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Pediatrics. 2020 Jan;145(1). pii: e20190593. doi: 10.1542/peds.2019-0593. Epub 2019 Dec 13.

Diagnostic Performance of C6 Enzyme Immunoassay for Lyme Arthritis.

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Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts;
Harvard Medical School, Harvard University, Boston, Massachusetts.
Division of Emergency Medicine, Alfred I. Dupont Hospital for Children and Jefferson School of Medicine, Wilmington, Delaware.
Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Pediatric Emergency Medicine, Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee, Wisconsin.
Division of Emergency Medicine, UPMC Children's Hospital of Pittsburgh and School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts.
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts; and.
Department of Pediatrics and Emergency Medicine, Hasbro Children's Hospital and Alpert Medical School, Brown University, Providence, Rhode Island.



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.


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.


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.


In Lyme disease endemic areas, a C6 EIA result could be used to guide initial clinical decision-making, without misclassifying children with septic arthritis.


Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: Dr Branda has received research funding from Alere, bioMerieux, DiaSorin, and Immunetics, and he is a paid consultant to AdvanDx, Diasorin, and T2 Biosystems; the other authors have indicated they have no potential conflicts of interest to disclose.

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