Lyme disease

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Ixodes ticks acquire Borrelia from reservoir hosts and transmit organisms during feeding. Exposure occurs in woodland, heath, moorland, gardens and other vegetated habitats in the UK and abroad. Nymphs are small and bites are often unnoticed, so absence of a remembered tick does not exclude disease.

Local replication in skin produces erythema migrans. Haematogenous dissemination can seed the nervous system, heart, joints and additional skin sites. Host inflammation accounts for many manifestations; clinical pattern and timing are therefore more informative than a non-specific list of fatigue or pain.

There is no single diagnostic gold standard across every stage. Erythema migrans is diagnosed clinically, while later suspected disease uses two-tier antibody testing interpreted against pre-test probability. Serology may be negative early and remains positive for years, so it cannot distinguish active from previously treated infection by itself.

Treatment is selected by the involved organ, not by antibody titre. Persistent non-specific symptoms after adequate therapy require a careful search for organ damage, reinfection, treatment complications and alternative diagnoses; repeated or prolonged antibiotics are not offered without evidence of active infection.

Key points

Lyme borreliosis is caused by Borrelia burgdorferi sensu lato transmitted by infected Ixodes ticks; risk rises with attachment duration but a recalled bite is not required.
Erythema migrans is an expanding erythematous lesion, usually appearing one to four weeks after a bite; it is not usually hot, painful or itchy and may lack textbook central clearing.
Diagnose erythema migrans clinically and treat without laboratory testing because early serology can be negative.
Without erythema migrans, first-line testing is a validated Lyme antibody ELISA followed by immunoblot when the ELISA is positive or equivocal.
If an ELISA is negative within four weeks of symptom onset but suspicion remains, repeat it four to six weeks after the first sample.
Early disseminated disease includes multiple erythema migrans lesions, cranial neuropathy, painful radiculopathy, lymphocytic meningitis and carditis.
Late manifestations include intermittent large-joint arthritis, acrodermatitis chronica atrophicans and uncommon neurological syndromes; antibodies can remain positive after cure.
First-line adult treatment for erythema migrans or non-focal symptoms is doxycycline 100 mg twice daily or 200 mg once daily for 21 days.
Unstable Lyme carditis requires monitored admission and ceftriaxone 2 g intravenously once daily for 21 days, switching to oral doxycycline when clinically appropriate.
Do not give routine antibiotic prophylaxis to an asymptomatic person after a tick bite in the UK; remove the tick promptly and explain symptoms that require review.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Borrelia complex

Lyme borreliosis is caused by several Borrelia burgdorferi sensu lato genospecies, with differing tendencies towards neurological, skin or joint disease.

Ixodes tick vector

Hard-bodied Ixodes ticks transmit spirochaetes while feeding; small nymphs cause many infections because they can remain unnoticed.

Reservoir ecology

Small mammals and birds maintain Borrelia, while deer support adult tick populations but are not the principal reservoir for infection.

Environmental exposure

Woodland, heath, moorland, grass and gardens can support infected ticks; outdoor occupation and recreation increase contact risk.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Cutaneous inoculation
Tick saliva facilitates local spirochaetal survival and outward migration through skin, producing the expanding erythema migrans lesion.
2
Haematogenous dissemination
Organisms enter blood and spread to additional skin sites, peripheral nerves, meninges, myocardium and synovial tissues.
3
Inflammatory injury
Innate and adaptive immune responses clear organisms but also produce radicular pain, meningitis, conduction disease and synovitis.
4
Antibody persistence
Long-lived humoral responses remain measurable after microbiological cure, preventing serology from functioning as an activity marker or test of cure.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Erythema migrans

A gradually expanding red or bluish-red patch develops days to weeks after exposure, often exceeding 5 cm and sometimes becoming annular.

Early systemic illness

Fever, malaise, headache, neck discomfort, myalgia and fatigue may accompany erythema migrans but are individually non-specific.

NeuroborreliosisRed flag

Facial palsy, painful radiculoneuritis, sensory symptoms or lymphocytic meningitis can appear weeks after infection and require objective localisation.

Lyme carditisRed flag

Fluctuating atrioventricular block causes dizziness, syncope, palpitations, chest discomfort or breathlessness; myocarditis and ventricular dysfunction are less common.

Lyme arthritis

Recurrent or persistent swelling of one or a few large joints, especially the knee, may be striking despite limited systemic illness.

Late skin disease

Acrodermatitis chronica atrophicans causes chronic bluish-red swelling followed by thin atrophic skin, usually on an extensor limb.

Red flags requiring action

Syncope, presyncope, chest pain, dyspnoea or palpitations with PR prolongation or atrioventricular block may be Lyme carditis and can deteriorate rapidly.
Facial palsy with meningism, radicular pain, objective weakness, bladder dysfunction, encephalopathy or focal deficit requires an urgent neurological pathway.
A hot swollen joint still requires septic-arthritis assessment; Lyme arthritis cannot be assumed from exposure or a positive antibody result alone.
Pregnancy does not justify delayed treatment; choose a pregnancy-compatible regimen with obstetric and infection advice when disease is disseminated.
Immunocompromise, diagnostic uncertainty or progression despite an appropriate first course warrants specialist review and reconsideration of alternatives.
Erythema migrans is a clinical diagnosis and should be treated promptly even when serology is negative or has not been sent.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Clinical diagnosis of erythema migransFirst step
Why
Recognise the manifestation that does not require laboratory confirmation.
Interpretation and limitations
An expanding compatible lesion with plausible exposure is sufficient to treat; photograph and measure it, but do not delay for serology or biopsy.
02
First-line Lyme antibody ELISAFirst line
Why
Screen a symptomatic person without erythema migrans when Lyme disease is clinically plausible.
Interpretation and limitations
A negative early test does not exclude infection; a positive or equivocal result requires confirmatory immunoblot rather than diagnosis from ELISA alone.
03
Confirmatory immunoblotConfirmatory
Why
Improve specificity after a positive or equivocal screening ELISA.
Interpretation and limitations
Interpret IgM and IgG patterns with symptom duration and syndrome; a positive result documents exposure but cannot prove that current non-specific symptoms are caused by Lyme disease.
04
Repeat serology
Why
Detect evolving antibodies when an initial sample was taken early.
Interpretation and limitations
When the initial ELISA was negative within four weeks of symptom onset and suspicion persists, repeat four to six weeks after the first sample.
05
ECG and cardiac assessment
Why
Detect conduction disease, myocarditis and haemodynamic consequences in suspected carditis.
Interpretation and limitations
Measure PR interval and rhythm, add troponin, electrolytes and echocardiography as indicated; syncope or significant block requires telemetry and urgent cardiology review.
06
CSF analysis for suspected central neuroborreliosis
Why
Identify meningeal inflammation and support intrathecal Borrelia antibody assessment after specialist review.
Interpretation and limitations
Send paired CSF and serum when advised; lymphocytic pleocytosis supports active CNS disease, while an isolated serum antibody result does not localise infection.
07
Joint aspiration
Why
Exclude septic arthritis and crystal disease in an acutely swollen joint.
Interpretation and limitations
Send cell count, Gram stain, culture and crystal analysis; blood serology supports Lyme arthritis, while synovial PCR is reserved for specialist diagnostic problems.
08
Alternative-diagnosis testing
Why
Avoid attributing common symptoms to an incidental positive antibody result.
Interpretation and limitations
Select FBC, inflammatory markers, renal and liver profiles, thyroid testing, autoimmunity, imaging or other infection tests from the actual presentation.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Tick-bite reaction

A small itchy erythematous area appears soon after attachment and resolves within days rather than progressively expanding.

Cellulitis or tinea

Cellulitis is typically hot, tender and rapidly inflammatory, while tinea has scale and a slower superficial annular edge.

Alternative neurological disease

Bell palsy, viral meningitis, Guillain–Barré syndrome, multiple sclerosis and compressive radiculopathy require syndrome-specific neurological assessment and appropriate imaging or sampling.

Alternative arthritis

Septic arthritis, crystal disease, reactive arthritis and inflammatory arthropathy can all produce a swollen large joint.

Other causes of heart block

Ischaemia, medicines, electrolyte disturbance, infiltrative disease and idiopathic conduction degeneration remain important, particularly without exposure evidence.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ERYTHEMA MIGRANSDiagnose and treat clinicallyFirst stepA typical expanding lesion follows plausible tick exposure, with or without constitutional symptoms.

1Document lesion size, appearance, onset and exposure; distinguish it from a small immediate hypersensitivity reaction that appears and resolves quickly after a bite.
2Do not request serology routinely because antibodies may be absent and the result does not alter treatment of a typical lesion.
3First lineGive first-line doxycycline 100 mg orally twice daily or 200 mg once daily for 21 days when suitable.
4AlternativeUse amoxicillin 1 g orally three times daily for 21 days when doxycycline is unsuitable; azithromycin 500 mg daily for 17 days is a second alternative after interaction and cardiac review.

02NO RASHUse two-tier serologyCompatible objective features are present without diagnostic erythema migrans.

1Estimate pre-test probability from tick habitat, season, geography, timing and objective neurological, cardiac, joint or skin signs rather than fatigue alone.
2Request ELISA first, followed by immunoblot for a positive or equivocal result; use a laboratory participating in external quality assurance.
3Repeat a negative early ELISA four to six weeks after the first sample when symptoms began within four weeks and suspicion remains.
4AlternativeRefer to a specialist when serology and clinical findings conflict, symptoms are focal or severe, or an alternative diagnosis remains likely.

03FOCAL DISEASEMatch treatment to organ involvementNeurological, cardiac, joint or late cutaneous Lyme disease is suspected or confirmed.

1For cranial-nerve or peripheral nervous-system disease, use doxycycline 100 mg twice daily or 200 mg once daily for 21 days when oral treatment is appropriate.
2For central nervous-system disease, give ceftriaxone 2 g intravenously twice daily or 4 g once daily for 21 days, switching to oral doxycycline when clinically appropriate.
3AlternativeFor arthritis or acrodermatitis chronica atrophicans, give doxycycline 100 mg twice daily or 200 mg once daily for 28 days; amoxicillin is the first alternative.
4For unstable carditis, admit with monitoring and give ceftriaxone 2 g intravenously once daily for 21 days, switching to oral doxycycline when stable.

04FOLLOW-UPAssess response without unnecessary retreatmentSymptoms persist or recur after a recommended course.

1Confirm the original syndrome, adherence, dose and duration, then examine for continuing objective inflammation, conduction disease or neurological deficit.
2Consider reinfection, irreversible tissue injury, Jarisch–Herxheimer symptoms, medicine adverse effects and unrelated diagnoses before labelling treatment failure.
3Seek specialist advice before a second course; do not use serological titres as a test of cure because antibodies often remain detectable.
4Do not offer repeated or prolonged antibiotic treatment for persistent non-specific symptoms without evidence of active infection.

05PREVENTReduce tick exposureA person lives in, works in or visits tick habitat.

1Use long clothing, suitable repellent and pale fabric, keep to paths where practical, and inspect skin and clothing after outdoor exposure.
2Remove an attached tick promptly with fine-tipped tweezers or a tick tool, grasping close to the skin and pulling steadily without crushing the body.
3Clean the bite and explain erythema migrans and systemic symptoms that should prompt review over the following weeks.
4Do not offer routine antibiotic prophylaxis to an asymptomatic person after a tick bite in UK practice.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

First-line oral treatment for most adult Lyme manifestations when pregnancy, age and tolerability allow.

Doxycycline

Give 100 mg orally twice daily or 200 mg once daily for 21 days for erythema migrans, non-focal symptoms, cranial or peripheral neurological disease and stable carditis; use 28 days for arthritis or acrodermatitis.

Avoid routinely in pregnancy and children under 12 years, separate from antacids and mineral supplements, counsel on oesophagitis and photosensitivity, and check whether severe CNS disease requires higher-dose specialist therapy.

First alternative when doxycycline is unsuitable and oral beta-lactam treatment matches the manifestation.

Amoxicillin

Give 1 g orally three times daily for 21 days for erythema migrans or non-focal disease, and for 28 days for arthritis or acrodermatitis when selected.

Check immediate penicillin allergy, renal function and rash history; oral amoxicillin is not the recommended substitute for unstable carditis or central nervous-system disease.

First-line parenteral treatment for unstable carditis and central nervous-system Lyme disease, with oral switch when clinically appropriate.

Ceftriaxone

Give 2 g intravenously once daily for 21 days for unstable Lyme carditis; for central nervous-system disease NICE specifies 2 g twice daily or 4 g once daily for 21 days.

Confirm beta-lactam allergy, review biliary and renal-hepatic risk, arrange intravenous access safely and reassess daily for oral switch rather than prolonging parenteral therapy automatically.

Limited alternative oral regimen rather than first-line therapy.

Azithromycin

Give 500 mg orally once daily for 17 days only as a second alternative for erythema migrans or non-focal disease when doxycycline and amoxicillin are unsuitable.

Do not use for Lyme disease with cardiac abnormalities because of pro-arrhythmic risk; check QT prolongation, interactions, liver function and specialist advice.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

High-grade heart block

Inflammation of conduction tissue can progress rapidly from PR prolongation to complete atrioventricular block, syncope and temporary pacing.

Neuroborreliosis

Meningitis, cranial neuropathy and painful radiculopathy may leave prolonged pain, weakness or sensory dysfunction despite microbiological treatment.

Lyme arthritis

Large-joint synovitis may recur, and a minority have persistent post-infectious inflammation requiring rheumatology rather than indefinite antibiotics.

Acrodermatitis chronica atrophicans

Untreated late cutaneous infection causes progressive inflammation and skin atrophy, sometimes accompanied by persistent pain, sensory change or peripheral neuropathy.

Persistent symptoms

Fatigue, pain and cognitive complaints can continue after treatment, requiring rehabilitation and alternative-diagnosis assessment without assuming viable organisms.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review skin expansion, fever and systemic symptoms after starting treatment; an early Jarisch–Herxheimer reaction is usually self-limiting but must be distinguished from allergy or deterioration.
Use continuous ECG monitoring for unstable carditis and repeat ECGs until atrioventricular conduction is reliably improving; temporary pacing may be required after cardiology assessment.
For neuroborreliosis, record cranial-nerve, motor, sensory, reflex, pain, gait and bladder findings so objective recovery can be separated from residual fatigue.
Reassess joint swelling and function after a 28-day course, aspirating again when septic arthritis remains possible and seeking specialist advice before retreatment.
Do not repeat serology to demonstrate cure; falling or persistent antibody titres do not reliably track viable infection.
Check doxycycline, amoxicillin, ceftriaxone or azithromycin adverse effects, interactions and adherence according to the chosen regimen.
Provide a clear safety net for syncope, breathlessness, progressive weakness, meningism, a new swollen joint or a recurrent expanding rash.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The rash need not be a bullseye

Erythema migrans is defined by expansion and context; uniform, irregular and bruise-like lesions occur and central clearing is not required.

Treat the patient, not the titre

Antibodies can persist long after resolved infection, so a positive test supports exposure only when the clinical syndrome is compatible.

Early tests can be negative

The antibody response may not yet be detectable during erythema migrans or early disseminated infection, making timing essential.

Cardiac block can fluctuate

Atrioventricular conduction may change over hours, which is why symptomatic or advanced block requires monitored admission rather than one reassuring ECG.

A tick bite is not a diagnosis

Many bites are uninfected and many symptoms are common; objective manifestations and appropriate testing prevent overdiagnosis.

Scope boundary

Lyme-specific recognition, testing and treatment are covered here; generic facial palsy, meningitis, arrhythmia and monoarthritis pathways still apply in parallel.

11Common pitfallsFrequent interpretation and management errors.

01
Do not dismiss erythema migrans because it lacks central clearing or because no tick bite was remembered.
02
Do not delay treatment of a typical erythema migrans lesion for an antibody result that may be negative early.
03
Do not diagnose active Lyme disease from a positive screening ELISA without confirmatory testing and a compatible syndrome.
04
Do not use a positive antibody result to explain every chronic non-specific symptom without evaluating alternative causes.
05
Do not give routine post-bite antibiotics to an asymptomatic person in UK practice.
06
Do not manage syncope or advanced atrioventricular block as routine outpatient Lyme disease.
07
Do not repeat or prolong antibiotics solely because antibodies remain positive after an adequate course.