N-terminal pro-B-type natriuretic peptide diagnostic algorithm versus American Heart Association algorithm for Kawasaki disease.

BACKGROUND: Diagnosis of Kawasaki disease (KD) can be challenging in the absence of a confirmatory test or pathognomonic finding, especially when clinical criteria are incomplete. We recently proposed serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunctive diagnostic test. METHODS: We retrospectively tested a new algorithm to help KD diagnosis based on NT-proBNP, coronary artery dilation (CAD) at onset, and abnormal serum albumin or C-reactive protein (CRP). The goal was to assess the performance of the algorithm and compare its performance with that of the 2004 American Heart Association (AHA)/American Academy of Pediatrics (AAP) algorithm. RESULTS: The algorithm was tested on 124 KD patients with NT-proBNP measured on admission at the present institutions between 2007 and 2013. Age at diagnosis was 3.4 ± 3.0 years, with a median of five diagnostic criteria; and 55 of the 124 patients (44%) had incomplete KD. CA complications occurred in 64 (52%), with aneurysm in 14 (11%). Using this algorithm, 120/124 (97%) were to be treated, based on high NT-proBNP alone for 79 (64%); on onset CAD for 14 (11%); and on high CRP or low albumin for 27 (22%). Using the AHA/AAP algorithm, 22/47 (47%) of the eligible patients with incomplete KD would not have been referred for treatment, compared with 3/55 (5%) with the NT-proBNP algorithm (P < 0.001). CONCLUSION: This NT-proBNP-based algorithm is efficient to identify and treat patients with KD, including those with incomplete KD. This study paves the way for a prospective validation trial of the algorithm.

Incidence Rate and Epidemiological and Clinical Aspects of Kawasaki Disease in Children of Maghrebi Origin in the Province of Quebec, Canada, Compared to the Country of Origin.

The incidence of Kawasaki disease in Maghreb countries is apparently low, unlike those living in the province of Quebec, Canada. This retrospective study compared Maghrebi children living in Quebec to the countries of origin, Morocco, Algeria, and Tunisia. The annualized incidence rate in Quebec (18.49/year/100 000 children under 5 years of age) was 4 to 12 times higher than in Tunisia, Morocco, and Algeria (0.95, 4.52, and 3.15, respectively). The prevalence of incomplete diagnostic criteria was higher in Quebec at 39%, Morocco 43%, and Tunisia 39% compared to Algeria at 8%, with minimal delayed diagnosis (7%) only in Quebec compared to 30%, 35%, and 62%, respectively (P < .001). The rate of coronary aneurysms was comparable however (11% in Quebec vs 4%, 10%, and 25%, in Tunisia, Morocco, and Algeria, respectively; P = .31). The higher incidence of Kawasaki disease in the Maghreb community in Quebec versus the countries of origin seems due to underdiagnosis, which represents a public health concern in those countries.

N-terminal pro-brain natriuretic peptide in acute Kawasaki disease correlates with coronary artery involvement.

BACKGROUND: We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease. OBJECTIVES: We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin. METHODS: We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5-10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated. RESULTS: There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05-22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04-0.02), but not during convalescence at 2-3 months (odds ratio 1.28 [95% confidence interval 0.23-7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1). CONCLUSION: Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.

Autonomous adenomas caused by somatic mutations of the thyroid-stimulating hormone receptor in children.

In adults, autonomous adenomas of the thyroid causing hyperthyroidism are relatively common and are most often due to somatic mutations that increase the constitutive activity of the thyroid-stimulating hormone receptor (TSHR). By contrast, autonomous adenomas in hyperthyroid children are exceptional and reports of their clinical and molecular characteristics are few. We reviewed papers describing 16 autonomous adenomas due to a somatic mutation activating the TSHR and diagnosed in patients younger than 18 years, to which we added two of our own unpublished observations in a 4- and 8-year-old with the same TSHR mutation (c.CAG>CAC; p.Asp633His). This revealed that (a) autonomous adenomas occur more often in the right lobe (11 of 14 with available information) and the associated hyperthyroidism tends to be more severe, possibly reflecting the richer vascular supply of the right thyroid lobe, and (b) mutations found in benign adenomas in children have been associated with cancer in adults, suggesting that malignancy requires a second 'hit' at a later age.

Marked variations in serial coronary artery diameter measures in Kawasaki disease: a new indicator of coronary involvement.

BACKGROUND: The long-term risk of patients with Kawasaki disease is not well defined. A great proportion of patients with Kawasaki disease have important variation of their coronary artery (CA) diameters, but the significance of this variation is not known. The aim of this study was to test the hypothesis that patients within the normal range of CA diameters but with important Z-score variation have a stronger inflammatory response and increased resistance to treatment than those without such Z-score variation. METHODS: A retrospective study was conducted in 197 patients with Kawasaki disease with serial echocardiograms up to 12 months after diagnosis. Patients with occult CA dilatation (variation > 2 Z-score units but within the normal range) were compared with patients with definite CA dilatation (Z score > 2.5) and with patients with normal CA for resistance to treatment and systemic inflammatory parameters. RESULTS: A total of 63 patients (32.0%) were identified with Z scores always within the normal range but with important variation of CA diameter during follow-up (occult dilatation). There was a strong statistically significant trend of increasing inflammatory marker levels across patient categories (normal > occult dilatation > definite dilatation). Furthermore, resistance to intravenous immunoglobulin therapy was significantly increased in patients with occult dilatation compared with patients with normal CAs (relative risk, 2.6; 95% confidence interval, 1.21-5.44; P = .006). CONCLUSIONS: The suggested definition of occult CA dilatation identified patients with CA involvement currently unrecognized per the current guidelines. These patients might be at a higher CA risk than previously thought.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease.

BACKGROUND: The aim of the present study was to investigate the diagnostic value of the N-terminal B-type natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis. METHODS: Basic biological tests and serum NT-proBNP levels obtained from acute KD patients were compared to that of febrile controls. NT-proBNP was considered abnormal based on the following definitions: above a cut-off determined on receiver operator characteristic (ROC) analysis, above the upper limit for age, or above 2 SD calculated from healthy children. Analyses were also performed for KD cases with complete or incomplete criteria combined and separately. RESULTS: There were 81 patients and 49 controls aged 3.60 ± 2.77 versus 4.25 ± 3.88 years (P= 0.69). ROC analysis yielded significant area under the curve for NT-proBNP. The sensitivity, specificity, positive and negative predictive values were 70.4-88.9%, 69.4-91.8%, 82.8-93.4%, and 65.2-79.1%. The odds ratios based on NT-proBNP definitions varied between 18.13 (95% confidence interval [CI]: 7.21-45.57), 20.82 (95%CI: 8.18-53.0), and 26.71 (95%CI: 8.64-82.57; P < 0.001). Results were reproducible for cases with complete or incomplete criteria separately. CONCLUSION: NT-proBNP is a reliable marker for the diagnosis of KD. Prospective clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed.