01Approach to the Critical Patient/attcp43

Alarm features requiring immediate action

›Cardiac involvement triggers

›Syncope or presyncope with bradycardia

›High-degree AV block risk (second-degree type II or third-degree)

›Lyme carditis — 1–2% of untreated patients

›Palpitations, chest pain, or dyspnea

›Obtain ECG immediately

›PR prolongation is earliest conduction finding

›If second- or third-degree AV block, admit for IV antibiotics and cardiology

›Temporary pacing may be required for complete heart block

›Class I recommendation for cardiology consultation

›Neurologic involvement triggers

›Facial droop or cranial nerve palsy

›CN VII palsy — 10–15% of untreated patients

›May be bilateral

›Severe headache with neck stiffness and photophobia

›Lymphocytic meningitis from early dissemination

›If neuroborreliosis suspected, escalate to IV ceftriaxone and neurology

›LP for CSF analysis if meningitis features present

›Coinfection alarm features

›Persistent high fever >1 day despite appropriate antibiotics

›Anaplasma or Babesia coinfection

›Babesiosis: hemolytic anemia, thrombocytopenia

›If coinfection suspected, add targeted therapy

›Doxycycline covers Anaplasma

›Atovaquone plus azithromycin for Babesia

Monitoring and targets

›Monitoring priorities in admitted patients

02History/hx57

Tick exposure and bite history

›Geographic exposure

›Northeastern US — Virginia to Maine (highest endemicity)

›14 states account for 95% of US cases

›Upper Midwest — Wisconsin, Minnesota

›Northern California (smaller endemic pocket)

›Outdoor activity type

›Hiking or camping in wooded or grassy areas

›Gardening or yard work in suburban endemic areas

›Occupational field exposure

›Tick bite recall

›Only 25–30% of patients recall a bite

›Estimated attachment duration — ≥36 hours significantly increases transmission risk

›Ixodes scapularis (black-legged tick) — primary vector in northeastern and midwestern US

Rash characteristics

›Erythema migrans onset and course

›Onset 7–14 days post-bite (range 3–30 days)

›Gradually expanding erythematous lesion at bite site

›Usually painless and non-pruritic

›Warm to touch

›Important negatives distinguishing EM from mimics

›No purulent drainage

›Not appearing within hours of bite (hypersensitivity reaction — not EM)

›Not intensely pruritic (allergic reaction pattern)

›Not static in size (granuloma annulare, tinea)

Constitutional symptoms

›Systemic symptoms accompanying EM

›Fatigue and malaise — most common systemic complaint

03Physical Exam/exam43

Skin examination

›Erythema migrans characterization

›Size — must be ≥5 cm to meet diagnostic criteria

›Lesions <5 cm may represent bite hypersensitivity, not EM

›Shape — expanding erythematous macule or patch at bite site

›Pattern variants

›Uniformly erythematous — most common presentation

›Central clearing with target appearance — classic but minority of cases

›Enhanced central erythema with outer ring

›Vesicular or necrotic center — uncommon variant

›Temperature — warm to palpation

›Tenderness — usually absent or minimal

›Skin survey for additional lesions

›Multiple EM lesions at sites distant from bite indicate early disseminated disease

›Document all lesion locations, sizes, and morphology

Lymphatic exam

›Regional lymphadenopathy

›Ipsilateral to bite site

›Usually non-tender

›Present in minority of Stage 1 patients

Vital signs and hemodynamic assessment

›Temperature

›Low-grade fever possible in Stage 1

›High fever suggests coinfection or disseminated disease

›Heart rate

›Tachycardia with fever — expected in constitutional illness

›Bradycardia — raises concern for cardiac conduction disease

›Blood pressure

04Differential Diagnosis/ddx56

Dermatologic mimics

›Cellulitis

›ICD-10: L03.90

›Typically tender, warm, rapidly spreading without central clearing

›Lacks gradual expansion and oval/circular morphology of EM

›Often has defined leading edge of erythema

›Tinea corporis

›ICD-10: B35.4

›Annular with scaly border and central clearing

›KOH preparation positive for fungal elements

›Pruritic — distinguishing feature from EM

›Nummular eczema

›ICD-10: L30.0

›Coin-shaped, pruritic, scaly plaques

›Does not expand progressively from a central point

›Granuloma annulare

›ICD-10: L92.0

›Flesh-colored to erythematous annular plaques

›Non-expanding, non-warm, no bite history

›Fixed drug eruption

›ICD-10: L27.1

›Recurs at same anatomic site with medication re-exposure

›No tick bite history or constitutional symptoms

›Contact dermatitis

›ICD-10: L25.9

›Pruritic, vesicular, corresponds to exposure pattern (linear or geometric)

›No expanding ring morphology

›Erythema multiforme

05Laboratory Tests/lt43

Serology — two-tiered testing

›Two-tiered serologic testing for Lyme

›Tier 1: Enzyme immunoassay (EIA) for B. burgdorferi antibodies

›Sensitivity <40% in first 2 weeks of early localized disease

›High false-negative rate in Stage 1 — diagnosis is clinical

›Tier 2: Western blot (IgM and IgG) — only if Tier 1 positive or equivocal

›IgM blot: 2 of 3 bands (23, 39, 41 kDa) required for positivity

›IgG blot: 5 of 10 bands required

›Modified two-tier testing: Second EIA instead of Western blot — equivalent performance

›Indications for serology in Stage 1

›NOT indicated for typical EM in endemic area — clinical diagnosis is sufficient

›IDSA/AAN/ACR 2020 strong recommendation against routine serology for classic EM

›Indicated for atypical or uncertain EM presentation

›Repeat convalescent serology in 2–3 weeks if initially negative and suspicion persists

Coinfection workup

›Complete blood count with differential

›Leukopenia or thrombocytopenia — suggests Anaplasma coinfection

›Hemolytic anemia — suggests Babesia coinfection

›Obtain if persistent high fever after 24 hours on appropriate antibiotics

›Comprehensive metabolic panel

›Transaminase elevation — mild elevation possible in Lyme and Anaplasma

›Generally normal in uncomplicated Stage 1

›Lactate dehydrogenase and indirect bilirubin

›Hemolysis markers for Babesia screening

›Anaplasma PCR

›High sensitivity in acute febrile phase

›Submit before antibiotics if coinfection suspected

›Babesia PCR and peripheral blood smear

06Diagnostic Tests/dt59

Scoring Systems

›Clinical diagnostic criteria for EM (no formal score)

›Expanding erythematous skin lesion ≥5 cm

›At site of known or likely tick bite

›In an endemic geographic area

›Present ≥3 days after exposure

›Diagnosis is clinical — no point-based score required

›IDSA/AAN/ACR 2020: clinical diagnosis does not require serologic confirmation for classic EM

›Sensitivity of clinical diagnosis by experienced clinician >95% in endemic areas

›Modified Duke-like approach for atypical presentations

›Major criterion: EM ≥5 cm with characteristic expansion

›In tick-endemic area with plausible exposure

›Minor criteria supporting diagnosis

›Constitutional symptoms (fatigue, arthralgias, myalgias)

›Regional lymphadenopathy ipsilateral to rash

›Positive two-tier serology (useful only in atypical cases)

MRI

›MRI indications in Lyme disease

›Not indicated for Stage 1 (early localized) disease

›Relevant in disseminated disease with neurologic involvement

›MRI brain findings in Lyme neuroborreliosis

›White matter T2/FLAIR hyperintensities — non-specific

›May resemble demyelinating disease

›Leptomeningeal enhancement with gadolinium — meningitis pattern

›Cranial nerve enhancement — particularly CN VII

›MRI spine indications

›Radiculopathy or myelopathy in disseminated disease

›Not a Stage 1 indication

07Disposition/dispo39

Discharge criteria (majority of Stage 1)

›Outpatient management criteria

›Single EM lesion consistent with Stage 1 (early localized)

›No cardiac, neurologic, or rheumatologic symptoms

›Tolerating oral antibiotics

›Reliable follow-up available

›Hemodynamically stable

Admission criteria

›Cardiac indications for admission

›Symptomatic Lyme carditis — any degree of symptomatic AV block

›High-degree AV block — second-degree type II or complete (third-degree)

›First-degree AV block with PR interval >300 ms — admission for monitoring

›Even if asymptomatic due to risk of rapid progression to complete heart block

›Neurologic indications

›Meningitis — lymphocytic, confirmed or strongly suspected

›Encephalopathy or altered mental status

›Severe radiculopathy requiring parenteral therapy

›Systemic indications

›Inability to tolerate oral antibiotics

›Hemodynamic instability

›Severe coinfection requiring IV therapy (Babesia with hemolysis, severe Anaplasma)

Observation and intermediate care

›Observation indications

›First-degree AV block with PR >300 ms without symptoms

›PR interval trending upward in serial ECGs

›Uncertain tolerance of oral antibiotics

Referral and consultation

›Infectious disease consultation triggers

08Treatment/t60

First-line antibiotics — oral (IDSA/AAN/ACR 2020 strong recommendation)

›Doxycycline — preferred first-line agent

›Dose: 100 mg PO twice daily

›Duration: 10 days

›Take with food and full glass of water

›Remain upright for 30 minutes after dosing — prevents esophagitis

›Avoid dairy products within 2 hours of dosing

›Advantages over alternatives

›Also covers Anaplasma phagocytophilum coinfection

›Shorter course than beta-lactam alternatives

›Contraindications

›Pregnancy — avoid (teratogenic)

›Children <8 years — relative contraindication (tooth discoloration)

›Known doxycycline or tetracycline allergy

›Amoxicillin — first alternative

›Dose: 500 mg PO three times daily

›Duration: 14 days

›Does not cover Anaplasma — supplement if coinfection suspected

›Preferred in pregnancy and young children

›Cefuroxime axetil — second alternative

›Dose: 500 mg PO twice daily

›Duration: 14 days

›Preferred for beta-lactam-tolerant patients who cannot take doxycycline

Second-line antibiotic (use only if unable to take doxycycline AND beta-lactams)

›Azithromycin — less effective, use with caution

›Dose: 500 mg PO once daily

›Duration: 7 days (preferred in US practice)

›Monitor closely for treatment failure

09Special Populations/sp66

Pregnancy

›Antibiotic selection in pregnancy

›Doxycycline — avoid in all trimesters

›Teratogenic: fetal bone and tooth development effects

›Amoxicillin 500 mg PO three times daily x 14 days — preferred first choice

›Safe in all trimesters

›Cefuroxime axetil 500 mg PO twice daily x 14 days — preferred second choice

›Safe in all trimesters

›Fetal and maternal risks of untreated Lyme in pregnancy

›Potential for transplacental transmission — rare but documented

›Adverse outcomes (stillbirth, fetal anomalies) — case reports; not definitively proven

›Early treatment reduces any fetal risk

›Serologic testing in pregnancy

›Standard two-tiered testing applies

›Test if atypical presentation or high clinical suspicion without EM

›Post-exposure prophylaxis in pregnancy

›Doxycycline single-dose prophylaxis is contraindicated

›Discuss risk/benefit of prophylaxis with patient and obstetrics

›Close monitoring for EM development after high-risk tick bite

›Delivery and neonatal considerations

›Inform neonatology if active infection at time of delivery

›Neonatal Lyme disease is rare with appropriate maternal treatment

Geriatric

›Presentation differences in older adults

›Tick bite less likely recalled due to less acute skin sensitivity

›Constitutional symptoms may be attributed to other chronic conditions

›Fatigue and cognitive effects more pronounced — delirium risk

›Antibiotic considerations in older adults

›Doxycycline — renal and hepatic adjustment rarely needed but consider comorbidities

›Amoxicillin — adjust for renal function (GFR <30: reduce dose)

›Drug interactions — warfarin interaction with doxycycline and amoxicillin

›Monitor INR closely if on anticoagulation

›Cardiac risk in older adults

›Higher baseline prevalence of conduction disease

›Lyme carditis may be misattributed to age-related conduction abnormality

›Lower threshold for ECG in older patients with constitutional symptoms

›Coinfection risk in older adults

›Babesiosis may be severe in asplenic or immunocompromised elderly patients

›Higher mortality from Babesia in older cohorts — early recognition critical

›Functional recovery

›Recovery time may be longer but prognosis with appropriate treatment remains good

›Post-infectious fatigue more common in older adults

Pediatrics

›Pediatric antibiotic dosing

›Doxycycline — preferred for all ages ≥8 years and for children <8 with severe disease

›4 mg/kg/day divided twice daily (maximum 200 mg/day)

›Duration: 10 days

›Short courses do not cause clinically significant tooth staining — AAP supports doxycycline in all ages when indicated

›Amoxicillin — preferred for children <8 years (mild to moderate disease)

›50 mg/kg/day divided three times daily (maximum 1500 mg/day)

›Duration: 14 days

›Cefuroxime axetil — alternative for beta-lactam-tolerant children <8 years

›30 mg/kg/day divided twice daily (maximum 1000 mg/day)

›Duration: 14 days

›Pediatric presentation features

›EM morphology identical to adults

›Constitutional symptoms common

›Bimodal age distribution — children 5–15 years at elevated risk

›Higher outdoor activity exposure in this age group

›Pediatric alarm features

›Facial nerve palsy — CN VII most common neurologic manifestation

›Lyme arthritis — more common in children than adults with disseminated disease

›Lyme carditis — rare in pediatric patients but reported

›Serologic testing in children

›Same two-tier approach as adults

›Clinical diagnosis applies for classic EM — no testing required

›School and activity return

›No restriction required once tolerating antibiotics and afebrile

›Educate family on tick prevention for future exposures

10Background/b69

Epidemiology

›Incidence and geographic distribution

›Most common vector-borne disease in the United States

›~476,000 estimated new cases per year (CDC surveillance and modeling)

›14 states account for 95% of reported US cases

›Northeastern states: Maine, Vermont, New Hampshire, Connecticut, Rhode Island, Massachusetts, New York, New Jersey, Pennsylvania, Delaware, Maryland, Virginia

›Midwestern states: Wisconsin, Minnesota

›Expanding geographic range — climate warming extending Ixodes scapularis habitat

›Seasonal distribution

›Peak incidence May through August

›Corresponds to nymphal Ixodes scapularis activity — primary transmission stage

›Adult tick activity — fall and winter; lower transmission rate

›Age distribution

›Bimodal: children aged 5–15 years and adults aged 45–65 years

›Both groups have higher outdoor recreational exposure

›Tick vector biology

›Ixodes scapularis — northeastern and midwestern US

›Ixodes pacificus — western US (northern California)

›Nymph stage responsible for most human infections — small size (poppy seed) reduces detection

›Attachment duration ≥36 hours required for B. burgdorferi transmission in most cases

›Global burden

›Also endemic in Europe (Ixodes ricinus vector) and Asia

›European strains: B. afzelii and B. garinii — different clinical manifestations

Pathophysiology

›Causative organism

›Borrelia burgdorferi sensu stricto — primary US pathogen

›Spirochete: gram-negative, highly motile, obligate intracellular parasite of tick midgut

›Linear chromosome — unusual bacterial genome architecture

›Transmission mechanism

›B. burgdorferi resides in midgut of unfed Ixodes tick

›Tick feeding triggers spirochete migration to salivary glands

›Transmission requires 36–48 hours of attachment for sufficient inoculation

›Tick saliva immunomodulatory properties facilitate initial immune evasion

›Skin invasion and EM development

›Spirochetes inoculated into dermis at bite site

›Local innate immune response triggers expanding inflammatory reaction — EM

›EM is an immunopathologic response, not direct spirochete toxicity

›Spirochetes spread centrifugally — explains expanding border of EM

›Dissemination mechanism

›Hematogenous spread to heart (Purkinje fibers), nervous system, and joints if untreated

›B. burgdorferi binds decorin on collagen — explains tropism for connective tissue

›~60% of untreated patients develop disseminated disease

›Immune response

›IgM antibodies detectable at 2–4 weeks after infection

›IgG antibodies peak at 4–8 weeks — explains low serology sensitivity in Stage 1

›Antibodies persist long after treatment — complicate serologic diagnosis of reinfection

›Post-treatment Lyme disease syndrome (PTLDS)

›Persistent fatigue, pain, cognitive complaints after adequate antibiotic therapy

›Mechanism unclear — not active infection

›Prolonged antibiotic therapy not effective — IDSA strong recommendation

Therapeutic Considerations

›Clinical cure rate with appropriate oral antibiotics

›Rapid resolution of EM within days of initiating antibiotics

›Complete symptom resolution in >90% of patients

›Some patients experience Jarisch-Herxheimer-like reaction in first 24 hours

›Transient worsening of symptoms: fever spike, rash expansion, myalgias

›Self-limiting — not a sign of treatment failure

›Antibiotic course length evidence

›RCT (Stupica et al., Lancet Infectious Diseases 2023): 7 days vs 14 days doxycycline non-inferior for solitary EM

›US guidelines (IDSA/AAN/ACR 2020) still recommend 10 days for doxycycline

›European guidelines moving toward shorter courses

›Reinfection vs treatment failure

›Reinfection with a new B. burgdorferi strain is possible and should not be confused with relapse

›True relapse after adequate therapy is rare

›Persistent symptoms after adequate treatment are PTLDS — not an indication for re-treatment

›Doxycycline and Anaplasma co-coverage

›Single-drug coverage for two common coinfecting tick-borne pathogens

›Clinical advantage in areas with high Anaplasma prevalence

›Vaccine status

›No commercially available Lyme vaccine in the US (as of 2025)

›VLA15 (mRNA-based) and other candidates in late-stage clinical trials

›Primary prevention relies on tick avoidance and prophylaxis

11Patient Discharge Instructions/pdi41

copy discharge instructions

›Diagnosis and expected recovery

›Diagnosis of early Lyme disease (Stage 1)

›Caused by a bacterium called Borrelia burgdorferi transmitted by tick bites

›With a full course of antibiotics, most patients recover quickly and completely

›The rash (erythema migrans) usually begins to fade within a few days of starting antibiotics

›Full resolution typically occurs within 2–4 weeks

›Some temporary worsening of symptoms may occur in the first 24 hours after starting antibiotics

›This is a normal response — not a sign that the treatment is not working

›Antibiotic instructions

›Take all prescribed antibiotics exactly as directed — complete the full course

›Do not stop early even if you feel better

›If taking doxycycline

›Take with a full glass of water and with food or milk

›Stay upright for at least 30 minutes after each dose

›Avoid dairy products within 2 hours of each dose

›Use sunscreen and avoid prolonged sun exposure — doxycycline causes sun sensitivity

›If taking amoxicillin or cefuroxime

›Take with or without food

›If you develop severe diarrhea, contact your doctor — could indicate C. difficile colitis

›Return to emergency department immediately for any of the following

›New rashes appearing at sites away from the original bite

›Facial drooping or weakness on one or both sides

›Severe headache with stiff neck or sensitivity to light

›Palpitations, racing or skipping heartbeat, chest pain, or fainting

›Shortness of breath or lightheadedness

›Joint swelling — especially the knee

›Numbness, tingling, or shooting pain in the arms or legs

12References/r48

Guidelines and key sources

›IDSA/AAN/ACR 2020 Lyme Disease Guidelines

›Lantos PM, Rumbaugh J, Bockenstedt LK, et al.

›Clinical Practice Guidelines for Prevention, Diagnosis and Treatment of Lyme Disease

›Clinical Infectious Diseases 2021; Arthritis and Rheumatology 2021; Neurology 2021

›PMID: 33417672

›CDC Tickborne Diseases Reference Manual (2022)

›Shadick N, Maher N, Hoak D.

›Tickborne Diseases of the United States: A Reference Manual for Healthcare Providers, 6th Edition

›United States Centers for Disease Control and Prevention 2022

›Strle F, Strle K, Marques A, et al.

›Lyme Borreliosis

›Nature Reviews Disease Primers 2026

›PMID: 41888159

›Sanchez E, Vannier E, Wormser GP, Hu LT.

›Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A Review

›JAMA 2016

›doi: 10.1001/jama.2016.2884

›Williams AL, Bevan J, Arnold MJ.

›Lyme Disease: Updated Recommendations From the IDSA, AAN, and ACR

›American Family Physician 2021

›PMID: 34913653

›Stupica D, Collinet-Adler S, Blagus R, et al.

›Treatment of Erythema Migrans With Doxycycline for 7 Days Versus 14 Days in Slovenia: A Randomised Open-Label Non-Inferiority Trial

›Lancet Infectious Diseases 2023

›PMID: 36209759

›Shapiro ED.

›Lyme Disease

Evidence & Review

Evidence & Review