Sensitivity of Two-Tiered Lyme Disease Serology in Children With an Erythema Migrans Lesion.

In our prospective cohort of 192 children with a physician-diagnosed erythema migrans (EM) lesion, two-tier Lyme disease serology had higher sensitivity in children with multiple EM lesions (76.8% multiple lesions vs. 38.1% single EM; difference 38.7%, 95% confidence interval 24.8%-50.4%). The diagnosis of cutaneous Lyme disease should be based on careful physical examination rather than laboratory testing.

Biomarkers for Pediatric Bacterial Musculoskeletal Infections in Lyme Disease-Endemic Regions.

OBJECTIVES: Bacterial musculoskeletal infections (MSKIs) are challenging to diagnose because of the clinical overlap with other conditions, including Lyme arthritis. We evaluated the performance of blood biomarkers for the diagnosis of MSKIs in Lyme disease-endemic regions. METHODS: We conducted a secondary analysis of a prospective cohort study of children 1 to 21 years old with monoarthritis presenting to 1 of 8 Pedi Lyme Net emergency departments for evaluation of potential Lyme disease. Our primary outcome was an MSKI, which was defined as septic arthritis, osteomyelitis or pyomyositis. We compared the diagnostic accuracy of routinely available biomarkers (absolute neutrophil count, C-reactive protein, erythrocyte sedimentation rate, and procalcitonin) to white blood cells for the identification of an MSKI using the area under the receiver operating characteristic curve (AUC). RESULTS: We identified 1423 children with monoarthritis, of which 82 (5.8%) had an MSKI, 405 (28.5%) Lyme arthritis, and 936 (65.8%) other inflammatory arthritis. When compared with white blood cell count (AUC, 0.63; 95% confidence interval [CI], 0.55-0.71), C-reactive protein (0.84; 95% CI, 0.80-0.89; P < .05), procalcitonin (0.82; 95% CI, 0.77-0.88; P < .05), and erythrocyte sedimentation rate (0.77; 95% CI, 0.71-0.82; P < .05) had higher AUCs, whereas absolute neutrophil count (0.67; 95% CI, 0.61-0.74; P < .11) had a similar AUC. CONCLUSIONS: Commonly available biomarkers can assist in the initial approach to a potential MSKI in a child. However, no single biomarker has high enough accuracy to be used in isolation, especially in Lyme disease-endemic areas.

Multiplex High-Definition Polymerase Chain Reaction Assay for the Diagnosis of Tick-borne Infections in Children.

Background: Ixodes scapularis ticks can carry Borrelia species as well as other pathogens that cause human disease. The frequency of tick-borne infections and coinfections in children with suspected Lyme disease is unknown, creating clinical uncertainty about the optimal approach to diagnosis. Methods: We enrolled children aged 1-21 years presenting to 1 of 8 Pedi Lyme Net emergency departments for evaluation of Lyme disease. We selected cases with serologically or clinically diagnosed Lyme disease (erythema migrans or early neurologic disease) matched by symptoms, age, gender, and center to control subjects without Lyme disease. We tested whole blood samples collected at the time of diagnosis using a multiplex high-definition polymerase chain reaction (HDPCR) panel to identify 9 bacterial or protozoan pathogens associated with human disease. We compared the frequency of tick-borne coinfections in children with Lyme disease to matched controls. Results: Of the 612 selected samples, 594 (97.1%) had an interpretable multiplex HDPCR result. We identified the following non-Borrelia tick-borne infections: Anaplasma phagocytophilum (2), Ehrlichia chaffeensis (1), and Babesia microti (12). Children with Lyme disease were more likely to have another tick-borne pathogen identified than matched controls (15/297 [5.1%] Lyme cases vs 0/297 [0%]; difference, 5.1% [95% confidence interval, 2.7%-8.2%]). Conclusions: Although a substantial minority of children with Lyme disease had another tick-borne pathogen identified, either first-line Lyme disease antibiotics provided adequate treatment or the coinfection was subclinical and did not require specific treatment. Further studies are needed to establish the optimal approach to testing for tick-borne coinfections in children.

The complete acute and post-acute care course of children affected by acute flaccid myelitis in Western Pennsylvania: A case series.

Acute flaccid myelitis (AFM) is a "polio-like" neurologic disorder of the spinal cord gray matter characterized by asymmetric, flaccid limb weakness of rapid onset following prodromal viral illness. It has affected the pediatric population of the United States since 2014, but there is a paucity of literature describing the post-acute comprehensive rehabilitation management that maximizes functional outcomes for patients. This case series attempts to mitigate this by describing the complete acute and post-acute care course of six children diagnosed with AFM in Western Pennsylvania. It is critical that pediatric rehabilitation medicine providers be knowledgeable about the complex medical and rehabilitation management for patients with AFM.

Racial Differences in the Diagnosis of Lyme Disease in Children.

Black children with Lyme disease compared with children of other races were less likely to have an erythema migrans lesion diagnosed (adjusted odds ratio, 0.34; 95% confidence interval, .14-.79) but more likely to have a swollen joint (adjusted odds ratio, 3.68; 95% confidence interval, 2.13-6.36) after adjustment for age and local Lyme incidence.

A Clinical Prediction Rule for Bacterial Musculoskeletal Infections in Children with Monoarthritis in Lyme Endemic Regions.

STUDY OBJECTIVE: Children with a bacterial musculoskeletal infection (MSKI) require prompt identification and treatment. In Lyme disease endemic areas, children with an MSKI can present similarly to those with Lyme arthritis. Our goal was to derive a clinical prediction rule to accurately identify children at a low risk for an MSKI. METHODS: We enrolled children with monoarthritis presenting to 1 of 6 Pedi Lyme Net centers and performed a procalcitonin (PCT) and a first-tier Lyme C6 enzyme immunoassay (EIA) test. Our primary outcome was an MSKI (septic arthritis, osteomyelitis, or pyomyositis). Using recursive partitioning with k-fold cross validation, we derived a clinical prediction rule to identify children at a low risk of an MSKI. We calculated the accuracy of our novel rule in a derivation cohort. RESULTS: Of the 735 children in the derivation cohort with an available research biosample, 39 (5%) had an MSKI (18 had septic arthritis, 20 had osteomyelitis, and 1 had pyomyositis), 260 (37%) had Lyme arthritis, and 436 (53%) had other inflammatory arthritis. Children with a PCT level of more than or equal to 0.50 ng/mL and those with a C-reactive protein (CRP) level of more than or equal to 0.6 mg/dL with a negative Lyme C6 EIA were classified as not low risk for an MSKI. Of the 451 (61%) children categorized as low risk, none had an MSKI (sensitivity 100%, 95% confidence interval 91.0% to 100%; specificity 74.2%, 95% confidence interval 70.5% to 77.6%). CONCLUSION: A novel clinical decision rule that includes PCT, CRP, and a first-tier Lyme EIA was highly sensitive for MSKIs. Although broader external validation is required, the application of this rule may safely reduce invasive testing, procedures, and treatment for low risk children.

Empiric antibiotics for children with suspected Lyme disease.

In our prospective cohort of children undergoing evaluation for non-cutaneous Lyme disease, 02 (13.9% of those with Lyme disease) were not initially treated with an appropriate antibiotics and 356 (13.3% without Lyme disease) received potentially unnecessary antibiotics. Rapid and accurate diagnostics are needed to further improve initial antibiotic treatment decisions.

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

OBJECTIVE: 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/mm3 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%), 234 Lyme 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, 63.6-73.3; 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.

Seasonality of Acute Lyme Disease in Children.

Due to the life cycle of its vector, Lyme disease has known seasonal variation. However, investigations focused on children have been limited. Our objective was to evaluate the seasonality of pediatric Lyme disease in three endemic regions in the United States. We enrolled children presenting to one of eight Pedi Lyme Net participating emergency departments. Cases were classified based on presenting symptoms: early (single erythema migrans (EM) lesion), early-disseminated (multiple EM lesions, headache, cranial neuropathy, or carditis), or late (arthritis). We defined a case of Lyme disease by the presence of an EM lesion or a positive two-tier Lyme disease serology. To measure seasonal variability, we estimated Fourier regression models to capture cyclical patterns in Lyme disease incidence. While most children with early or early-disseminated Lyme disease presented during the summer months, children with Lyme arthritis presented throughout the year. Clinicians should consider Lyme disease when evaluating children with acute arthritis throughout the year.

Two-Tier Lyme Disease Serology in Children with Previous Lyme Disease.

Background: A history of Lyme disease can complicate the interpretation of Lyme disease serology in acutely symptomatic patients. Materials and Methods: We prospectively enrolled children undergoing evaluation for Lyme disease in the emergency department of one of eight participating Pedi Lyme Net centers. We selected symptomatic children with a Lyme disease history (definite, probable, or none) as well as an available research biosample. We defined a Lyme disease case with either an erythema migrans (EM) lesion or positive two-tier serology with compatible symptoms. Using a generalized estimating equation, we examined the relationship between time from previous Lyme disease diagnosis and current Lyme disease after adjustment for patient demographics and symptoms as well as clustering by center. Results: Of 2501 prospectively enrolled study patients, 126 (5.0%) reported a history of definite or probable Lyme disease. Of these children with previous Lyme disease, 47 met diagnostic criteria for Lyme disease at the time of enrollment (37.3%; 95% confidence interval [CI] 29.1-45.7%); 2 had an EM lesion, and 45 had positive two-tier Lyme disease serology. Over time from the previous Lyme disease diagnosis, the less likely the patient met diagnostic criteria for Lyme disease (adjusted odds ratio 0.62 per time period; 95% CI 0.46-0.84). Conclusions: For children with a history of Lyme disease before enrollment, one-third met the diagnostic criteria for acute Lyme disease with a declining rate over time from previous Lyme disease diagnosis. Novel Lyme disease diagnostics are needed to help distinguish acute from previous Lyme disease.

Pediatric emergency medicine fellowship point-of-care ultrasound training in 2020.

OBJECTIVES: The primary objective was to survey pediatric emergency medicine (PEM) leaders and fellows regarding point-of-care ultrasound (POCUS) training in PEM fellowship programs, including teaching methods, training requirements, and applications taught. Secondary objectives were to compare fellows' and program leaders' perceptions of fellow POCUS competency and training barriers. METHODS: This was a cross-sectional survey of U.S. PEM fellows and fellowship program leaders of the 78 fellowship programs using two online group-specific surveys exploring five domains: program demographics; training strategies and requirements; perceived competency; barriers, strengths, and weaknesses of POCUS training; and POCUS satisfaction. RESULTS: Eighty-three percent (65/78) of programs and 53% (298/558) of fellows responded. All participating PEM fellowship programs included POCUS training in their curriculum. Among the 65 programs, 97% of programs and 92% of programs utilized didactics and supervised scanning shifts as educational techniques, respectively. Sixty percent of programs integrated numerical benchmarks and 49% of programs incorporated real-time, hands-on demonstration as training requirements. Of the 19 POCUS applications deemed in the literature as core requirements for fellows, at least 75% of the 298 fellows reported training in 13 of those applications. Although less than half of fellows endorsed competency for identifying intussusception, ultrasound-guided pericardiocentesis, and transvaginal pregnancy evaluation, a higher proportion of leaders reported fellows as competent for these applications (40% vs. 68%, p ≤ 0.001; 21% vs. 39%, p = 0.003; and 21% vs. 43%, p ≤ 0.001). Forty-six percent of fellows endorsed a lack of PEM POCUS evidence as a training barrier compared to 31% of leaders (p = 0.02), and 39% of leaders endorsed a lack of local financial support as a training barrier compared to 23% of fellows (p = 0.01). CONCLUSIONS: Although most PEM fellowship programs provide POCUS training, there is variation in content and requirements. Training does conform to many of the expert recommended guidelines; however, there are some discrepancies and perceived barriers to POCUS training remain.

Electrocardiogram as a Lyme Disease Screening Test.

OBJECTIVE: To examine the association between electrocardiographic (ECG) evidence of carditis at the time of Lyme disease evaluation and a diagnosis of Lyme disease. STUDY DESIGN: We performed an 8-center prospective cohort study of children undergoing emergency department evaluation for Lyme disease limited to those who had an ECG obtained by their treating clinicians. The study cardiologist reviewed all ECGs flagged as abnormal by the study sites to assess for ECG evidence of carditis. We defined Lyme disease as the presence of an erythema migrans lesion or a positive 2-tier Lyme disease serology. We used logistic regression to measure the association between Lyme disease and atrioventricular (AV) block or any ECG evidence of carditis. RESULTS: Of the 546 children who had an ECG obtained, 214 (39%) had Lyme disease. Overall, 42 children had ECG evidence of carditis, of whom 24 had AV block (20 first-degree). Of the patients with ECG evidence of carditis, only 21 (50%) had any cardiac symptoms. The presence of AV block (OR 4.7, 95% CI 1.8-12.1) and any ECG evidence of carditis (OR 2.3, 95% CI 1.2-4.3) were both associated with diagnosis of Lyme disease. CONCLUSIONS: ECG evidence of carditis, especially AV block, was associated with a diagnosis of Lyme disease. ECG evidence of carditis can be used as a diagnostic biomarker for Lyme disease to guide initial management while awaiting Lyme disease test results.

Validation of the Rule of 7's for Identifying Children at Low-risk for Lyme Meningitis.

BACKGROUND: The Rule of 7's classifies children as low-risk for Lyme meningitis with the absence of the following: ≥7 days of headache, any cranial neuritis or ≥70% cerebrospinal fluid mononuclear cells. We sought to broadly validate this clinical prediction rule in children with meningitis undergoing evaluation for Lyme disease. METHODS: We performed a patient-level data meta-analysis of 2 prospective and 2 retrospective cohorts of children ≤21 years of age with cerebrospinal fluid pleocytosis who underwent evaluation for Lyme disease. We defined a case of Lyme meningitis with a positive 2-tier serology result (positive or equivocal first-tier enzyme immunoassay followed by a positive supplemental immunoblot). We applied the Rule of 7's and report the accuracy for the identification of Lyme meningitis. RESULTS: Of 721 included children with meningitis, 178 had Lyme meningitis (24.7%) and 543 had aseptic meningitis (75.3%). The pooled data from the 4 studies showed the Rule of 7's has a sensitivity of 98% [95% confidence interval (CI): 89%-100%, I2 = 71%], specificity 40% (95% CI: 30%-50%, I2 = 75%), and a negative predictive value of 100% (95% CI: 95%-100%, I2 = 55%). CONCLUSIONS: The Rule of 7's accurately identified children with meningitis at low-risk for Lyme meningitis for whom clinicians should consider outpatient management while awaiting Lyme disease test results.

Two-Tier Lyme Disease Serology Test Results Can Vary According to the Specific First-Tier Test Used.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Diagnostic Performance of C6 Enzyme Immunoassay for Lyme Arthritis.

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

The Lyme Disease Polymerase Chain Reaction Test Has Low Sensitivity.

Background: The Lyme PCR is a direct detection test, but has not been rigorously evaluated in children undergoing evaluation for acute Lyme disease. Methods: We performed a six-center prospective cohort study of children aged 1 to 21 years undergoing acute evaluation for Lyme disease. For this planned secondary analysis, we limited our cohort to children undergoing evaluation for Lyme disease who had any Lyme PCR test obtained by a treating clinician (blood, synovial fluid, or cerebrospinal fluid). We defined a case of Lyme disease with a positive two-tier Lyme disease serology: a positive or equivocal enzyme immunoassay followed by a positive supplemental immunoblot interpreted using standard criteria. We report the test characteristics of Lyme PCR for the diagnosis of Lyme disease. Results: We identified 124 children of whom 54 (43.5%) had Lyme disease. Overall, 23 had a positive PCR test (sensitivity 41.8%; 95% confidence interval [CI] 29.7-55.0; specificity 100%, 95% CI: 94.2-100). All children with a positive Lyme PCR also had a positive two-tiered Lyme disease serology. Conclusions: The Lyme disease PCR test did not improve the diagnosis of children undergoing evaluation for acute Lyme disease. Given the additional costs of this low utility test, clinicians should not order Lyme PCR testing in the acute care setting.

A minority of children diagnosed with Lyme disease recall a preceding tick bite.

Of 1770 children undergoing emergency department evaluation for Lyme disease, 362 (20.5%) children had Lyme disease. Of those with an available tick bite history, only a minority of those with Lyme disease had a recognized tick bite (60/325; 18.5%, 95% confidence interval 14.6-23.0%). Lack of a tick bite history does not reliably exclude Lyme disease.

New Cluster of Acute Flaccid Myelitis in Western Pennsylvania.

Acute flaccid myelitis is a debilitating illness characterized by acute onset of limb weakness, with one or more spinal segments displaying magnetic resonance imaging-confirmed gray matter lesions. Since the first outbreak in 2014, tracking by the Centers for Disease Control and Prevention has demonstrated biennial epidemics in the United States, with a current outbreak occurring in 2018. The cases of 3 children with acute flaccid myelitis who were initially thought to have common nonneurologic diagnoses are presented. Emergency physicians need to be vigilant to recognize the subtleties of acute flaccid myelitis because the illness progression is rapid and therapy is nuanced.

Higher C6 enzyme immunoassay index values correlate with a diagnosis of noncutaneous Lyme disease.

The correlation between the Food and Drug Administration-cleared C6 enzyme immunoassay (EIA) C6 index values and a diagnosis of Lyme disease has not been examined. We used pooled patient-level data from 5 studies of adults and children with Lyme disease and control subjects who were tested with the C6 EIA. We constructed a receiver operating characteristic curve using regression clustered by study and measured the area under the curve (AUC) to examine the accuracy of the C6 index values in differentiating between patients with noncutaneous Lyme disease and control subjects. In the 4821 included patients, the C6 index value had excellent ability to distinguish between patients with noncutaneous Lyme disease and control subjects [AUC 0.99; 95% confidence interval (CI) 0.99-1.00]. An index value cut point of ≥3.0 had a sensitivity of 90.9% (95% CI, 87.8-93.3) and specificity of 99.0% (95% CI, 98.6-99.2%) for Lyme disease.

Positive 2-Tiered Lyme Disease Serology is Uncommon in Asymptomatic Children Living in Endemic Areas of the United States.

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%).