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It is worth assessing the risks by considering the pathogenesis and clinical features of Lyme disease - negative serology does not exclude the diagnosis.
In more than half of people affected by this condition there is no history of tick bite.
The diagnosis is unreliable early. Check Treponema pallidum haemoglutination is negative before accepting a positive result.
Diagnosis (1)
Clinical assessment
- diagnose Lyme disease in people with erythema migrans, a red rash that:
- increases in size and may sometimes have a central clearing
- is not usually itchy, hot or painful
- usually becomes visible from 1 to 4 weeks (but can appear from 3 days to 3 months) after a tick bite and lasts for several weeks
- is usually at the site of a tick bite
- be aware that a rash, which is not erythema migrans, can develop as a reaction to a tick bite that:
- usually develops and recedes during 48 hours from the time of the tick bite
- is more likely than erythema migrans to be hot, itchy or painful
- may be caused by an inflammatory reaction or infection with a common skin pathogen
NICE suggest that a clinician should consider the possibility of Lyme disease in people presenting with several of the following symptoms, because Lyme disease is a possible but uncommon cause of:
- 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
NICE also suggest that should consider the possibility of Lyme disease in people presenting with symptoms and signs relating to 1 or more organ systems (focal symptoms) because Lyme disease is a possible but uncommon cause of:
- neurological symptoms, such as facial palsy or other unexplained cranial nerve palsies, meningitis, mononeuritis multiplex or other unexplained radiculopathy; or rarely encephalitis, neuropsychiatric presentations or unexplained white matter changes on brain imaging
- inflammatory arthritis affecting 1 or more joints that may be fluctuating and migratory
- cardiac problems, such as heart block or pericarditis
- eye symptoms, such as uveitis or keratitis
- skin rashes such as acrodermatitis chronica atrophicans or lymphocytoma Do not rule out the possibility of Lyme disease in people with symptoms but no clear history of tick exposure Be cautious about diagnosing Lyme disease in people without a supportive history or positive serological testing because of the risk of:
- missing an alternative diagnosis
- providing inappropriate treatment
Laboratory testing of the disease follows a two step approach:
- first stage - enzyme-linked immunosorbent assays (ELISA) (1,2). IgM peaks at 3-6 weeks; IgG appears more slowly and may take months or years
- diagnose and treat Lyme disease without laboratory testing in people with erythema migrans (1)
- 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
- if there is a clinical suspicion of Lyme disease in people without erythema migrans (1):
- offer an enzyme-linked immunosorbent assay (ELISA) test for Lyme disease and
- consider starting treatment with antibiotics while waiting for the results if there is a high clinical suspicion
- test for both IgM and IgG antibodies using ELISAs based on purified or recombinant antigens derived from the VlsE protein or its IR6 domain peptide (such as C6 ELISA)
- if the ELISA is positive or equivocal:
- perform an immunoblot test for Lyme disease and
- consider starting treatment with antibiotics while waiting for the results if there is a high clinical suspicion of Lyme disease
- if the ELISA for Lyme disease is negative and the person still has symptoms, review their history and symptoms, and think about the possibility of an alternative diagnosis
- if Lyme disease is still suspected in people with a negative ELISA who were tested within 4 weeks from symptom onset, repeat the ELISA 4 to 6 weeks after the first ELISA 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
- sensitivity of the test depends on the timing of the test and early in the disease there can be false negative results (3)
- chances of a positive test during the first two weeks is around 30% and about 80% by six weeks
- in late stages the chances of a positive antibody test is greater than 99% (4)
- false positive results are seen in other conditions like mononucleosis, autoimmune states, and Treponema pallidum infection
- second stage - immuno-blotting (western blotting)
- done if the above test is positive or in an indeterminate result (3)
- gives out more accurate assessment of the presence of Borrelia antibodies (4)
- diagnose Lyme disease in people with symptoms of Lyme disease and a positive immunoblot test (1)
- if the immunoblot test for Lyme disease is negative (regardless of the ELISA result) but symptoms persist, consider a discussion with or referral to a specialist, to:
- review whether further tests may be needed for suspected Lyme disease, for example, synovial fluid aspirate or biopsy, or lumbar puncture for cerebrospinal fluid analysis or
- consider alternative diagnoses (both infectious, including other tick-borne diseases, and non-infectious diseases)
- choose a specialist appropriate for the person's history or symptoms, for example, an adult or paediatric infection specialist, rheumatologist or neurologist
- if the immunoblot test for Lyme disease is negative and symptoms have resolved, explain to the person that no treatment is required.
The antibody is not affected by treatment. ESR is elevated.
Use of the polymerase chain reaction to detect the presence of Borrelia burgdorferi DNA in specimens from patients may become the most reliable means of determining who has been infected with this organism and when infection has been eliminated.
Notes:
- serum Borrelia IgG may persist for decades. Therefore, serology cannot be used to monitor disease activity or eradication (5)
- background seroprevalence exists, from 5% in the general population in endemic regions to 50% in hunters
- cerebrospinal fluid (CSF) analysis (5)
- similar to PCR, CSF cultures for Borrelia spp have a low yield
- diagnosis relies on indirect measures of meningeal inflammation: pleocytosis, intrathecal antibody production
- intrathecal Borrelia antibody is measured by calculating the CSF:serum antibody index and has been shown to persist for years after successful treatment, and thus cannot be used to monitor treatment
- chemokine C-X-C motif ligand 13 (CXCL13) is an early biomarker and its concentration falls rapidly after initiation of antibiotic therapy. Elevated CXCL13 concentrations in CSF may also be detected in other disorders, particularly neurosyphilis and central nervous system lymphoma
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