Borrelia (spirochaete) infection, spread by ticks (Ixodes), common in localized areas of Europe and North America (forest environments).
Differential includes possible co-infection from other tick born organisms viz anaplasmosis, or babesiosis.
Vaccine available if likely to be at risk.
Clinical
Infection occurs a minimum of 48 hours after bite!
Skin – Erythema migrans is the classic skin lesion, a spreading ring usually at the site of the bite but can be multiple and at different sites. Typically not hot, itchy or painful. Takes a while for central clearing to develop. Develops over 1-4 weeks (from 3 days to 3 months!), can last months. Looks like erythema multiforme, but time scale different. Insect bite hypersensitivity/superinfection looks similar but usually hot, itchy and/or painful, and develops/recedes within 48 hours!
Lyme lymphocytoma is a painless bluish red nodule or plaque, especially on the ear but also reported on the nipple and scrotum. More common in children. May persist for months, can precede other features. Acrodermatitis chronica atrophicans (ACA) is almost exclusively seen in adults, predominantly women, and is an eruption with chronic, progressive red or bluish-red lesions, usually on the extensor surfaces, with later atrophic, fibroid or sclerodermic changes.
Consider Lyme as possible (but unlikely) cause for:
- fever and sweats
- swollen glands
- malaise
- fatigue
- neck pain or stiffness
- migratory joint or muscle aches and pain
- cognitive impairment, such as memory problems and difficulty concentrating (sometimes described as ‘brain fog’)
- headache
- paraesthesia
Arthritis – uncommon, presents as recurrent inflammation of 1 or more large joints, usually the knee. Swelling can be disproportionate to pain. Can become more persistent – in a minority, despite treatment, inflammation becomes chronic (presumably immune-mediated).
Carditis occurs rarely, and almost always with other clinical features. Usually partial heart block, but can be complete, usually resolves within a week.
Neurological – isolated facial palsy, meningitis, other cranial nerve palsies, meningoencophalitis, polyradiculopathy. There is a small proportion of children who can present with non-specific headache, fatigue, neck pain without clear neurological signs (and also the rare case of raised intracranial pressure).
Other rare disease manifestations include uveitis, iridocyclitis and keratitis.
Diagnosis
For erythema migrans, clinical diagnosis is adequate, and antibodies only positive in 30-70% anyway!
Use a combination of clinical presentation and laboratory testing to guide diagnosis and treatment in people without erythema migrans. Do not rule out diagnosis if tests are negative but there is high clinical suspicion of Lyme disease.
- Offer an enzyme-linked immunosorbent assay (ELISA) test for Lyme disease – consider starting treatment with antibiotics while waiting for the results if there is a high clinical suspicion. (Test for both IgM and IgG antibodies)
- If the ELISA is positive or equivocal, perform an immunoblot test for Lyme disease (again, consider starting treatment with antibiotics while waiting for the results if there is a high clinical suspicion). [Western blot increases specificity, but cut offs (for both serology and Western blot) can be an issue, with potential false positives for other acute infections and autoimmune conditions. Definitely needs to be an approved lab…]
- If ELISA negative and the person still has symptoms, review their history and symptoms, and think about the possibility of an alternative diagnosis. If tested within 4 weeks from symptom onset, repeat the ELISA 4 to 6 weeks after the first test.
- If Lyme disease is still suspected in people with a negative ELISA who have had symptoms for 12 weeks or more, perform an immunoblot test. If negative, consider synovial fluid aspirate/biopsy, or lumbar puncture [PCR – culture is difficult – or CSF antibodies for neuroborreliosis; consider for isolated facial palsy]
- If immunoblot negative and symptoms resolved, no treatment is required.
For early neuroborreliosis, antibodies 80% sensitive, rises to virtually 100% for late or ACA.
Early antibiotic treatment is also believed to potentially block antibody production.
Antibodies can then persist for months or even years after successful treatment of the infection, so repeat testing is not useful for monitoring treatment success.
First line ELISA test can have false positives for other spirochaetes, glandular fever and autoimmune conditions.
The idea that there are seronegative “chronic Lyme” cases has little evidence to support it, with only 2 possible cases reported (ACA and arthritis, not neuro).
NICE says “Discuss the diagnosis and management of Lyme disease in children and young people under 18 years with a specialist, unless they have a single erythema migrans lesion and no other symptoms. Choose a specialist appropriate for the child or young person’s symptoms dependent on availability, for example, a paediatrician, paediatric infectious disease specialist or a paediatric neurologist.”
Treatment [check NICE]
The most commonly recommended first-line treatments for different stages of Lyme borreliosis in Europe are:
- Erythema migrans/borrelial lymphocytoma: 10-14 days Doxycycline if 9yr+ (initially 5 mg/kg in 2 divided doses on day 1, then 2.5 mg/kg daily in 1–2 divided doses, max dose 200mg, for a total of 21 days, option for higher dosing) – 10 days courses of doxy effective in US trials. Else Amoxicillin 50mg/kg/d, max 500mg TDS (10-14 days)[BNFc says 30mg/kg/d, max 1g, TDS for 21 days]. Don’t delay treatment pending test results. Scandinavia use 10 days Pen V (100mg/kg/d, max 1000mg TDS). BNFc says Azithromycin as alternative.
- Isolated facial palsy: 14 days Oral doxycycline – else as above. Doesn’t probably help resolution but may prevent later complications.
- Meningitis/radiculopathy: PO Doxycycline or IV Ceftriaxone 50-100mg/kg/d, max 2g daily (14-21 days). [BNFc talks about CNS disease separate from cranial/peripheral nerves]
- Encephalitis, myelitis: Ceftriaxone (14 days)
- Lyme arthritis: Doxycycline (28 days) else Amoxicllin (21-28 days)
- Carditis: Ceftriaxone during pacing, else PO doxycycline (14 days)
Ceftriaxone is the most commonly preferred parenteral agent, with once-daily dosing facilitating outpatient treatment. Recent prospective studies have shown that oral doxycycline is noninferior to ceftriaxone in neuroborreliosis, and it is now recommended in Europe for the treatment of acute facial palsy (FP), meningitis and radiculoneuritis. Ceftriaxone currently remains the preferred choice for children with other presentations of neuroborreliosis and for those with contraindications to doxycycline.
Several recent EM treatment studies have incorporated noninfected control groups. Excellent responses were seen, with resolution of rash within 7–14 days. Nonspecific symptoms including headache, myalgia, arthralgia, fatigue and parasthesias were no more common in cases than controls at 6-month follow up.
[position statement by the British Infection Association, J Inf 2011;62:329]
[Pediatric Infectious Disease Journal Volume 33(4), April 2014, p 407–409]