

›Seasonal and vector epidemiology

›Ixodes scapularis — black-legged tick — primary vector in eastern US

›Ixodes pacificus — western black-legged tick — primary vector in western US

›Ixodes ricinus — primary European vector

›Nymphal stage ticks responsible for most human transmission

›Small size — 1–2 mm — contributes to missed detection

›Peak nymphal activity May through July

Pathophysiology

›Infectious agent and transmission

›Borrelia burgdorferi sensu stricto — causative spirochete in North America

›Gram-negative spirochete with unique outer surface proteins

›Outer surface protein C (OspC) critical for tick transmission and early infection

›Transmission mechanism

›Tick attachment triggers spirochete migration from tick midgut to salivary glands

›Transmission requires at least 36 hours of tick attachment

›Risk increases substantially after 48–72 hours attachment

›Dissemination mechanism

›Hematogenous spread from initial skin inoculation site

›Bacteremic phase follows initial local skin infection

›Spirochetes cross vascular endothelium and invade target tissues

›Tissue tropism in Stage 2

›Skin — seeding of distant sites producing multiple EM lesions

›Nervous system — predilection for meninges, cranial nerves, spinal roots

›Heart — AV nodal tissue preferentially affected causing conduction block

›Cardiac pathophysiology

›AV nodal inflammation and functional conduction block

›Lymphocytic infiltration of AV node and Bundle of His

›Functional rather than structural damage — explains reversibility with antibiotics

›Rapid fluctuation of block degree reflects inflammatory state

›Myopericarditis from direct spirochete infiltration

›Pan-myocarditis with eosinophilic and lymphocytic infiltrate

›Rarely results in permanent cardiomyopathy

›Neurologic pathophysiology

›Lyme neuroborreliosis mechanisms

›Direct spirochetal invasion of meninges and nerve roots

›Perivascular lymphocytic infiltration along cranial nerves

›Vasculitis contributing to ischemic neuropathy in some cases

Therapeutic Considerations

›Evidence base for treatment recommendations

›IDSA/AAN/ACR 2020 joint clinical practice guidelines

›Most current US consensus guidelines for Lyme disease management

›Supersede previous IDSA 2006 guidelines

›Strong recommendations supported by moderate-quality evidence for antibiotic selection

›Wilderness Medical Society 2021 guidelines

›PR interval >300 ms threshold for admission based on expert consensus

›Telemetry monitoring duration recommendations

›Antibiotic mechanism and selection rationale

›Doxycycline — tetracycline class

›Bacteriostatic against B. burgdorferi

›Excellent oral bioavailability approaching IV levels

›CNS penetration sufficient for meningitis treatment

›Beta-lactams — amoxicillin, cefuroxime, ceftriaxone

›Bactericidal against B. burgdorferi

›Ceftriaxone achieves high CNS concentrations — preferred for meningitis and carditis

›Culture and PCR not routinely used for diagnosis

›Sensitivity too low for clinical use

›Two-tiered serology remains the diagnostic standard

›Post-treatment Lyme disease syndrome — PTLDS

›Definition — persistent symptoms beyond 6 months after appropriate antibiotic treatment

›Fatigue, musculoskeletal pain, cognitive symptoms

›Approximately 10% of adequately treated patients

›Prolonged antibiotic therapy — not recommended

›Multiple RCTs show no benefit over placebo

›Associated with significant adverse effects including line sepsis and C. difficile

›ICD-10 coding for Lyme disease

›A69.20 — Lyme disease unspecified

›A69.21 — Meningitis due to Lyme disease

›A69.22 — Other neurologic disorders in Lyme disease

›A69.23 — Arthritis due to Lyme disease

›A69.29 — Other conditions associated with Lyme disease

11Patient Discharge Instructions/pdi43

copy discharge instructions

›Discharge instructions for Lyme Disease Stage 2

›Your diagnosis

›You have been diagnosed with early disseminated Lyme disease (Stage 2)

›This is a bacterial infection spread by tick bites that has spread to other parts of your body

›With antibiotic treatment, the great majority of patients recover fully

›Your medications

›Take all antibiotic doses as prescribed — complete the full course even if feeling better

›If prescribed doxycycline — take with a full glass of water and food to prevent stomach upset

›If prescribed doxycycline — avoid dairy products within 2 hours of a dose

›If prescribed doxycycline — avoid prolonged sun exposure and use sunscreen

›Do not take antacids, calcium supplements, or iron tablets within 2 hours of doxycycline

›Activity

›Rest as needed during treatment — fatigue is common

›No specific activity restrictions unless you have heart involvement

›If you have heart involvement, limit strenuous exercise until cleared by your doctor

›Facial palsy care if applicable

›Use lubricating eye drops during the day to protect your eye

›Tape your eyelid closed at night if you cannot fully close it

›Wear eye protection outdoors

›Follow-up appointments

›Return for follow-up within 1 to 2 weeks of completing antibiotics

›If you had heart involvement — repeat ECG should be done within 1 to 2 weeks

›Facial palsy may take weeks to months to fully resolve

›Return to the emergency department immediately if you experience

›Fainting, passing out, or near-fainting

›Worsening or new palpitations or irregular heartbeat

›Chest pain or difficulty breathing

12References/r28

Guidelines and key sources

›IDSA/AAN/ACR 2020 Joint Clinical Practice Guidelines

›Lantos PM et al. Clinical Practice Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clinical Infectious Diseases. 2021

›Published simultaneously in Clinical Infectious Diseases, Neurology, and Arthritis and Rheumatology

›Primary US reference for Lyme disease management across all stages

›CDC Tickborne Diseases Reference Manual — 6th edition 2022

›Shadick NA et al. Tickborne Diseases of the United States: A Reference Manual for Healthcare Providers

›Comprehensive tick-borne illness management reference for clinicians

›JAMA Review 2016

›Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis. JAMA. 2016

›Covers differential diagnosis of co-infections and management algorithm

›NEJM Review — Shapiro ED 2014

›Shapiro ED. Lyme Disease. New England Journal of Medicine. 2014

›Key reference for Lyme carditis management including pacing guidance

›Wilderness Medical Society 2021 Guidelines

›Ho BM et al. WMS Clinical Practice Guidelines for Prevention and Management of Tick-Borne Illness. Wilderness and Environmental Medicine. 2021

›PR interval thresholds and admission criteria for Lyme carditis

›BMJ Review — Kullberg et al 2020

›Kullberg BJ, Vrijmoeth HD, van de Schoor F, Hovius JW. Lyme Borreliosis: Diagnosis and Management. BMJ. 2020

›International perspective including European Borrelia species

›IDSA/ASM Microbiology Laboratory Guide 2024

›Miller JM et al. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update. Clinical Infectious Diseases. 2024

›Modified two-tiered testing algorithm recommendation

›PLoS ONE — Uzomah et al 2021

›Uzomah UA et al. Incidence of Carditis and Predictors of Pacemaker Implantation in Patients Hospitalized with Lyme Disease. PLoS One. 2021

›Population-level data on Lyme carditis outcomes and pacemaker avoidance

›Nature Reviews Disease Primers — Strle et al 2026

›Strle F, Strle K, Marques A et al. Lyme Borreliosis. Nature Reviews Disease Primers. 2026

Evidence & Review

Evidence & Review