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Lyme Disease

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Lyme disease\: tick-borne illness caused by B o r r e l i a species, common in Europe and USA; a
Europe, 275,000 in USA (2010-2019).
Transmission\: spread by I x o d e s ticks, requires attachment for >48 hours for infection.
Risk factors\: living in tick-dense regions, outdoor activities, tick attachment >48 hours.
Symptoms\: erythema migrans rash (80% of cases), fatigue, headache, fever, myalgia, arthralgia; cardiac, neurological, and
musculoskeletal manifestations in disseminated disease.
Diagnosis\: clinical diagnosis with erythema migrans; serology (EIA, Western blot) if rash absent or for disseminated disease.
Management\: oral doxycycline or amoxicillin for localised disease (21 days); IV ceftriaxone for severe cardiac or
neurological involvement.
Complications\: cardiac (AV block), neurological (meningitis, facial palsy), musculoskeletal (arthritis), Jarisch-Herxheimer
reaction.
Prevention\: tick-bite prevention, post-exposure prophylaxis with doxycycline in high-risk cases.
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A comprehensive topic overview

Introduction

Lyme disease, also known as Lyme borreliosis, is an infectious tick-borne illness common throughout Europe and the USA.
It is one of the most common vector-borne diseases worldwide.
1-2
Lyme disease a
cases of Lyme disease in Europe each year, and over 275,000 cases were reported in the USA between 2010-2019.
2-3
Lyme disease is caused by the B o r r e l i a b u r g d o r f e r i sensu lato complex, a group of pathogenic B o r r e l i a genospecies.
1-3

Aetiology

Causative organisms

Lyme disease in the USA is primarily caused by B o r r e l i a b u r g d o r f e r i (B . b u r g d o r f e r i ) and, less commonly, B o r r e l i a
m a y o n i i .
1-3
In Europe and Asia, Lyme disease is caused by B . b u r g d o r f e r i , B o r r e l i a a f z e l l i (B . a f z e l l i ) and B o r r e l i a g a r i n i i .
1-3
B o r r e l i a s p p are obligate,
4

Transmission

Lyme disease is spread via tick bites from various species of I x o d e s ticks.
2-4
I . s c a p u l a r i s and I . p a c i
2-3
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Ticks become infected with B . b u r g d o r f e r i by feeding on infected animals. Small animals, including mice, squirrels, and
birds, are common reservoirs of B . b u r g d o r f e r i .

Environmental factors

As Lyme disease is spread by ticks, it is prevalent in regions where I x o d e s ticks are common. High prevalence areas include
the north-eastern and mid-western states of the USA. In 2019, over 90% of cases occurred in 14 states with dense tick
populations.
2-3
Figure 1. Distribution of Lyme disease in the USA in 2011
While not natural reservoirs for B . b u r g d o r f e r i , deer are major hosts for I x o d e s ticks. Therefore, Lyme disease is also
frequently observed in regions with dense deer populations.
2-3
Additionally, the incidence of Lyme disease is increasing due to factors such as climate change enabling ticks to survive in
more environments, increasing deer populations, and increased human development in rural and wooded areas.
2-3

Pathophysiology

B . b u r g d o r f e r i is inoculated into the skin via tick saliva and establishes an acute infection by binding to epithelial and dermal
glycoproteins. This typically takes up to 48 hours. Once established, B . b u r g d o r f e r i rapidly multiplies and disseminates
locally through the extracellular matrix of the skin, causing a characteristic rash.
2, 5
After 48-72 hours, B . b u r g d o r f e r i begins to disseminate to distant sites, resulting in systemic manifestations of Lyme
disease. Within several weeks of inoculation, B . b u r g d o r f e r i may have spread to numerous sites including the blood,
central nervous system, myocardium, muscle and bones.
2
B . b u r g d o r f e r i is adept at evading host immune responses. IgM antibodies are generated against B . b u r g d o r f e r i surface
proteins within days of infection. However, the bacteria evade this humoral response by downregulating the expression of
key surface proteins, preventing antibody-mediated killing. Many strains of B . b u r g d o r f e r i also possess mechanisms which
inactivate neutrophil and macrophage recruitment and express proteins which inactivate complement enzymes.
2, 5

Risk factors

Risk factors for Lyme disease include\:
2, 6
Residence or travel in tick-dense regions
Outdoor activities (in woods or
Tick attachment > 48 hours (inoculation requires blood feeding duration > 48 hours)

Clinical features

The clinical presentation of Lyme disease varies considerably and can be broken down into local and disseminated stages.

Early localised disease

The most common feature of localised disease is erythema migrans (EM).
2, 7
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Figure 2. Erythema migrans rash
Erythema migrans
EM usually appears within 1-2 weeks of the tick bite and occurs in approximately 80% of cases. The lesion typically
expands over the course of several days-weeks and demonstrates central clearing, yielding the characteristic
bullseye appearance. 2, 6-7
However, not all erythema associated with tick bites represents EM.
The most common locations for EM rashes correlate with areas of the skin commonly exposed and prone to tick
bites, including the axillae, popliteal fossae, neck and belt line.
2, 7
Early disease may also manifest with constitutional symptoms that mimic a viral syndrome. Symptoms may include\:
2, 7
Fatigue
Headache
Low-grade fever
Arthralgia
Myalgia
Lymphadenopathy
Anorexia

Early disseminated disease

Early disseminated Lyme disease typically manifests within several weeks-months of inoculation. In the absence of EM, it
may be the
2, 7
As B . b u r g d o r f e r i is known to spread to several body sites, the potential manifestations of disseminated Lyme disease vary
considerably.
Systemic manifestations of disseminated Lyme include\:
2, 7
Cardiac\: atrioventricular (AV) block, myopericarditis, sudden cardiac death
Neurological\: aseptic meningitis, cranial nerve palsies (most commonly the facial nerve), radiculopathy, peripheral
neuropathy
Ocular\: conjunctivitis, uveitis, keratitis, choroiditis, optic neuropathy
Musculoskeletal\: arthritis, arthralgia, persistent synovitis
Cutaneous\: multiple discrete EM lesions (indicates spirochetaemia rather than multiple tick bites), borrelial
lymphocytoma
Figure 3. Borrelial lymphocytoma
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Borrelial lymphocytoma
Borrelial lymphocytoma is a rare cutaneous manifestation of Lyme disease, which predominantly a
presents as a painless blue-red swelling which most commonly arises on the earlobe, nipple or scrotal area. Most
cases resolve within several weeks following treatment.
2

Late disseminated disease

Late-stage Lyme disease can manifest from 6 months to several years post-inoculation.
2
The most common feature of late Lyme disease is arthritis, which may be chronic or intermittent and typically a
large joints, most commonly the knee.
7
While rare, late Lyme disease is also associated with neurological manifestations, which di
Possible presentations include mononeuritis multiplex, peripheral sensory neuropathy, encephalopathy and
encephalomyelitis.
2, 7
Acrodermatitis chronica atrophicans (ACA) is a cutaneous manifestation of late Lyme disease, which presents as blue-red
indurated lesions on sun-exposed skin of the extremities. ACA is strongly associated with B . a f z e l l i and a
cases in Europe.
2, 7

Di

Common di
2, 6
In
Tick allergy
Cellulitis/erysipelas
Viral exanthem
Erythema multiforme
Ringworm
Urticaria
Southern tick-associated rash illness
As disseminated Lyme disease can manifest with various systemic features, the potential di
numerous. To construct appropriate diexamination, and
considering risk factors are important.

Investigations

Serological measurements of Lyme-speci
2, 8-9
Other relevant investigations include\:
Enzyme immunoassay (EIA)
Immunoblot tests (e.g. Western blot)
Polymerase chain reaction tests\: less commonly available, only useful in select cases
Selection of further investigations should be guided by clinical presentation and may include\:
2, 9
ECG\: if cardiac involvement is suspected
CT or MRI head\: if neurological manifestations are present, to exclude other causes
X-rays\: if Lyme arthritis is present, to exclude other causes (e.g. fracture, gout, haemarthrosis)

Diagnosis

The approach to diagnosis depends on the stage of disease and whether an EM rash is present.
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Erythema migrans present

In patients with an EM rash and con
investigations, unless there is uncertainty.
2. 8-9

Erythema migrans absent

Laboratory testing is indicated in patients with con
speci
diagnosis.
The most commonly accepted method involves a two-step process involving an initial EIA followed by an immunoblot
test\:
2, 9
If the initial EIA is positive, a western blot assay should be obtained for con
If the initial EIA is negative, no further testing is required
In early disease testing may precede antibody response. Therefore, repeat serology after two weeks can be considered if
concerns persist.
9
In patients with previously treated Lyme disease, serological testing is less reliable as Lyme-speci
persist for several years. Specialist opinion should be obtained in such cases.
9

Management

Prevention

Currently, no vaccine is available for B . b u r g d o r f e r i . Therefore, preventative measures primarily aim to prevent tick-bites
and B . b u r g d o r f e r i inoculation.
When travelling through tick-dense regions, it is advisable to wear suitable clothing (e.g. long sleeves) to minimise
exposed skin and use tick-repellent products. It is equally important to check for attached ticks following activities in high-
risk environments and ensure any identi
10
Post-exposure prophylaxis
Post-exposure prophylaxis with oral doxycycline can be considered in high-risk cases (e.g. tick attachment > 36
hours, travel through endemic region) within 72 hours of the bite.
2, 10

Antibiotics

Antibiotics are the mainstay of treatment for Lyme disease.
Localised disease
For patients with EM and no features of disseminated Lyme disease, NICE recommends\:
2, 6, 8
Oral doxycycline 100 mg twice daily (BD), or
Oral amoxicillin 500 mg – 1 g three times daily
The recommended duration of treatment is 21 days.
2
In patients with suspected Lyme disease who do not have EM, it is reasonable to initiate oral antibiotics while awaiting
serological investigation results if there is su
2
Cardiac involvement
For patients with evidence of cardiac involvement who do not require hospitalisation and are not at risk of severe cardiac
complications, the recommended antibiotics are the same as for localised disease.
2
Those with signi
cardiac complications should be admitted to hospital for intravenous (IV) antibiotics and cardiac monitoring.
2
IV ceftriaxone 2 g once daily for 14-21 days is the preferred treatment regimen. Alternative options include benzylpenicillin
or cefotaxime.
2
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Neurological involvement
In patients with acute neurological manifestations con
for initial management. Options include IV ceftriaxone, cefotaxime or benzylpenicillin. However, oral doxycycline has been
demonstrated to have equal e
2
Patients with central nervous system or brain parenchymal involvement (e.g. encephalitis) must be treated with IV
antibiotics.
2
Musculoskeletal involvement
Patients with Lyme arthritis should be treated with oral antibiotics as per early localised disease and simple analgesics,
including non-steroidal anti-in
If symptoms persist or recur, treatment should be escalated to IV ceftriaxone. Failure to respond to antibiotics warrants a
rheumatology opinion.
Jarisch Herxheimer reaction
A Jarisch Herxheimer reaction (JHR) is an acute, transient reaction which may occur within 24 hours of initiating
antibiotic therapy for a spirochetal infection.
The mechanism of JHR is not fully understood. It is suspected to result from an acute in
release of spirochetal lipoproteins into the bloodstream after death of the organism.
11
JHR may manifest with\:
Fever
Rigors
Tachycardia
Hypotension
Nausea and vomiting
Headache
Flushing
JHR is usually self-limiting, however, it can result in profound hypotension requiring resuscitation.

Complications

Complications of Lyme disease include\:
2, 7, 11
Cardiac manifestations
Neurological manifestations
Musculoskeletal manifestations
Lymphocytoma borreliosis
Jarisch-Herxheimer reaction

References

StatPearls. Lyme disease. Published in 2024. Available from\: [LINK]
BMJ Best Practice. Lyme disease. Published in 2024. Available from\: [LINK]
UpToDate. Epidemiology of Lyme Disease. Published in 2023. Available from\: [LINK]
UpToDate. Microbiology of Lyme Disease. Published in 2023. Available from\: [LINK]
UpToDate. Immunopathogenesis of Lyme Disease. Published in 2024. Available from\: [LINK]
NICE CKS. Lyme disease. Published in 2024. Available from\: [LINK]
UpToDate. Clinical manifestations of Lyme disease in adults. Published in 2024. Available from\: [LINK]
NICE. Lyme disease. Published in 2018. Available from\: [LINK]
https\://app.geekymedics.com/notebook/2833/ 6/711/14/24, 10\:58 AM Lyme Disease
UpToDate. Diagnosis of Lyme Disease. Published in 2023. Available from\: [LINK]
UpToDate. Prevention of Lyme Disease. Published in 2023. Available from\: [LINK]
StatPearls. Jarisch-Herxheimer Reaction. Published in 2023. Available from\: [LINK]

Image references

Figure 1. National Institute of Standards and Technology. Lyme disease. Available from\: [LINK] License\: Public domain
Figure 2. Garrison H. Erythema migrans. Available from\: [LINK] License\: [CC BY-SA 2.5]
Figure 3. Gzzz. Borrelial lymphocytoma. Available from\: [LINK] License\: [CC BY-SA 4.0]

Reviewer

Dr Grant Rutledge
General Practitioner

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Contents

Introduction
Aetiology
Risk factors
Clinical features
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