Borrelia burgdorferi
From IDWiki
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
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%
- EIA should be positive by 4 to 6 weeks; if negative, Lyme is unlikely
- 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
- 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clin Infect Dis. 2020. doi: 10.1093/cid/ciaa1215
- Health Quality Ontario (2018). Management of Tick Bites and Investigation of Early Localized Lyme Disease.