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Background Lyme disease commonly present as arthritis (LA) and may mimic septic arthritis (SA). SA has worse prognosis and requires hospitalization. LA diagnosis guidelines suggest two-tiered algorithm. Results take 3–5 days to return, putting children at risk by mismanagement. For children with acute arthritis, timely recognition improves quality of care. Methods We retrieved charts of children with joint complaint in a Lyme endemic region (January 2011–July 2016). We identified SA and LA and characterized presentations. We reviewed all Lyme [anti-VlsE] chemiluminescent immunoassay screens, (January 2015–January 2017). The study was approved by IRB. Results We reviewed 705 charts. SA was found in 24 patients, including 5 with knee arthritis. Seventy-two had confirmed LA, 70 in the knee [fig 1]. Laboratory and physical findings are summarized in Table 1. 2,341 anti-VlsE screens reviewed. 92% were negative. Of the 88 patients with high levels (>8), 53% had arthritis [Figure 2]. Conclusion In children with knee arthritis, LA is 14 times more common than SA. Delayed diagnosis put many children at risk of mismanagement. Physical and laboratory findings may direct clinical suspicion but are limited when differentiating between LA and SA. High value anti-VlsE screens suggest symptomatic disease and may confirm LA diagnosis within hours. This correlates with the hypothesis of this B. burgdoferi’s surface protein’s role in immune evasion, leading to dysregulated inflammation. Figure 1. Study cohorts Table 1: Laboratory and Physical Findings in Children with Knee SA and Knee LA Lyme Arthritis–Knee (70) Septic Arthritis–Knee (5) P-Value N Results (Average) Abnormal (%) N Result (Average) Abnormal (%) Peripheral WBC 58 5–15 (8.9) 0 4 12.6–15.6 (14.5) 75 0.0009 Synovial WBC 28 2–115 (37) 100 5 3–186 (69) 100 0.1171 CRP (mg/dL) 54 0–104 (19) 70 3 10–156 (72) 100 0.2558 ESR (mm/hour) 63 6–97 (33) 75 4 17–33 (24.5) 100 0.0148 Lyme screen CLIA* 15 8.43 - >12.4 (12) 100 1 + 0 / - 1 0 EIA** 43 + 43 / - 0 100 1 + 0 / - 1 0 Lyme WB IgG bands 66 5–10 (9) 100 IgM bands 65 0–3 (1) 41 Synovial Culture 26 + 1 / - 25 4 5 + 3 / - 2 60 Synovial PCR 21 + 11 / - 10 54 2 + 2 / - 0 100 Fever 64 + 10 / - 54 16 4 + 3 / - 1 75 Non weight bearing 70 + 21 / - 49 30 4 + 3 / - 1 75 *Chemiluminescent immunoassay. **Enzyme-linked immunoassay. Figure 2. Lyme [anti-VlsE] CLIA screen (*) Disclosures All authors: No reported disclosures.