Epidemiological and clinical features of Kawasaki disease in Spain over 5 years and risk factors for aneurysm development. (2011-2016): KAWA-RACE study group

Abstract

Background Kawasaki disease (KD) is an acute self-limited systemic vasculitis of unknown etiology affecting mainly children less than 5 years of age. Risk factors for cardiac involvement and resistance to treatment are insufficiently studied in non-Japanese children. Objective This study aimed to investigate the epidemiology, clinical features and risk factors for resistance to treatment and coronary artery lesions (CAL) in KD in Spain. Methods Retrospective study (May 2011-June 2016) of all patients less than 16 years of age diagnosed with KD included in KAWA-RACE network (84 Spanish hospitals). Results A total of 625 cases were analyzed, 63% were males, 79% under 5 year-olds and 16.8% younger than 12 months. On echocardiographic examination CAL were the most frequent findings (23%) being ectasia the most common (12%). Coronary aneurysms were diagnosed in 9.6%, reaching 20% in infants under 12 months ( p <0.001). A total of 97% of the patients received intravenous immunoglobulin (IVIG) with a median number of days from fever onset to IVIG administration of 7.2. A second dose was given to 15.7% and steroids to 14.5% patients. Only 1.4% patients received infliximab. No deaths were reported. A multivariate analysis identified anemia, hypoalbuminemia, hyponatremia, higher creatinine and procalcitonin as independent risk factors for treatment failure and length under 103 cm, hemoglobin < 10.2 mg/dL, platelets > 900,000 cells/mm 3 , maximum temperature < 39.5°C, total duration of fever > 10 days and fever before treatment ≥ 8 days as independent risk factors for developing coronary aneurysms. Conclusions In our population, children under 12 months develop coronary aneurysms more frequently and children with KD with anemia and leukocytosis have high risk of cardiac involvement. Adding steroids early should be considered in those patients, especially if the treatment is not started before 8 days of fever. A score applicable to non-Japanese children able to predict the risk of aneurysm development and IVIG resistance is necessary.

Defining the risk of first intravenous immunoglobulin unresponsiveness in non-Asian patients with Kawasaki disease

“…The sensitivity remained good in our 3 main ethnic subgroups (74 to 88%). Besides our new score, other predictors of IVIg resistance recently identified include proportion of neutrophils, hemoglobin level, CRP level, procalcitonin level, erythrocyte sedimentation rate, albumin level, creatinine level, sodium level, N-terminal pro-brain natriuretic peptide, interleukin-6 and −10 levels 19,39,40 and baseline Z-score ≥2 or echocardiogram alteration, all found to predict high risk KD patients 19,41 .…”

“…Scoring systems have been established and validated in the Japanese population but they have some limitations. First, resistance to IVIG has not a universal definition in terms of persistence or length of reappraisal of fever, second, fever alone may not be the unique indicator of insufficient response as persistence of elevated CRP is associated also with cardiac complications, and finally those scores have not been validated outside the Japanese population [15][16][17][18][19] . We took the opportunity of the Kawanet, the widest prospective epidemiologic tool ever set up in France, a non-Asian country including multiple ethnic groups and also mixed ethnicities, to evaluate the frequency of secondary treatment after standard treatment i.e.…”

“…However, and to our knowledge, for the first time, we observed a better performance of two of these scores in African/Afro-Caribbean patients compared to other ethnic groups, with the exclusion of Asians. Prediction of IVIg resistance is crucial to intensify initial treatment combined with IVIg to prevent cardiac complications 12,14,36,37 , but none of the currently www.nature.com/scientificreports www.nature.com/scientificreports/ published scores have good sensitivity in Caucasian populations [15][16][17][18][19]36,38 . In our multiethnic population, we identified predictive factors of IVIg resistance based on real-life practice, and built a scoring system and obtained for the first time, good sensitivity (77%) and acceptable specificity (60%) in our non-Asian population.…”

“…However, the limitations include selection biases: adult patients were not included, potentially most severe patients in intensive care units were not recruited, the recruitment was voluntary and finally, our study could not compare Asian and non-Asian patients. In order to minimize risk of aneurysms associated with unresponsiveness to IVIg 19 , we maximized sensitivity of the score despite an acceptable slight decrease in specificity.…”

CD32a polymorphism rs1801274 affects the risk of Kawasaki disease

“…Kawasaki disease (KD) is an acute pediatric rash and fever disease with unclear pathogenesis also called mucocutaneous lymph node syndrome (MCLS) [1]. The disease mainly attacks patients under 5 years old, especially among those between 6 and 18 months old, with boys facing higher risk [2]. Major pathological change in KD refers to systemic non-specific vasculitis, involving small and middle-sized blood vessels, especially coronary artery [3,4].…”