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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.

Er71 mutant embryos are nonviable and lack hematopoietic and endothelial lineages. To further define the functional role for ER71 in cell lineage decisions, we generated genetically modified mouse models. We engineered an Er71-EYFP transgenic mouse model by fusing the 3.9 kb Er71 promoter to the EYFP reporter gene. Using FACS and transcriptional profiling, we examined the EYFP+ population of cells in Er71 mutant and wild-type littermates. In the absence of ER71, we observed an increase in the number of EYFP-expressing cells, increased expression of the cardiac molecular program and decreased expression of the hemato-endothelial program, as compared with wild-type littermate controls. We also generated a novel Er71-Cre transgenic mouse model using the same 3.9 kb Er71 promoter. Genetic fate-mapping studies revealed that the ER71-expressing cells give rise to the hematopoietic and endothelial lineages in the wild-type background. In the absence of ER71, these cell populations contributed to alternative mesodermal lineages, including the cardiac lineage. To extend these analyses, we used an inducible embryonic stem/embryoid body system and observed that ER71 overexpression repressed cardiogenesis. Together, these studies identify ER71 as a critical regulator of mesodermal fate decisions that acts to specify the hematopoietic and endothelial lineages at the expense of cardiac lineages. This enhances our understanding of the mechanisms that govern mesodermal fate decisions early during embryogenesis.