Pediatric Lyme Disease Workup

The most sensitive and specific test for Lyme disease is identifying the erythema migrans rash. For cases without a rash, workup for pediatric Lyme disease may include blood studies and serology, as well as polymerase chain reaction (PCR) or lumbar puncture if indicated.

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In patients with Lyme disease, the white blood cell (WBC) count can be normal or elevated. The erythrocyte sedimentation rate (ESR) is usually elevated. The serum aspartate transaminase (AST) may be elevated. C3 and C4 levels are generally normal or slightly elevated. Antinuclear antibody (ANA) and rheumatoid factor test results are negative.

Microscopic hematuria and mild proteinuria have also been described. Joint fluid in patients with arthritis may have 25,000-125,000 WBCs/µL, often with a polymorphonuclear predominance. Cerebrospinal fluid (CSF) in patients with meningitis often reveals a mild pleocytosis (< 1000 cells/µL) with lymphocyte predominance.

Culturing B burgdorferi is impractical; the organism is difficult to culture and requires an invasive procedure, such as biopsy or lumbar puncture, to obtain adequate samples.

Serology is the standard of diagnosis in later stages of the disease. Reported specificity of Lyme serology is only 90-95%. Therefore, the positive predictive value of the test is highly dependent on the prevalence of disease. Lyme serology should not be performed in children with nonspecific symptoms without history of tick exposure or from nonendemic areas. Antibodies are known to persist for many years despite eradication of the infection. Diagnosis of repeat infection or evidence of cure can be difficult based on serology alone.

Lyme serology should be performed by a reference laboratory and should include a 2-step process. Step 1 is to perform an enzyme-linked immunosorbent assay (ELISA) or immunofluorescent assay (IFA). Step 2, performed if the ELISA or IFA result is positive, is a Western blot analysis against specific antigens. This step is not interpretable in the absence of a positive ELISA or IFA result. Most assays require immunoglobulin (Ig) against at least 3 specific proteins (for IgM) or 5 specific proteins (for IgG) for results to be considered positive.

• Early disease: Only one third of patients have a positive titer result; therefore, clinicians rely on the presence of the rash to make the diagnosis. For patients without an EM rash but in whom Lyme disease is suspected, serial titers eventually can be used to confirm the diagnosis. Patients with early Lyme disease who are treated with antibiotics may never develop positive titer results.
• Early disseminated disease: 90% of patients have a positive titer result.
• Late disease: All patients have a positive titer result.

In response to the need for improved serological tests for the diagnosis and monitoring of Lyme disease, a study recently examined Luciferase Immunoprecipitation Systems (LIPS).^[5] Antibody responses to several B burgdorferi antigens were measured, including VlsE, Flagellin (FlaB), BmpA, DbpA, and DbpB.

The best diagnostic performance was achieved with the synthetic protein consisting of a VlsE-OspC-VlsE-OspC peptide sequence, designated VOVO. The study concluded that LIPS screening using VOVO and other B burgdorferi antigens provided an efficient quantitative approach for evaluating antibody responses in Lyme disease.

With the exception of synovial fluid, PCR testing is not recommended because of unacceptable low sensitivity, especially from the CSF (though it does have high specificity if the result is positive). CSF titers to B burgdorferi should not be used for diagnosis of Lyme meningitis but may have value in patients who have recurrent infection or for following serial markers in patients with persistent symptoms. CSF titers should be performed and interpreted at a reference laboratory.

With regard to Lyme arthritis, one study reported that results from standard and quantitative polymerase chain reaction (PCR) techniques included findings that B burgdorferi were active and viable in the skin lesions of erythema migrans patients, but were moribund or dead in the synovial fluid of Lyme arthritis patients. These results suggest that detection of B burgdorferi DNA in synovial fluid is not a reliable test for active joint infection in Lyme disease.^[6]

Whether all patients with cranioneuropathy require lumbar puncture before treatment is controversial. Occasionally Lyme disease presents as pseudotumor cerebri; an opening pressure is essential for diagnosis.

Currently, in most patients with isolated Bell palsy and no associated signs of aseptic meningitis, most physicians do not perform a lumbar puncture. For most other patients with cranioneuropathies and suspected Lyme disease, a lumbar puncture should be performed, particularly in patients who live in an endemic area and present during peak Lyme disease season or with headache; CSF pleocytosis leads to treatment as indicated for CNS Lyme disease.

Computed tomography (CT) scan or magnetic resonance imaging (MRI) should be performed before the lumbar puncture if increased intracranial pressure or mass lesion is suspected. Occasionally, Lyme disease presents as pseudotumor with frank papilledema; imaging should be done prior to lumbar puncture in these cases.

Joint aspiration for diagnostic reasons is unnecessary if only Lyme disease is suspected (and not septic arthritis or another etiology of effusion).