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Karatza AA, Fouzas S, Gkentzi D, Kostopoulou E, Loukopoulou C, Dimitriou G, Sinopidis X. Missed or Delayed Diagnosis of Heart Disease by the General Pediatrician. CHILDREN (BASEL, SWITZERLAND) 2025; 12:366. [PMID: 40150649 PMCID: PMC11941687 DOI: 10.3390/children12030366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 03/12/2025] [Accepted: 03/13/2025] [Indexed: 03/29/2025]
Abstract
Missed or delayed heart disease diagnoses pose a major challenge in pediatric primary care. Many cardiac conditions present with subtle or nonspecific symptoms that resemble benign childhood illnesses, making their prompt recognition difficult. This review describes congenital and acquired heart diseases prone to diagnostic delays, including critical congenital heart disease, coarctation of the aorta, atrial and ventricular septal defects, myocarditis, Kawasaki disease, heart failure, and pulmonary arterial hypertension. The atypical presentations of these disorders and the associated diagnostic pitfalls are emphasized. Furthermore, the importance of alarming symptoms and signs, such as chest pain, palpitations, syncope, and abnormal heart murmurs, is underscored. A structured approach to these red flags is presented to assist primary care pediatricians in identifying children at risk, initiating appropriate management, and referring them for specialized evaluation. The importance of preparticipation screening for athletes is also discussed, highlighting how it can be applied to all children during routine health visits to identify those with heart disease. Appropriate training is essential to increase pediatricians' ability to recognize and manage cardiac patients.
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Affiliation(s)
- Ageliki A. Karatza
- Department of Pediatrics, University Hospital, School of Medicine, University of Patras, 26504 Patras, Greece; (A.A.K.); (S.F.); (D.G.); (E.K.); (C.L.); (G.D.)
| | - Sotirios Fouzas
- Department of Pediatrics, University Hospital, School of Medicine, University of Patras, 26504 Patras, Greece; (A.A.K.); (S.F.); (D.G.); (E.K.); (C.L.); (G.D.)
| | - Despoina Gkentzi
- Department of Pediatrics, University Hospital, School of Medicine, University of Patras, 26504 Patras, Greece; (A.A.K.); (S.F.); (D.G.); (E.K.); (C.L.); (G.D.)
| | - Eirini Kostopoulou
- Department of Pediatrics, University Hospital, School of Medicine, University of Patras, 26504 Patras, Greece; (A.A.K.); (S.F.); (D.G.); (E.K.); (C.L.); (G.D.)
| | - Christina Loukopoulou
- Department of Pediatrics, University Hospital, School of Medicine, University of Patras, 26504 Patras, Greece; (A.A.K.); (S.F.); (D.G.); (E.K.); (C.L.); (G.D.)
| | - Gabriel Dimitriou
- Department of Pediatrics, University Hospital, School of Medicine, University of Patras, 26504 Patras, Greece; (A.A.K.); (S.F.); (D.G.); (E.K.); (C.L.); (G.D.)
| | - Xenophon Sinopidis
- Department of Pediatric Surgery, University Hospital, School of Medicine, University of Patras, 26504 Patras, Greece
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Jin J, Zhao Y, Fang Y, Pan Y, Wang P, Fan Z, Yu H. Neutrophil extracellular traps promote the activation of the NLRP3 inflammasome and PBMCs pyroptosis via the ROS-dependent signaling pathway in Kawasaki disease. Int Immunopharmacol 2025; 145:113783. [PMID: 39647285 DOI: 10.1016/j.intimp.2024.113783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/26/2024] [Accepted: 12/01/2024] [Indexed: 12/10/2024]
Abstract
Kawasaki disease (KD) is an acute systemic vasculitis predominantly affecting infants and children under the age of 5. Recent studies have indicated that excessively released neutrophil extracellular traps (NETs) are involved in the progression of vasculitis. The purpose of this study was to investigate the role of NETs, especially their interaction with peripheral blood mononuclear cells (PBMCs), in the pathogenesis of KD. First, we demonstrated that the levels of NETs (cfDNA, MPO, and NE) in the serum of KD patients were significantly higher than those in healthy controls (HCs) and notably decreased after treatment. During the acute phase of KD, inflammatory markers (CRP and ESR) were positively correlated with NETs levels. Furthermore, we observed that neutrophils from KD patients in the acute phase produced elevated levels of NETs, and aspirin could effectively regulate the release of NETs. Additionally, NETs significantly increased the mRNA levels of NLRP3 and IL-1β in PBMCs, as well as the protein expression of NLRP3, caspase-1, ASC and gasdermin D, and the concentration of IL-1β in the cell supernatant. Moreover, NETs stimulated the production of reactive oxygen species (ROS) in PBMCs. N-acetylcysteine significantly reduced the expression of inflammatory factors and pyroptosis-related proteins in PBMCs. In conclusion, our findings suggest that NETs induce the generation of ROS, which in turn activates the NLRP3 inflammasome to mediate PBMCs pyroptosis and perpetuate inflammation in KD patients. This study reveals that targeting NETs or ROS could be a potential therapeutic approach for alleviating systemic inflammation, and that NETs may be a novel target for aspirin in the treatment of KD patients.
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Affiliation(s)
- Jing Jin
- Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Yan Zhao
- Department of Ultrasonography, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Yuying Fang
- Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Yuting Pan
- Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Panpan Wang
- Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Zhidan Fan
- Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing, China.
| | - Haiguo Yu
- Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing, China.
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Alibrahim I, Mirza A, Khojah A. Polyarteritis nodosa mimics Kawasaki disease. BMJ Case Rep 2024; 17:e260544. [PMID: 39433394 DOI: 10.1136/bcr-2024-260544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2024] Open
Abstract
Polyarteritis nodosa (PAN) is a rarely seen vasculitis that often affects small-sized and medium-sized arteries. PAN can present with diverse clinical features depending on the organs involved, including potential cardiac involvement. Typical cardiac manifestations of PAN in the paediatric age group include pericarditis, valvular heart disease and coronary artery aneurysms. In contrast to PAN, Kawasaki disease (KD) is often associated with coronary artery abnormalities. Herein, we report a case of a young boy presented with KD-like features, including a coronary artery aneurysm confirmed by an echocardiogram (ECHO) and eventually diagnosed as PAN. The patient was treated with steroids, methotrexate and tocilizumab with improvement of the symptoms. Repeated ECHO revealed the resolution of the coronary artery aneurysms. Our paper highlights a rare presentation of PAN mimicking KD presentation. Physicians should consider PAN in chronic or severe courses of KD or coronary artery aneurysms.
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Affiliation(s)
| | - Aisha Mirza
- Pediatrics, Maternity and Children Hospital, Makkah, Saudi Arabia
| | - Amer Khojah
- Pediatrics, Umm Al-Qura University College of Medicine, Makkah, Saudi Arabia
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Exploring the Mechanism of Aspirin in the Treatment of Kawasaki Disease Based on Molecular Docking and Molecular Dynamics. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:9828518. [PMID: 35990842 PMCID: PMC9391120 DOI: 10.1155/2022/9828518] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 06/26/2022] [Accepted: 07/18/2022] [Indexed: 11/17/2022]
Abstract
Purpose The research aims to investigate the mechanism of action of aspirin in the treatment of Kawasaki disease. Methods We predicted the targets of aspirin with the help of the Drugbank and PharmMapper databases, the target genes of Kawasaki disease were mined in the GeneCards and Disgenet databases, the intersection targets were processed in the Venny database, and the gene expression differences were observed in the GEO database. The Drugbank and PharmMapper databases were used to predict the target of aspirin, and the target genes of Kawasaki disease were explored in the GeneCards and Disgenet databases, and the Venny was used for intersection processing. We observed the gene expression differences in the GEO database. The disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulation verification was carried out to combine the active ingredient and the target with a stable combination. The supercomputer platform was used to measure and analyze the binding free energy, the number of hydrogen bonds, the stability of the protein target at the residue level, the radius of gyration, and the solvent accessible surface area. Results Aspirin had 294 gene targets, Kawasaki disease had 416 gene targets, 42 intersecting targets were obtained, we screened 13 core targets by PPI; In the GO analysis, we learned that the biological process of Kawasaki disease involved the positive regulation of chemokine biosynthesis and inflammatory response; pathway enrichment involved PI3K-AKT signaling pathway, tumor necrosis factor signaling pathway, etc. After molecular docking, the data showed that CTSG, ELANE, and FGF1 had the best binding degree to aspirin. Molecular dynamics was used to prove and analyze the binding stability of active ingredients and protein targets, and Aspirin/ELANE combination has the strongest binding energy. Conclusion In the treatment of Kawasaki disease, aspirin may regulate inflammatory response and vascular remodeling through CTSG, ELANE, and FGF1.
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A Retrospective Cohort Study of Intravenous Immunoglobulin Therapy in the Acute Phase of Kawasaki Disease: The Earlier, the Better? Cardiovasc Ther 2021; 2021:6660407. [PMID: 34239607 PMCID: PMC8233071 DOI: 10.1155/2021/6660407] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/24/2021] [Accepted: 05/31/2021] [Indexed: 11/17/2022] Open
Abstract
Background Although intravenous immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities of Kawasaki disease (KD) in the acute phase, the timing and effectiveness of IVIG remain to be determined. The association of timing of IVIG administration in KD patients with coronary artery abnormalities is evaluated in this cohort study. Methods We systematically studied KD patients from two participating institutions between 2015 and 2017. To reveal the effectiveness of IVIG treatment, these patients were classified into four groups regarding the time of IVIG treatment. Primary outcome was coronary artery abnormalities by echo at diagnosis and 12 months follow-up; secondary outcomes included inflammatory markers. Results A total of 1281 patients were included in this study. The best time of IVIG treatment cut-off values in 12 months follow-up for predicting coronary artery abnormalities was days 7.5 of illness onset. According to the best time of IVIG treatment cut-off values, all patients were classified into 4 groups. Group 1 was defined as earlier IVIG treatment administration on days ≤4 of the illness (n = 77). Group 2 was defined with days 5-7 (n = 817), group 3 with days 8-10 (n = 249), group 4 with days >10 (n = 138). A greater proportion of IVIG-resistant KD patients were group 4 than the other three groups, and there were significant differences (p < 0.05). The incidence of coronary artery lesions (CALs) and coronary artery aneurysms (CAAs) in group 3 and group 4 was higher than that in group 1 (p < 0.05) and group 2 (p < 0.05) during a 12-month follow-up. Additionally, the incidence of CALs in group 1 was higher than that in group 2 but without statistical significance (p > 0.05). The OR was significantly higher for those who started IVIG administration more than 7 days from the onset was positively associated with the occurrence of CALs (OR, 5.3; 95% CI, 2.0-13.9) and CAAs (OR, 13.5; 95% CI, 2.9-14.1) 12 months after initial onset. Multivariate regression revealed that the timing of IVIG treatment and IVIG-resistance was independent risk factors of CALs. Conclusions IVIG treatment less than 7 days after illness onset are found to be sufficient for preventing developing coronary artery abnormalities in KD patients. Earlier IVIG treatment administration within 4 days may not increase the higher incidence of coronary artery abnormalities and IVIG resistance (Chinese Clinical Trial Registry:ChiCTR1800015800).
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Wang LJ, Tsai ZY, Chang LS, Kuo HC. Cognitive development of children with Kawasaki disease and the parenting stress of their caregivers in Taiwan: a case-control study. BMJ Open 2021; 11:e042996. [PMID: 34083326 PMCID: PMC8183223 DOI: 10.1136/bmjopen-2020-042996] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE Kawasaki disease (KD) is an acute form of febrile vasculitis that occurs in early childhood. The multisystemic vasculitis common in patients with KD may influence blood perfusion in the brain, and thus caregivers of children with KD may feel stress with regard to caring for them. Intravenous immunoglobulin (IVIG) infusion is the standard treatment for acute KD, and the most serious complication of KD is coronary artery aneurysms (coronary artery lesion (CAL)). This study aimed to investigate the relationships between KD heterogeneity and the risk of patients' cognitive impairment or caregivers' parenting stress. DESIGN A case-control study with consecutive sampling. SETTING A medical centre (Kaohsiung Chang Gung Memorial Hospital, Taiwan). PARTICIPANTS This study consisted of 176 patients with KD (mean age: 5.5 years, 60.8% boys) and 85 healthy children (mean age: 6.4 years, 54.1% boys). PRIMARY AND SECONDARY OUTCOME MEASURES Based on the children's age, each patient with KD and control subject was administered an assessment using the Mullen Scales of Early Learning or the Wechsler Intelligence Scale, and parenting function of their caregivers was assessed using the Parenting Stress Index (PSI)-Short Form. RESULTS We observed no significant differences in any developmental index, cognitive function or parenting stress between patients with KD and controls. Among the children with KD, IVIG administration nor CAL was associated with children's cognitive scores. However, the caregivers of patients who had CAL suffered from greater PSI total scores than those of patients without CAL. Furthermore, the caregivers who had education levels of a master's degree or above showed less parenting stress than those who had an education level of college or lower. CONCLUSION Caregivers' education is associated to parenting stress, and caregivers of patients with KD who developed CAL may feel stress about the unpredictable sequela caused by CAL for their children. Such caregivers may require support to fulfil their parenting roles.
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Affiliation(s)
- Liang-Jen Wang
- Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Kaohsiung, Taiwan
| | - Zi-Yu Tsai
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ling-Sai Chang
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ho-Chang Kuo
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Abstract
Kawasaki disease is an acute systemic febrile vasculitis of medium and small arteries, most often occurring in children under age 5 years. This condition is the most common cause of acquired heart disease in children in the developed world. The cause is unclear but is thought to be a hyperimmune reaction to an infectious agent. Diagnosis is clinical; the classic presentation includes persistent fever, lymphadenopathy, oral mucosal changes, conjunctivitis, and rash. Although the disease technically is self-limiting, treatment with IV immunoglobulin (IVIG) and high-dose aspirin is necessary to prevent cardiac complications, such as coronary artery aneurysm, pericarditis, or myocarditis. This article reviews the pathophysiology, clinical presentation, diagnosis, and treatment of Kawasaki disease.
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Circulating microRNAs differentiate Kawasaki Disease from infectious febrile illnesses in childhood. J Mol Cell Cardiol 2020; 146:12-18. [PMID: 32634388 DOI: 10.1016/j.yjmcc.2020.06.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 06/22/2020] [Accepted: 06/29/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Kawasaki Disease (KD) is an acute vasculitis of unknown etiology in children that can lead to coronary artery lesions (CAL) in 25% of untreated patients. There is currently no diagnostic test for KD, and the clinical presentation is often difficult to differentiate from other febrile childhood illnesses. Circulating microRNAs (miRNAs) are small noncoding RNA molecules that control gene expression by inducing transcript degradation or by blocking translation. We hypothesize that the expression of circulating miRNAs will differentiate KD from non-KD febrile illnesses in children. METHODS Circulating miRNA profiles from 84 KD patients and 29 non-KD febrile controls (7 viral and 22 bacterial infections) were evaluated. 3 ul of serum from each subject was submitted to 3 freeze/heat cycles to ensure miRNA release from microvesicles or interaction with serum proteins. miRNAs were reverse transcribed using a pool of primers specific for each miRNA. Real-time PCR reactions were performed in a 384 well plate containing sequence-specific primers and TaqMan probes in the ABI7900. '. RESULTS KD patients (3.6 ± 2.2 yrs., 58% male) were found to have a unique circulating miRNA profile, including upregulation of miRNA-210-3p, -184, and -19a-3p (p < .0001), compared to non-KD febrile controls (8.5 ± 6.1 yrs., 72% male). CONCLUSIONS Circulating miRNAs can differentiate KD from infectious febrile childhood diseases, supporting their potential as a diagnostic biomarker for KD.
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Sudden death of a young adult with coronary artery vasculitis, coronary aneurysms, parvovirus B19 infection and Kawasaki disease. Forensic Sci Med Pathol 2020; 16:498-503. [PMID: 32495258 DOI: 10.1007/s12024-020-00263-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/12/2020] [Indexed: 10/24/2022]
Abstract
We present a case of a 20-year-old man who suffered from Kawasaki disease (KD) associated with a florid parvovirus infection, and who died suddenly from thrombotic occlusion of the coronary arteries. The autopsy revealed several aneurysms of the coronary arteries, a chronic vasculitis and a myofibroblast proliferation leading to focal luminal narrowing. The inflammatory response as well as the detection of the viral particles by PCR in blood and in the lesional tissue demonstrated a possible cause by Parvovirus infection. The expression of endoglin on endothelial cells of neoangiogenesis indicates the involvement of the TGF-beta pathway, necessary for maintaining chronic inflammation. In addition, a possible connection between the intake of methylphenidate, arteritis and a possible pre-existing heart disease must be discussed. Furthermore, KD must also be considered as a cause of sudden death in the adult population.
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Matsubara Y, Matsubara D, Ae R, Kosami K, Aoyama Y, Yashiro M, Makino N, Matsubara S, Nakamura Y. Cumulative incidence of Kawasaki disease with cardiac sequelae in Japan. Pediatr Int 2020; 62:444-450. [PMID: 31960532 DOI: 10.1111/ped.14164] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 12/10/2019] [Accepted: 01/15/2020] [Indexed: 01/01/2023]
Abstract
BACKGROUND Some patients with Kawasaki disease (KD) develop cardiac sequelae, which increase the risk of subsequent ischemic heart events. Knowing the cumulative incidence (CI) of KD with cardiac sequelae may contribute to developing health policies to prevent subsequent ischemic events in these patients. METHODS Study participants consisted of 254 984 patients aged 0-9 years with KD who were registered in nationwide surveys in Japan from 1991-2016. We calculated the incidence probabilities by dividing the number of patients with KD aged 0-9 years by the population used in vital statistics of each calendar year. We calculated the cumulative proportion of those not affected by KD, by multiplying each probability in patients aged from age 0-9 years. The CI of KD was obtained by subtracting this value from 1. We also calculated the number of patients in each birth cohort (BC). The same was done to calculate the CI of KD-related cardiac sequelae. RESULTS The CIBC steadily increased from 0.005067 in males and 0.003668 in females in 1991 to 0.011431 in males and 0.0088253 in females in 2007. The CIBC of KD with cardiac sequelae decreased from 0.000478 in males and 0.000213 in females in 1997 to 0.000339 in males and 0.000169 in females in 2007. CONCLUSION The increasing CIBC of KD indicates an increased susceptibility to KD in accordance with birth year. The decreasing CIBC of cardiac sequelae suggests the efficacy of KD treatment.
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Affiliation(s)
- Yuri Matsubara
- Department of Public Health, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Daisuke Matsubara
- Department of Pediatrics, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Ryusuke Ae
- Department of Public Health, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Koki Kosami
- Department of Public Health, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Yasuko Aoyama
- Department of Public Health, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Mayumi Yashiro
- Department of Public Health, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Nobuko Makino
- Department of Public Health, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Shigeki Matsubara
- Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Yosikazu Nakamura
- Department of Public Health, Jichi Medical University, Shimotsuke, Tochigi, Japan
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Xiao ZH, Zhang GY, Zheng XR. [Pyrexia and hemoptysis for eight days in a school-age child]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2019; 21:589-593. [PMID: 31208515 PMCID: PMC7389584 DOI: 10.7499/j.issn.1008-8830.2019.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 04/08/2019] [Indexed: 06/09/2023]
Abstract
A girl was diagnosed with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) due to pyrexia and hemoptysis for eight days. The girl was a school-age child with major clinical manifestations of pyrexia, skin rash, enlargement of bilateral cervical lymph nodes, conjunctival hyperaemia, red and cracked lips and strawberry-like tongue, followed by swelling of both hands and feet. Laboratory examination showed significant increases in white blood cell count, platelet count, C-reactive protein, erythrocyte sedimentation rate and liver enzymes, a significant reduction in albumin, and the presence of aseptic pyuria. After the first course of IVIG treatment, the girl still had recurrent pyrexia, with hemoptysis on day 2 after admission, and lung CT showed uneven luminance and patchy shadow. The symptoms were quickly alleviated after the second course of IVIG treatment combined with methylprednisolone and aspirin treatment. KD is a febrile disease characterized by multiple systemic vasculitis in childhood and can involve various organ systems such as the heart, lungs, kidneys and the nervous system. Therefore, it is necessary to carefully monitor and recognize the rare symptoms of KD, and early recognition of pulmonary complications of KD can avoid delay in diagnosis, prevent the development of more serious complications, and help with early treatment and disease recovery.
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Affiliation(s)
- Zhao-Hua Xiao
- Department of Pediatrics, Xiangya Hospital of Central South University, Changsha 410008, China.
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Guile L, Parke S, Kelly A, Tulloh R. Giant coronary artery aneurysms in a 12-week-old infant with incomplete Kawasaki disease. BMJ Case Rep 2018; 2018:bcr-2018-224479. [PMID: 29593004 PMCID: PMC5878266 DOI: 10.1136/bcr-2018-224479] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Kawasaki disease (KD) is an acute inflammatory vasculitis that occurs worldwide and disproportionately affects male children, most commonly between the ages of 6 months and 5 years. KD can present with only a few features and thus be difficult to diagnose, particularly in the youngest and oldest patients. We describe a 12-week-old Caucasian female infant who presented with rash and fever but no other features of KD, who developed giant coronary artery aneurysms. Considering how common is the presentation of a febrile infant with a rash, this case highlights the importance of considering KD early in the differential diagnosis for any infant with unexplained fever. Furthermore, it emphasises how echocardiography can help in the investigation of a febrile child with no clear source of infection.
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Affiliation(s)
- Lucy Guile
- School of Clinical Sciences, University of Bristol, Bristol, UK.,Department of Paediatric Surgery, Bristol Royal Hospital For Children, Bristol, UK
| | - Simon Parke
- Department of Paediatrics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Alison Kelly
- Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Bristol, UK
| | - Robert Tulloh
- School of Clinical Sciences, University of Bristol, Bristol, UK.,Department of Paediatric Cardiology, Bristol Royal Hospital For Children, Bristol, UK
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Pilania RK, Bhattarai D, Singh S. Controversies in diagnosis and management of Kawasaki disease. World J Clin Pediatr 2018; 7:27-35. [PMID: 29456929 PMCID: PMC5803562 DOI: 10.5409/wjcp.v7.i1.27] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Revised: 12/13/2017] [Accepted: 12/28/2017] [Indexed: 02/06/2023] Open
Abstract
Kawasaki disease (KD) is a common medium vessel systemic vasculitis that usually occurs in small children. It has a predilection for the coronary arteries, but other medium sized arteries can also be involved. The etiology of this disorder remains a mystery. Though typical presentation of KD is quite characteristic, it may also present as incomplete or atypical disease in which case the diagnosis can be very challenging. As both incomplete and atypical forms of KD can be associated with serious coronary artery complications, the pediatrician can ill afford to miss these diagnoses. The American Heart Association has enunciated consensus guidelines to facilitate the clinical diagnosis and treatment of this condition. However, there are still several issues that remain controversial. Intravenous immunoglobulin remains the cornerstone of management but several other treatment modalities, especially glucocorticoids, are increasingly finding favour. We review here some of the contemporary issues, and the controversies thereon, pertaining to management of KD.
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Affiliation(s)
- Rakesh Kumar Pilania
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Dharmagat Bhattarai
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Surjit Singh
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
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Wang LJ, Kuo HC. Cognitive Development After Kawasaki Disease - Clinical Study and Validation Using a Nationwide Population-Based Cohort. Circ J 2018; 82:517-523. [PMID: 28890525 DOI: 10.1253/circj.cj-17-0557] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND This purpose of this study was to investigate whether Kawasaki disease (KD) increases the risk of cognitive impairment. In this clinical study, cognitive profiles were compared between KD patients, control subjects, and a nationwide population-based cohort to determine the potential correlation between KD and a subsequent diagnosis of an intellectual disability. METHODS AND RESULTS The clinical study consisted of 168 KD patients (mean age 5.6 years, 62.5% male) and 81 healthy controls (mean age 6.4 years, 54.3% male). The nationwide cohort consisted of 4,286 KD patients and 50,038 controls retrieved from the Taiwan National Health Insurance Research Database between 1996 and 2000. The clinical study sample revealed no significant difference in any developmental index or cognitive function between KD patients and controls across various age groups (P>0.05). In the nationwide cohort, Cox regression analysis showed that a diagnosis of KD did not significantly affect the likelihood of developing an intellectual disability (adjusted hazard ratio 0.87, 95% confidence interval 0.68-1.11). CONCLUSIONS Both the clinical data and the population-based cohort consistently demonstrated that KD does not increase a child's risk of future cognitive impairment. Although the outcome of the present study is negative, caregivers and patients with KD can be reassured that KD will have no effect on developmental milestones or cognitive function later in life.
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Affiliation(s)
- Liang-Jen Wang
- Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital
- Chang Gung University College of Medicine
| | - Ho-Chang Kuo
- Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital
- Chang Gung University College of Medicine
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15
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Donà D, Gnoato E, Giaquinto C, Moretti C. An Unexpected Fever Post Serogroup B Meningococcal Sepsis. Pediatr Rep 2016; 8:6613. [PMID: 27994836 PMCID: PMC5136770 DOI: 10.4081/pr.2016.6613] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 10/20/2016] [Accepted: 10/24/2016] [Indexed: 11/23/2022] Open
Abstract
This case report describes an invasive meningococcal group B infection followed by the development of Kawasaki disease (KD) complicated by macrophage activation syndrome (MAS) in a 2-year-old child. The presented case indicates the possible etiologic relationship between meningococcal sepsis and KD as support of bacterial toxin induced theory. It's important to maintain a high grade of suspicious for KD in every relapse of fever also during convalescence phase of severe infection. Usually, initial treatment with intravenous immunoglobulin is sufficient to control the disease; but, in case of refractory KD complicated by MAS, corticosteroid therapy represents a good option inducing prompt fever resolution and clinical improvement.
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Affiliation(s)
- Daniele Donà
- Pediatric Infectious Diseases Division, University of Padua, Italy
| | - Elisa Gnoato
- Pediatric Pulmonology and Allergy Division, University of Padua, Italy
| | - Carlo Giaquinto
- Pediatric Infectious Diseases Division, University of Padua, Italy
| | - Carlo Moretti
- Pediatric Diabetology Division, Department for Woman and Child Health, University of Padua, Italy
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Agarwal S, Agrawal DK. Kawasaki disease: etiopathogenesis and novel treatment strategies. Expert Rev Clin Immunol 2016; 13:247-258. [PMID: 27590181 DOI: 10.1080/1744666x.2017.1232165] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Kawasaki disease is an acute febrile systemic vasculitis that predominantly occurs in children below five years of age. Its etiopathogenesis is still not clear, but it is thought to be a complex interplay of genetic factors, infections and immunity. Areas covered: This review article discusses in detail Kawasaki disease, with particular emphasis on the recent updates on its pathogenesis and upcoming alternate treatment options. Though self-limiting in many cases, it can lead to severe complications like coronary artery aneurysms and thrombo-embolic occlusions, and hence requires early diagnosis and urgent attention to avoid them. Intravenous immunoglobulin (IVIG) with or without aspirin has remained the sole treatment option for these cases, but 10-15% cases develop resistance to this treatment. Expert commentary: There is a need to develop additional treatment strategies for children with Kawasaki disease. Targeting different steps of pathogenesis could provide us with alternate therapeutic options.
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Affiliation(s)
- Shreya Agarwal
- a Department of Clinical & Translational Science , Creighton University School of Medicine , Omaha , NE , USA
| | - Devendra K Agrawal
- a Department of Clinical & Translational Science , Creighton University School of Medicine , Omaha , NE , USA
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17
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Malakan Rad E, Malekzadeh I, Ziaee V, Rajabi R, Shahabi Z. Novel Echocardiographic Indices for Assessing the Left Main Coronary Artery in Children With Kawasaki Disease. IRANIAN JOURNAL OF PEDIATRICS 2016; 26:e6189. [PMID: 27761202 PMCID: PMC5056600 DOI: 10.5812/ijp.6189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 05/08/2016] [Indexed: 11/16/2022]
Abstract
BACKGROUND Kawasaki disease (KD) is the most common cause of acquired myocardial infarction in children. Coronary artery involvement is the most serious feature of this vasculitis syndrome. Timely diagnosis of coronary artery involvement is of utmost importance since it can prevent long-term morbidity and mortality. The current methods for the diagnosis of coronary artery dilation in KD are inconsistent and are also not capable of detecting all the abnormal coronary arteries or the so-called occult dilations present. OBJECTIVES The aim of this study was to determine the sensitivity and specificity of three novel allometric indices for the diagnosis of left main coronary artery (LMCA) involvement in KD. METHODS We performed a prospective case-control study in 69 children (38 with KD and 31 healthy children). All the followed up patients underwent two complete echocardiographic examinations at the time of admission and 4 - 6 weeks later. We measured the size of the LMCA, coronary sinus (CS) and aorta (A) and calculated the LMCA/CS, LMCA/A and LMCA/CS/A ratios. We also calculated the cut-off scores for each index using receiver operating characteristic curves both in the acute phase and 4 - 6 weeks later. RESULTS In the acute phase, the cut-off scores for the LMCA/A ratio was > 0.23; LMCA/CS, > 0.44; and LMCA/CS/A, > 0.03. This implied 60% sensitivity and 80% specificity for the detection of abnormal LMCA in KD. Four to six weeks after the acute phase, the LMCA/A cut-off score was > 0.23; LMCA/CS, > 0.73; and LMCA/CS/A, > 0.73. This implied 100% sensitivity and 100% specificity for the detection of abnormal LMCA. There was a significant decrease in the size of the CS in comparison with the control group (1.92 ± 0.363 mm; P = 0.007 and 0.023). CONCLUSIONS The LMCA/A, LMCA/CS and LMCA/CS/A ratios seem to provide simple and patient-specific indices for the detection of abnormal LMCA in KD, both in the acute and subacute phase. Further, a decrease in the size of the CS may imply a decrease in coronary artery flow in the acute and subacute phases of KD.
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Affiliation(s)
- Elaheh Malakan Rad
- Department of Pediatrics, Tehran University of Medical Sciences, Tehran, IR Iran
- Children's Medical Center, Pediatric Center of Excellence, Tehran, IR Iran
| | - Iran Malekzadeh
- Department of Pediatrics, Tehran University of Medical Sciences, Tehran, IR Iran
- Children's Medical Center, Pediatric Center of Excellence, Tehran, IR Iran
| | - Vahid Ziaee
- Department of Pediatrics, Tehran University of Medical Sciences, Tehran, IR Iran
- Children's Medical Center, Pediatric Center of Excellence, Tehran, IR Iran
- Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Raheleh Rajabi
- Children's Medical Center, Pediatric Center of Excellence, Tehran, IR Iran
| | - Zohreh Shahabi
- Children's Medical Center, Pediatric Center of Excellence, Tehran, IR Iran
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18
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Sotelo-Cruz N. [Atypical and incomplete Kawasaki disease in pediatric age]. BOLETIN MEDICO DEL HOSPITAL INFANTIL DE MEXICO 2016; 73:147-148. [PMID: 29421201 PMCID: PMC7128410 DOI: 10.1016/j.bmhimx.2016.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 05/11/2016] [Indexed: 12/16/2022] Open
Affiliation(s)
- Norberto Sotelo-Cruz
- Departamento de Medicina de la Universidad de Sonora, Hermosillo, Sonora, México.
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19
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Sotelo-Cruz N. Atypical and incomplete Kawasaki disease in the pediatric age. BOLETÍN MÉDICO DEL HOSPITAL INFANTIL DE MÉXICO (ENGLISH EDITION) 2016. [PMCID: PMC7148875 DOI: 10.1016/j.bmhime.2017.05.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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20
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Abstract
The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.
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Affiliation(s)
- Susanna Esposito
- a Paediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation , Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy
| | - Sonia Bianchini
- a Paediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation , Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy
| | - Rosa Maria Dellepiane
- b Medium Intensive Care Unit , Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy
| | - Nicola Principi
- a Paediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation , Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy
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