Borrelia burgdorferi: Difference between revisions
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Borrelia burgdorferi
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− | == |
+ | ==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 |
||
+ | *Transmitted by ''[[Ixodes scapularis]]'' (deer or black-legged tick), or ''[[Ixodes pacificus]]'' in the Pacific US |
||
− | === Europe === |
||
+ | *Reservoirs include deer and small mammals such as rodents |
||
− | * Three species of ''[[Borrelia]]'' exist in Europe |
||
+ | *Lyme species are different outside of North America |
||
− | ** ''B. burgdorferi'' |
||
− | ** ''B. afzelii'' |
||
− | ** ''B. garinii'' |
||
− | * The species have cross-reactivity with Lyme serology |
||
− | == |
+ | ====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=== |
||
[[File:lifecycle.jpg|tick lifecycle]] |
[[File:lifecycle.jpg|tick lifecycle]] |
||
− | == |
+ | ===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 |
||
− | ** If appears immediately and rapidly, think about local irritation and allergy, rather than Lyme |
||
+ | **Spreads over days |
||
− | ** Can present atypically, without target appearance, with ulceration, or with vesicles |
||
+ | **Can present atypically, without target appearance, with ulceration, or with vesicles |
||
− | ** Spreads 2-3 days daily |
||
+ | **If appears immediately and rapidly; need to consider local irritation and allergy, rather than Lyme |
||
− | * Fever, fatigue, malaise, lethargy |
||
+ | *Fever, fatigue, malaise, lethargy |
||
− | * Mild headache and neck stiffness |
||
− | * |
+ | *Mild headache and neck stiffness |
+ | *Myalgias and arthralgias |
||
− | * May have mildly elevated liver enzymes |
||
+ | *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 |
||
− | * Multiple rashes |
||
+ | **[[Carditis]] with [[heart block]] |
||
− | * Cranial nerve palsies, lymphocytic meningitis, conjunctivitis, arthralgia, myalgia, headache, fatigue, carditis (heart block) |
||
+ | **Secondary skin lesions |
||
+ | **[[Conjunctivitis]] |
||
− | === |
+ | ===Neuroborreliosis=== |
+ | *Refers specifically to the neurological manifestations of early disseminated Lyme disease |
||
− | * Meningo-radiculitis, meningitis, and peripheral facial palsy |
||
+ | *More common with [[Borrelia garinii]] |
||
− | * CSF shows lymphocytic pleocytosis, slightly elevated protein, and normal glucose |
||
+ | *[[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 artophicans=== |
− | * |
+ | *Chronic red or bluish-red leions, usually on the extensor surgaces |
− | * |
+ | *Initially doughy, eventually atrophic |
− | * |
+ | *Can occur up to 8 years after infection |
− | === |
+ | ===Late neuroborereliosis=== |
− | * |
+ | *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 |
− | === |
+ | ===Coinfection=== |
+ | |||
+ | *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]] |
||
− | * Can have thrombocytopenia and anemia if coinfected with ''Anaplasma'' or ''Babesia'' |
||
+ | * [[Septic arthritis]] |
||
+ | * [[Viral arthritis]] |
||
+ | * [[Psoriatic arthritis]] |
||
+ | * [[Juvenile oligoarthritis]] |
||
+ | * [[Reactive arthritis]] |
||
+ | * [[Sarcoidosis]] |
||
+ | * Early [[rheumatoid arthritis]] |
||
+ | * [[Seronegative spondyloarthropathies]] |
||
− | === |
+ | === Acrodermatitis Chronic Atrophicans === |
+ | * Old age |
||
− | * Subjective symptoms that persist following treatment, without objective clinical findings of infection |
||
+ | * 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=== |
{| class="wikitable" |
{| class="wikitable" |
||
− | ! |
+ | !EIA |
− | ! |
+ | !Western blot |
− | ! |
+ | !Interpretation |
− | ! |
+ | !Action |
|- |
|- |
||
| + |
| + |
||
| + |
| + |
||
− | | |
+ | |Early disseminated or late disease<br />Previous exposure, treated or not |
− | | |
+ | |Treat if compatible symptoms and history |
|- |
|- |
||
| + |
| + |
||
− | | |
+ | |– |
− | | |
+ | |Early disease<br />Early disease, treated<br />European Lyme<br />False-positive |
− | | |
+ | |If <8 weeks from exposure, repeat<br />If >8 weeks, look for other cause<br />Rule out HIV, hepatitis C, and syphilis<br />Assess for autoimmune diseases<br />Consider European Lyme |
|- |
|- |
||
− | | |
+ | |– |
− | | |
+ | |– |
− | | |
+ | |Very early Lyme <2 weeks<br />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). [https://www.hqontario.ca/Evidence-to-Improve-Care/Evidence-and-Health-Quality-Ontario/Guidance-Documents Management of Tick Bites and Investigation of Early Localized Lyme Disease]. |
{{DISPLAYTITLE:''Borrelia burgdorferi''}} |
{{DISPLAYTITLE:''Borrelia burgdorferi''}} |
Revision as of 13:51, 17 August 2020
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 artophicans
- Chronic red or bluish-red leions, usually on the extensor surgaces
- Initially doughy, eventually atrophic
- Can occur up to 8 years after infection
Late neuroborereliosis
- 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
Coinfection
- 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
- Health Quality Ontario (2018). Management of Tick Bites and Investigation of Early Localized Lyme Disease.