Acute Kawasaki Disease Research Articles

The role of interleukin-9 and interleukin-17 in myocarditis with different etiologies

Abstract Objective Myocarditis is an inflammatory disease of the cardiac muscle. Prognosis is most often good but, in some patients, the disease can be fulminant. Our aim with this study was to determine interleukin-9 (IL-9) and interleukin-17 (IL-17) levels in myocarditis cases with different etiologies. Materials and methods Thirty one patients with myocarditis and 30 healthy controls of similar age and gender without a history of chronic disease were included in the study. All 31 patients were clinically myocarditis. In some of these patients, the cause of myocarditis is acute rheumatic fever or Kawasaki disease. Serum samples of the patients were taken during diagnosis in order to analyze serum IL-9 and IL-17 levels and sedimentation rate, CRP, ASO, pro-BNP, CK-MB, and Troponin-I tests were performed. Results It was found that IL-17 levels were statistically significant in all acute rheumatic fever, Myocarditis and Kawasaki patients compared to the control group (p = 0.001) and that cut-off was 4.30 pg/mL. This value was determined to be 71% sensitive and 67% specific for IL-17 (AUC = 0.761). Conclusions Both of the mean and median levels of IL-17 were significantly higher in pediatric patients with myocarditis than in healthy children. Our study made us think that complications of myocarditis and associated morbidity can be prevented by IL17 inhibitors. The high levels of IL17 found in our study may be a reference for future study.

Circulating Markers of Inflammation Persist in Children and Adults With Giant Aneurysms After Kawasaki Disease.

The sequelae of Kawasaki disease (KD) vary widely with the greatest risk for future cardiovascular events among those who develop giant coronary artery aneurysms (CAA). We sought to define the molecular signature associated with different outcomes in pediatric and adult KD patients. Molecular profiling was conducted using mass spectrometry-based shotgun proteomics, transcriptomics, and glycomics methods on 8 pediatric KD patients at the acute, subacute, and convalescent time points. Shotgun proteomics was performed on 9 KD adults with giant CAA and matched healthy controls. Plasma calprotectin was measured by ELISA in 28 pediatric KD patients 1 year post-KD, 70 adult KD patients, and 86 healthy adult volunteers. A characteristic molecular profile was seen in pediatric patients during the acute disease, which resolved at the subacute and convalescent periods in patients with no coronary artery sequelae but persisted in 2 patients who developed giant CAA. We, therefore, investigated persistence of inflammation in KD adults with giant CAA by shotgun proteomics that revealed a signature of active inflammation, immune regulation, and cell trafficking. Correlating results obtained using shotgun proteomics in the pediatric and adult KD cohorts identified elevated calprotectin levels in the plasma of patients with CAA. Investigation of expanded pediatric and adult KD cohorts revealed elevated levels of calprotectin in pediatric patients with giant CAA 1 year post-KD and in adult KD patients who developed giant CAA in childhood. Complex patterns of biomarkers of inflammation and cell trafficking can persist long after the acute phase of KD in patients with giant CAA. Elevated levels of plasma calprotectin months to decades after acute KD and infiltration of cells expressing S100A8 and A9 in vascular tissues suggest ongoing, subclinical inflammation. Calprotectin may serve as a biomarker to inform the management of KD patients following the acute illness.

Implications of hepatic dysfunction in Kawasaki disease: Time-related changes in aspartate aminotransferase, alanine aminotransferase, total bilirubin, and C-reactive protein levels.

ImportanceThe cause of the hepatic dysfunction that commonly accompanies Kawasaki disease (KD) remains unclear.ObjectiveWe tried to clarify the cause of the hepatic dysfunction.MethodsA total of 381 consecutive patients with acute KD, who had undergone inpatient treatment with intravenous immunoglobulin until the 7th day of illness, were divided into a group of 199 patients with an alanine aminotransferase (ALT) level ≥ 40 IU/L on admission (group I), a group of 52 patients with an ALT level ≥ 40 IU/L at some point after admission (group II), and a group of 130 patients with ALT levels consistently < 40 IU/L throughout hospitalization (group III). Aspartate aminotransferase (AST), ALT, total bilirubin (T‐Bil), and C‐reactive protein (CRP) levels were analyzed over time, and time‐courses were compared.ResultsIn the initial stage of illness, in group I, AST, ALT, T‐Bil peaked on days 1–3, and AST tended to improve significantly on the 4th day (P < 0.001). T‐Bil improved on day 5 (P < 0.01), and ALT improved significantly on day 6 (P < 0.001). CRP increased every day up to day 6 (P < 0.001). In group II, AST and ALT increased after admission, and thereafter CRP increased, then decreased. The frequency of use of aspirin and aspirin doses did not differ significantly in the three groups.InterpretationRecovery from liver dysfunction occurred in the initial stage of illness in group I—within the period of CRP exacerbation, which is an indicator of systemic inflammation.

Genome-wide transcriptome analysis to further understand neutrophil activation and lncRNA transcript profiles in Kawasaki disease

Kawasaki disease (KD) is the most common cause of acquired cardiac disease in children in developed countries. However, little is known regarding the role of transcriptomic targets of KD in the disease progression and development of complications, especially coronary artery aneurysms (CAA). The aim of our study was to identify transcripts affected by KD and their potential role in the disease. We enrolled 37 KD patients and collected blood samples along a comprehensive time-course. mRNA profiling demonstrated an abundance of CD177 transcript in acute KD, and in the intravenous immunoglobulin (IVIG)-resistant group compared to in the IVIG-sensitive group. lncRNA profiling identified XLOC_006277 as the most highly expressed molecule. XLOC_006277 expression in patients at acute stage was 3.3-fold higher relative to patients with convalescent KD. Moreover, XLOC_006277 abundance increased significantly in patients with CAA. XLOC_006277 knockdown suppressed MMP-8 and MMP-9 expression, both associated with heart lesions. Our result suggested that the increase of CD177pos neutrophils was associated with KD. Moreover, this study provided global long non-coding RNA transcripts in the blood of patients with KD, IVIG-resistant KD, or CAA. Notably, XLOC_006277 abundance was associated with CAA, which might contribute to further understanding of CAA pathogenesis in KD.

Diagnostic Value of Serum MiR-1 in Patients with Acute Kawasaki Disease.

The current study aims to investigate the expression of miR-1 in serum of patients with Kawasaki disease (KD) and its clinical significance. The serum samples of 33 patients with KD and 15 healthy people were collected from January 2017 to June 2017 at the Affiliated Hospital of North China University of Science and Technology. The expression of serum miR-1 was detected by real-time quantitative PCR (RT-qPCR). The diagnostic value of miR-1 as a marker of KD disease was evaluated by receiver operating characteristic (ROC) curve. The level of miR-1 in serum of children with acute KD was significantly higher than that of healthy children, but it decreased to normal level in convalescence. ROC curves showed that the area under the curve (AUC) of miR-1 for KD diagnosis was 0.754 (95% CI: 0.541 - 0.952). When the critical value (diagnostic threshold) was 1.08, the diagnostic sensitivity and specificity were 0.867 and 0.735, respectively. In addition, we further divided the KD patients according to clinical characteristics. Here, we showed that the expression of miR-1 was higher in the serum of KD patients with higher platelet level. In summary, serum miR-1 in patients with acute KD was significantly increased, which may be one of the potential serum markers for the diagnosis of KD.

A new scoring system to predict Kawasaki disease with coronary artery lesions.

To clarify the independent risk factors and construct a scoring system for Kawasaki disease (KD) with coronary artery lesions (CAL) at acute and subacute stages. Data of KD inpatients at acute and subacute stages were reviewed in a tertiary care center from January 2009 to December 2014. A total of 2305 acute and subacute KD cases were enrolled in this study with a CAL rate of 24.1%. The OR (95%CI) values of male, total fever duration ≥ 8days, IVIG resistance (IVIGR), albumin (ALB) ≤ 35.9g/L, eosionphils (EO) ≥ 2.2%, and monocytes (MO) ≥ 5.9% were 1.45 (1.15-1.82), 1.78 (1.43-2.22), 1.42 (1.09-1.85), 1.53 (1.23-1.91), 1.17 (0.94-1.45), and 1.37 (1.09-1.69), respectively. In patients ≤ 6months old, the OR (95%CI) values for total fever duration ≥8days, delayed diagnosis, and ALB ≤ 35.9g/L were 3.61 (2.02-6.45), 3.49 (1.49-8.16), and 2.07 (1.14-3.74), respectively. ROC curve showed that the AUC value and sensitivity and specificity of predicting KD with CAL in patients ≤ 6months old were 0.731, 64.7%, and 80.9%, respectively. The independent risk factors for acute and subacute KD combined with CAL, including being a boy, long fever duration, IVIGR, low ALB, elevated EO, and MO. Joint of parameters (total fever duration ≥ 8days, delayed diagnosis, and ALB ≤ 35.9g/L) can be used to predict the occurrence of CAL in KD patients ≤ 6months old.

Bifid T waves on the ECG and genetic variation in calcium channel voltage-dependent beta 2 subunit gene (CACNB2) in acute Kawasaki disease.

We previously described the association of genetic variants in calcium channel genes and susceptibility to Kawasaki disease (KD), an acute, self-limited vasculitis, and the most common cause of acquired cardiac disease in children. Abnormal repolarization of cardiomyocytes and changes in T wave morphology have been reported in KD but have not been studied systematically. We analyzed acute and convalescent ECG T wave morphology in two independent cohorts of KD subjects and studied the association between bifid T waves and genetic variants in previously reported genes with SNVs associated with cardiac repolarization. Bifid T waves in limb leads were identified in 24% and 27% of two independent cohorts of acute KD subjects. Calcium channel voltage-dependent beta 2 subunit gene (CACNB2) (rs1409207) showed association with bifid T waves in both cohorts (nominal P = .04 and P = .0003, respectively). This CACNB2 polymorphism also showed association with KD susceptibility in a previously published KD genome wide association study data (nominal P = .009). This genotype/phenotype association study uncovered a variant in CACNB2 that may be associated with both KD susceptibility and bifid T waves, a novel signature of altered myocardial repolarization. The present study combined with published reports suggests that genetic variants in calcium channels and intracellular calcium signaling play a prominent role in shaping susceptibility to KD.

Predictors for coronary artery dilatation in Kawasaki disease

Background Kawasaki disease (KD) is an acute, self-limited, febrile illness of unknown cause that predominantly affects children below 5 years of age. It has a high incidence of coronary complications such as aneurysms. The current treatment of choice is intravenous immunoglobulin, which is costly, with aspirin. Identifying the predictive factors for coronary artery dilatation or aneurysm is important in order to establish the indications for giving immunoglobulin, especially when resources are limited.&#x0D; Objective&#x0D; To identify the predictors for the development of coronary artery dilatation in patients with Kawasaki disease&#x0D; Methods This cross-sectional study was done between January 2003 and July 2013. Inclusion criteria were patients who fulfilled the American Heart Association criteria for acute Kawasaki disease, and had complete clinical, echocardiogram, and laboratory data [hemoglobin, leukocyte, platelet, albumin, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR)]. All of them received immunoglobulin and aspirin.&#x0D; Results Of 667 KD patients, 275 met the inclusion criteria. There were 185 (67%) males. Subjects’ ages varied between 1 to 157 months. The frequency of coronary artery dilatation at the acute phase was 33.3%. Multivariate analysis showed that &gt;7-day duration of fever and hypoalbuminemia were significant predictive factors for coronary artery dilatation.&#x0D; Conclusion Predictive factors for coronary artery dilatation are duration of fever over 7 days and hypoalbuminemia, while age, gender, hemoglobin level, leukocyte count, and platelet count are not. Frequency of coronary artery dilatation at the acute phase is 33.3%.

A Decade of NT-proBNP in Acute Kawasaki Disease, from Physiological Response to Clinical Relevance.

Kawasaki disease (KD) is an inflammatory febrile illness of early childhood and the primary cause of acquired heart disease during childhood. Coronary artery aneurysms (CAA) are a serious complication of KD, leading to ischemic heart disease, myocardial infarction, and sudden cardiac death. Timely diagnosis in the first ten days of fever is crucial to reduce the risk of coronary artery complications. Nitrogen-terminal B-type natriuretic peptide (NT-proBNP), originally used for the management of adults with heart disease, was shown to be useful in the diagnosis and management of patients with KD. NT-proBNP is released by cardiomyocytes in response to mechanical factors such as the dilation of cardiac chambers, and to pro-inflammatory cytokines. The utility of NT-proBNP as a biological marker in KD is based on the universal myocardial inflammatory component early in the course of the disease. Patients with KD have higher NT-proBNP at the time of diagnosis than febrile controls, with a pooled sensitivity of 89% (95% confidence interval 78–95), and a specificity of 72% (95% confidence interval 58–82). The positive likelihood ratio is 3.2:1 (95% confidence interval 2.1–4.8). Moreover, patients with resistance to intravenous immunoglobulin treatment and CAA were found to have higher levels of NT-proBNP, suggesting a prognostic role. Nevertheless, the non-specificity of NT-proBNP to KD limits its use as a stand-alone test. In this light, a tentative associative retrospective diagnostic algorithm was highly reliable for including all cases at risk of CAA, which warrants further prospective studies for a better diagnostic index of suspicion and risk stratification of patients.

Circulating adipokines are associated with Kawasaki disease

BackgroundThe pathogenesis of Kawasaki disease are still not well understood. It was designed to investigate the relationship between adipokines including chemerin, omentin-1, adiponectin and acute Kawasaki disease.MethodsEnzyme-linked immunosorbent (ELISA) was used to detect serum levels of chemerin, omentin-1, adiponectin, and inflammatory cytokines IL-1β and TNF-α in 80 cases of patients diagnosed with Kawasaki disease (KD). In addition, 20 cases of children with fever and 20 cases of healthy children were selected as febrile and normal controls.Results(1) Serum levels of chemerin in KD group (87.736 ± 56.310) are higher than that of both the healthy (41.746 ± 10.824) and the febrile controls (59.683 ± 18.282) (P < 0.01). (2) Circulating omentin-1 levels in Kawasaki disease group (389.773 ± 238.611) are significantly lower than that of febrile control (542.075 ± 177.995) (P < 0.01), also serum adiponectin levels in Kawasaki disease group (16.400 ± 12.243) reduced obviously compared with the febrile control group (35.074 ± 12.486). (3)Serum cytokine levels of IL-1β in Kawasaki disease group (13.656 ± 31.151) are higher than those of normal controls (2.415 ± 6.313) (P < 0.05). (4) Correlation analysis indicates that serum levels of chemerin are positively correlated with omentin-1 (r = 0.224, 95% CI 0.06–0.529, P < 0.05). Further, serum omentin-1 levels and total cholesterol (TC) are positively correlated (r = 0.358, 95% CI 0.169–0.518, P < 0.01).ConclusionsCirculating chemerin increased significantly in the acute stage of Kawasaki disease, while omentin-1 and adiponectin levels are decreased. These adipokines are closely associated with the early inflammation and lipid metabolism disorders of acute Kawasaki disease.

Changes and significance of histone acetylation associated with forkhead box P3 gene during the acute phase of Kawasaki disease

Objective To investigate the histone acetylation status of forkhead box P3(Foxp3) gene and its roles in immunological pathogenesis of Kawasaki disease(KD). Methods Forty-two children with KD and 32 age-matched healthy children consented to participate in this study as a control group.Co-immunoprecipitation and real-time PCR were performed to determine acetylation levels of histone H4 associated with Foxp3 gene and binding abilities of Kruppel like factor 10(KLF10) and p300/CBP-associated factor (PCAF) with Foxp3 gene in CD4+ T cells.The proportion of CD4+ CD25high Foxp3+ cells (Treg) and protein levels of Foxp3, KLF10, PCAF, phosphated SMAD family member 2/3(pSmad2/3) and itchy E3 ubiquitin protein ligase(Itch) were analyzed by flow cytometry.Quantitative real-time PCR was used to evaluate the levels of Foxp3, transforming growth factor-β1 receptor Ⅱ (TGF-βRⅡ), transforming growth factor-β1 receptor Ⅰ(TGF-βRⅠ), tyrosine kinase 2(Tyk2), SH2 domain-containing protein-tyrosine phosphatase-2(SHP2) and cytotoxic T-lymphocyte-associated protein 4(CTLA4) mRNA in Treg.Plasma concentrations of TGF-β and interleukin-6(IL-6) were measured by enzyme-linked immunosorbent assay. Results (1)Compared with the control group, the proportion of Treg, expression levels of Foxp3 and TGF-β, and histone acetylation levels of Foxp3 promoter decreased remarkably during acute KD, and the differences were all statistically significant(all P<0.05), and restored after IVIG therapy(all P<0.05). Meanwhile, the 5 indexes aforementioned in KD patients with coronary artery lesions (KD-CAL+ ) were lower than those without coronary artery lesions(KD-CAL-), and the differences were all statistically significant (all P<0.05). (2)Compared with the control group, protein levels of KLF10 and PCAF in Treg cells, and their binding abilities with Foxp3 gene were significantly down-regulated during acute KD, and the differences were all statistically significant(all P<0.05), and restored to some extent after IVIG treatment(all P<0.05). Positive correlations between protein levels of KLF10 and PCAF, and mRNA level of Foxp3 were detected in acute KD patients (r=0.47, 0.59, all P<0.05). Furthermore, protein levels of KLF10 and PCAF and their binding abilities with Foxp3 gene in KD-CAL+ group were lower than those in KD-CAL- group, and the differences were all statistically significant(all P<0.05). (3) Compared with the control group, the plasma concentration of TGF-β and expressions of TGF-βRⅡ/Ⅰ, pSmad2/3, Itch, CTLA4 and SHP2 in Treg were down-regulated during the acute phase of KD, and the differences were all statistically significant(all P<0.05), as well as plasma concentration of IL-6 and expression its downstream molecule Tyk2 increased remarkably in patients with acute KD(all P<0.05). All the indexes mentioned before restored significantly after IVIG treatment (all P<0.05). Simultaneously, the 7 former indexes in KD-CAL+ group were found to be lower than those in KD-CAL- group, while 2 indexes of the latter in KD-CAL+ group were higher than those in KD-CAL- group, and the differences were all statistically significant(all P<0.05). Conclusion Histone hypoacetylation of Foxp3 promoter might be one of the important factors contributing to insufficiency and dysfunction of regulatory T cells during acute Kawasaki disease. Key words: Kawasaki disease; Foxp3; Histone; Acetylation; Immune

Serum levels of C1q/tumor necrosis factor-related protein-1 in children with Kawasaki disease.

BackgroundTo investigate the serum C1q/tumor necrosis factor-related protein-1 (CTRP1) levels in children with acute Kawasaki disease (KD), as well as the relationship between CTRP1 levels and laboratory variables.MethodsEighty-seven children with KD and 38 healthy controls (HCs) were included in this study. General characteristics were obtained from all subjects. Serum CTRP1 levels in all subjects and serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels in KD patients were measured using enzyme-linked immunosorbent assay.ResultsCompared with the HC group, serum CTRP1 levels were significantly elevated in the KD group. Significantly higher serum TNF-α, IL-1β, IL-6, and CTRP1 levels were observed in patients with KD with coronary artery lesions (KD-CALs) than in patients with KD without CALs (KD-NCALs). Serum CTRP1 levels were positively correlated with white blood cell counts (WBC), percentage of neutrophils (N%), thrombin time (TT), procalcitonin (Pct), TNF-α, IL-1β, and IL-6 levels. Meanwhile, CTRP1 levels were negatively correlated with the percentage of leukomonocytes (L%) in KD patients. Furthermore, serum CTRP1 levels were positively correlated with the time point of intravenous immunoglobulin (IVIG), WBC, N%, TNF-α, IL-1β, and IL-6 levels in the KD-CAL group.ConclusionCTRP1 may participate in the process of vasculitis and blood coagulation during the acute phase of KD.

Safety study of live, oral human rotavirus vaccine: A cohort study in United States health insurance plans

ABSTRACTAs part of a regulatory commitment for post-licensure safety monitoring of live, oral human rotavirus vaccine (RV1), this study compared the incidence rates (IR) of intussusception, acute lower respiratory tract infection (LRTI) hospitalization, Kawasaki disease, convulsion, and mortality in RV1 recipients versus inactivated poliovirus vaccine (IPV) recipients in concurrent (cIPV) and recent historical (hIPV) comparison cohorts. Vaccine recipients were identified in 2 claims databases from August 2008 – June 2013 (RV1 and cIPV) and January 2004 – July 2008 (hIPV). Outcomes were identified in the 0–59 days following the first 2 vaccine doses. Intussusception, Kawasaki disease, and convulsion were confirmed via medical record review. Outcome IRs were estimated. Incidence rate ratios (IRRs) were obtained from Poisson regression models. A post-hoc self-controlled case series (SCCS) analysis compared convulsion IRs in a 0–7 day post-vaccination period to a 15–30 day post-vaccination period. We identified 57,931 RV1, 173,384 cIPV, and 159,344 hIPV recipients. No increased risks for intussusception, LRTI, Kawasaki disease, or mortality were observed. The convulsion IRRs were elevated following RV1 Dose 1 (cIPV: 2.07, 95% confidence interval [CI]: 1.27 – 3.38; hIPV: 2.05, 95% CI: 1.24 – 3.38), a finding which is inconclusive as it was observed in only one of the claims databases. The IRR following RV1 Dose 1 in the SCCS analysis lacked precision (2.40, 95% CI: 0.73 – 7.86). No increased convulsion risk was observed following RV1 Dose 2. Overall, this study supports the favorable safety profile of RV1. Continued monitoring for safety signals through routine surveillance is needed to ensure vaccine safety.

Infliximab Pharmacokinetics are Influenced by Intravenous Immunoglobulin Administration in Patients with Kawasaki Disease.

Infliximab, a monoclonal antibody directed against tumor necrosis factor-α, is being evaluated as adjunctive therapy to intravenous immunoglobulin (IVIG) for treatment of young children with acute Kawasaki disease (KD). The aim of this study was to develop a population pharmacokinetic (PopPK) model for infliximab in children with KD, and to evaluate the impact of covariates on infliximab disposition. Specifically, we wanted to investigate the effect of body weight and IVIG administration on PK parameters. In the current PopPK analysis, 70 subjects with a median (interquartile range) age of 2.9years (1.3-4.4) were included from two randomized controlled trials. Infliximab concentration-time data were best described by a two-compartment model with first-order elimination using non-linear mixed-effects modeling (NONMEM 7.3). The clearance, volume of distribution of the central (V1) and peripheral (V2) compartment, and intercompartmental clearance estimates (95% confidence interval) from the PopPK analysis were 0.117 (0.091-0.134) L/day, 0.801 (0.545-0.960) L, 0.962 (0.733-1.759) L, and 0.692 (0.482-1.779) L/day, respectively. Allometric body weight was included on all parameters of the structural model and a covariate analysis revealed that administering infliximab after IVIG, as opposed to before, resulted in a 50% decrease in V2. Our study shows that the timing of infliximab administration relative to IVIG administration affects the disposition of the monoclonal antibody. These results may have important implications for other monoclonal antibodies administered in combination with IVIG for treating inflammatory diseases.

MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki Disease

Kawasaki Disease (KD) is an acute inflammatory disease that takes the form of systemic vasculitis. Endothelial microparticles (EMPs) have been recognized as an important transcellular delivery system. We hypothesized whether EMPs are involved in vasculitis in acute KD. Fifty patients with acute KD were enrolled, divided into two subgroups: those with coronary artery lesions (CAL) (n = 5) and those without CAL (NCAL) (n = 45). EMPs were measured using flow cytometry, and microRNA (miR) expression profiling was performed by microRNA array. The percentage of EMPs in acute KD was significantly higher than in controls (P < 0.0001). EMPs in patients with CAL rapidly increased after the initial treatment, and was significantly higher than those in NCAL (P < 0.001). In patients with CAL, we identified 2 specific miRs encapsulated in EMPs, hsa-miR-145-5p and hsa-miR-320a, which are predicted to affect monocyte function using in silico analysis, and were demonstrated to upregulate inflammatory cytokine mRNAs in THP-1 monocytes. In situ hybridization confirmed that hsa-miR-145-5p was preferentially expressed in CAL. EMPs may serve as a sensitive marker for the severity of vasculitis in acute KD. Moreover, these 2 specific miRs encapsulated in EMPs might be involved in inflammatory cytokine regulation and the pathogenesis of vasculitis in acute KD.

Management of sequelae of Kawasaki disease in adults.

Background: A growing population of young adults is presenting to cardiologists with late manifestations of Kawasaki disease (KD) that include cardiomyopathy, ischemia, and infarction. The management of these conditions differs in important ways from atherosclerotic heart disease, and yet there is little awareness in the adult cardiology community regarding the special challenges posed by the cardiovascular sequelae of KD.Methods: Observations were made on a population of 140 adult KD patients enrolled in the San Diego Adult KD Collaborative Study.Results: Coronary artery aneurysms resulting from KD in childhood are associated with a high risk of thrombosis and stenosis at the inlet or outlet of the aneurysm. These aneurysms are often highly calcified and may contain a large thrombus burden that may obscure the true size of the aneurysm. Pitfalls in the management of these patients stem largely from failure to recognize the nature of the lesions, which leads to attempts to dilate highly calcified stenotic segments and undersizing of stents. Intravascular ultrasound is helpful in appreciating the true dimensions of the aneurysm, which may be filled with thrombus. Thrombolysis and use of anti-platelet agents followed by systemic anti-coagulation are appropriate management strategies for patients presenting with acute infarction. Bypass grafting with the internal thoracic arteries can be a successful strategy, but care must be taken to avoid competitive flow through the native vessel leading to graft failure. In contrast to the individuals who developed coronary artery aneurysms, young adults who had documented normal echocardiograms associated with their acute KD in childhood and who have no evidence of calcium deposition in the arterial wall as assessed by computed tomography (CT) calcium score appear to have no increased cardiovascular risk in the medium term. Long-term outcomes for adults post-KD in childhood are still being defined.Conclusions: KD poses special management challenges for the adult cardiologist who must recognize the unique features of the cardiovascular lesions in this growing population of patients.

Frequently asked questions regarding treatment of Kawasaki disease.

[first paragraph of article]The mainstay of therapy for acute Kawasaki disease (KD) is intravenous immunoglobulin (IVIG), which was first described in a case series from Japan and later proven through a nationwide clinical trial in the U.S. published in 1986. Since completion of the initial clinical trials, many questions have arisen regarding the nuances of KD treatment. In the absence of an evidence base, what follows is an attempt to devise rational responses to these questions that draw upon common sense and the personal experience of this author.

C-reactive protein and N-terminal pro-brain natriuretic peptide discrepancy: a differentiation of adenoviral pharyngoconjunctival fever from Kawasaki disease.

PurposeTo differentiate adenoviral pharyngoconjunctival fever (PCF) from acute Kawasaki disease (KD) using laboratory tests before results of virus-real time polymerase chain reaction and ophthalmologic examination are obtained.MethodsBaseline patient characteristics and laboratory measurements were compared between 40 patients with adenovirus infection and 123 patients with KD.ResultsThe patients with adenovirus infection were generally older than those with KD (median: 3.9 years vs. 2 years, P=0.000). White blood cell and, platelet count, and aspartate aminotransferase, alanine aminotransferase, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels showed significant differences between the 2 groups, but the C-reactive protein (CRP) levels did not (6.8±3.0 mg/dL vs. 8.3±5.8 mg/dL, P=0.126). In the adenovirus infection group, the CRP levels were <1, <3, <10, and ≥10 mg/dL in 2 (5%), 3 (7.5%), 30 (75%), and 5 patients (12.5%), respectively. The cutoff NT-proBNP level was 265 pg/mL. Discrepancy was defined as CRP and NT-proBNP levels of ≥3 or <3 mg/dL, and <265 or ≥265 pg/mL, respectively. Among the 35 patients with adenovirus infection whose CRP levels were ≥3 mg/dL, 29 (82.9%) showed a discrepancy. Conversely, of the 103 patients with KD whose CRP levels were ≥3 mg/dL, 83 (80.6%) showed no discrepancy. Between the groups, a significant difference in discrepancy rate was observed (P=0.000). None of the patients with adenovirus infection had CRP and NT-proBNP levels of <3 mg/dL and ≥265 pg/mL, respectively.ConclusionWith a sensitivity of 82.9% and a specificity of 80.6%, CRP and NT-proBNP levels may differentiate between adenoviral PCF and acute KD.

Clinical implications in laboratory parameter values in acute Kawasaki disease for early diagnosis and proper treatment.

PurposeThis study aimed to analyse laboratory values according to fever duration, and evaluate the relationship across these values during the acute phase of Kawasaki disease (KD) to aid in the early diagnosis for early-presenting KD and incomplete KD patients.MethodsClinical and laboratory data of patients with KD (n=615) were evaluated according to duration of fever at presentation, and were compared between patients with and without coronary artery lesions (CALs). For evaluation of the relationships across laboratory indices, patients with a fever duration of 5 days or 6 days were used (n=204).ResultsThe mean fever duration was 6.6±2.3 days, and the proportions of patients with CALs was 19.3% (n=114). C-reactive proteins (CRPs) and neutrophil differential values were highest and hemoglobin, albumin, and lymphocyte differential values were lowest in the 6-day group. Patients with CALs had longer total fever duration, higher CRP and neutrophil differential values and lower hemoglobin and albumin values compared to patients without CALs. CRP, albumin, neutrophil differential, and hemoglobin values at the peak inflammation stage of KD showed positive or negative correlations each other.ConclusionThe severity of systemic inflammation in KD was reflected in the laboratory values including CRP, neutrophil differential, albumin, and hemoglobin. Observing changes in these laboratory parameters by repeated examinations prior to the peak of inflammation in acute KD may aid in diagnosis of early-presenting KD patients.

Review of Kawasaki Disease

Background: Kawasaki disease is one of the leading causes of acquired heart disease in children. It is an acute self-limited vasculitis that predominantly affects infants and children younger than 5 years of age. These patients present with nonspecific symptoms, such as fever and lymphadenopathy, making the diagnosis challenging. This disease can have serious and potentially fatal outcomes, and prompt recognition of this disease is vital to the patient’s outcome. We present a complete review of the disease, including the epidemiology, pathophysiology, diagnosis and management of acute Kawasaki disease, the natural history of this disease, and follow up of these patients as they transition into the adult cardiology practice.