RESUMO
The long-term prognosis of patients with Kawasaki disease (KD) complicated by coronary artery aneurysms (CAA) is still unclear. The present, multicenter registry study aimed to study the factors associated with coronary events (CE) and determine an appropriate management method for patients with KD complicated with CAA. Patients with KD with onset after 2015 and with a medium-sized or large CAA having an actual diameter ≥ 4 mm or a Z-score ≥ 5.0 at 30 days and later after KD onset were included in the annual survey. The primary endpoint was the time-dependent incidence of CE. Associated factors were also examined. In total, 179 patients from 53 centers were enrolled and followed up for a median of 501 days. The median age at KD onset was 2.2 years, 137 patients were male (77%), 47 had incomplete KD (26%), and 36 had large CAA (20%). CE occurred in 13 patients (7%; 95% confidence interval: 4-12%); eight (62%) experienced CE within 1 year, and all the patients experienced a CE within 2 years. All but one patient received antiplatelet drugs and warfarin. Patients with a large CAA had significantly more CAA (2.8 vs. 1.7, p < 0.001), more cases of warfarin use (86% vs. 43%, p < 0.001), and were more likely to have CE (28% vs. 2%, p < 0.001) than those with a medium-sized CAA. On univariate Cox regression analysis, the factors significantly associated with CE were large CAA (hazard ratio (HR): 17.0), three or more CAA (HR: 23.3), and beaded CAA (HR: 15.9). Multivariable Cox regression analysis revealed that the only associated factor was a large CAA. CONCLUSION: Patients with a large CAA were more likely to have a CE within 2 years. Antithrombotic therapy with warfarin did not eliminate the CE risk, and better therapies are desirable. WHAT IS KNOWN: ⢠Coronary artery aneurysms are a serious complication of Kawasaki disease, and coronary events are sometimes fatal. ⢠In previous, retrospective studies in Japan, large aneurysms, male sex, and refractoriness to initial immunoglobulin therapy were considered risk factors for coronary events. WHAT IS NEW: ⢠Of 179 patients with a medium sized or large aneurysm, 13 (7%) experienced coronary events, all of which occurred within 2 years of onset. Factors significantly associated with coronary events were large aneurysms, three or more aneurysms, and beaded aneurysms.
Assuntos
Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , Humanos , Masculino , Lactente , Pré-Escolar , Feminino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Estudos Retrospectivos , Varfarina/uso terapêutico , Vasos Coronários , Aneurisma Coronário/epidemiologia , Aneurisma Coronário/etiologia , Imunoglobulinas Intravenosas/uso terapêuticoRESUMO
Kawasaki disease (KD) is an acute inflammatory syndrome of unknown etiology that is complicated by cardiovascular sequelae. Chronic inflammation (vasculitis) due to KD might cause vascular cellular senescence and vascular endothelial cell damage, and is a potential cause of atherosclerosis in young adults. This study examined the effect of KD and HMG-CoA inhibitors (statins) on vascular cellular senescence and vascular endothelial cells. Candida albicans water-soluble fraction (CAWS) was administered intraperitoneally to 5-week-old male apolipoprotein E-deficient (ApoE-) mice to induce KD-like vasculitis. The mice were then divided into three groups: control, CAWS, and CAWS+statin groups. Ten weeks after injection, the mice were sacrificed and whole aortic tissue specimens were collected. Endothelial nitric oxide synthase (eNOS) expression in the ascending aortic intima epithelium was evaluated using immunostaining. In addition, eNOS expression and levels of cellular senescence markers were measured in RNA and proteins extracted from whole aortic tissue. KD-like vasculitis impaired vascular endothelial cells that produce eNOS, which maintains vascular homeostasis, and promoted macrophage infiltration into the tissue. Statins also restored vascular endothelial cell function by promoting eNOS expression. Statins may be used to prevent secondary cardiovascular events during the chronic phase of KD.
Assuntos
Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Síndrome de Linfonodos Mucocutâneos , Vasculite , Masculino , Camundongos , Animais , Síndrome de Linfonodos Mucocutâneos/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Células Endoteliais/metabolismo , Vasculite/etiologia , Aterosclerose/etiologia , Aterosclerose/complicações , Óxido Nítrico Sintase Tipo III/metabolismoRESUMO
BACKGROUND: Kawasaki disease (KD) is a systemic inflammatory disease resulting in an acute febrile syndrome commonly affecting children younger than 5 years. Coronary arteritis in KD is occasionally non-responsive to several treatments. Recently, adipose tissue-derived stem cells (ADSCs) have been shown to have anti-inflammatory, immunosuppressive, and tissue-repair characteristics and are considered a useful treatment for inflammatory disease. The present study aimed to elucidate whether the administration of ADSCs can suppress KD-associated vasculitis in vivo. METHODS: Candida albicans water-soluble fraction is often used to model KD via the induction of severe coronary arteritis. Kawasaki disease model mice were intravenously administered ADSCs and phosphate-buffered saline (PBS). On day 29, the mice were sacrificed and hearts from mice in each group were dissected. This was followed by serum collection. Cardiac tissue sections were subjected to histopathological examination to evaluate the inflammatory area. The levels of pro-inflammatory cytokines in the serum were analyzed at days 15 and 29. The survival rates of both groups were compared. RESULTS: The mean inflammatory area in coronary arteritis was significantly lower in the ADSC group compared to the PBS group (P < 0.01). Furthermore, the levels of pro-inflammatory cytokines, such as IL-1ß, IL-12, IL-17, RANTES, INF-γ, and TNF-α, in the ADSC group were significantly lower than those in the PBS group. Moreover, the ADSC group had a significantly higher survival rate than the PBS group. CONCLUSIONS: These findings highlight that ADSCs have anti-inflammatory and immune regulatory functions that could provide novel cell-based therapeutic strategies for severe KD.
Assuntos
Tecido Adiposo/citologia , Arterite/terapia , Síndrome de Linfonodos Mucocutâneos/terapia , Células-Tronco/citologia , Animais , Candida albicans , Doença da Artéria Coronariana/terapia , Vasos Coronários/patologia , Citocinas/sangue , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos DBA , Transplante de Células-Tronco/métodosRESUMO
Kawasaki disease (KD) is a systemic inflammatory process that affects the medium-sized arteries, causing various cardiovascular complications. However, it is not clear if the vascular sequelae following KD can predispose to the development of atherosclerosis later in life. Our aim was to examine the macrophage phenotypes in the coronary arteries forming giant aneurysms after KD to gain insight into the pathogenesis of vascular lesions in KD. We examined histological sections of the coronary arteries from five patients with KD who underwent coronary bypass grafting procedure as treatment for giant aneurysms and subsequent stenosis. Immunohistochemical expression of M1- and M2-macrophage markers was assessed to determine the macrophage phenotype of KD to compare with that of atherosclerosis in eight adult patients. All the KD specimens showed a mild to moderate degree of intimal thickening consisting of mature fibrous tissue and distortion of elastic fibers, mimicking the histological features of atherosclerosis. The total number of CD68 positive macrophages was higher in atherosclerosis than in KD specimens. Among the CD68 positive macrophages, the proportion of M1 phenotype, detected by CD86 or SOCS3, was higher in KD than in atherosclerosis. In contrast, the proportion of M2 phenotype, detected by CD163 or MRC1, was higher in patients with atherosclerosis. Despite similar histological features, KD and atherosclerosis appear to have a different immunological etiology for progression of the chronic vascular lesions. A further study enrolling a larger number of cases is required to delineate underlying mechanisms of vascular complications in KD.
Assuntos
Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Doença da Artéria Coronariana/imunologia , Vasos Coronários/imunologia , Macrófagos/imunologia , Glicoproteínas de Membrana/análise , Síndrome de Linfonodos Mucocutâneos/imunologia , Placa Aterosclerótica , Receptores de Superfície Celular/análise , Receptores Imunológicos/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença da Artéria Coronariana/diagnóstico , Vasos Coronários/patologia , Tecido Elástico/patologia , Feminino , Humanos , Lactente , Macrófagos/patologia , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Neointima , FenótipoRESUMO
BACKGROUND: Giant coronary aneurysm is the most severe sequela in Kawasaki disease, occurring in approximately 0.2% of patients in Japan. Regression is rare, while myocardial infarction (MI) and sudden death are relatively common. Herein, we reviewed patients with giant coronary aneurysm in a 10-year period.MethodsâandâResults:A nationwide questionnaire survey was conducted based on a national epidemiological database from 1999 to 2010. We identified 355 giant coronary aneurysm patients, of whom 209 were analyzed. The 5- and 10-year total cardiac event-free rates were 0.72 and 0.68, respectively. Twelve patients died, and MI was observed in 32 patients (18.1%). Five and 6 deaths were due to coronary rupture and MI, respectively. All ruptures occurred within 1 month of onset, while most MI occurred within 18 months. There was no death beyond 2 years. Aneurysm size was significantly related to the occurrence of MI in both the right and left coronary arteries. At the time of writing, 55% of patients had no exercise limitations. And including patients who cannot perform strenuous exercises, 81% of patients were leading ordinary lives. CONCLUSIONS: Severe cardiac events are likely to occur within 2 years from onset of Kawasaki disease, while no deaths occurred beyond this time. Hence, careful monitoring is needed especially for the first 2 years. Most patients with giant coronary aneurysms can lead ordinary lives with appropriate management.
Assuntos
Aneurisma Coronário/etiologia , Síndrome de Linfonodos Mucocutâneos/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Japão/epidemiologia , Masculino , Síndrome de Linfonodos Mucocutâneos/terapia , Infarto do Miocárdio , Avaliação de Resultados em Cuidados de Saúde , Inquéritos e Questionários , Análise de Sobrevida , Fatores de TempoRESUMO
OBJECTIVE: Kawasaki disease (KD) occurs via activation of the innate immune system. Nucleotide oligomerization domain-1 (NOD1) is a pattern recognition receptor regulating the innate immunity. We characterized histopathology of arteritis induced by FK565, a ligand for NOD1, in mice, compared with Candida albicans water-soluble fraction (CAWS)-induced model. METHODS: Vasculitis was induced by injection of FK565 or CAWS into C57BL6/J mice (n = 9 and n = 11, respectively). At 4 weeks, they were sacrificed, and plasma cytokines and chemokines were measured. RESULTS: FK565 injection induced vasculitis mainly involving bilateral coronary arteries whereas the aortic root was diffusely affected in CAWS mice. In FK565 animals, the abdominal aorta and its branching arteries also exhibited inflammation with atherosclerosis. IL-1α, IL-1ß, IL-5 and RANTES were increased in FK565 group whereas IL-6, IL-13, G-CSF, IFN-γ, and TNF-α were higher in CAWS animals (p < .05 for all variables). The total area of inflammation in FK565 mice appeared to correlate with IL-1ß levels (r = 0.71, p = .05). CONCLUSIONS: Histopathology of FK565-induced model demonstrated 'site-specific' coronary arteritis mimicking KD. This histopathological difference from CAWS model may be due to different cytokine expression profiles.
Assuntos
Adjuvantes Imunológicos/toxicidade , Candida albicans/química , Síndrome de Linfonodos Mucocutâneos/etiologia , Oligopeptídeos/toxicidade , Adjuvantes Imunológicos/farmacologia , Animais , Candida albicans/imunologia , Modelos Animais de Doenças , Fator Estimulador de Colônias de Granulócitos/sangue , Interleucina-6/sangue , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Síndrome de Linfonodos Mucocutâneos/metabolismo , Síndrome de Linfonodos Mucocutâneos/patologia , Proteína Adaptadora de Sinalização NOD1/metabolismo , Oligopeptídeos/farmacologia , Ligação Proteica , Frações Subcelulares/imunologia , Fator de Necrose Tumoral alfa/sangueAssuntos
Cardiologia/normas , Doenças Cardiovasculares/terapia , Síndrome de Linfonodos Mucocutâneos/terapia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Consenso , Medicina Baseada em Evidências/normas , Humanos , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/epidemiologia , PrognósticoRESUMO
BACKGROUND: Adipose tissue-derived mesenchymal stem cells (ADSCs) are used for the treatment of various diseases because of their rapid proliferation and high anti-inflammatory and tissue repair properties. Kawasaki disease is a systemic vasculitis with coronary arteritis and aneurysms occurring in pediatric patients. In this study, we examined serologically and pathologically whether the administration of human ADSCs (hADSCs) to a mouse model of Kawasaki disease could suppress vasculitis. METHODS: Candida albicans water-soluble fractions were intraperitoneally injected into DBA/2 mice for 5 consecutive days to generate a mouse model of Kawasaki disease. The model mice were intravenously administered hADSCs or phosphate-buffered saline (PBS). Serum samples collected on days 15 and 29 were used to compare cytokine levels. Mouse hearts dissected on day 29 were subjected to hematoxylin and eosin and immunohistological staining using Galectin-1 (Gal-1), a protein involved in cardiovascular homeostasis, and CD44, a cell-surface marker of hADSCs. RESULTS: Comparison of inflammation-related cytokines showed a significant decrease in IL-1α expression at day 15 (P<0.05) and IL-6 expression at day 29 (P<0.01) in the hADSCs-treated group compared to the PBS group. Evaluation by hematoxylin and eosin staining showed decreased inflammatory cell infiltration and a tendency towards increased Gal-1 expression in the hADSCs group. CD44 expression was not observed in both the groups. The survival curve showed that the hADSCs group had a significantly longer survival time (P<0.05). CONCLUSIONS: The present experimental results indicate that hADSCs have an early anti-inflammatory effect, and that Gal-1 may be involved in preventing inflammation and reducing tissue damage.
Assuntos
Tecido Adiposo , Modelos Animais de Doenças , Síndrome de Linfonodos Mucocutâneos , Animais , Síndrome de Linfonodos Mucocutâneos/terapia , Humanos , Tecido Adiposo/citologia , Camundongos Endogâmicos DBA , Interleucina-6/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Interleucina-1alfa/metabolismo , Receptores de Hialuronatos/metabolismo , Células-Tronco Mesenquimais , Vasos Coronários/patologia , Masculino , CamundongosRESUMO
BACKGROUND: The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment. METHODS: Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan. RESULTS: The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFß receptors. Measurement of the inflammatory cytokines IL-1ß, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan. CONCLUSIONS: Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.
Assuntos
Benzimidazóis , Compostos de Bifenilo , Candida albicans , Modelos Animais de Doenças , Síndrome de Linfonodos Mucocutâneos , Tetrazóis , Animais , Benzimidazóis/farmacologia , Benzimidazóis/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Tetrazóis/farmacologia , Tetrazóis/administração & dosagem , Candida albicans/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Camundongos Endogâmicos DBA , Solubilidade , Água , Vasculite/tratamento farmacológico , Masculino , Camundongos , Citocinas/metabolismo , Interleucina-6/metabolismoRESUMO
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.
Assuntos
Amônia , Circulação Coronária , Síndrome de Linfonodos Mucocutâneos , Imagem de Perfusão do Miocárdio , Radioisótopos de Nitrogênio , Tomografia por Emissão de Pósitrons , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Masculino , Feminino , Amônia/sangue , Tomografia por Emissão de Pósitrons/métodos , Criança , Pré-Escolar , Imagem de Perfusão do Miocárdio/métodos , Oclusão Coronária/etiologia , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/fisiopatologia , Aneurisma Coronário/etiologia , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/fisiopatologia , Adolescente , Lactente , HemodinâmicaRESUMO
BACKGROUND: Evidence indicates that corticosteroid therapy might be beneficial for the primary treatment of severe Kawasaki disease. We assessed whether addition of prednisolone to intravenous immunoglobulin with aspirin would reduce the incidence of coronary artery abnormalities in patients with severe Kawasaki disease. METHODS: We did a multicentre, prospective, randomised, open-label, blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec 2, 2010. Patients with severe Kawasaki disease were randomly assigned by a minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin group plus prednisolone 2 mg/kg per day given over 15 days after concentrations of C-reactive protein normalised). Patients and treating physicians were unmasked to group allocation. The primary endpoint was incidence of coronary artery abnormalities during the study period. Analysis was by intention to treat. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000000940. FINDINGS: We randomly assigned 125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to the intravenous immunoglobulin group. Incidence of coronary artery abnormalities was significantly lower in the intravenous immunoglobulin plus prednisolone group than in the intravenous immunoglobulin group during the study period (four patients [3%] vs 28 patients [23%]; risk difference 0·20, 95% CI 0·12-0·28, p<0·0001). Serious adverse events were similar between both groups: two patients had high total cholesterol and one neutropenia in the intravenous immunoglobulin plus prednisolone group, and one had high total cholesterol and another non-occlusive thrombus in the intravenous immunoglobulin group. INTERPRETATION: Addition of prednisolone to the standard regimen of intravenous immunoglobulin improves coronary artery outcomes in patients with severe Kawasaki disease in Japan. Further study of intensified primary treatment for this disease in a mixed ethnic population is warranted. FUNDING: Japanese Ministry of Health, Labour and Welfare.
Assuntos
Anti-Inflamatórios/uso terapêutico , Doença da Artéria Coronariana/prevenção & controle , Anomalias dos Vasos Coronários/prevenção & controle , Imunoglobulinas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Prednisolona/uso terapêutico , Aspirina/uso terapêutico , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Lactente , Masculino , Estudos ProspectivosRESUMO
In paediatric primary Sjögren's syndrome (SS), the initial symptoms manifest systemically, such as fever, general fatigue, and lymphadenopathy, rather than sicca symptoms. Most children with primary SS have autoantibodies, such as antinuclear, anti-Ro/SS-A, and/or anti-La/SS-B antibodies; however, some patients are seronegative. Similar to paediatric patients with primary SS, those with Takayasu arteritis (TAK) initially only present constitutional symptoms, making it difficult to suspect, unless characteristic features are present. To our knowledge, there have been no reports of the coexistence of both diseases in children. We present a rare case of seronegative SS complicated by TAK in a 9-year-old girl who presented with a persistent low-grade fever, general fatigue, cervical lymphadenopathy, and multiple caries. Although blood examination revealed all autoantibodies to be negative, a lip biopsy revealed lymphocytic sialadenitis, and a sialoscintigraphy indicated hypofunctional salivary glands, leading to the diagnosis of seronegative SS. The patient was treated with low-dose glucocorticoid and immunosuppressant administration to inhibit persistent inflammation and the progression of salivary gland dysfunction; although the symptoms resolved, inflammatory markers remained elevated. When the patient was 14 years old, cervical bruits were incidentally found, and TAK was suspected based on cervical ultrasonography and magnetic resonance angiography findings. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography results demonstrated increased fluorodeoxyglucose accumulation from the ascending to descending aorta. Therefore, she was diagnosed with SS complicated by TAK, which is rare. Aortitis should be suspected when the cause of persistent inflammation cannot be ascertained in patients with SS.
Assuntos
Linfadenopatia , Síndrome de Sjogren , Arterite de Takayasu , Adolescente , Feminino , Humanos , Autoanticorpos , População do Leste Asiático , Fluordesoxiglucose F18 , Inflamação/complicações , Linfadenopatia/complicações , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Arterite de Takayasu/complicações , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/tratamento farmacológicoRESUMO
Three patients, aged 2â¯years 0â¯months, 2â¯years 2â¯months, and 6â¯years 1â¯month at the time of plain old balloon angioplasty (POBA), developed an aneurysm in the left anterior descending coronary branch after suffering from Kawasaki disease. POBA was subsequently performed due to 99â¯% stenosis proximal to the aneurysm. There was no restenosis within a few years after percutaneous coronary intervention, and there was no evidence of ischemia, although 75â¯% restenosis occurred in two patients after 7â¯years.Although calcified lesions are more likely to occur 6â¯years after the onset of Kawasaki disease, none of the patients in this study had calcified lesions within 4â¯years of Kawasaki disease onset, and good results were obtained with POBA alone. POBA can be safely performed in children and is an effective treatment for improving myocardial ischemia if calcification has not progressed. Learning objective: Plain old balloon angioplasty (POBA) can be performed effectively and safely for Kawasaki disease coronary artery stenosis in early childhood if calcification is minimal, with little restenosis for at least several years. POBA is a useful tool in the treatment of coronary artery stenosis in early childhood.
RESUMO
Trisomy 21 (Down syndrome) is sometimes complicated by congenital heart disease; however, comorbid type I diabetes mellitus and diseases involving autoantibodies, such as Hashimoto disease and Graves disease, are not uncommon. Autoinflammatory diseases such as Kawasaki disease and systemic juvenile idiopathic arthritis are rare. We report a rare case of trisomy 21 with systemic juvenile idiopathic arthritis that responded well to the initial course of methylprednisolone pulse therapy but flared up and was complicated by macrophage activation syndrome (MAS). Subsequent methylprednisolone pulse therapy and cyclosporine resolved this condition. Cytokines were analyzed at several time points during the clinical course and revealed that interleukin-18, interleukin-6, and chemokine ligand 9 levels were elevated at MAS onset in the present patient, even though clinical symptoms had abated. Thus, early analysis of cytokine profiles should be performed to assess MAS risk and determine treatment intensity, even in T21 patients.
Assuntos
Artrite Juvenil , Síndrome de Down , Síndrome de Ativação Macrofágica , Humanos , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Síndrome de Down/complicações , Citocinas , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/etiologia , Síndrome de Ativação Macrofágica/tratamento farmacológico , Metilprednisolona , Progressão da DoençaRESUMO
BACKGROUND: Residual shunt after closure of an inferior sinus venosus defect (ISVD) is a rare complication with a high rate of reintervention. CASE PRESENTATION: Here, we report a rare case of a recurrent defect identified 22 years after closure of an ISVD. The defect (25 × 10 mm) was located at the inferior vena cava-right atrial junction and was closed directly when the patient was 5 years of age. No residual shunt was detected and follow-up was discontinued at age 12 years. However, a residual atrial septal defect shunt was detected incidentally at age 27 years. During the second surgery, the lower end of the original defect was opened and then closed with an expanded polytetrafluoroethylene patch. CONCLUSIONS: Because of the high rate of reintervention for residual shunt after ISVD closure, patch closure was selected as a better option to reduce tension at the inferior-posterior border. Patients with this profile should be followed closely, at least during childhood, including by echocardiography.
Assuntos
Comunicação Interatrial , Humanos , Criança , Adulto , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/cirurgia , Ecocardiografia , Átrios do CoraçãoRESUMO
Current treatments for patients with coronary aneurysms caused by Kawasaki disease (KD) are based primarily on aneurysm size. This ignores hemodynamic factors influencing myocardial ischemic risk. We performed patient-specific computational hemodynamics simulations for 15 KD patients, with parameters tuned to patients' arterial pressure and cardiac function. Ischemic risk was evaluated in 153 coronary arteries from simulated fractional flow reserve (FFR), wall shear stress, and residence time. FFR correlated weakly with aneurysm [Formula: see text]-scores (correlation coefficient, [Formula: see text]) but correlated better with the ratio of maximum-to-minimum aneurysmal lumen diameter ([Formula: see text]). FFR dropped more rapidly distal to aneurysms, and this correlated more with the lumen diameter ratio ([Formula: see text]) than [Formula: see text]-score ([Formula: see text]). Wall shear stress correlated better with the diameter ratio ([Formula: see text]), while residence time correlated more with [Formula: see text]-score ([Formula: see text]). Overall, the maximum-to-minimum diameter ratio predicted ischemic risk better than [Formula: see text]-score. Although FFR immediately distal to aneurysms was nonsignificant, its rapid rate of decrease suggests elevated risk.
Assuntos
Aneurisma Coronário , Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Síndrome de Linfonodos Mucocutâneos , Isquemia Miocárdica , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/complicações , Hemodinâmica , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/complicações , Vasos Coronários/diagnóstico por imagem , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Angiografia CoronáriaRESUMO
Background Coronary arterial aneurysms (CAAs) associated with Kawasaki disease (KD) significantly affect prognosis. However, the clinical course of CAAs and factors associated with CAA regression have not been well analyzed. Methods and Results The cohort of the Z-Score 2nd Project Stage study, a multicenter, retrospective, cohort study involving 44 institutions in Japan including 1006 patients with KD, was examined. CAAs were classified by the z score of their internal diameter in the acute phase: small (z<5), medium (5≤z<10), and large (z≥10). The lower limit of small CAA was based on the Japanese Ministry of Health, Labour and Welfare criteria. In the right coronary artery, the CAA regression rates 10 years after diagnosis were 95.5% for small, 83.2% for medium, and 36.3% for large. In the proximal left anterior descending artery, the regression rates 10 years after diagnosis were 95.3% for small, 80.1% for medium, and 28.8% for large. Cox regression analysis showed that diagnosis under the age of 1 year and onset of KD in 2010 to 2012 for the right coronary artery and the left anterior descending artery, and female for the right coronary artery were significantly associated with a high regression rate, whereas large CAAs for the right coronary artery and the left anterior descending artery were significantly associated with a low regression rate. Conclusions The current study, the largest Japanese study of its kind, found that small aneurysm, recent onset, and diagnosis under the age of 1 year predict regression, and that even giant aneurysms could regress. These data may contribute to long-term management of coronary aneurysms. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000010606.
Assuntos
Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , Humanos , Feminino , Lactente , Aneurisma Coronário/etiologia , Aneurisma Coronário/complicações , Vasos Coronários/diagnóstico por imagem , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Estudos Retrospectivos , Estudos de CoortesRESUMO
Kawasaki disease (KD) is an acute form of systemic vasculitis that may promote atherosclerosis in adulthood. This study examined the relationships between KD, atherosclerosis, and the long-term effects of HMG-CoA inhibitors (statins). Candida albicans water-soluble fraction (CAWS) was injected intraperitoneally into 5-week-old male apolipoprotein-E-deficient (Apo E-/-) mice to create KD-like vasculitis. Mice were divided into 4 groups: the control, CAWS, CAWS+statin, and late-statin groups. They were sacrificed at 6 or 10 weeks after injection. Statin was started after CAWS injection in all groups except the late-statin group, which was administered statin internally 6 weeks after injection. Lipid plaque lesions on the aorta were evaluated with Oil Red O. The aortic root and abdominal aorta were evaluated with hematoxylin and eosin staining and immunostaining. CAWS vasculitis significantly enhanced aortic atherosclerosis and inflammatory cell invasion into the aortic root and abdominal aorta. Statins significantly inhibited atherosclerosis and inflammatory cell invasion, including macrophages. CAWS vasculitis, a KD-like vasculitis, promoted atherosclerosis in Apo E-/- mice. The long-term oral administration of statin significantly suppressed not only atherosclerosis but also inflammatory cell infiltration. Therefore, statin treatment may be used for the secondary prevention of cardiovascular events during the chronic phase of KD.