Investigations
1st investigations to order
enzyme immunoassay or immunofluorescence assay
Test
Serological diagnosis includes IgM and IgG antibodies via a 2-tier approach. Use a sensitive enzyme immunoassay (EIA) or immunofluorescence assay (IFA) as a first step. Confirm positive or equivocal results with the standardised Western blot assay or second EIA.[30][31][32] In the US, some EIAs have been approved by the Food and Drug Administration for serological diagnosis of Lyme disease and can be used in place of Western blot assays for the second step.[32] For early Lyme disease (first 4 weeks), test for both IgM and IgG antibodies in the second confirmatory step.
No further testing is needed if specimens are negative by a sensitive EIA or IFA. However, in a patient with suspected early Lyme disease who has a negative EIA, carry out a repeat serological test during the convalescent phase (paired sera samples) >2 weeks later. Background seropositivity in highly endemic areas can exceed 4%.[30]
Use IgM blots in only the first month of infection.[30]
Both IgG and IgM may remain positive for a long period (months to years) after previous treatment.
Guidelines from the National Institute for Health and Care Excellence in the UK recommend that 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 continues to be suspected in those with a negative ELISA who have had symptoms for 12 weeks or more, perform an immunoblot assay.[33]
Result
positive
Investigations to consider
Lyme-specific IgM and IgG (immunoblot assays)
Test
Order immunoblot (such as Western blot) assays for Lyme-specific IgM and IgG for patients with equivocal or positive enzyme immunoassay (EIA) or immunofluorescence assay (IFA) results.[30][31] In the US, some EIAs have been approved by the Food and Drug Administration for the serological diagnosis of Lyme disease and can be used in place of Western blot assays for the second step.[32]
For early Lyme disease (first 4 weeks), test for both IgM and IgG antibodies.[30]
Sensitivity is low in early disease, but specificity is high.[30]
People with disseminated or late Lyme disease show a strong IgG response to Borrelia burgdorferi antigens.[30]
Both IgG and IgM may remain positive for a long period (months to years) after previous treatment.
In some patients with Lyme disease, antibodies in serum may be passively transferred to cerebrospinal fluid (CSF); therefore, if neuroborreliosis is suspected, collect CSF and serum on the same day and dilute to match total IgG concentration. A CSF/serum IgG ratio of >1.0 indicates active intrathecal antibody production.[35] To achieve a higher specificity, a CSF/serum antibody index ratio of >1.3 has been suggested as a threshold for supporting diagnosis of neuroborreliosis.[36]
Result
positive
skin biopsy culture
Test
Borrelia cultures are rarely performed. Culture requires special media, takes a long time (up to 8 weeks or longer), and is generally not available.
Generally performed in Barbour-Stoenner-Kelly medium.
A positive culture result is likely with skin from biopsy specimens taken from erythema migrans lesions, but is less likely with serum and cerebrospinal fluid samples.[37] There are only anecdotal reports about joint fluid samples yielding positive results.
Result
positive
polymerase chain reaction (PCR)
Test
PCR of skin and other tissue biopsy specimens can be used as an adjunctive test in select cases, to confirm the diagnosis when serology is positive but clinical presentation is atypical. Not widely available and requires referral to specialists for biopsy.
PCR shows positive results in synovial fluid prior to antibiotic administration.[36]
Result
positive
ECG
Test
An ECG is indicated only in patients with signs and symptoms of cardiac disease, such as shortness of breath, oedema, chest pain, palpitations, lightheadedness, or syncope.[25]
ECG findings typically include acute onset of varying degrees of intermittent atrioventricular block with rapidly fluctuating complete heart block.
Atrial and ventricular arrhythmias may occur.
Myopericarditis occurs rarely.
Result
atrioventricular block
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