Diagnostic Performance of C6 Enzyme Immunoassay for Lyme Arthritis

Nigrovic, Lise E.; Bennett, Jonathan E.; Balamuth, Fran; Levas, Michael N.; Neville, Desiree N; Lyons, Todd W.; Branda, John A.; Maulden, Alexandra B.; Lewander, David P.; Garro, Aris; Net, Pedi Lyme

doi:10.1542/peds.2019-0593

Cited by 12 publications

(14 citation statements)

References 30 publications

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“…Presentation with SA is rarer than presentation with LA in areas in which LA is endemic. In a recent study from New England, Nigrovic et al showed that the prevalence of Lyme disease in acute monoarthritis was 23% compared with 1% for SA 21 . In the study by Milewski et al 9 of a group of 391 children presenting ROC curve and corresponding AUC estimate (with 95% CI) for the best diagnostic algorithm to identify LA compared with SA.…”

Section: Discussionmentioning

confidence: 99%

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Lyme Arthritis in the Pediatric Knee

et al. 2022

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Background:Lyme disease is the most prevalent tick-borne illness in the United States, especially endemic in the Northeast and Upper Midwest. Distinguishing Lyme arthritis (LA), the most common manifestation of the disease in children, from septic arthritis (SA) can be challenging because of overlap in clinical presentations. This study examined the role of magnetic resonance imaging (MRI) as an adjunct to clinical and laboratory features used to differentiate between LA and SA in children and adolescents.Methods:The medical records and MRI scans of children who presented between 2009 and 2019 with an acute knee effusion ultimately diagnosed as LA or SA were retrospectively reviewed. Data collection included clinical information on the modified Kocher criteria (weight-bearing, fever, blood serology including white blood-cell [WBC] count, C-reactive protein [CRP], and erythrocyte sedimentation rate [ESR]), MRI findings, and serology confirmation of LA or bacterial SA. A total of 87 cases of confirmed LA and 9 cases of SA were identified.Results:The 2 cohorts had substantial clinical overlap with regard to the ability to bear weight, fever, and joint aspirate WBC count. Differences between the 2 groups in several MRI characteristics, specifically vastus lateralis myositis, subcutaneous edema, and lymphadenopathy, were significant. A multivariate analysis demonstrated that weight-bearing, CRP of <3 mg/L, absence of subcutaneous edema, myositis of multiple muscles including the vastus lateralis, and lymphadenopathy were predictive of LA.Conclusions:LA should be strongly suspected in endemic areas of the United States when children present with a knee effusion. The addition of MRI criteria to clinical and laboratory findings significantly improved the predictive value for identifying LA.Level of Evidence:Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

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Section: Discussionmentioning

confidence: 99%

“…However, these tests can take a considerable amount of time. Nigrovic et al recently reported on the use of a more rapid C6 enzyme immunoassay (EIA) test with a turnaround of a couple of hours, but this still requires validation 21 .…”

Section: Discussionmentioning

confidence: 99%

Lyme Arthritis in the Pediatric Knee

et al. 2022

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“…In a recent Pedi Lyme Net study of 911 children with acute arthritis (any joint), none of those with septic arthritis had either a positive or equivocal C6 EIA test. 16 Our septic knee arthritis clinical prediction rule could be used in combination with newer biomarkers as well as the C6 EIA to guide initial patient management.…”

Section: Discussionmentioning

confidence: 99%

Validation of Septic Knee Monoarthritis Prediction Rule in a Lyme Disease Endemic Area

et al. 2021

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In Lyme disease endemic areas, Lyme and septic arthritis often present similarly. A published septic knee arthritis clinical prediction rule includes 2 high-risk predictors: absolute neutrophil count of 10,000 cells/mm 3 or greater and erythrocyte sedimentation rate of 40 mm/h or greater. The objective of the study was to externally validate this prediction rule in a multicenter prospective cohort. Methods:We enrolled a prospective cohort of children with knee monoarthritis undergoing evaluation for Lyme disease at 1 of 8 Pedi Lyme Net emergency departments located in endemic areas. We defined a case of septic arthritis with a positive synovial fluid culture or a synovial fluid white blood cell count of 50,000 or greater per high powered field with a positive blood culture and Lyme arthritis with a positive or equivocal C6 EIA, followed by a positive supplemental immunoblot. Other children were classified as having inflammatory arthritis. We report the performance of the septic arthritis clinical prediction rule in our study population.Results: Of the 543 eligible children, 13 had septic arthritis (2.4%), 234Lyme arthritis (43.1%), and 296 inflammatory arthritis (54.5%). Of the 457 children (84.2%) with available laboratory predictors, all children with septic arthritis were classified as high risk (sensitivity, 100%; 95% confidence interval [CI], 77.2%-100%; specificity, 68.1%; 95% CI, negative predictive value, 278/278 [100%]; 95% CI, 98.6%-100%). Of the 303 low-risk children, 52 (17.2%) underwent diagnostic arthrocentesis. Conclusions:The septic knee arthritis clinical prediction rule accurately distinguished between septic and Lyme arthritis in an endemic area. Clinical application may reduce unnecessary invasive diagnostic procedures.

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“…An additional limitation of the study is the ever-increasing regions where Lyme disease is endemic, making the applicability of this prediction tool less useful over time. However, in non-Lyme endemic areas, were a patient to have a likely exposure to Lyme disease and a concern for septic arthritis, serum sampling for the C6 enzyme immunoassay test should be considered, as a positive or equivocal test result had a high sensitivity (100%) and specificity (94%) for Lyme disease in a multicenter study by Nigrovic et al ( 17 ), and such a result may prevent the unnecessary arthrocentesis.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Criteria for the Painful Swollen Pediatric Knee: Distinguishing Septic Arthritis From Aseptic Effusion in a Non-Lyme Endemic Area

et al. 2021

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Purpose: The child with a painful swollen knee must be worked-up for possible septic arthritis; the classic clinical prediction algorithms for septic arthritis of the hip may not be the best models to apply to the knee.Materials and methods: This was a retrospective case-control study of 17 years of children presenting to one hospital with a chief complaint of a painful swollen knee, to evaluate the appropriateness of applying a previously described clinical practice algorithm for the hip in differentiating between the septic and aseptic causes of the painful knee effusions. The diagnoses of true septic arthritis, presumed septic arthritis, and aseptic effusion were established, based upon the cultures of synovial fluid, blood cultures, synovial cell counts, and clinical course. Using a logistic regression model, the disease status was regressed on both the demographic and clinical variables.Results: In the study, 122 patients were included: 51 with true septic arthritis, 37 with presumed septic arthritis, and 34 with aseptic knee effusion. After applying a backward elimination, age <5 years and C-reactive protein (CRP) >2.0 mg/dl remained in the model, and predicted probabilities of having septic knee arthritis ranged from 15% for the lowest risk to 95% for the highest risk. Adding a knee aspiration including percent polymorphonucleocytes (%PMN) substantially improved the overall model performance, lowering the lowest risk to 11% while raising the highest risk to 96%.Conclusions: This predictive model suggests that the likelihood of pediatric septic arthritis of the knee is >90% when both “age <5 years” and “CRP > 2.0 mg/dl” are present in a child with a painful swollen knee, though, in the absence of these factors, the risk of septic arthritis remains over 15%. Aspiration of the knee for those patients would be the best next step.

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Diagnostic Performance of C6 Enzyme Immunoassay for Lyme Arthritis

Cited by 12 publications

References 30 publications

Lyme Arthritis in the Pediatric Knee

Lyme Arthritis in the Pediatric Knee

Validation of Septic Knee Monoarthritis Prediction Rule in a Lyme Disease Endemic Area

Diagnostic Criteria for the Painful Swollen Pediatric Knee: Distinguishing Septic Arthritis From Aseptic Effusion in a Non-Lyme Endemic Area

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