Borrelia burgdorferi

Background

Epidemiology

North America

• Transmitted by Ixodes scapularis (deer or black-legged tick), or Ixodes pacificus in the Pacific US
• Reservoirs include deer and small mammals such as rodents
• Lyme species are different outside of North America

Europe

• Three main species of Borrelia exist in Europe: B. burgdorferi, B. afzelii, B. garinii
• The vectors are Ixodes ricinus (in Europe and the Near East, and Ixodes persulcatus in Asia
• The species have cross-reactivity with Lyme serology

Life Cycle

Pathophysiology

• Tick bites host
• Borrelia migrates from hidgut to mouth over ~36 hours, then gets regurgitated into the wound
• Local multiplication followed by dissemination

Risk Factors

• Hiking or camping in Vermont or other endemic area, with known or possible tick exposure

Clinical Manifestations

• May not remember tick bite
• There can be overlap between the three stages (early localized, early disseminated, late)

Early Localized Disease (7 days)

• Presents within 1 month of exposure
• Erythema migrans in 80%; appears 7-14 days after tick bite (range 3 to 32 days)
  • Expanding red or bluish-red patch ≥5 cm, with or without central clearing
  • Spreads over days
  • Can present atypically, without target appearance, with ulceration, or with vesicles
  • If appears immediately and rapidly; need to consider local irritation and allergy, rather than Lyme
• Fever, fatigue, malaise, lethargy
• Mild headache and neck stiffness
• Myalgias and arthralgias
• May have mildly elevated liver enzymes

Early Disseminated Disease (14-21 days)

• Early disseminated (weeks to months), inflammatory phase
• Can be a non-specific febrile illness with headaches, arthralgias and fatigue, but can also cause a number of other symptoms
  • Bell palsy, unilateral or bilateral, or other cranial nerve palsies
  • Aseptic meningitis with lymphocytosis
  • Carditis with heart block
  • Secondary skin lesions
  • Conjunctivitis

Neuroborreliosis

• Refers specifically to the neurological manifestations of early disseminated Lyme disease
• More common with Borrelia garinii
• Meningo-radiculitis, meningitis, and peripheral facial nerve palsy
• Rarely, encephalitis or myelitis or cerebral vasculitis
• CSF shows lymphocytic pleocytosis, slightly elevated protein, and normal glucose

Cardiac Lyme

• AV conduction dysfunction, arrhythmia, and sometimes myocarditis or pericarditis, without other explanation
• Resolves with treatment, so only ever needs temporary pacemaker

Late Disease

• Late or chronic (months to years), less inflammatory, usually within a single body site
• Arthritis in 60% of untreated patients, now down to 15-20%
  • PCR of synovial fluid
• Encephalomyelitis/encephalopathy next-most common
  • LP fairly benign, with slightly elevated protein
  • Diagnose with simultaneous serum/CSF antibodies
• Peripheral neuropathy
• Affects heart, nervous system and joints; arrhythmias, heart block and sometimes myopericarditis; recurrent arthritis affecting large joints (i.e., knees); peripheral neuropathy; central nervous system manifestations – meningitis; encephalopathy (i.e., behavior changes, sleep disturbance, headaches); and fatigue

Lyme Arthritis

• Recurrent attacks or persisting arthritis involving one or more large joints, without other explanation
• Arthrocentesis shows 25,000 cells (range 500 to 110,000), mostly PMNs

Acrodermatitis Chronica Atrophicans

• Chronic red or bluish-red leions, usually on the extensor surgaces
• Initially doughy, eventually atrophic
• Can occur up to 8 years after infection

Late Neuroborreliosis

• Encephalopathy, encephalitis, and peripheral neuropathy

Complications

• Carditis in 5% of untreated patients
  • Heart block
  • Cardiomyopathy
• Neurologic involvement in 15% of untreated patients
  • Uni- or bilateral cranial nerve defects, especially CN VII
  • Meningitis and encephalitis
• Migratory arthralgias in 60% of untreated patients
• Conjunctivitis in 10% of untreated patients
• Regional or generalized lymphadenopathy

Borrelial Lymphocytoma

• Painless bluish-red nodule, usually on the ear, nipple, or scrotum
• More common in adults

Ocular Manifestations

• Conjunctivitis, uveitis, papillitis, episcleritis, keratitis

Coinfections

• Can have thrombocytopenia and anemia if coinfected with Anaplasma or Babesia

Post-Lyme Disease Syndrome

• Subjective symptoms that persist following treatment, without objective clinical findings of infection

Differential Diagnosis

Erythema Migrans

• Tick or insect bite hypersensitivity reaction
• Cellulitis, erysipelas
• Erythema multiforme
• STARI
• Tinea
• Nummular eczema
• Granuloma annulare
• Contact dermatitis
• Urticaria
• Fixed drug eruption
• Pityriasis rosea
• Parvovirus B19 (in children)

Borrelial Lymphocytoma

• Breast cancer
• B-cell lymphoma
• Pseudolymphoma

Lyme neuroborreliosis

• Other causes of facial nerve palsy
• Viral meningitis
• Mechanical radiculopathy
• First episode of relapsin-remitting multiple sclerosis
• Primary progressive multiple sclerosis

Lyme carditis

• Other causes of heart block or myopericarditis

Lyme arthritis

• Gout or pseudogout
• Septic arthritis
• Viral arthritis
• Psoriatic arthritis
• Juvenile oligoarthritis
• Reactive arthritis
• Sarcoidosis
• Early rheumatoid arthritis
• Seronegative spondyloarthropathies

Acrodermatitis Chronic Atrophicans

• Old age
• Chillblains
• Chronic venous insufficiency
• Superficial thrombophlebitis
• Hypostatic eczema
• Arterial obliterative disease
• Acrocyanosis
• Livedo reticularis
• Lymphoedema
• Erythromelalgia
• Scleroderma
• Rheumatoid nodules
• Gouty tophi
• Erythema nodosum

Diagnosis

• Treatment should be based on symptoms and compatible exposure history
  • If EM present, further testing is unhelpful outside of unusual cases
• Usually done by serology, with EIA followed by reflexive Western blot
  • EIA should be positive by 4 to 6 weeks; if negative, Lyme is unlikely
    • Usually positive around 2 weeks
    • False negatives common early in clinical course
    • False positives with HIV, hepatitis C, and syphilis
    • Cross-reacts with European Lyme
  • Western blot split into IgM and IgG if positive or equivocal
    • IgM 4 weeks, IgG 8 weeks
    • IgM is prone to over-interpretation and false positives
    • Does NOT cross-react with European Lyme (in Ontario)
  • Serology is most helpful when the pretest probability is >20%
• CSF antibodies is useful for neuroborreliosis, but persist years after treatment
• PCR may be helpful in cases where patients are from populations with high seroprevalence
  • Pretty good for joint, less sensitive for CSF

Lyme Serology

EIA	Western blot	Interpretation	Action
+	+	Early disseminated or late disease Previous exposure, treated or not	Treat if compatible symptoms and history
+	–	Early disease Early disease, treated European Lyme False-positive	If <8 weeks from exposure, repeat If >8 weeks, look for other cause Rule out HIV, hepatitis C, and syphilis Assess for autoimmune diseases Consider European Lyme
–	–	Very early Lyme <2 weeks Negative	Treat if erythema migrans

Management

• Doxycycline 100mg po BID x14 days
  • 7 to 21 days, depending on severity
• Alternative: amoxicillin 500mg po TID or cefuroxime 500mg po BID or azithromycin
• Parenteral antibiotics for CNS or cardiac disease

Further Reading

• Health Quality Ontario (2018). Management of Tick Bites and Investigation of Early Localized Lyme Disease.