Amy D. Thompson

Acute Pediatric Monoarticular Arthritis: Distinguishing Lyme Arthritis From Other Etiologies

OBJECTIVE. Identify clinical predictors of Lyme arthritis among patients with acute monoarticular arthritis. METHODS. A medical chart review was conducted of children ≤18 years of age with monoarticular arthritis who underwent arthrocentesis in a pediatric emergency department located in the northeast United States. Patients were classified into 3 categories of arthritis: septic, Lyme, or nonseptic non-Lyme arthritis. Historical, clinical, and laboratory data were compared to identify distinguishing features of Lyme arthritis. RESULTS. One hundred seventy-nine patients were studied: 46 (26%) patients with septic arthritis, 55 (31%) patients with Lyme arthritis, and 78 (43%) patients with nonseptic non-Lyme arthritis. Compared with those with septic arthritis, patients with Lyme disease were more likely to have a tick-bite history, knee involvement, and less likely to have a history of fever or elevated temperature at triage. Erythrocyte sedimentation rate, C-reactive protein, joint white blood cell count, and joint neutrophil percentage were also statistically lower. In comparison to nonseptic non-Lyme arthritis, knee involvement and tick-bite history were predictors of Lyme. Erythrocyte sedimentation rate, joint white blood cell count, and joint neutrophil percentage were also statistically different. Multivariate analysis comparing Lyme to septic arthritis demonstrated fever history and elevated C-reactive protein level to be negative predictors of Lyme arthritis and knee involvement to be a positive predictor (model sensitivity: 88%; specificity: 82%). CONCLUSIONS. Lyme arthritis shares features with both septic and nonseptic non-Lyme arthritis. This overlap prevents the creation of a clinically useful predictive model for Lyme arthritis. In endemic areas, Lyme testing should be performed on all patients presenting with acute monoarticular arthritis.

Clinical Predictors of Lyme Disease Among Children With a Peripheral Facial Palsy at an Emergency Department in a Lyme Disease–Endemic Area

INTRODUCTION. Although Lyme disease can cause peripheral facial palsy in Lyme disease–endemic areas, diagnostic predictors in children have not been described. OBJECTIVE. Our goal was to determine clinical predictors of Lyme disease as the etiology of peripheral facial palsy in children presenting to an emergency department in a Lyme disease–endemic area. METHODS. We reviewed all available electronic medical charts of children ≤20 years old with peripheral facial palsy who were evaluated in the emergency department of a tertiary care pediatric center from 1995 to 2007. We used the Centers for Disease Control Lyme disease definition: presence of erythema migrans lesion or serologic evidence of infection with Borrelia burgdorferi. We performed binary logistic regression with bootstrapping validation to determine independent clinical predictors of Lyme disease. RESULTS. We identified 313 patients with peripheral facial palsy evaluated for Lyme disease. The mean age was 10.7 years, and 52% were male. Of these, 106 (34%) had Lyme disease facial palsy. After adjusting for year of study, the following were independently associated with Lyme disease facial palsy: onset of symptoms during peak Lyme disease season (June to October), absence of previous herpetic lesions, presence of fever, and history of headache. In the subset of patients without meningitis, both onset of symptoms during Lyme disease season and presence of headache remained significant independent predictors. CONCLUSIONS. Lyme disease is a frequent cause of facial palsy in children living in an endemic region. Serologic testing and empiric antibiotics should be strongly considered, especially when children present during peak Lyme disease season or with a headache.

Validation of a Clinical Prediction Rule to Distinguish Lyme Meningitis From Aseptic Meningitis

Objectives: The “Rule of 7′s,” a Lyme meningitis clinical prediction rule, classifies children at low risk for Lyme meningitis when each of the following 3 criteria are met: <7 days of headache, <70% cerebrospinal fluid (CSF) mononuclear cells, and absence of seventh or other cranial nerve palsy. The goal of this study was to test the performance of the Rule of 7′s in a multicenter cohort of children with CSF pleocytosis. Methods: We performed a retrospective cohort study of children evaluated at 1 of 3 emergency departments located in Lyme disease–endemic areas with CSF pleocytosis and Lyme serology obtained. Lyme meningitis was defined using the Centers for Disease Control and Prevention criteria (either positive Lyme serology test result or an erythema migrans [EM] rash). We calculated the performance of the Rule of 7′s in our overall study population and in children without physician-documented EM. Results: We identified 423 children, of whom 117 (28% [95% confidence interval (CI): 24%–32%]) had Lyme meningitis, 306 (72% [95% CI: 68%–76%]) had aseptic meningitis, and 0 (95% CI: 0%–1%) had bacterial meningitis. Of the 130 classified as low risk, 5 had Lyme meningitis (sensitivity, 112 of 117 [96% (95% CI: 90%–99%)]; specificity, 125 of 302 [41% (95% CI: 36%–47%)]). In the 390 children without EM, 3 of the 127 low-risk patients had Lyme meningitis (2% [95% CI: 0%–7%]). Conclusions: Patients classified as low risk by using the Rule of 7′s were unlikely to have Lyme meningitis and could be managed as outpatients while awaiting results of Lyme serology tests.

The Fecal Microbiota Profile and Bronchiolitis in Infants.

BACKGROUND: Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants. METHODS: We conducted a case–control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 115 age-matched healthy controls. By applying 16S rRNA gene sequencing and an unbiased clustering approach to these 155 fecal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. RESULTS: Overall, the median age was 3 months, 55% were male, and 54% were non-Hispanic white. Unbiased clustering of fecal microbiota identified 4 distinct profiles: Escherichia-dominant profile (30%), Bifidobacterium-dominant profile (21%), Enterobacter/Veillonella-dominant profile (22%), and Bacteroides-dominant profile (28%). The proportion of bronchiolitis was lowest in infants with the Enterobacter/Veillonella-dominant profile (15%) and highest in the Bacteroides-dominant profile (44%), corresponding to an odds ratio of 4.59 (95% confidence interval, 1.58–15.5; P = .008). In the multivariable model, the significant association between the Bacteroides-dominant profile and a greater likelihood of bronchiolitis persisted (odds ratio for comparison with the Enterobacter/Veillonella-dominant profile, 4.24; 95% confidence interval, 1.56–12.0; P = .005). In contrast, the likelihood of bronchiolitis in infants with the Escherichia-dominant or Bifidobacterium-dominant profile was not significantly different compared with those with the Enterobacter/Veillonella-dominant profile. CONCLUSIONS: In this case–control study, we identified 4 distinct fecal microbiota profiles in infants. The Bacteroides-dominant profile was associated with a higher likelihood of bronchiolitis.

Integrating Spatial Epidemiology into a Decision Model for Evaluation of Facial Palsy in Children

OBJECTIVE To develop a novel diagnostic algorithm for Lyme disease among children with facial palsy by integrating public health surveillance data with traditional clinical predictors. DESIGN Retrospective cohort study. SETTING Childrens Hospital Boston emergency department, 1995-2007. PATIENTS Two hundred sixty-four children (aged <20 years) with peripheral facial palsy who were evaluated for Lyme disease. MAIN OUTCOME MEASURES Multivariate regression was used to identify independent clinical and epidemiologic predictors of Lyme disease facial palsy. RESULTS Lyme diagnosis was positive in 65% of children from high-risk counties in Massachusetts during Lyme disease season compared with 5% of those without both geographic and seasonal risk factors. Among patients with both seasonal and geographic risk factors, 80% with 1 clinical risk factor (fever or headache) and 100% with 2 clinical factors had Lyme disease. Factors independently associated with Lyme disease facial palsy were development from June to November (odds ratio, 25.4; 95% confidence interval, 8.3-113.4), residence in a county where the most recent 3-year average Lyme disease incidence exceeded 4 cases per 100,000 (18.4; 6.5-68.5), fever (3.9; 1.5-11.0), and headache (2.7; 1.3-5.8). Clinical experts correctly treated 68 of 94 patients (72%) with Lyme disease facial palsy, but a tool incorporating geographic and seasonal risk identified all 94 cases. CONCLUSIONS Most physicians intuitively integrate geographic information into Lyme disease management, but we demonstrate quantitatively how formal use of geographically based incidence in a clinical algorithm improves diagnostic accuracy. These findings demonstrate potential for improved outcomes from investments in health information technology that foster bidirectional communication between public health and clinical settings.

Nasal Airway Microbiota Profile and Severe Bronchiolitis in Infants: A Case-control Study

Background: Little is known about the relationship of airway microbiota with bronchiolitis in infants. We aimed to identify nasal airway microbiota profiles and to determine their association with the likelihood of bronchiolitis in infants. Methods: A case-control study was conducted. As a part of a multicenter prospective study, we collected nasal airway samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 110 age-matched healthy controls. By applying 16S ribosomal RNA gene sequencing and an unbiased clustering approach to these 150 nasal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. Results: Overall, the median age was 3 months and 56% were male. Unbiased clustering of airway microbiota identified 4 distinct profiles: Moraxella-dominant profile (37%), Corynebacterium/Dolosigranulum-dominant profile (27%), Staphylococcus-dominant profile (15%) and mixed profile (20%). Proportion of bronchiolitis was lowest in infants with Moraxella-dominant profile (14%) and highest in those with Staphylococcus-dominant profile (57%), corresponding to an odds ratio of 7.80 (95% confidence interval, 2.64–24.9; P < 0.001). In the multivariable model, the association between Staphylococcus-dominant profile and greater likelihood of bronchiolitis persisted (odds ratio for comparison with Moraxella-dominant profile, 5.16; 95% confidence interval, 1.26–22.9; P = 0.03). By contrast, Corynebacterium/Dolosigranulum-dominant profile group had low proportion of infants with bronchiolitis (17%); the likelihood of bronchiolitis in this group did not significantly differ from those with Moraxella-dominant profile in both unadjusted and adjusted analyses. Conclusions: In this case-control study, we identified 4 distinct nasal airway microbiota profiles in infants. Moraxella-dominant and Corynebacterium/Dolosigranulum-dominant profiles were associated with low likelihood of bronchiolitis, while Staphylococcus-dominant profile was associated with high likelihood of bronchiolitis.

Interpretation of Cerebrospinal Fluid White Blood Cell Counts in Young Infants With a Traumatic Lumbar Puncture

Study objective We determine the optimal correction factor for cerebrospinal fluid WBC counts in infants with traumatic lumbar punctures. Methods We performed a secondary analysis of a retrospective cohort of infants aged 60 days or younger and with a traumatic lumbar puncture (cerebrospinal fluid RBC count ≥10,000 cells/mm3) at 20 participating centers. Cerebrospinal fluid pleocytosis was defined as a cerebrospinal fluid WBC count greater than or equal to 20 cells/mm3 for infants aged 28 days or younger and greater than or equal to 10 cells/mm3 for infants aged 29 to 60 days; bacterial meningitis was defined as growth of pathogenic bacteria from cerebrospinal fluid culture. Using linear regression, we derived a cerebrospinal fluid WBC correction factor and compared the uncorrected with the corrected cerebrospinal fluid WBC count for the detection of bacterial meningitis. Results Of the eligible 20,319 lumbar punctures, 2,880 (14%) were traumatic, and 33 of these patients (1.1%) had bacterial meningitis. The derived cerebrospinal fluid RBCs:WBCs ratio was 877:1 (95% confidence interval [CI] 805 to 961:1). Compared with the uncorrected cerebrospinal fluid WBC count, the corrected one had lower sensitivity for bacterial meningitis (88% uncorrected versus 67% corrected; difference 21%; 95% CI 10% to 37%) but resulted in fewer infants with cerebrospinal fluid pleocytosis (78% uncorrected versus 33% corrected; difference 45%; 95% CI 43% to 47%). Cerebrospinal fluid WBC count correction resulted in the misclassification of 7 additional infants with bacterial meningitis, who were misclassified as not having cerebrospinal fluid pleocytosis; only 1 of these infants was older than 28 days. Conclusion Correction of the cerebrospinal fluid WBC count substantially reduced the number of infants with cerebrospinal fluid pleocytosis while misclassifying only 1 infant with bacterial meningitis of those aged 29 to 60 days.

Treatment complications in children with lyme meningitis.

Background: The rate and type of treatment complications in children treated for Lyme meningitis have not been described. Methods: We performed a retrospective cohort study of children with Lyme meningitis who presented to 1 of 3 emergency departments located in Lyme disease endemic areas between 1997 and 2010. We defined a case of Lyme meningitis as a child with cerebrospinal fluid pleocytosis and either positive Lyme serology or an erythema migrans rash. We identified prescribed treatment and reasons for all return visits. Our primary outcome was the presence of any treatment complication within 30 days of diagnosis. Results: We identified 157 patients with Lyme meningitis with a median age of 10 years (interquartile range: 7–13 years). Of the 149 children with Lyme meningitis and available follow-up records, 39 (26%) had 1 or more complications, and 21 (14%) required a change in prescribed antibiotic therapy. The median time for developing the first complication was 11 days (interquartile range: 9–14 days). Ten percent of the patients had an adverse drug reaction. Of the 144 children who had a peripherally inserted central catheter placed, 25 (17%) had at least 1 peripherally inserted central catheter-associated complication: 14 (10%) had a mechanical problem, 11 (8%) had an infectious complication and 1 (1%) had a venous thromboembolism. Conclusions: As current Lyme meningitis treatment regimens have substantial associated morbidity, future research should investigate the efficacy of alternate regimens.

Herpes simplex virus infection in infants undergoing meningitis evaluation

In this study, HSV infection was identified in 0.42% of 26 533 encounters in 0 to 60-day-old infants being evaluated by LP for CNS infection. BACKGROUND: Although neonatal herpes simplex virus (HSV) is a potentially devastating infection requiring prompt evaluation and treatment, large-scale assessments of the frequency in potentially infected infants have not been performed. METHODS: We performed a retrospective cross-sectional study of infants ≤60 days old who had cerebrospinal fluid culture testing performed in 1 of 23 participating North American emergency departments. HSV infection was defined by a positive HSV polymerase chain reaction or viral culture. The primary outcome was the proportion of encounters in which HSV infection was identified. Secondary outcomes included frequency of central nervous system (CNS) and disseminated HSV, and HSV testing and treatment patterns. RESULTS: Of 26 533 eligible encounters, 112 infants had HSV identified (0.42%, 95% confidence interval [CI]: 0.35%–0.51%). Of these, 90 (80.4%) occurred in weeks 1 to 4, 10 (8.9%) in weeks 5 to 6, and 12 (10.7%) in weeks 7 to 9. The median age of HSV-infected infants was 14 days (interquartile range: 9–24 days). HSV infection was more common in 0 to 28-day-old infants compared with 29- to 60-day-old infants (odds ratio 3.9; 95% CI: 2.4–6.2). Sixty-eight (0.26%, 95% CI: 0.21%–0.33%) had CNS or disseminated HSV. The proportion of infants tested for HSV (35%; range 14%–72%) and to whom acyclovir was administered (23%; range 4%–53%) varied widely across sites. CONCLUSIONS: An HSV infection was uncommon in young infants evaluated for CNS infection, particularly in the second month of life. Evidence-based approaches to the evaluation for HSV in young infants are needed.

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger

Objective To determine the impact of a cerebrospinal fluid enterovirus polymerase chain reaction (PCR) test performance on hospital length of stay (LOS) in a large multicenter cohort of infants undergoing evaluation for central nervous system infection. Study design We performed a planned secondary analysis of a retrospective cohort of hospitalized infants ≤60 days of age who had a cerebrospinal fluid culture obtained at 1 of 18 participating centers (2005–2013). After adjustment for patient age and study year as well as clustering by hospital center, we compared LOS for infants who had an enterovirus PCR test performed vs not performed and among those tested, for infants with a positive vs negative test result. Results Of 19 953 hospitalized infants, 4444 (22.3%) had an enterovirus PCR test performed and 945 (21.3% of tested infants) had positive test results. Hospital LOS was similar for infants who had an enterovirus PCR test performed compared with infants who did not (incident rate ratio 0.98 hours; 95% CI 0.89–1.06). However, infants PCR positive for enterovirus had a 38% shorter LOS than infants PCR negative for enterovirus (incident rate ratio 0.62 hours; 95% CI 0.57–0.68). No infant with a positive enterovirus PCR test had bacterial meningitis (0%; 95% CI 0–0.4). Conclusions Although enterovirus PCR testing was not associated with a reduction in LOS, infants with a positive enterovirus PCR test had a one‐third shorter LOS compared with infants with a negative enterovirus PCR test. Focused enterovirus PCR test use could increase the impact on LOS for infants undergoing cerebrospinal fluid evaluation.