RESUMEN
Kawasaki disease (KD), a systemic vasculitic condition predominantly affecting children, remains a significant challenge in pediatric health care. First identified in 1967, KD is now recognized as the primary cause of pediatric ischemic heart disease in developed countries. This review provides a comprehensive update of KD, focusing on biomarkers, pathophysiology, and genetic associations. KD's clinical manifestation, including symptoms such as persistent fever and mucocutaneous changes, often overlaps with other pediatric conditions, complicating its diagnosis. This ambiguity, especially in cases of incomplete KD, highlights the critical need for specific biomarkers and more precise diagnostic methods. Recent studies have made promising advancements in identifying serum biomarkers and microRNAs, contributing to the development of rapid diagnostic tools. However, these are yet to be fully integrated into clinical practice. The article focuses on the pathophysiological aspects of KD, highlighting the potential for targeted therapies and personalized medicine approaches based on genetic predispositions. Collaborative efforts in global research and raising public awareness about KD are emphasized as key strategies for improving its management. This review presents the current understanding of KD while pointing out the gaps and future directions in research and clinical care. The ultimate goal is to enhance diagnostic accuracy, optimize treatment strategies, and improve patient outcomes, thereby addressing the complexities of this enigmatic and potentially life-threatening condition in pediatric medicine.
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Predisposición Genética a la Enfermedad , Síndrome Mucocutáneo Linfonodular , Síndrome Mucocutáneo Linfonodular/genética , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/fisiopatología , Humanos , Biomarcadores/sangre , Niño , MicroARNs/genética , Medicina de Precisión/métodosAsunto(s)
Síndrome de Activación Macrofágica , Síndrome Mucocutáneo Linfonodular , Humanos , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/fisiopatología , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/etiología , Niño , PreescolarRESUMEN
Aims/Background Kawasaki disease is an acute inflammatory condition primarily affecting the young children. It can lead to coronary artery abnormalities, which can worsen the prognosis. Early diagnosis of coronary disease is crucial for the effective treatment and the prognosis evaluation. To explore the clinical significance of ultrasound examination characteristics, peripheral blood red cell distribution width, and changes in N-terminal pro-brain natriuretic peptide levels for the early detect coronary artery abnormality in children with Kawasaki disease. Methods The case-control study was conducted. 85 Kawasaki disease patients diagnosed in our hospital from January 2020 to December 2023 were selected as the Kawasaki disease group. 100 healthy children who received physical examination in the Department of Child Healthcare during the same period were selected as control group. The cardiac ultrasound indicators, erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, N-terminal pro-brain natriuretic peptide of two groups were compared. The Kawasaki disease group was further divided into the coronary artery lesion group and the non-coronary artery lesion group based on whether coronary artery lesions occurred in the Kawasaki disease patients. The differences of above indicators were compared. Results The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of the Kawasaki disease group were all higher than those of the control group (p < 0.05). There was no significant difference in left ventricular ejection fraction between Kawasaki disease group and control group (p > 0.05). The erythrocyte sedimentation rate, C-reactive protein, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease group were all higher than those of control group (p < 0.05). The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions (p < 0.05). The left ventricular ejection fraction of Kawasaki disease patients with coronary artery lesions was lower than that of Kawasaki disease patients without coronary artery lesions (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions, and the differences were statistically significant (p < 0.05). After treatment, the left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions significantly decreased (p < 0.05), and the left ventricular ejection fraction significantly increased (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with or without coronary artery lesions significantly decreased after treatment compared with before treatment in the same group (p < 0.05). Conclusion Kawasaki disease patients with coronary artery lesions exhibit significantly increased coronary artery vessel diameter, as well as elevated red cell distribution width and N-terminal pro-brain natriuretic peptide concentration. The combined use of ultrasound combined with red cell distribution width and N-terminal pro-brain natriuretic peptide examination can assist in determining whether Kawasaki disease patients have coronary artery lesions and assessing the clinical treatment effect.
Asunto(s)
Ecocardiografía , Índices de Eritrocitos , Síndrome Mucocutáneo Linfonodular , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Humanos , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/fisiopatología , Péptido Natriurético Encefálico/sangre , Masculino , Femenino , Estudios de Casos y Controles , Preescolar , Lactante , Fragmentos de Péptidos/sangre , Sedimentación Sanguínea , Niño , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Biomarcadores/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismoRESUMEN
BACKGROUND: Although occlusion of the right coronary artery (RCA) is common in the remote stages of Kawasaki disease, revascularization of the RCA is challenging in children and is usually managed by observation without intervention. METHODS: Using adenosine-stress 13N-ammonia myocardial perfusion positron emission tomography, we evaluated coronary circulation in 14 patients (12 males) with RCA occlusion to identify ischemia (myocardial flow ratio < 2.0) in the RCA region and examined hemodynamics, cardiac function, and coronary aneurysm diameter. These variables were also compared in patients with/without RCA segmental stenosis (SS). RESULTS: There were five cases of ischemia in the RCA region. RCA myocardial blood flow (MBF) at rest was higher in patients with ischemia than in those without ischemia, but the difference was not significant (1.27 ± 0.21 vs. 0.82 ± 0.16 mL/min/g, p = 0.2053). Nine patients presented with RCA SS, and age at onset of Kawasaki disease tended to be lower in those with SS. The maximum aneurysm diameter of RCA was significantly smaller in patients with SS (10.0 ± 2.8 vs. 14.7 ± 1.6, p = 0.0239). No significant differences in other variables were observed between patients with/without ischemia and SS. CONCLUSIONS: At rest, MBF in the RCA region was relatively well preserved, even in patients with RCA occlusion, and there was no progressive deterioration in cardiac function. Adenosine stress showed microcirculatory disturbances in only half of the patients, indicating that it is reversible in children with Kawasaki disease.
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Amoníaco , Circulación Coronaria , Síndrome Mucocutáneo Linfonodular , Imagen de Perfusión Miocárdica , Radioisótopos de Nitrógeno , Tomografía de Emisión de Positrones , Humanos , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/fisiopatología , Síndrome Mucocutáneo Linfonodular/diagnóstico por imagen , Masculino , Femenino , Amoníaco/sangre , Tomografía de Emisión de Positrones/métodos , Niño , Preescolar , Imagen de Perfusión Miocárdica/métodos , Oclusión Coronaria/etiología , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/fisiopatología , Aneurisma Coronario/etiología , Aneurisma Coronario/diagnóstico por imagen , Aneurisma Coronario/fisiopatología , Adolescente , Lactante , HemodinámicaRESUMEN
BACKGROUND: This study investigates the incidence of ocular involvement in Kawasaki disease (KD) and evaluates the relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin (IVIG) resistance. METHODS: We conducted a cross-sectional study with 58 KD patients from June 2021 to March 2023. For all patients, a complete ophthalmologic examination and echocardiography were performed in the acute phase before starting the treatment. We analyzed the age, sex, mean of white blood cell (WBC) count, platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), echocardiographic findings and IVIG responses for all patients and compared the group with ocular involvement with the group without involvement. RESULTS: The incidence of bilateral acute conjunctivitis was 70.7%, while that of acute uveitis was 30%. Patients with uveitis had significantly higher rates of Coronary artery dilatation and IVIG resistance, as well as higher mean levels of WBC, platelet, and CRP compared to those without uveitis. (P < 0.05). Additionally, the age of patients with uveitis involvement was lower than those without involvement. No significant relationships existed between ESR, AST, or ALT values and uveitis (P > 0.05). Furthermore, no significant correlations existed between any examined items and acute bilateral conjunctivitis. CONCLUSION: Uveitis in KD is significantly associated with coronary artery dilatation, IVIG resistance, higher WBC count, platelet count, and CRP level.
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Resistencia a Medicamentos , Ecocardiografía , Inmunoglobulinas Intravenosas , Síndrome Mucocutáneo Linfonodular , Humanos , Síndrome Mucocutáneo Linfonodular/epidemiología , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/fisiopatología , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Femenino , Estudios Transversales , Ecocardiografía/métodos , Preescolar , Lactante , Niño , Uveítis/etiología , Uveítis/epidemiología , Conjuntivitis/etiología , Conjuntivitis/epidemiología , Incidencia , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Sedimentación Sanguínea , Recuento de Leucocitos , Factores Inmunológicos/uso terapéutico , Recuento de PlaquetasRESUMEN
OBJECTIVES: To compare Kawasaki disease (KD) and multisystem inflammatory syndrome (MIS-C) in children. METHODS: Prospective collection of demographics, clinical and treatment data. Assessment of type 1 interferon (IFN) score, CXCL9, CXCL10, Interleukin (IL)18, IFNγ, IL6, IL1b at disease onset and at recovery. RESULTS: 87 patients (43 KD, 44 MIS-C) were included. Age was higher in MIS-C compared to KD group (mean 31±23 vs. 94±50 months, p<0.001). Extremities abnormalities (p=0.027), mucosal involvement (p<0.001), irritability (p<0.001), gallbladder hydrops (p=0.01) and lymphadenopathy (p=0.07) were more often recorded in KD. Neurological findings (p=0.002), gastrointestinal symptoms (p=0.013), respiratory involvement (p=0.019) and splenomegaly (p=0.026) were more frequently observed in MIS-C. Cardiac manifestations were higher in MIS-C (p<0.001), although coronary aneurisms were more frequent in KD (p=0.012). In the MIS-C group, the multiple linear regression analysis revealed that a higher IFN score at onset was related to myocardial disfunction (p<0.001), lymphadenopathy (p=<0.001) and need of ventilation (p=0.024). Both CXCL9 and CXCL10 were related to myocardial disfunction (p<0.001 and p=0.029). IL18 was positively associated to PICU admission (0.030) and ventilation (p=004) and negatively associated to lymphadenopathy (0.004). IFNγ values were related to neurological involvement and lymphadenopathy (p<0.001), IL1b to hearth involvement (0.006). A negative correlation has been observed between IL6 values, heart involvement (p=0.013) and PICU admission (p<0.001). CONCLUSIONS: The demographic and clinical differences between KD e MIS-C cohorts confirm previous reported data. The assessment of biomarkers levels at MIS-C onset could be useful to predict a more severe disease course and the development of cardiac complications.
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COVID-19/complicaciones , Síndrome Mucocutáneo Linfonodular , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/epidemiología , Síndrome Mucocutáneo Linfonodular/fisiopatología , Masculino , Femenino , Preescolar , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Niño , Estudios Prospectivos , Lactante , COVID-19/diagnóstico , Biomarcadores/sangreRESUMEN
BACKGROUND: The recognition ability of right ventricular-pulmonary artery (RV-PA) coupling for coronary artery lesions (CAL) in children with Kawasaki disease (KD) has not been well characterized. This study aimed to determine whether RV-PA coupling is an independent the risk factors for CAL in children with KD. METHODS: Between October 2021 and August 2023, RV-PA coupling was assessed in 59 KD children using the ratio between echocardiographic tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (PASP). Multivariable logistic regression analysis was used to identify the independent risk factors for CAL among the demographic, clinical, laboratory and echocardiographic data. RESULTS: Twenty-nine of 59 KD children had CAL according to the diagnostic criteria of echocardiography. There were significantly different white blood cell count, C-reactive protein, erythrocyte sedimentation rate, left ventricular ejection fraction, PASP and RV-PA coupling at admission, and significantly different acute/subacute phase ratio of RV-PA coupling between KD children with and without CAL ( P â <â 0.05). Multivariate logistic regression analysis identified that acute/subacute phase ratio of RV-PA coupling (ORâ =â 26.800; 95% CI, 1.276-562.668; P â =â 0.034) was an independent risk factor for CAL in children with KD. The area under receiver operating characteristic curve for the acute/subacute phase ratio of RV-PA coupling was 0.715 (95%CI: 0.624 - 0.825) to predict CAL in KD children ( P â <â 0.05), with a sensitivity of 81.25% and a specificity of 62.57% at the optimal cutoff value of 0.839. CONCLUSION: The acute/subacute phase ratio of RV-PA coupling was an independent risk factor for CAL in KD children.
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Síndrome Mucocutáneo Linfonodular , Arteria Pulmonar , Humanos , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/fisiopatología , Síndrome Mucocutáneo Linfonodular/diagnóstico , Masculino , Femenino , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/diagnóstico por imagen , Factores de Riesgo , Preescolar , Lactante , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/etiología , Ecocardiografía/métodos , Niño , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Función Ventricular Derecha/fisiología , Estudios RetrospectivosRESUMEN
There is a heterogeneous group of rare illnesses that fall into the vasculitis category and are characterized mostly by blood vessel inflammation. Ischemia and disrupted blood flow will cause harm to the organs whose blood arteries become inflamed. Kawasaki disease (KD) is the most prevalent kind of vasculitis in children aged 5 years or younger. Because KD's cardiovascular problems might persist into adulthood, it is no longer thought of as a self-limiting disease. KD is a systemic vasculitis with unknown initiating factors. Numerous factors, such as genetic predisposition and infectious pathogens, are implicated in the etiology of KD. As endothelial cell damage and inflammation can lead to coronary endothelial dysfunction in KD, some studies hypothesized the crucial role of pyroptosis in the pathogenesis of KD. Additionally, pyroptosis-related proteins like caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), proinflammatory cytokines like IL-1 and IL-18, lactic dehydrogenase, and Gasdermin D (GSDMD) have been found to be overexpressed in KD patients when compared to healthy controls. These occurrences may point to an involvement of inflammasomes and pyroptotic cell death in the etiology of KD and suggest potential treatment targets. Based on these shreds of evidence, in this review, we aim to focus on one of the well-defined inflammasomes, NLRP3, and its role in the pathophysiology of KD.
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Inflamasomas , Síndrome Mucocutáneo Linfonodular , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Inflamasomas/metabolismo , Inflamación , Síndrome Mucocutáneo Linfonodular/etiología , Síndrome Mucocutáneo Linfonodular/genética , Síndrome Mucocutáneo Linfonodular/patología , Síndrome Mucocutáneo Linfonodular/fisiopatología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , PiroptosisRESUMEN
We compared cardiac findings in patients with multisystem inflammatory syndrome in children and Kawasaki disease in the first 6 months of the 2020 coronavirus disease pandemic to patients with Kawasaki disease during 2016-2019. We saw a high rate of coronary aneurysms in 2020, with a similar rate of coronary involvement but greater volume and incidence of cardiac dysfunction compared with previous years.
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COVID-19/complicaciones , COVID-19/fisiopatología , Aneurisma Coronario/fisiopatología , Vasos Coronarios/fisiopatología , Síndrome Mucocutáneo Linfonodular/fisiopatología , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , COVID-19/sangre , Niño , Preescolar , Aneurisma Coronario/complicaciones , Ecocardiografía , Femenino , Humanos , Inmunoglobulina G , Lactante , Los Angeles , Masculino , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/fisiopatologíaAsunto(s)
Circulación Colateral/fisiología , Angiografía por Tomografía Computarizada/métodos , Aneurisma Coronario , Oclusión Coronaria , Efectos Adversos a Largo Plazo , Síndrome Mucocutáneo Linfonodular/complicaciones , Calcificación Vascular/diagnóstico por imagen , Adulto , Cuidados Posteriores/métodos , Niño , Aneurisma Coronario/diagnóstico , Aneurisma Coronario/etiología , Aneurisma Coronario/fisiopatología , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/etiología , Trombosis Coronaria/diagnóstico por imagen , Trombosis Coronaria/etiología , Diagnóstico Diferencial , Diarrea/diagnóstico , Diarrea/etiología , Humanos , Procesamiento de Imagen Asistido por Computador , Efectos Adversos a Largo Plazo/líquido cefalorraquídeo , Efectos Adversos a Largo Plazo/etiología , Efectos Adversos a Largo Plazo/fisiopatología , Masculino , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/fisiopatología , Síndrome Mucocutáneo Linfonodular/terapia , Índice de Severidad de la Enfermedad , Vómitos/diagnóstico , Vómitos/etiologíaRESUMEN
Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) are inflammatory conditions that present diagnostic and therapeutic challenges to the physician. Although many of their features overlap, they are two distinct conditions. KD is a febrile illness most commonly affecting children younger than five years. It manifests with prolonged fever and at least four of the following features: bilateral bulbar conjunctivitis, mucositis, diffuse maculopapular rash, extremity changes, and cervical lymphadenopathy of 1.5 cm or more in diameter. Patients with MIS-C may have many of the same manifestations but tend to have higher rates of gastrointestinal and neurocognitive symptoms and signs of shock on presentation. Both conditions are associated with cardiac sequelae, including coronary artery aneurysms, although children with MIS-C are at high risk of developing ventricular dysfunction and depressed cardiac output. Lymphocytopenia, thrombocytopenia, elevated troponin, and elevated B-type natriuretic peptide are key laboratory findings of MIS-C that can help distinguish it from KD. The use of intravenous immune globulin is well established in KD and also appears to have a role in the treatment of MIS-C. Aspirin has been used in KD for an anti-inflammatory effect, and low-dose aspirin is recommended for MIS-C to reduce the risk of thrombosis. In addition to supportive care, patients with MIS-C may benefit from immunomodulatory medications, although data on this topic are evolving.
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COVID-19/fisiopatología , Síndrome Mucocutáneo Linfonodular/fisiopatología , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , COVID-19/complicaciones , COVID-19/epidemiología , Correlación de Datos , Humanos , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/epidemiologíaRESUMEN
Kawasaki disease (KD) is the leading cause of acquired heart disease among children. Murine and human data suggest that the NLRP3-IL-1ß pathway is the main driver of KD pathophysiology. NLRP3 can be activated during defective autophagy/mitophagy. We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to examine the role of autophagy/mitophagy on cardiovascular lesion development. LCWE-injected mice had impaired autophagy/mitophagy and increased levels of ROS in cardiovascular lesions, together with increased systemic 8-OHdG release. Enhanced autophagic flux significantly reduced cardiovascular lesions in LCWE-injected mice, whereas autophagy blockade increased inflammation. Vascular smooth muscle cell-specific deletion of Atg16l1 and global Parkin-/- significantly increased disease formation, supporting the importance of autophagy/mitophagy in this model. Ogg1-/- mice had significantly increased lesions with increased NLRP3 activity, whereas treatment with MitoQ reduced vascular tissue inflammation, ROS production, and systemic 8-OHdG release. Treatment with MN58b or Metformin (increasing AMPK and reducing ROS) resulted in decreased cardiovascular lesions. Our results demonstrate that impaired autophagy/mitophagy and ROS-dependent damage exacerbate the development of murine KD vasculitis. This pathway can be efficiently targeted to reduce disease severity. These findings enhance our understanding of KD pathogenesis and identify potentially novel therapeutic avenues for KD treatment.
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Autofagia , Mitofagia , Síndrome Mucocutáneo Linfonodular/patología , Síndrome Mucocutáneo Linfonodular/fisiopatología , Especies Reactivas de Oxígeno/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina/sangre , Animales , Autofagia/genética , Proteínas Relacionadas con la Autofagia/genética , Butanos/farmacología , Extractos Celulares , Pared Celular , Vasos Coronarios/patología , ADN Glicosilasas/genética , Modelos Animales de Enfermedad , Hipoglucemiantes/farmacología , Lacticaseibacillus casei , Masculino , Metformina/farmacología , Ratones , Mitofagia/genética , Síndrome Mucocutáneo Linfonodular/inducido químicamente , Síndrome Mucocutáneo Linfonodular/genética , Miocardio/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Compuestos Organofosforados/farmacología , Compuestos de Piridinio/farmacología , Ubiquinona/análogos & derivados , Ubiquinona/farmacología , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
PURPOSE OF REVIEW: In this article, I have reviewed current reports that explore differences and similarities between multisystem inflammatory syndrome in children (MIS-C) and other known multisystem inflammatory diseases seen in children, particularly Kawasaki disease. RECENT FINDINGS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronavirus causing the COVID-19 disease which emerged in China in December 2019 and spread rapidly to the entire country and quickly to other countries. Currently, there is a pandemic of SARS-CoV-2 infection that results in 20% of patients admitted to hospital with illness, with 3% developing intractable acute respiratory distress syndrome (ARDS) with high mortality. However, pediatric COVID-19 is still reported to be a mild disease, affecting only 8% of children. Pathogenesis in children is comparable to adults. There are suggested impaired activation of IFN-alpha and IFN regulator 3, decreased cell response causing impaired viral defense, yet the clinical course is mild, and almost all children recover from the infection without major complications. Interestingly, there is a subset of patients that develop a late but marked immunogenic response to COVID-19 and develop MIS-C. Clinical features of MIS-C resemble certain pediatric rheumatologic diseases, such as Kawasaki disease (mucocutaneous lymph node syndrome) which affects small-medium vessels. Other features of MIS-C resemble those of macrophage activation syndrome (MAS). However, recent research suggests distinct clinical and laboratory differences between MIS-C, Kawasaki disease, and MAS. Since the start of the SARS-CoV-2 pandemic, MIS-C has become the candidate for the most common cause of acquired heart disease in children.
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COVID-19/inmunología , Síndrome de Activación Macrofágica/inmunología , Síndrome Mucocutáneo Linfonodular/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , COVID-19/fisiopatología , Humanos , Inmunidad Celular/inmunología , Factor 3 Regulador del Interferón/inmunología , Interferón-alfa/inmunología , Síndrome de Activación Macrofágica/fisiopatología , Síndrome Mucocutáneo Linfonodular/fisiopatología , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatologíaRESUMEN
Overlapping clinical features promoted the discussion of whether Kawasaki disease (KD) and PIMS-TS share pathophysiological features and disease outcomes. Medical records from English patients with KD (2015-02/20, N = 27) and PIMS-TS (02/2020-21, N = 34) were accessed to extract information. Children with PIMS-TS were older and more frequently of minority ethnicity background. They patients more commonly exhibited cytopenias and hyperferritinemia, which associated with diffuse cardiac involvement and functional impairment. In some PIMS-TS cases, cardiac pathology developed late, but outcomes were more favorable. In both, KD and PIMS-TS, baseline coronary diameter was a predictor of outcomes. PIMS-TS treatment more frequently included respiratory and cardiovascular support, and corticosteroids with IVIG. Cardiac involvement in PIMS-TS may be the result of a cytokine storm. Though more severe and diffuse when compared to KD, cardiac involvement of PIMS-TS has a more favorable prognosis, which may, after recovery, mitigate the need for long-term follow up.
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COVID-19/patología , Síndrome Mucocutáneo Linfonodular/patología , Miocardio/patología , Síndrome de Respuesta Inflamatoria Sistémica/patología , Adolescente , Corticoesteroides/uso terapéutico , COVID-19/fisiopatología , COVID-19/terapia , Niño , Preescolar , Aneurisma Coronario/patología , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Masculino , Síndrome Mucocutáneo Linfonodular/fisiopatología , Síndrome Mucocutáneo Linfonodular/terapia , Pronóstico , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Síndrome de Respuesta Inflamatoria Sistémica/terapiaRESUMEN
INTRODUCTION: Viral infections have been described as triggers for Kawasaki Disease (KD), a medium vessel vasculitis that affects young children. Akin to the H1N1 pandemic in 2009, there is a similar rise in the incidence of KD in children affected with Coronavirus disease 2019 (COVID-19). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has been reported to induce an exaggerated systemic inflammatory response resulting in multi-organ involvement, particularly initiated with pulmonary parenchymal damage. This review article will discuss KD-like manifestations in COVID-19 patients in the pediatric cohort. METHODOLOGY: Search terms "Kawasaki" "COVID-19" "SARS-COV-2" "PIM-TS" and "MIS-C" were used to look for relevant articles in PubMed and Google Scholar published in the last 5 years. RESULTS: There is some evidence to suggest that SARS-CoV-2 stimulates dysfunctional and hyperactive immune reactions mimicking KD in young patients. CONCLUSIONS: Therapeutic options, both investigational and repurposed, include intravenous immunoglobulins, steroids and anticoagulation. More studies are required to evaluate the effectiveness of these treatment options.
Asunto(s)
COVID-19/complicaciones , Síndrome Mucocutáneo Linfonodular , Niño , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/fisiopatología , Síndrome Mucocutáneo Linfonodular/virología , SARS-CoV-2RESUMEN
BACKGROUND: This study aimed to assess the occurrence of coronary artery lesions (CAL) in patients with Kawasaki disease (KD) according to serum C-reactive protein (CRP) levels. METHODS: This retrospective analysis was based on the nationwide survey of KD conducted in the Republic of Korea between 2015 and 2017. We enrolled 9131 patients and defined low (< 3 mg/dL) and high (≥3 mg/dL) CRP groups. Demographic data, clinical characteristics, z-scores, and scores based on the Japanese criteria for CAL were compared between the two groups. Logistic regression analysis was used to identify CAL risk factors. RESULTS: The low CRP group accounted for 23% of patients. The mean age at diagnosis was higher in high CRP group compared to the low CRP group (34.4 ± 24.9 vs 31.7 ± 24.8 months, p < 0.001). Fever duration before treatment was not significantly different between the two groups (5.1 ± 1.7 days vs. 5.2 ± 2.1 days; p = 0.206). A non-response to intravenous immunoglobulin treatment was found in 1377 patients (20.1%) and 225 patients (11.7%) in the high and low CRP groups, respectively (p < 0.001). CAL were found in 12.9 and 18.3% of the high and low CRP patients, respectively (p < 0.001), based on z-scores; and in 9.9 and 12.5%, respectively (p = 0.001), based on the Japanese criteria in the acute phase. The giant coronary artery aneurysm occurrence ratio was similar between groups (p = 1.0). CONCLUSIONS: CAL occurred in patients with both high and low CRP. Therefore, patients with KD should be carefully monitored regardless of their CRP levels.
Asunto(s)
Proteína C-Reactiva/análisis , Aneurisma Coronario , Inmunoglobulinas Intravenosas , Síndrome Mucocutáneo Linfonodular , Biomarcadores Farmacológicos/análisis , Preescolar , Aneurisma Coronario/diagnóstico por imagen , Aneurisma Coronario/etiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunoglobulinas Intravenosas/efectos adversos , Masculino , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/fisiopatología , Síndrome Mucocutáneo Linfonodular/terapia , Evaluación de Resultado en la Atención de Salud , Gravedad del Paciente , República de Corea/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been characterized by high transmission rates and high mortality in adults with predisposing factors, including age>70 years, obesity, diabetes, systemic hypertension and other underlying diseases. During the second week of viral pneumonia, acute respiratory distress syndrome can occur and carries high mortality. Unlike most common respiratory viruses, children seem to be less susceptible to SARS-CoV-2 infection, and generally develop mild disease with low mortality. However, clusters of severe shock associated with high levels of cardiac biomarkers and unusual vasoplegia requiring inotropes, vasopressors and volume loading have recently been described. Both the clinical symptoms (i.e. high and persistent fever, gastrointestinal disorders, skin rash, conjunctival injection and dry cracked lips) and the biological signs (e.g. elevated C-reactive protein/procalcitonin and high levels of ferritinaemia) mimicked Kawasaki disease. In most cases, intravenous immunoglobin therapy improved cardiac function and led to full recovery within a few days. Adjunctive steroid therapy and sometimes biotherapy (e.g. anti-interleukin 1Ra and anti-interleukin 6 monoclonal antibodies) were often necessary. Although almost all children fully recovered within a week, some of them later developed coronary artery dilation or aneurysm. Thus, a new "multisystem inflammatory syndrome in children" related to SARS-CoV-2 has recently been described. Similarities with Kawasaki disease and the physiopathology of this syndrome still need further exploration.
Asunto(s)
COVID-19/complicaciones , Síndrome Mucocutáneo Linfonodular/diagnóstico , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Adolescente , Biomarcadores , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/etiología , Niño , Diagnóstico Diferencial , Susceptibilidad a Enfermedades , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Tiempo de Internación/estadística & datos numéricos , Masculino , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/fisiopatología , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia , Choque Séptico/diagnóstico , Evaluación de Síntomas , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/etiologíaRESUMEN
OBJECTIVES: To evaluate electrocardiogram markers to predict coronary involvement in patients with Kawasaki disease by assessing measures of ventricular repolarization parameters on the 12-lead electrocardiogram. STUDY DESIGN: This cross-sectional study included 180 Spanish and Japanese patients ≤14 years of age with Kawasaki disease, with or without coronary involvement, from 2011 to 2016. We manually measured the Tp-Te/QT ratio and QTc interval (with Bazett's formula) in 12-lead electrocardiogram in the acute and recovery period and explored their potential association with coronary involvement. RESULTS: No association was found between Tp-Te/QT ratio obtained manually in V5 and V6 leads and coronary involvement in the acute (V5:0.25 [IQR, 0.21-0.27] vs 0.25 [IQR, 0.20-0.27], P = .80; V6:0.24 [IQR, 0.21-0.27] vs 0.25 [IQR, 0.20-0.27], P = .86) or the recovery (V5: 0.23 [IQR, 0.20-0.25] vs 0.23 [IQR, 0.19-0.25], P = .68; V6: 0.23 [IQR, 0.20-0.25] vs 0.23 [IQR, 0.17-0.25], P = .50) period. By contrast, QTc in V5 and V6 was significantly lower in patients with Kawasaki disease and coronary involvement in the acute period (V5: 378 ms [IQR, 364-395 ms] vs 390 ms [IQR, 371-411 ms], P = .04; V6: 377 ms [IQR, 364-392 ms] vs 390 ms [IQR, 371-410 ms], P = .01). A QTc interval of <385 ms in lead V6 was associated with a 2.5-fold increased risk of coronary involvement (OR, 2.5; 95% CI, 1.2-5.3; P = .02). CONCLUSIONS: Manually measured QTc interval may be a marker of coronary disease in the acute period of Kawasaki disease.
Asunto(s)
Cardiopatías/diagnóstico , Cardiopatías/etiología , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/fisiopatología , Preescolar , Estudios Transversales , Electrocardiografía , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Cardiopatías/fisiopatología , Ventrículos Cardíacos/fisiopatología , Humanos , Lactante , Masculino , Síndrome Mucocutáneo Linfonodular/metabolismo , Reproducibilidad de los ResultadosRESUMEN
Coronary artery abnormalities (CAAs) are a severe complication of Kawasaki disease (KD) that may lead to cardiovascular events. Given the evidence that brachial artery flow-mediated dilation (FMD) decreases in children after the onset of KD, we hypothesized that it could be an early marker of CAA development in the acute stage and investigated its relationship with variation in the coronary artery diameter. A total of 326 sex- and age-matched children were enrolled, including 120 with KD, 109 febrile children and 97 healthy controls. In this study, FMD was significantly decreased in the KD group compared with the febrile and healthy groups. FMD was lower in the CAA group than in the no coronary artery abnormality group. The comparison of FMD showed an obvious difference among the CAA subgroups. The FMD in the coronary aneurysm (CA) group showed a strong negative correlation with the pretreatment maximum coronary artery Z-score (preZmax). While preZmax was 2.5, the receiver operating characteristic curve indicated an optimal cutoff point of 3.44% for FMD. FMD ≤ 3.44% could be considered as a signal of coronary lesions in acute stage of KD.
Asunto(s)
Arteria Braquial/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico , Fiebre/fisiopatología , Síndrome Mucocutáneo Linfonodular/fisiopatología , Adolescente , Circulación Sanguínea , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Síndrome Mucocutáneo Linfonodular/complicaciones , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROCRESUMEN
BACKGROUND: Some patients with Kawasaki disease (KD) have siblings who developed the same disease. Using a large-scale epidemiologic dataset, the present study aimed to determine the clinical characteristics of this population. METHODS: We analyzed 89,725 patients diagnosed with KD during 2011-2018 who were registered in the nationwide Japanese KD survey database. Multivariable logistic regression analyses were performed to determine factors associated with sibling history of KD. RESULTS: Of the 89,725 patients, 1777 (2%) had sibling history of KD. Annual prevalence ranged from 1.5% to 2.3% during the study period and showed a tendency toward an increasing trend. Patients with recurrent KD and parental history of KD were significantly associated with sibling history of KD (adjusted odds ratio [95% confidence interval] = 2.15 [1.82-2.54] and 2.64 [2.02-3.47], respectively). Although patients with a sibling history of KD were significantly associated with initial intravenous immunoglobulin treatment resistance (1.14 [1.02-1.28]), no significant association was found between sibling history and coronary artery abnormality development. Among patients with a sibling history of KD, male patients were less likely to have recurrent KD than female patients (0.68 [0.49-0.96]). CONCLUSIONS: The significant association between sibling history and parental history may indicate genetic susceptibility to KD onset. Among those with a sibling history, recurrent KD was more likely to occur in female patients. Further studies focusing on this population may contribute toward identification of the cause of KD onset.