<p><strong>OBJECTIVES: </strong>In Lyme disease endemic areas, initial management of children with arthritis can be challenging because diagnostic tests take several days to return results, leading to potentially unnecessary invasive procedures. Our objective was to examine the role of the C6 peptide enzyme immunoassay (EIA) test to guide initial management.</p>

<p><strong>METHODS: </strong>We enrolled children with acute arthritis undergoing evaluation for Lyme disease presenting to a participating Pedi Lyme Net emergency department (2015-2019) and performed a C6 EIA test. We defined Lyme arthritis with a positive or equivocal C6 EIA test result followed by a positive supplemental immunoblot result and defined septic arthritis as a positive synovial fluid culture result or a positive blood culture result with synovial fluid pleocytosis. Otherwise, children were considered to have inflammatory arthritis. We report the sensitivity and specificity of the C6 EIA for the diagnosis of Lyme arthritis.</p>

<p><strong>RESULTS: </strong>Of the 911 study patients, 211 children (23.2%) had Lyme arthritis, 11 (1.2%) had septic arthritis, and 689 (75.6%) had other inflammatory arthritis. A positive or equivocal C6 EIA result had a sensitivity of 100% (211 out of 211; 95% confidence interval [CI]: 98.2%-100%) and specificity of 94.2% (661 out of 700; 95% CI: 92.5%-95.9%) for Lyme arthritis. None of the 250 children with a positive or equivocal C6 EIA result had septic arthritis (0%; 95% CI: 0%-1.5%), although 75 children underwent diagnostic arthrocentesis and 27 underwent operative joint washout.</p>

<p><strong>CONCLUSIONS: </strong>In Lyme disease endemic areas, a C6 EIA result could be used to guide initial clinical decision-making, without misclassifying children with septic arthritis.</p>

<p><strong>BACKGROUND: </strong>Variability in 2-tier Lyme disease test results according to the specific first-tier enzyme immunoassay (EIA) in children has not been examined rigorously. In this study, we compared paired results of clinical 2-tier Lyme disease tests to those of the C6 peptide EIA followed by supplemental immunoblotting (C6 2-tier test).</p>

<p><strong>METHODS: </strong>We performed a prospective cohort study of children aged ≥1 to ≤21 years who were undergoing evaluation for Lyme disease in the emergency department at 1 of 6 centers located in regions in which Lyme disease is endemic. The clinical first-tier test and a C6 EIA were performed on the same serum sample with supplemental immunoblotting if the first-tier test result was either positive or equivocal. We compared the results of the paired clinical and C6 2-tier Lyme disease test results using the McNemar test.</p>

<p><strong>RESULTS: </strong>Of the 1714 children enrolled, we collected a research serum sample from 1584 (92.4%). The clinical 2-tier EIA result was positive in 316 (19.9%) children, and the C6 2-tier test result was positive or equivocal in 295 (18.6%) children. The clinical and C6 2-tier test results disagreed more often than they would have by chance alone (P = .002). Of the 39 children with either a positive clinical or C6 2-tier test result alone, 2 children had an erythema migrans (EM) lesion, and 29 had symptoms compatible with early disseminated Lyme disease.</p>

<p><strong>CONCLUSIONS: </strong>Two-tier Lyme disease test results differed for a substantial number of children on the basis of the specific first-tier test used. In children for whom there is a high clinical suspicion for Lyme disease and who have an initially negative test result, clinicians should consider retesting for Lyme disease.</p>

<p>Knowing the frequency of positive Lyme disease serology in children without signs of infection facilitates test interpretation. Of 315 asymptomatic children from Lyme disease endemic regions, 32 had positive or equivocal C6 enzyme linked immunoassays, but only 5 had positive IgG or IgM supplemental immunoblots (1.6%, 95% confidence interval 0.7-3.7%).</p>

<p><strong>BACKGROUND: </strong>To make initial management decisions, clinicians must estimate the probability of Lyme disease before diagnostic test results are available. Our objective was to examine the accuracy of clinician suspicion for Lyme disease in children undergoing evaluation for Lyme disease.</p>

<p><strong>METHODS: </strong>We assembled a prospective cohort of children aged 1 to 21 years who were evaluated for Lyme disease at 1 of the 5 participating emergency departments. Treating physicians were asked to estimate the probability of Lyme disease (on a 10-point scale). We defined a Lyme disease case as a patient with an erythema migrans lesion or positive 2-tiered serology results in a patient with compatible symptoms. We calculated the area under the curve for the receiver operating curve as a measure of the ability of clinician suspicion to diagnose Lyme disease.</p>

<p><strong>RESULTS: </strong>We enrolled 1021 children with a median age of 9 years (interquartile range, 5-13 years). Of these, 238 (23%) had Lyme disease. Clinician suspicion had a minimal ability to discriminate between children with and without Lyme disease: area under the curve, 0.75 (95% confidence interval, 0.71-0.79). Of the 554 children who the treating clinicians thought were unlikely to have Lyme disease (score 1-3), 65 (12%) had Lyme disease, and of the 127 children who the treating clinicians thought were very likely to have Lyme disease (score 8-10), 39 (31%) did not have Lyme disease.</p>

<p><strong>CONCLUSIONS: </strong>Because clinician suspicion had only minimal accuracy for the diagnosis of Lyme disease, laboratory confirmation is required to avoid both under- and overdiagnosis.</p>