Definition & Key Features

• What is Lyme disease? A bacterial infection caused by Borrelia species, transmitted to humans through the bite of an infected tick.
• Pathophysiology: Infection is established after a tick bite, with bacteria disseminating from the skin to other parts of the body. Most tick bites do not transmit Lyme disease; prompt and correct tick removal reduces transmission risk.
• Hallmark Features:
  • Erythema Migrans: The characteristic rash of Lyme disease. It is a red, expanding rash that may have central clearing.
    • Appears 1 to 4 weeks (can be 3 days to 3 months) after a bite.
    • Lasts for several weeks.
    • Usually located at the site of the tick bite.
    • Crucially, it is not typically itchy, hot, or painful. A reaction to a tick bite that appears and recedes within 48 hours and is hot, itchy, or painful is likely inflammatory and not erythema migrans.
• Typical Signs/Symptoms:
  • Non-focal: Fever, sweats, swollen glands, malaise, fatigue, neck pain/stiffness, migratory joint/muscle pain, headache, paraesthesia, and cognitive impairment (‘brain fog’).
  • Focal (Organ-specific):
    • Neurological: Facial palsy, other cranial nerve palsies, meningitis, mononeuritis multiplex, radiculopathy. Rarely, encephalitis or neuropsychiatric presentations.
    • Musculoskeletal: Inflammatory arthritis in one or more joints (may be fluctuating and migratory).
    • Cardiac: Heart block, pericarditis.
    • Ophthalmic: Uveitis, keratitis.
    • Dermatological: Acrodermatitis chronica atrophicans, lymphocytoma.
• Complications if Untreated: The focal symptoms listed above represent complications from disseminated disease. Symptoms may take months or years to resolve after treatment, and some organ damage (e.g., nerve palsy) may be permanent.
• Jarisch–Herxheimer Reaction: A reaction to antibiotic treatment, not an allergic reaction. It is caused by the release of cytokines as bacteria are killed.
  • Features: Worsening of fever, chills, muscle pains, and headache.
  • Timing: Typically starts within hours of the first dose and resolves within 24-48 hours.
  • Action: Does not usually warrant stopping antibiotic treatment.

Epidemiology & Risk Factors

• Prevalence: Infected ticks are found throughout the UK and Ireland. Prevalence data is incomplete, but some areas have a higher known prevalence.
• Geographical Risk:
  • UK High-Risk Areas: South of England and the Scottish Highlands are particularly high-risk. However, infection can occur in many areas, including urban gardens and parks.
  • International High-Risk Areas: Parts of central, eastern, and northern Europe (including Scandinavia), Asia, the US, and Canada.
• Risk Factors:
  • Modifiable: Activities in grassy and wooded areas (e.g., hiking, camping). Not covering exposed skin or using tick repellents. Delayed or incorrect tick removal. History of travel to endemic areas. A tick bite may not be noticed, so lack of a remembered bite does not exclude risk.

Clinical Presentation & Diagnosis

• Typical Presentations:
  • With Erythema Migrans: This rash is diagnostic. No laboratory testing is required.
  • Without Erythema Migrans: Consider Lyme disease if a patient presents with a combination of non-focal symptoms (fever, fatigue, aches) or with focal symptoms (e.g., facial palsy, arthritis, heart block).
• Red Flags (Indications for Urgent Referral/Action):
  • Follow usual clinical practice for emergency referral for symptoms suggesting:
    • Central Nervous System (CNS) Infection (e.g., meningitis).
    • Uveitis.
    • Cardiac Complications, such as complete heart block.
• Diagnostic Criteria & Investigations:
  • Erythema Migrans Present: Diagnose and treat without laboratory tests.
  • Erythema Migrans Absent: Use a two-tier testing strategy combined with clinical assessment.

• First Test: Offer an enzyme-linked immunosorbent assay (ELISA) for both IgM and IgG antibodies. Use ELISAs based on VlsE protein or its IR6 domain peptide (e.g., C6 ELISA).
  • Consider starting antibiotics while awaiting results if clinical suspicion is high.
• If ELISA is Negative:
  • And symptoms began <4 weeks ago: Repeat the ELISA 4 to 6 weeks after the first test if Lyme disease is still suspected.
  • And symptoms have persisted for ≥12 weeks: Perform an immunoblot test.
• If ELISA is Positive or Equivocal:
  • Perform a confirmatory immunoblot test.
  • Consider starting antibiotics while awaiting results if clinical suspicion is high.

• Diagnosis Confirmation: A positive immunoblot test in a person with symptoms confirms the diagnosis.
• Negative Immunoblot: If the immunoblot is negative but symptoms persist, consider alternative diagnoses and/or refer to a specialist (infection specialist, rheumatologist, neurologist).
• Important Cautions for Investigations:
  • Do not test asymptomatic individuals, even after a tick bite.
  • Tests may be falsely negative if performed too early (before antibody development) or in immunosuppressed patients.
  • Only use laboratories that are UKAS-accredited, use validated tests, and participate in an external quality assurance programme. Be cautious with tests performed outside the NHS or by non-accredited labs.

Initial Management

• Non-Pharmacological Measures & Patient Education:
  • Advise on tick bite prevention: cover skin, use repellents, check for ticks.
  • Teach correct tick removal technique.
  • Manage symptoms like headache or muscle pain with standard analgesia.
  • Explain that symptoms may take months to resolve after treatment.
  • Warn about the Jarisch-Herxheimer reaction (see above).
• First-Line Pharmacological Treatment:
  • Adults and Young People (≥12 years):
    • Erythema Migrans or Non-focal Symptoms:
      • Doxycycline 100 mg twice daily OR 200 mg once daily for 21 days.
    • Cranial Nerve or Peripheral Nervous System Involvement:
      • Doxycycline 100 mg twice daily OR 200 mg once daily for 21 days.
    • Lyme Arthritis or Acrodermatitis Chronica Atrophicans:
      • Doxycycline 100 mg twice daily OR 200 mg once daily for 28 days.
    • Lyme Carditis (Haemodynamically Stable):
      • Doxycycline 100 mg twice daily OR 200 mg once daily for 21 days.
  • Children (<12 years) – All cases in children should be discussed with a specialist unless it is a single erythema migrans with no other symptoms.
    • Ages 9-11:
      • Erythema Migrans/Non-focal/Nerve Involvement: Doxycycline for 21 days. Dose: 5 mg/kg (in 2 doses) on day 1, then 2.5 mg/kg daily (in 1 or 2 doses). This is off-label.
      • Arthritis/Acrodermatitis: Doxycycline for 28 days (same dosing). This is off-label.
    • Under 9 years:
      • Erythema Migrans/Non-focal/Nerve Involvement: Amoxicillin for 21 days. Dose: 30 mg/kg 3 times a day (for children ≤33 kg).
      • Arthritis/Acrodermatitis: Amoxicillin for 28 days (same dosing).
• Contraindications & Major Side Effects:
  • Doxycycline: Contraindicated in pregnancy. Cautious use (off-label) in children under 12. Photosensitivity is a common side effect.
  • Amoxicillin: Penicillin allergy is a contraindication.
  • Azithromycin: Do not use to treat people with cardiac abnormalities associated with Lyme disease due to its effect on the QT interval.
• Initial Monitoring:
  • Consider a clinical review during or after treatment to assess for response and side effects.

Further Management & Escalation

• Second-Line Therapies (if first-line fails or is contraindicated):
  • Adults with Erythema Migrans/Non-focal Symptoms:
    • First Alternative: Amoxicillin 1 g three times daily for 21 days.
    • Second Alternative: Azithromycin 500 mg daily for 17 days. (Caution: QT interval).
  • Adults with Arthritis or Acrodermatitis:
    • First Alternative: Amoxicillin 1 g three times daily for 28 days.
    • Second Alternative: IV Ceftriaxone 2 g once daily for 28 days.
• Management of Severe or Disseminated Disease (requiring IV therapy/specialist input):
  • CNS Involvement:
    • Adults: IV Ceftriaxone 2 g twice daily or 4 g once daily for 21 days.
    • Children: IV Ceftriaxone 80 mg/kg (up to 4 g) once daily for 21 days.
  • Haemodynamically Unstable Lyme Carditis:
    • Adults/Children: IV Ceftriaxone (2 g daily for adults; 80 mg/kg daily for children) for 21 days.
• Referral & Escalation Criteria:
  • Emergency Referral: Suspected CNS infection, uveitis, or complete heart block.
  • Specialist Discussion/Referral:
    • All children and young people (<18 years), unless they have a single erythema migrans and no other symptoms.
    • Adults with focal symptoms (neurological, cardiac, rheumatological, ophthalmic).
    • Diagnostic uncertainty: If immunoblot is negative but symptoms persist.
    • Persistent symptoms after two courses of antibiotics: Do not offer further routine antibiotics. Refer to a specialist (e.g., infection specialist, rheumatologist) or discuss with a national reference laboratory.
• Surgical Options: Not applicable for treatment. Diagnostic procedures such as synovial fluid aspirate or biopsy may be considered by a specialist.

Follow-up & Safety Netting

• Follow-up Frequency: Offer regular clinical review and reassessment for people with ongoing symptoms. No specific frequency is mandated; tailor to the individual.
• Monitoring: Reassess symptoms. If symptoms persist, worsen, or recur after a full course of antibiotics, consider:
  • Treatment failure.
  • Re-infection (if new exposure and symptoms). Offer a new course of antibiotics if suspected.
  • An alternative diagnosis.
  • Permanent organ damage from the initial infection.
• Patient Advice & Self-Management:
  • Explain that full recovery can take months or years.
  • Advise patients to return if symptoms do not improve or if they recur.
  • Explain that infection does not confer lifelong immunity; re-infection is possible.
  • For ongoing symptoms (fatigue, chronic pain, depression), manage according to usual clinical practice and consider referrals to pain clinics, mental health services, or social care for a needs assessment.
• Warning Signs for Urgent Reassessment:
  • Significant worsening of symptoms during initial treatment (to differentiate Jarisch-Herxheimer reaction from allergy or progression).
  • Development of new focal symptoms (e.g., facial droop, chest pain, joint swelling).
  • Any signs suggesting emergency referral (see Red Flags above).

Take-Home Points

• Erythema Migrans is Diagnostic: If you see a characteristic expanding rash (not typically itchy or painful), diagnose and treat for 21 days without blood tests.
• No Rash? Use Two-Tier Testing: For other symptoms, use ELISA first. If positive/equivocal, confirm with an immunoblot. If ELISA is negative but symptoms are recent (<4 weeks), repeat in 4-6 weeks.
• First-Line is Doxycycline: For most adults, Doxycycline 100 mg BD for 21 days is first-line. Extend to 28 days for arthritis. Use Amoxicillin in pregnancy.
• Referral is Key: Refer ALL children (unless single, simple EM), adults with focal symptoms (neuro, cardiac, joint), cases of diagnostic uncertainty, and patients with persistent symptoms after two courses of antibiotics.
• Urgent Referral for Red Flags: Immediately refer for suspected meningitis/CNS infection, carditis (e.g., heart block), or uveitis.
• Manage Patient Expectations: Recovery can be slow and take months. Persistent symptoms do not always mean active infection.
• Warn about Jarisch-Herxheimer Reaction: Advise patients that symptoms can temporarily worsen at the start of antibiotic treatment and that this is not usually an allergy.
• Check for Pregnancy: Always ask about the possibility of pregnancy before prescribing doxycycline.
• No Immunity: A past infection does not protect against future tick bites causing a new infection. Reinforce prevention advice.

This MedDigest summary is intended for educational purposes only and should not be used for clinical purposes. It is an independent resource, prepared by MedDigest, to offer an accessible overview of information drawn from the NICE guidelines. The original NICE content is © Crown copyright and is used under the Open Government Licence v3.0. While MedDigest strives for accuracy in its educational summaries, this content has not been reviewed or produced by NICE. For comprehensive and definitive recommendations, please always refer to the complete NICE guidelines.

References

NICE (11 April 2018) Lyme disease. https://www.nice.org.uk/guidance/ng95