Marsha S. Anderson

Delayed Diagnosis of Kawasaki Syndrome: An Analysis of the Problem

Objective. Most pediatric providers in Colorado are familiar with Kawasaki syndrome (KS). However, in a recent outbreak, 30% of cases were diagnosed after illness day 10. We hypothesized that these children saw providers who were not familiar with KS, were given antibiotics for other diagnoses that delayed identification, had access-to-care issues, or presented atypically. Methods. A retrospective chart review of 106 consecutive KS cases seen at the Childrens Hospital in Denver during 1994–2000 was conducted. Results. Twenty-five of 106 children (23.6%) were diagnosed after day 10 of illness (delayed-diagnosis group [DDG]), and these 25 cases were compared with 81 cases diagnosed on or before day 10 (early-diagnosis group [EDG]). There were no differences between patients in the DDG and EDG in age, gender, number of visits, specialty of the primary care physician, time to the first medical visit, number of antibiotics received, coronary artery abnormalities, white blood cell count, or erythrocyte sedimentation rate. Patients in the DDG had significantly more days of fever, rash, red eyes, and oral changes. A platelet count of >450000/mm3 occurred more often in the DDG (56%) than the EDG (30%). After additional analysis, patients in the EDG had close clustering of symptom onset in the first few days of illness, but patients in the DDG had onset of symptoms scattered over 9 days. Patients in the DDG were 2.8 times more likely to have coronary artery aneurysms than patients in the EDG (DDG: 24%; EDG: 8.6%). Conclusions. Diagnosis after the 10th day of illness was not linked to type of medical provider, number of antibiotics received, or number of physician visits. Patients in the DDG exhibited the typical features of KS, but the onset of their symptoms was dispersed over time as opposed to the close clustering of symptoms in the EDG. Because coronary artery aneurysms occurred significantly more often in the patients in the DDG, more education is needed to teach health care providers to have a high index of suspicion for KS in young children presenting with fever/rash illnesses.

Multiplex MassTag-PCR for respiratory pathogens in pediatric nasopharyngeal washes negative by conventional diagnostic testing shows a high prevalence of viruses belonging to a newly recognized rhinovirus clade

Abstract Background Respiratory infections are the most common infectious diseases in humans worldwide and are a leading cause of death in children less than 5 years of age. Objectives Identify candidate pathogens in pediatric patients with unexplained respiratory disease. Study design Forty-four nasopharyngeal washes collected during the 2004–2005 winter season from pediatric patients with respiratory illnesses that tested negative for 7 common respiratory pathogens by culture and direct immunofluorescence assays were analyzed by MassTag-PCR. To distinguish human enteroviruses (HEV) and rhinoviruses (HRV), samples positive for picornaviruses were further characterized by sequence analysis. Results Candidate pathogens were detected by MassTag PCR in 27 of the 44 (61%) specimens that previously were rated negative. Sixteen of these 27 specimens (59%) contained picornaviruses; of these 9 (57%) contained RNA of a recently discovered clade of rhinoviruses. Bocaviruses were detected in three patients by RT-PCR. Conclusions Our study confirms that multiplex MassTag-PCR enhances the detection of pathogens in clinical specimens, and shows that previously unrecognized rhinoviruses, that potentially form a species HRV-C, may cause a significant amount of pediatric respiratory disease.

Abnormal liver panel in acute kawasaki disease.

Background and Aims: Abnormalities of liver panel (liver function test [LFT]) are frequently documented in patients with Kawasaki disease (KD). We sought to define the spectrum of abnormalities in liver panel tests in children with KD. We studied the characteristics of KD patients who presented with an abnormal liver panel and their response to treatment. Methods: We retrospectively reviewed the medical records of all KD patients admitted between 2004 and 2009 with one or more LFTs done at presentation and compared patients with and without at least 1 abnormal liver panel test including alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, and bilirubin. These patients were divided into 2 groups: those with normal LFTs (normal LFT group) and those with at least one abnormal LFT at presentation (abnormal LFT group). Results: Of 259 patients, 240 (92.7%) patients with KD reviewed had one or more LFTs performed. One hundred nine (45.4%) had at least 1 abnormal liver panel test. Patients in the abnormal LFT group presented earlier (P = 0.01) and were more likely to have intravenous immunoglobulin (IVIG) resistant disease (P = 0.01). There was no significant difference between groups in development of coronary artery abnormalities or aneurysms. Multivariate analysis identified C-reactive protein and total bilirubin at admission as significant predictors for IVIG resistant disease. Conclusion: We report the largest US single center study of the spectrum of liver panel abnormalities in children with acute KD. Abnormalities of LFTs are frequently found in patients with acute KD and children with abnormal LFTs were at higher risk for IVIG resistance.

Preventing Coronary Artery Abnormalities: A Need for Earlier Diagnosis and Treatment of Kawasaki Disease

Objectives: The aim of this study was to explore the timing of coronary artery (CA) abnormalities in light of the expanding clinical spectrum of Kawasaki disease (KD). Methods: We reviewed all cases of KD admitted to Children’s Hospital Colorado from January 2007 through February 2011 who had CA abnormalities. A retrospective chart review was conducted to collect demographic, clinical, laboratory and echocardiogram (ECHO) data. CA abnormalities were defined as Z score ≥2.5 or presence of ectasia or aneurysms. Results: A total of 210 patients with KD were identified. Fifty-seven (27.1%) of the 210 children with KD had CA abnormalities. Forty-six of the 57 (81%) children with CA abnormalities had CA abnormalities noted on their initial ECHO. Of the 46 children who had CA abnormalities detected on their initial ECHO, 37 (80%) had their ECHO on or before illness day 10. The median day of illness when abnormalities were detected on initial ECHO was day 7 (interquartile range: 5–8; range: 2–24 days). Only 25 of the 46 children (54%) were classified as complete KD, but 40 (87%) had the triad of conjunctivitis, rash and mucous membrane involvement. Thirteen (28%) had intravenous immunoglobulin–resistant disease. Conclusion: The majority of CA abnormalities in children with KD were identified in the initial ECHO, during the first week of illness. Earlier diagnosis and treatment is needed to impact the incidence of CA abnormalities in children with KD. Increased clinical suspicion and earlier use of ECHO in the initial workup of children with suspected KD may lead to more rapid diagnosis and treatment.

Investigation of Kawasaki syndrome risk factors in Colorado.

Risk factors for Kawasaki syndrome (KS) were evaluated through a case-control study during an investigation of a KS cluster in Denver, CO. KS was associated with a humidifier in the childs room (odds ratio, 7.3; 95% confidence interval, 1.8 to 29.3) and possibly with an antecedent respiratory illness. The use of humidifiers should be further investigated as part of future studies of KS.

Blinded Case‐Control Study of the Relationship between Human Coronavirus NL63 and Kawasaki Syndrome

Abstract We conducted a blinded, case‐control, retrospective study in pediatric patients hospitalized at The Children’s Hospital, Denver, Colorado, to determine whether human coronavirus (HCoV)–NL63 infection is associated with Kawasaki syndrome (KS). Over the course of a 7‐month period, nasopharyngeal‐wash samples from 2 (7.7%) of 26 consecutive children with KS and 4 (7.7%) of 52 matched control subjects tested positive for HCoV‐NL63 by reverse transcription–polymerase chain reaction. These data suggest that, although HCoV‐NL63 was circulating in children in our community during the time of the study, the prevalence of infection with HCoV‐NL63 was not greater in patients with KS than in control subjects.

Concurrent Respiratory Viruses and Kawasaki Disease

BACKGROUND: The diagnosis of Kawasaki disease (KD) remains challenging without a definitive diagnostic test and currently is guided by using clinical patient characteristics and supported by laboratory data. The role of respiratory viruses in the pathogenesis of KD is not fully understood. METHODS: Charts of patients with KD admitted to Children’s Hospital Colorado from January 2009 to May 2013 were retrospectively reviewed. Patients with KD who had a nasopharyngeal wash submitted for multiplex polymerase chain reaction (PCR) viral testing were included. Clinical characteristics, laboratory data, and outcomes of patients with and without positive respiratory viral PCR results were compared. RESULTS: Of 222 patients with KD admitted to the hospital, 192 (86%) had a respiratory viral PCR test performed on or shortly after admission. Ninety-three (41.9%) of the 192 patients with KD had a positive respiratory viral PCR, and the majority were positive for rhinovirus/enterovirus. No statistically significant differences were found in the clinical characteristics and laboratory values between the groups with and without positive respiratory viral PCR findings. Both groups had the same frequency of upper respiratory and gastrointestinal symptoms and had the same incidence of admission to the PICU, intravenous immunoglobulin–resistant disease, and coronary artery lesions. CONCLUSIONS: No differences in clinical presentations or outcomes in children with KD stratified according to positive or negative respiratory viral PCR testing were observed. A positive respiratory viral PCR or presence of respiratory symptoms at the time of presentation should not be used to exclude a diagnosis of KD.

Kawasaki disease and the pediatric gastroenterologist: a diagnostic challenge.

Background and Objectives: Gastrointestinal symptoms and signs are rarely the main clinical presentation of Kawasaki disease (KD). In the present study, we report a series of patients with KD in whom a gastroenterology consult was obtained before consideration of the diagnosis of KD. Methods: We retrospectively reviewed all patients with KD admitted to Childrens Hospital Colorado from January 2009 through February 2011 with prominent gastrointestinal symptoms, resulting in gastrointestinal service consultation before their diagnosis of KD. Results: We identified 7 of 118 (6%) patients with KD who met our criteria. All 7 patients were males, and the median age at admission was 9.7 years. All patients had abdominal pain and fever at presentation. Vomiting, diarrhea, and clinical jaundice were present in 70%, 50%, and 43% of patients, respectively. Aminotransferases and/or &ggr;-glutamyl transpeptidase abnormalities were observed in 6 (89%) patients. All of the patients had fever and rash on admission, and 86% had nonexudative conjunctivitis and 71% had mucosal changes. Median duration of illness at gastroenterology consultation was 5 days, whereas median duration of illness at infectious disease consultation was 6 days. One patient developed coronary artery dilation and 2 patients had intravenous immunoglobulin-resistant KD. Conclusions: Gastroenterologists should be aware of gastrointestinal presentations of KD. Unexplained gastrointestinal symptoms in the presence of fever, and 1 or 2 of the major clinical signs of KD, should prompt consideration of KD in the differential diagnosis.

Facilitated Peer Group Mentoring: A Case Study of Creating Leadership Skills Among the Associate Program Directors of the APPD

I t is well recognized that academic faculty benefit from mentoring relationships in order to achieve their professional goals, facilitate their scholarly productivity, and make meaningful contributions to their colleagues, trainees, institutions, and departments. Junior faculty are faced with many challenges in developing effective mentoring relationships, including lack of available senior faculty members with proper skill sets or interest in mentorship. Although many mentoring models exist, the most commonly pursued by academic faculty is dyadic mentoring. In traditional dyadic mentoring, one mentor is matched with one mentee (often geographically) based on common interests. Ideally, the dyad participates in a bidirectional relationship. There is a growing body of evidence that other innovative mentoring models, such as facilitated peer group mentoring (FPGM), may be more successful. In FPGM, a senior mentor is assigned to a small group of mentees. The group members serve as peer mentors to each other while working on common interests or projects. The process is facilitated by the senior mentor, who may or may not be a content expert. In this paper, we discuss a case study in which effective, productive mentoring was provided through the use of FPGM. This case study involving associate program directors is illustrative of a successful mentoring experience that resulted in academic productivity and enhanced leadership skills. Associate program directors are involved directly in the

Kawasaki Disease and Exposure to Fine Particulate Air Pollution.

OBJECTIVE To analyze associations of short-term exposure to fine particulate matter (diameter ≤ 2.5 µm [PM2.5]), a measurable component of urban pollution, with the event date of fever onset for patients with Kawasaki disease (KD) residing in 7 metropolitan regions. STUDY DESIGN A case-crossover study design was used. Time trends, seasonality, month, and weekday were controlled for by matching. We assembled PM2.5 exposure measurements from urban monitors and imputed PM2.5 to provide day-to-day temporal variability and resolution for time series indexes of exposures. Selected exposure windows (to 14 days) of PM2.5 were examined. RESULTS A total of 3009 KD events were included for which the subject resided within a study metropolitan area and the event date occurred during years with available PM2.5. The estimated ORs (with 95% CIs) of an event of KD associated with a 10 µg/m(3) PM2.5 lagged moving average concentration of lagged exposure period (ie, concurrent, preceding day[s]) revealed no evidence of a consistent, statistically significant, positive association between elevated PM2.5 exposure and increased risk of KD. Extended analysis with stratification by city, sex, age, ethnic origin, incomplete or complete clinical manifestations, the presence of coronary aneurysm, and intravenous immunoglobulin resistance did not provide evidence of a consistent, statistically significant, positive association between elevated exposure to PM2.5 and increased risk of KD for any of the strata studied. CONCLUSIONS This multicity study failed to establish a risk of the event of KD with short-term fine particulate exposure. Our negative findings add to the growing field of environmental epidemiology research of KD.