Borrelia burgdorferi: Difference between revisions
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Borrelia burgdorferi
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+ | ==Background== |
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− | = Lyme disease (''Borrelia burgdorferi'') = |
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+ | === Microbiology === |
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− | = Epidemiology = |
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+ | * Spirochete |
||
− | * Transmitted by ''Ixodes scapularis'' (deer or black-legged tick), or ''I. pacificus'' in the Pacific US |
||
+ | * Lyme disease can also be caused by [[Borrelia mayonii]] |
||
− | * Reservoirs include deer and small mammals such as rodents |
||
− | * Lyme species are different outside of North America |
||
+ | ===Epidemiology=== |
||
− | ![Map of Lyme disease in Ontario 2018](Ontario Lyme map 2018.png) |
||
+ | *Most cases occur during June and July, when nymphal ticks are most active and people are outdoors |
||
− | [[File:image-20190117091839996.png|image-20190117091839996]] |
||
+ | *Infection is possible year-round, though, with ticks being active any time temperatures are above freezing |
||
− | == |
+ | ====North America==== |
+ | *Transmitted by ''[[Ixodes scapularis]]'' (deer or black-legged tick), or ''[[Ixodes pacificus]]'' in the Pacific US |
||
− | * Three species of ''Borrelia'' exist in Europe, including ''B. burgdorferi'', though the species have cross-reactivity with Lyme serology |
||
+ | *Reservoirs include deer and small mammals such as rodents |
||
− | ** ''B. afzelii'' and ''B. garinii'' |
||
+ | *Lyme species are different outside of North America |
||
+ | ====Europe==== |
||
− | = Life Cycle = |
||
+ | |||
+ | *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 hindgut to mouth over ~36 hours, then gets regurgitated into the wound |
+ | **May take as little as 24 hours |
||
− | * Local multiplication followed by dissemination |
||
+ | *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) |
+ | *Requires minimum of 24 hours of tick attachment, but typically takes 36 hours or longer |
||
− | == |
+ | ===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 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=== |
+ | *''[[Anaplasma]]'' or ''[[Babesia]]'' may be transmitted by the same ticks in areas of endemicity |
||
− | * Can have thrombocytopenia and anemia if coinfected with ''Anaplasma'' or ''Babesia'' |
||
+ | *Can have [[thrombocytopenia]], [[leukopenia]], [[neutropenia]], and [[anemia]] |
||
+ | **Hemolytic anemia is highly suggestive of [[Babesia microti]] |
||
+ | *Other signs include fever lasting more than one day after start of antibiotics, especially for [[Babesia microti]] |
||
− | == |
+ | ===Post-Lyme Disease Syndrome=== |
− | * |
+ | *Subjective symptoms that persist following treatment, without objective clinical findings of infection |
− | = Diagnosis |
+ | ==Differential Diagnosis== |
+ | ===Erythema Migrans=== |
||
− | * 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 |
||
+ | *Tick or insect bite hypersensitivity reaction |
||
− | == Lyme Serology == |
||
+ | *[[Cellulitis]], [[erysipelas]] |
||
+ | *[[Erythema multiforme]] |
||
+ | *[[STARI]] |
||
+ | *[[Tinea]] |
||
+ | *[[Nummular eczema]] |
||
+ | *[[Granuloma annulare]] |
||
+ | *[[Contact dermatitis]] |
||
+ | *[[Urticaria]] |
||
+ | *[[Fixed drug eruption]] |
||
+ | *[[Pityriasis rosea]] |
||
+ | *[[Parvovirus B19]] (in children) |
||
+ | ===Borrelial Lymphocytoma=== |
||
− | {| |
||
+ | |||
− | ! EIA |
||
+ | *[[Breast cancer]] |
||
− | ! Western blot |
||
+ | *[[B-cell lymphoma]] |
||
− | ! Interpretation |
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+ | *[[Pseudolymphoma]] |
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− | ! Action |
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+ | |||
+ | ===Lyme Neuroborreliosis=== |
||
+ | |||
+ | *Other causes of [[facial nerve palsy]] |
||
+ | *[[Viral meningitis]] |
||
+ | *[[Mechanical radiculopathy]] |
||
+ | *First episode of relapsin-remitting [[multiple sclerosis]] |
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+ | *Primary progressive [[multiple sclerosis]] |
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+ | |||
+ | ===Lyme Carditis=== |
||
+ | |||
+ | *Other causes of [[heart block]] or [[myopericarditis]] |
||
+ | |||
+ | ===Lyme Arthritis=== |
||
+ | |||
+ | *[[Gout]] or [[pseudogout]] |
||
+ | *[[Septic arthritis]] |
||
+ | *[[Viral arthritis]] |
||
+ | *[[Psoriatic arthritis]] |
||
+ | *[[Juvenile oligoarthritis]] |
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+ | *[[Reactive arthritis]] |
||
+ | *[[Sarcoidosis]] |
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+ | *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 erythema migrans is present, further testing is unhelpful outside of unusual cases and is not routinely recommended |
||
+ | *The most commonly used test is serology from blood, with EIA followed by reflexive Western blot |
||
+ | *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=== |
||
+ | |||
+ | * Typically done as a screening EIA followed by reflexive Western blot |
||
+ | ** In Ontario, the screening test is Borrelia Vls1/pepC10 IgM/IgG ELISA |
||
+ | ** The Western blot is done for IgM and IgG |
||
+ | * 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 |
||
+ | ***False positives with [[spirochetes]] ([[syphilis]]), viruses ([[cytomegalovirus]], [[Epstein-Barr virus]], [[hepatitis B virus]], [[hepatitis C virus]], and [[parvovirus B19]]), and bacteria |
||
+ | **Does NOT cross-react with European Lyme (in Ontario) |
||
+ | *Serology is most helpful when the pretest probability is >20% |
||
+ | |||
+ | {| 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]] |
|} |
|} |
||
+ | * Health Canada now recommends a modified two-tier EIA with combined IgM/IgG, with the screening EIA done with whole-cell lysate and the confirmatory EIA done with a recombinant protein |
||
− | = Management = |
||
+ | ** This approach has increased sensitivity at all stages (50-60% for early Lyme, around 100% for late Lyme including Lyme arthritis), and maintains |
||
+ | ** If you get a negative result when there is high pre-test probability for early Lyme, then submit a follow-up serology 3 to 6 weeks later |
||
+ | |||
+ | {| class="wikitable" |
||
+ | !EIA 1 |
||
+ | !EIA 2 |
||
+ | !Interpretation |
||
+ | |- |
||
+ | |– |
||
+ | |N/A |
||
+ | |Negative; consider alternative diagnosis or resubmit in 3-6 weeks if compatible with early Lyme |
||
+ | |- |
||
+ | | +/± |
||
+ | | +/± |
||
+ | |Positive; treat based on clinical syndrome, if appropriate |
||
+ | |- |
||
+ | | +/± |
||
+ | |– |
||
+ | |Negative; consider alternative diagnosis or resubmit in 3-6 weeks if compatible with early Lyme |
||
+ | |} |
||
+ | |||
+ | ==Management== |
||
+ | |||
+ | ===Erythema Migrans=== |
||
+ | |||
+ | *[[Doxycycline]] 100 mg PO bid for 10 days |
||
+ | *Second-line: [[amoxicillin]] 500 mg PO tid for 14 days, [[cefuroxime]] 500 mg PO bid for 14 days |
||
+ | *Third-line: [[azithromycin]] for 7 days |
||
+ | |||
+ | ===Neurological Lyme Disease=== |
||
+ | |||
+ | *Any of the following: [[ceftriaxone]] IV, [[cefotaxime]] IV, [[penicillin G]] IV, [[doxycycline]] PO |
||
+ | *Duration of 14 to 21 days |
||
+ | *If there is parenchymal involvement, which is rare and usually based on MRI |
||
+ | **If present, prefer IV antibiotics and a 2 to 4 week course |
||
+ | *In cases of facial nerve palsy, they may also receive [[corticosteroids]] within 72 hours |
||
+ | |||
+ | ===Lyme Carditis=== |
||
+ | |||
+ | *See [[Lyme carditis#Management|Lyme carditis]] |
||
+ | |||
+ | ===Lyme Arthritis=== |
||
+ | |||
+ | *Oral antibiotics for 28 days |
||
+ | *If no response to oral antibiotics, can consider a course of [[ceftriaxone]] IV for 2 to 4 weeks |
||
+ | |||
+ | ===Post-Antibiotic Lyme Arthritis=== |
||
+ | |||
+ | *Refer to rheumatologist for consideration of DMARDs, biologics, intraarticular steroid injections, or arthroscopic synovectomy |
||
+ | |||
+ | ===Borrelial Lymphocytoma=== |
||
+ | |||
+ | *Oral antibiotics for 14 days |
||
+ | |||
+ | ===Acrodermatitis Chronica Atrophicans=== |
||
+ | |||
+ | *Oral antibiotics for 21 to 28 days |
||
+ | |||
+ | ==Prevention== |
||
+ | |||
+ | *Routine personal protective measures to reduce tick exposure |
||
+ | *DEET, picaridin, IR3535, oil of lemon eucalyptus, PMD, 2-undecanone, or permethrin |
||
+ | *Remove ticks with clean fine-tipped tweezer inserted between the tick body and the skin |
||
+ | **Do not cover, spray, or burn the tick |
||
+ | **See [[tick removal]] for more information |
||
+ | |||
+ | ===Prophylaxis=== |
||
+ | *Can be considered in children and adults within 72 hours of tick removal if all of the following criteria are met: |
||
− | * Doxycycline 100mg po BID x14 days |
||
+ | **[[Ixodes]] tick is identified |
||
− | ** 7 to 21 days, depending on severity |
||
+ | ***Small, tear-drop shaped |
||
− | * Alternative: amoxicillin 500mg po TID or cefuroxime 500mg po BID or azithromycin |
||
+ | ***Plain oval shield |
||
− | * Parenteral antibiotics for CNS or cardiac disease |
||
+ | ***Lack of festoons |
||
+ | **Occurs in a highly endemic area |
||
+ | **Tick was attached for ≥36 hours |
||
+ | ***You can get a sense by asking if the tick was flat or engorged |
||
+ | ***If definitely flat, almost certainly attached less than 36 hours |
||
+ | ***However, still looks flat at 24 hours |
||
+ | *Use a single oral dose of [[doxycycline]] 4.4 mg/kg (max 200 mg) for children or 200 mg for adults |
||
− | = |
+ | ==Further Reading== |
+ | *2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. ''Clin Infect Dis''. 2020. doi: [https://doi.org/10.1093/cid/ciaa1215 10.1093/cid/ciaa1215] |
||
− | * 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]. |
||
+ | *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''}} |
||
[[Category:Borrelioses]] |
[[Category:Borrelioses]] |
Revision as of 12:01, 29 May 2024
Background
Microbiology
- Spirochete
- Lyme disease can also be caused by Borrelia mayonii
Epidemiology
- Most cases occur during June and July, when nymphal ticks are most active and people are outdoors
- Infection is possible year-round, though, with ticks being active any time temperatures are above freezing
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 hindgut to mouth over ~36 hours, then gets regurgitated into the wound
- May take as little as 24 hours
- 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)
- Requires minimum of 24 hours of tick attachment, but typically takes 36 hours or longer
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
- Anaplasma or Babesia may be transmitted by the same ticks in areas of endemicity
- Can have thrombocytopenia, leukopenia, neutropenia, and anemia
- Hemolytic anemia is highly suggestive of Babesia microti
- Other signs include fever lasting more than one day after start of antibiotics, especially for Babesia microti
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 erythema migrans is present, further testing is unhelpful outside of unusual cases and is not routinely recommended
- The most commonly used test is serology from blood, with EIA followed by reflexive Western blot
- 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
- Typically done as a screening EIA followed by reflexive Western blot
- In Ontario, the screening test is Borrelia Vls1/pepC10 IgM/IgG ELISA
- The Western blot is done for IgM and IgG
- 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
- False positives with spirochetes (syphilis), viruses (cytomegalovirus, Epstein-Barr virus, hepatitis B virus, hepatitis C virus, and parvovirus B19), and bacteria
- Does NOT cross-react with European Lyme (in Ontario)
- Serology is most helpful when the pretest probability is >20%
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 |
- Health Canada now recommends a modified two-tier EIA with combined IgM/IgG, with the screening EIA done with whole-cell lysate and the confirmatory EIA done with a recombinant protein
- This approach has increased sensitivity at all stages (50-60% for early Lyme, around 100% for late Lyme including Lyme arthritis), and maintains
- If you get a negative result when there is high pre-test probability for early Lyme, then submit a follow-up serology 3 to 6 weeks later
EIA 1 | EIA 2 | Interpretation |
---|---|---|
– | N/A | Negative; consider alternative diagnosis or resubmit in 3-6 weeks if compatible with early Lyme |
+/± | +/± | Positive; treat based on clinical syndrome, if appropriate |
+/± | – | Negative; consider alternative diagnosis or resubmit in 3-6 weeks if compatible with early Lyme |
Management
Erythema Migrans
- Doxycycline 100 mg PO bid for 10 days
- Second-line: amoxicillin 500 mg PO tid for 14 days, cefuroxime 500 mg PO bid for 14 days
- Third-line: azithromycin for 7 days
Neurological Lyme Disease
- Any of the following: ceftriaxone IV, cefotaxime IV, penicillin G IV, doxycycline PO
- Duration of 14 to 21 days
- If there is parenchymal involvement, which is rare and usually based on MRI
- If present, prefer IV antibiotics and a 2 to 4 week course
- In cases of facial nerve palsy, they may also receive corticosteroids within 72 hours
Lyme Carditis
- See Lyme carditis
Lyme Arthritis
- Oral antibiotics for 28 days
- If no response to oral antibiotics, can consider a course of ceftriaxone IV for 2 to 4 weeks
Post-Antibiotic Lyme Arthritis
- Refer to rheumatologist for consideration of DMARDs, biologics, intraarticular steroid injections, or arthroscopic synovectomy
Borrelial Lymphocytoma
- Oral antibiotics for 14 days
Acrodermatitis Chronica Atrophicans
- Oral antibiotics for 21 to 28 days
Prevention
- Routine personal protective measures to reduce tick exposure
- DEET, picaridin, IR3535, oil of lemon eucalyptus, PMD, 2-undecanone, or permethrin
- Remove ticks with clean fine-tipped tweezer inserted between the tick body and the skin
- Do not cover, spray, or burn the tick
- See tick removal for more information
Prophylaxis
- Can be considered in children and adults within 72 hours of tick removal if all of the following criteria are met:
- Ixodes tick is identified
- Small, tear-drop shaped
- Plain oval shield
- Lack of festoons
- Occurs in a highly endemic area
- Tick was attached for ≥36 hours
- You can get a sense by asking if the tick was flat or engorged
- If definitely flat, almost certainly attached less than 36 hours
- However, still looks flat at 24 hours
- Ixodes tick is identified
- Use a single oral dose of doxycycline 4.4 mg/kg (max 200 mg) for children or 200 mg for adults
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.