Subject(s)
Macrophage Activation Syndrome , Mucocutaneous Lymph Node Syndrome , Humans , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/physiopathology , Macrophage Activation Syndrome/diagnosis , Macrophage Activation Syndrome/etiology , Child , Child, PreschoolABSTRACT
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.
Subject(s)
Ammonia , Coronary Circulation , Mucocutaneous Lymph Node Syndrome , Myocardial Perfusion Imaging , Nitrogen Radioisotopes , Positron-Emission Tomography , Humans , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/physiopathology , Mucocutaneous Lymph Node Syndrome/diagnostic imaging , Male , Female , Ammonia/blood , Positron-Emission Tomography/methods , Child , Child, Preschool , Myocardial Perfusion Imaging/methods , Coronary Occlusion/etiology , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/physiopathology , Coronary Aneurysm/etiology , Coronary Aneurysm/diagnostic imaging , Coronary Aneurysm/physiopathology , Adolescent , Infant , HemodynamicsABSTRACT
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.
Subject(s)
Drug Resistance , Echocardiography , Immunoglobulins, Intravenous , Mucocutaneous Lymph Node Syndrome , Humans , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/physiopathology , Immunoglobulins, Intravenous/therapeutic use , Male , Female , Cross-Sectional Studies , Echocardiography/methods , Child, Preschool , Infant , Child , Uveitis/etiology , Uveitis/epidemiology , Conjunctivitis/etiology , Conjunctivitis/epidemiology , Incidence , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Blood Sedimentation , Leukocyte Count , Immunologic Factors/therapeutic use , Platelet CountABSTRACT
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.
Subject(s)
COVID-19/complications , Mucocutaneous Lymph Node Syndrome , Systemic Inflammatory Response Syndrome , Humans , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/physiopathology , Male , Female , Child, Preschool , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Child , Prospective Studies , Infant , COVID-19/diagnosis , Biomarkers/bloodABSTRACT
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.
Subject(s)
Mucocutaneous Lymph Node Syndrome , Pulmonary Artery , Humans , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/physiopathology , Mucocutaneous Lymph Node Syndrome/diagnosis , Male , Female , Pulmonary Artery/physiopathology , Pulmonary Artery/diagnostic imaging , Risk Factors , Child, Preschool , Infant , Coronary Artery Disease/physiopathology , Coronary Artery Disease/epidemiology , Coronary Artery Disease/diagnosis , Coronary Artery Disease/etiology , Echocardiography/methods , Child , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Ventricular Function, Right/physiology , Retrospective StudiesABSTRACT
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.
Subject(s)
Inflammasomes , Mucocutaneous Lymph Node Syndrome , NLR Family, Pyrin Domain-Containing 3 Protein , Humans , Inflammasomes/metabolism , Inflammation , Mucocutaneous Lymph Node Syndrome/etiology , Mucocutaneous Lymph Node Syndrome/genetics , Mucocutaneous Lymph Node Syndrome/pathology , Mucocutaneous Lymph Node Syndrome/physiopathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , PyroptosisABSTRACT
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.
Subject(s)
COVID-19/complications , COVID-19/physiopathology , Coronary Aneurysm/physiopathology , Coronary Vessels/physiopathology , Mucocutaneous Lymph Node Syndrome/physiopathology , Systemic Inflammatory Response Syndrome/physiopathology , COVID-19/blood , Child , Child, Preschool , Coronary Aneurysm/complications , Echocardiography , Female , Humans , Immunoglobulin G , Infant , Los Angeles , Male , Mucocutaneous Lymph Node Syndrome/complications , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/complications , Ventricular Dysfunction, Left/complications , Ventricular Dysfunction, Left/physiopathologySubject(s)
Collateral Circulation/physiology , Computed Tomography Angiography/methods , Coronary Aneurysm , Coronary Occlusion , Long Term Adverse Effects , Mucocutaneous Lymph Node Syndrome/complications , Vascular Calcification/diagnostic imaging , Adult , Aftercare/methods , Child , Coronary Aneurysm/diagnosis , Coronary Aneurysm/etiology , Coronary Aneurysm/physiopathology , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/etiology , Coronary Thrombosis/diagnostic imaging , Coronary Thrombosis/etiology , Diagnosis, Differential , Diarrhea/diagnosis , Diarrhea/etiology , Humans , Image Processing, Computer-Assisted , Long Term Adverse Effects/cerebrospinal fluid , Long Term Adverse Effects/etiology , Long Term Adverse Effects/physiopathology , Male , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/physiopathology , Mucocutaneous Lymph Node Syndrome/therapy , Severity of Illness Index , Vomiting/diagnosis , Vomiting/etiologyABSTRACT
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.
Subject(s)
COVID-19/physiopathology , Mucocutaneous Lymph Node Syndrome/physiopathology , Systemic Inflammatory Response Syndrome/physiopathology , COVID-19/complications , COVID-19/epidemiology , Correlation of Data , Humans , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/epidemiologyABSTRACT
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.
Subject(s)
Autophagy , Mitophagy , Mucocutaneous Lymph Node Syndrome/pathology , Mucocutaneous Lymph Node Syndrome/physiopathology , Reactive Oxygen Species/metabolism , 8-Hydroxy-2'-Deoxyguanosine/blood , Animals , Autophagy/genetics , Autophagy-Related Proteins/genetics , Butanes/pharmacology , Cell Extracts , Cell Wall , Coronary Vessels/pathology , DNA Glycosylases/genetics , Disease Models, Animal , Hypoglycemic Agents/pharmacology , Lacticaseibacillus casei , Male , Metformin/pharmacology , Mice , Mitophagy/genetics , Mucocutaneous Lymph Node Syndrome/chemically induced , Mucocutaneous Lymph Node Syndrome/genetics , Myocardium/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Organophosphorus Compounds/pharmacology , Pyridinium Compounds/pharmacology , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Ubiquitin-Protein Ligases/geneticsABSTRACT
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.
Subject(s)
COVID-19/immunology , Macrophage Activation Syndrome/immunology , Mucocutaneous Lymph Node Syndrome/immunology , Systemic Inflammatory Response Syndrome/immunology , COVID-19/physiopathology , Humans , Immunity, Cellular/immunology , Interferon Regulatory Factor-3/immunology , Interferon-alpha/immunology , Macrophage Activation Syndrome/physiopathology , Mucocutaneous Lymph Node Syndrome/physiopathology , SARS-CoV-2 , Severity of Illness Index , Systemic Inflammatory Response Syndrome/physiopathologyABSTRACT
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.
Subject(s)
C-Reactive Protein/analysis , Coronary Aneurysm , Immunoglobulins, Intravenous , Mucocutaneous Lymph Node Syndrome , Biomarkers, Pharmacological/analysis , Child, Preschool , Coronary Aneurysm/diagnostic imaging , Coronary Aneurysm/etiology , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Female , Humans , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/adverse effects , Male , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/physiopathology , Mucocutaneous Lymph Node Syndrome/therapy , Outcome Assessment, Health Care , Patient Acuity , Republic of Korea/epidemiology , Retrospective Studies , Risk FactorsABSTRACT
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.
Subject(s)
COVID-19/complications , Mucocutaneous Lymph Node Syndrome , Child , Humans , Immunoglobulins, Intravenous/therapeutic use , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/physiopathology , Mucocutaneous Lymph Node Syndrome/virology , SARS-CoV-2ABSTRACT
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.
Subject(s)
COVID-19/pathology , Mucocutaneous Lymph Node Syndrome/pathology , Myocardium/pathology , Systemic Inflammatory Response Syndrome/pathology , Adolescent , Adrenal Cortex Hormones/therapeutic use , COVID-19/physiopathology , COVID-19/therapy , Child , Child, Preschool , Coronary Aneurysm/pathology , Female , Heart Disease Risk Factors , Humans , Immunoglobulins, Intravenous/therapeutic use , Infant , Male , Mucocutaneous Lymph Node Syndrome/physiopathology , Mucocutaneous Lymph Node Syndrome/therapy , Prognosis , Systemic Inflammatory Response Syndrome/physiopathology , Systemic Inflammatory Response Syndrome/therapyABSTRACT
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.
Subject(s)
Heart Diseases/diagnosis , Heart Diseases/etiology , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/physiopathology , Child, Preschool , Cross-Sectional Studies , Electrocardiography , Female , Heart Conduction System/physiopathology , Heart Diseases/physiopathology , Heart Ventricles/physiopathology , Humans , Infant , Male , Mucocutaneous Lymph Node Syndrome/metabolism , Reproducibility of ResultsABSTRACT
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.
Subject(s)
COVID-19/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Biomarkers , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/etiology , Child , Diagnosis, Differential , Disease Susceptibility , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Length of Stay/statistics & numerical data , Male , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/physiopathology , Shock, Cardiogenic/etiology , Shock, Cardiogenic/therapy , Shock, Septic/diagnosis , Symptom Assessment , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/etiologyABSTRACT
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.
Subject(s)
Genetic Predisposition to Disease , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/genetics , Siblings , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Japan/epidemiology , Male , Mucocutaneous Lymph Node Syndrome/physiopathology , Odds Ratio , Parents , Prevalence , Recurrence , Risk Factors , Surveys and QuestionnairesABSTRACT
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.
Subject(s)
Brachial Artery/physiopathology , Coronary Artery Disease/diagnosis , Fever/physiopathology , Mucocutaneous Lymph Node Syndrome/physiopathology , Adolescent , Blood Circulation , Case-Control Studies , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Mucocutaneous Lymph Node Syndrome/complications , Predictive Value of Tests , Prospective Studies , ROC CurveABSTRACT
Kawasaki disease (KD) can be associated with high morbidity and mortality due to coronary artery aneurysms formation and myocardial dysfunction. Aim of this study was to evaluate the diagnostic performance of non-invasive myocardial work in predicting subtle myocardial abnormalities in Kawasaki disease (KD) children with coronary dilatation (CADL). A total of 100 patients (age 8.7 ± 5 years) were included: 45 children with KD and CADL (KD/CADL) (Z-score > 2.5), 45 age-matched controls (CTRL) and, finally, an additional group of 10 children with KD in absence of coronary dilatation (KD group). Left ventricular (LV) systolic function and global longitudinal strain (GLS) were assessed. Global myocardial work index (MWI) was calculated as the area of the LV pressure-strain loops. From MWI, global Constructive Work (MCW), Wasted Work (MWW) and Work Efficiency (MWE) were estimated. Despite normal LV systolic function by routine echocardiography, KD/CADL patients had lower MWI (1433.2 ± 375.8 mmHg% vs 1752.2 ± 265.7 mmHg%, p < 0.001), MCW (1885.5 ± 384.2 mmHg% vs 2175.9 ± 292.4 mmHg%, p = 0.001) and MWE (994.0 ± 4.8% vs 95.9 ± 2.0%, p = 0.030) compared to CTRL. Furthermore, MWI was significantly reduced in children belonging to the KD group in comparison with controls (KD: 1498.3 ± 361.7 mmHg%; KD vs CTRL p = 0.028) and was comparable between KD/CADL and KD groups (KD/CADL vs KD p = 0.896). Moreover, KD/CADL patients with normal GLS (n = 38) preserved significant differences in MWI and MCW in comparison with CTRL. MWI, MCW and MWE were significantly reduced in KD children despite normal LVEF and normal GLS. These abnormalities seems independent from CADL. Thus, in KD with normal LVEF and normal GLS, estimation of MWI may be a more sensitive indicator of myocardial dysfunction.
Subject(s)
Mucocutaneous Lymph Node Syndrome/pathology , Myocardium/pathology , Adolescent , Child , Child, Preschool , Echocardiography , Female , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Male , Mucocutaneous Lymph Node Syndrome/diagnostic imaging , Mucocutaneous Lymph Node Syndrome/physiopathology , Pressure , Reproducibility of Results , Stroke VolumeABSTRACT
BACKGROUND: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. METHODS: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. RESULTS: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. CONCLUSION: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.