Fatal late cardiovascular sequelae of previously unrecognized Kawasaki disease in 12-year- old child

Fatal late cardiovascular sequelae of previously unrecognized Kawasaki disease in 12-year- old child | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Fatal late cardiovascular sequelae of previously unrecognized Kawasaki disease in 12-year- old child Tereza Fremuthová, Michal Huml, Alexandra Kotková, Josef Sýkora, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7567526/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Nov, 2025 Read the published version in International Journal of Emergency Medicine → Version 1 posted 8 You are reading this latest preprint version Abstract Background Kawasaki disease (KD), previously termed mucocutaneous lymph node syndrome, is a childhood vasculitis affecting medium-sized arteries and is the leading cause of acquired heart disease in children. It primarily affects children under five years of age. If left untreated, KD can lead to serious cardiovascular complications, particularly coronary artery aneurysms (CAA) and thrombosis. Incomplete KD presents with fewer clinical criteria, making it more difficult to diagnose. Importantly, long-term sequelae such as CAA may remain clinically silent for years. This case highlights the critical need for awareness that even minimal or transient symptoms can be the only warning sign of life-threatening complications in adolescents with a remote history of incomplete or unrecognized KD. Case presentation We describe a fatal case of a 12-year-old boy with a history of presumed myocarditis at age five, which retrospectively fulfilled criteria for incomplete KD but remained undiagnosed. From age five to twelve, he was asymptomatic except for occasional, brief chest tightness. At twelve, he presented with mild chest pain followed by rapid clinical deterioration, cardiac arrest, and death. Post-mortem imaging and autopsy revealed a thrombosed giant aneurysm of the left anterior descending coronary artery, consistent with chronic coronary disease. Conclusion This case illustrates the potentially fatal long-term cardiovascular sequelae of unrecognized and untreated incomplete KD. Early recognition and treatment with IVIG are critical to reduce coronary complications. Healthcare providers must maintain clinical vigilance for patients with a history of KD. Even subtle or transient symptoms in patients with a history of KD should prompt immediate evaluation to prevent fatal outcomes Kawasaki disease incomplete Kawasaki disease coronary aneurysm myocardial infarction pediatric cardiac arrest case report Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction/Background Kawasaki disease (KD), formerly called mucocutaneous lymph node syndrome, is one of the most common vasculitides of childhood. The syndrome is characterized by vasculitis of the medium-sized arteries. The acute illness is self-limited and includes high fever, non-exudative conjunctivitis, inflammation of the oral mucosa, rash, cervical adenopathy and findings in the extremities (edema of hands and feet) [ 1 ]. Kawasaki disease mainly affects infants and children under five years of age. The incidence is higher in Japan (> 200/100,000) than in Western countries (5–22/100,000) and males are more commonly affected (1.5:1) [ 2 ]. The cause of KD is unknown, although it is suspected to be triggered by an unidentified infectious pathogen in genetically predisposed children. KD might not be a normal immune response to an unusual environmental stimulus, but rather a genetically determined unusual and uncontrolled immune response to a common stimulus [ 2 , 3 ]. KD is the leading cause of acquired heart disease among children and unrecognized and untreated children are at risk for serious cardiovascular sequelae, particularly abnormalities of the coronary arteries (CA). The article presents a fatal case of late cardiovascular complication of previously unrecognized KD in a 12-year-old boy. He remained virtually asymptomatic from the age of five, when he experienced myocarditis of unknown origin, most likely representing an unrecognized case of incomplete Kawasaki disease. Case presentation We present the case report of a 12-year-old Ukrainian boy with a history of myocarditis of unknown etiology at the age of 5. The patient was admitted at the age of 5 to a local pediatric infectious disease department for 1 week of fever, cervical lymphadenopathy and pharyngitis. At the time of admission, he was on oral amoxicillin/clavulanic acid for 5 days. On admission, his labs showed leukocytosis 20, ESR 26, CRP 20mg/L, ALT 89 U/L (1,48 ukat/L), AST 39 U/L (0,65 ukat/L). After the admission, the serology for viruses was negative (EBV, CMV, adenovirus, HHV6). Throat swab was positive for Streptococcus pneumoniae. The antibiotic was changed do 3rd- generation cephalosporin (ceftazidime). For persisting fever and epigastric pain, CXR and abdominal CT scan were performed, both without pathological findings. Due to an increase of Troponin-I 114 ng/mL (normal range 0-0,04 ng/mL) and CK-MB 187 U/L (normal range 5-25 U/L) and suspicion of acute myocarditis, he was transferred to the pediatric cardiology department. The initial echocardiogram showed mildly decreased left ventricular function (EF 52%) without structural defects. The echo report did not mention examination of coronary arteries. One dose of intravenous immunoglobulin (IVIG) was given (1g/kg) and methylprednisolone (4mg/day) was started, tapered off within 2 weeks. Follow-up echocardiogram showed improvement in left ventricular function (EF 65%). The values of Troponin-I 0,326ng/L a CK-MB 22U/L normalized. He was dismissed with no medication and the condition was concluded as myocarditis of unclear etiology. He was followed by the cardiologist with several echocardiograms showing normal function, the examination of coronary arteries was not mentioned in either of the reports. The follow-up was completed at the age of 8 years. In the next period, the patient was in good condition. He actively played football with a good tolerance for physical activity. He occasionally described feeling a brief pressure on the chest that spontaneously subsided within minutes. Since discharge from cardiology follow-up, he had not been monitored by a cardiologist. The patient was recently admitted at the age of 12 years to our pediatric department with a short episode (several hours) of mild chest pain localized in the lower left sternal border with no recent history of acute respiratory tract infection or fever. On admission, there were no clinical signs of respiratory or circulatory compromise. Changes in repolarization were evident on the ECG ( figure 1), with only a mild elevation of high sensitive troponin T = 51 ng/L (<14 ng/L), NT pro BNP 110 ng/L (<14 ng/L) and normal levels of CK of 1.76 μkat/L (1.1-4.8 μkat/L). An interstitial pattern was visualized on the X-ray of the lungs. The chest pain resolved spontaneously within admission to the ward. Shortly after admission, the patient developed progressive tachypnea and increased work of breathing. Our differential diagnoses included pulmonary embolism, myocarditis, primary pulmonary pathology, aortic dissection, acute coronary syndrome and multisystem inflammatory syndrome in children (MIS-C). CT angiography was indicated. A brief improvement in his clinical status was followed by a sudden deterioration, circulatory and respiratory collapse, and the need for intubation with rapid progression to cardiac arrest.The initial rhythm was pulseless ventricular tachycardia. After the first shock, pulseless electrical activity refractory to treatment and ultimately resulted in death. At the time of ongoing resuscitation, the result of CT angiography was not available. Due to the unavailability of extracorporeal resuscitation in our institution, resuscitation was terminated after 40 minutes. Nasopharyngeal and tracheal Covid-19 Multiplex RT-PCR Kit (DIANA Biotechnologies, Czech Republic) was negative, as patient had no recent signs of respiratory infection. CT angiography subsequently revealed diffuse pulmonary congestion with thickened interstitium and severe dilatation of the proximal left anterior descending artery (LAD) with thrombotic occlusion ( figure 2 ). Autopsy of lungs and heart Lungs Both lungs were heavy and edematous (right 740 g, left 660 g), with frothy, blood-tinged fluid on the cut surface. Microscopically, marked pulmonary edema and congestion with areas of intra-alveolar hemorrhage. No hyaline membranes, no interstitial fibrosis. Bronchioles contained focal blood, pulmonary vessels were patent without thrombi. Conclusion: Findings consistent with acute cardiogenic pulmonary edema due to left-sided heart failure. No features of diffuse alveolar damage or COVID-19-related pneumonia. Heart Aneurysm of the left ventricular wall (40 × 20 × 15 mm) filled with organized, adherent thrombus ( figure 3). Several well-demarcated foci of myocardial softening (6–10 mm) in the anterior septum and left ventricular wall, consistent with old infarcts. Coronary arteries (LAD, circumflex, RCA) showed marked intimal thickening, focal calcification, and severe luminal narrowing. Microscopy: Chronic inflammatory infiltrate with fibrous intimal thickening and focal calcifications in coronary arteries; loss of elastic fibers. Myocardium with cardiomyocyte hypertrophy and areas of replacement fibrosis. ( figure 4 and 5 ) Conclusion: Chronic coronary disease with advanced vascular changes, myocardial ischemic injury with old infarcts and aneurysm formation, complicated by coronary thrombosis. Discussion KD is an inflammatory disorder of young children, associated with vasculitis of CA with subsequent aneurysm formation in up to one-third of untreated patients [ 4 ]. Typical KD is diagnosed when fever lasting more than 4–5 days is associated with ≥ 4 principal clinical criteria (bilateral non-exudative conjunctivitis, changes of lips and oral mucosa, cervical lymphadenopathy, polymorphous exanthema, changes of the extremities and perineal region). Incomplete KD, mostly seen in children younger than 12 months, is suggested if a fever lasting for more than 5 days is associated with < 4 (2–3/5) principal clinical features, compatible laboratory or echocardiographic findings and other febrile illnesses have been excluded. [ 5 , 6 ]. We assume that the myocarditis seen in our patient at the age of 5 was most likely an incomplete form of KD. According to the parents and available medical records, our patient presented with fever, pharyngitis and neck lymphadenopathy at that time. No coronary pathology had been diagnosed on echocardiography scans and the patient had been treated for myocarditis (insufficient immunosuppressive therapy had been initiated). In our opinion, the coronary artery aneurysm (CAA) in our patient developed due to inflammatory involvement at the age of 5. CAA may regress, remain stable or enlarge over time. Fortunately, up to half of CAA regress spontaneously within the first 2 years of disease onset. Predicting the risk of developing CAA remains challenging [ 4 , 7 ]. CA complications are the primary cause of morbidity and mortality related to KD and have become the leading form of acquired heart disease in children in developed countries [ 4 , 7 ]. A standardized imaging protocol supervised by an experienced pediatric echocardiographer, including a specific sequence of imaging views to clearly delineate all segments of the CA, is necessary for an accurate and complete assessment. [ 8 ]. Serial echocardiographic studies in acute KD show that CA dilatation may be visible early in the illness, but maximal development is usually in the second and third week of the acute illness [ 9 ]. The initial CA diameter is a factor determining the risk of CA [ 7 ]. The proximal LAD and the proximal right CA are the most frequent locations of CAA, and the posterior descending artery is the least common. [ 5 ]. This corresponds to the findings in our patient. Patients with CAA might develop thrombosis or stenotic lesions of CA leading to myocardial ischemia, infarction, or death. [ 10 , 11 ] The risk of aneurysm thrombosis is greatest in the first 2 years after the acute episode but persists lifelong. Despite the 3-year follow-up in the cardiac center, no CA pathology had been diagnosed at the time of the acute illness or during the follow-up period in our patient. The presence of an aneurysm of the LAD artery had most likely been overlooked. No chronic antithrombotic therapy was initiated. Our patient had presented no episodes of severe chest pain, shortness of breath or other severe clinical symptoms despite the regular intensive physical activity (club soccer player). Only occasionally he reported a short feeling of tightness in the chest, which always resolved spontaneously within minutes, and which did not limit his physical activity. The main goal of treatment in the acute phase of KD is to suppress systemic inflammation to minimize the risk of CAA development. The highest risk reduction of CAA development is achieved when the treatment is initiated as early as possible within the first 7 days of illness and no later than 10 days after disease onset. The rate of CA aneurysm development increases significantly after days 8–9. Numerous international treatment guidelines have been published [ 5 , 12 , 13 , 14 ]. Aspirin and IVIG are two drugs that are conventionally used to treat KD. The early single transfusion of IVIG (2g/kg) is currently the most effective anti-inflammatory treatment of KD, substantially reducing the prevalence of persistent CA lesions [ 12 , 13 , 14 ]. Historically, high dosages of aspirin were used during the acute phase of KD for anti-inflammatory effects, but there is no evidence of a benefit with high versus low dose aspirin when considering coronary vascular damage. Aspirin treatment does not reduce the risk of coronary aneurysms but risk of CA thrombosis [ 15 , 16 ]. The duration of antiplatelet therapy is determined by the extent of CA involvement. In the absence of CA involvement, aspirin is administered for a total of 6–8 weeks, in the transient involvement of CA up to complete regression and in the presence of CAA for life. Children diagnosed with incomplete KD are at an increased risk of cardiac complications. The lack of recognition and subsequent absence of appropriate anti-inflammatory and antithrombotic treatments significantly elevate the likelihood of thrombotic events, as illustrated in the case of our patient. Aneurysm size is the strongest predictor of major cardiac events. Our patient developed a giant aneurysm and met the criteria for combined anticoagulation and antiplatelet therapy. However, this treatment was not initiated as the diagnosis was not recognized [ 10 ]. Inflammatory vasculopathy resembling acute KD affecting children who had prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged recently. The term MIS-C associated with COVID-19 has been used to describe the condition. As MIS-C shares clinical features with acute KD, this condition must be included in differential diagnosis of acute KD [ 17 , 18 , 19 ]. As our patient did not present with signs and symptoms corresponding to MIS-C, and PCR was negative from nasopharyngeal and tracheal sample. There were also no signs of inflammation corresponding to MIS-C or Covid-19 infection in the histology of the lungs. Recent evidence shows that the outcome regarding coronary arteries in patients with MIS-C is generally excellent [ 20 ]. The development of critical myocardial ischemia and malignant arrhythmia are among the most serious complications of long-term CA disease. When compared with the incidence of KD, only a limited number of cases described in the literature suffered from sudden death, underwent autoptic and histologic examination as this condition is rarely fatal [ 21 ]. Pediatric services are largely unfamiliar with the detection and management of myocardial ischemia due to its rarity in children. Patients with a previous history of KD presenting with acute chest pain should be urgently transported to the tertiary pediatric cardiac surgical center as clinical features cannot reliably determine the underlying etiology. Patients with STEMI (ST elevation myocardial infarction) require urgent catheter re-vascularization or surgical revascularization. Thrombolysis is initiated in cases of CAA occluded by a thrombus [ 10 , 11 ]. The diagnostic methods of choice for non-STEMI (non-ST- elevation myocardial infarction), as demonstrated in our patient’s case, is ECG, serial high sensitive troponin levels, echocardiography and coronary imaging with CT or coronary angiography. Due to possible development of significant coronary collaterals over time, serial ECG and high sensitive Troponin levels may be unremarkable, even with significant myocardial ischemia [ 10 , 11 ]. The level of Troponin (hsTnT) in our patient was in the grey zone and the immediate correct interpretation of CT angiography was crucial and would have allowed timely initiation of therapy (systemic thrombolysis), which may potentially reduce risk of a fatal outcome. Conclusion KD is the leading cause of acquired coronary disease in children, and patients with CAA remain at lifelong risk of myocardial infarction, arrhythmia, and sudden death. Early recognition and prompt initiation of appropriate therapy are essential to prevent long-term complications. Emergency physicians should be aware, that clinical symptoms of patients with late CA complications may be subtle, and patients with a previous history of KD or previous unexplained myocarditis presenting with suspected cardiac emergency require timely referral to a pediatric congenital cardiac center. List of Abbreviations CA Coronary artery CAA Coronary artery aneurysm COVID-19 Coronavirus Disease 2019 CT Computed Tomography ECG Electrocardiogram EF Ejection fraction IVIG Intravenous immunoglobulin KD Kawasaki disease LAD Left anterior descending (artery) MIS-C Multisystem Inflammatory Syndrome in Children RT-PCR Reverse transcription polymerase chain reaction SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 STEMI ST-elevation myocardial infarction non-STEMI non-ST- elevation myocardial infarction Declarations Competing interests The authors declare that they have no competing interests. Funding This work was supported by Charles University under the Cooperatio Program. The funding body had no role in study design, data collection, interpretation, or writing of the manuscript. Author Contribution FJ, FT - original draft preparation; writing – review and editing, HM, KA, SJ, BJ, HL contributed to clinical evaluation, imaging, and post-mortem analysis. All authors critically revised the manuscript and approved the final version Acknowledgements None. References Burns JC, Glodé MP. Kawasaki syndrome. Lancet. 2004;364:533–44. Elakabawi K, Lin J, Jiao F, Guo N, Yuan Z. Kawasaki disease: global burden and genetic background. Cardiol Res. 2020;11(1):9–14. Noval Rivas M, Arditi M. Kawasaki disease: pathophysiology and insights from mouse models. Nat Rev Rheumatol. 2020;16(7):391–405. Rajasekaran K, Duraiyarasan S, Adefuye M, Manjunatha N, Ganduri V. Kawasaki disease and coronary artery involvement: a narrative review. Cureus. 2022;14(8):e28358. Jone PN, Tremoulet A, Choueiter N, et al. 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Initial intravenous immunoglobulin therapy without aspirin for acute Kawasaki disease: a retrospective cohort study with Bayesian inference. BMJ Paediatr Open. 2024;8(1):e002312. Cannon L, Campbell MJ, Wu EY. Multisystemic inflammatory syndrome in children and Kawasaki disease: parallels in pathogenesis and treatment. Curr Allergy Asthma Rep. 2023;23(6):341–50. Netea SA, Biesbroek G, van Stijn D, et al. Kawasaki disease diagnosis and treatment in over 1000 patients: a continuum of dysregulated inflammatory responses. Biomedicines. 2024;12(9):2014. Cem E, Böncüoğlu E, Kıymet E, et al. Which findings make multisystem inflammatory syndrome in children different from the pre-pandemic Kawasaki disease? Pediatr Cardiol. 2023;44(2):424–32. Truong DT, Trachtenberg FL, Hu C, et al. Six-month outcomes in the long-term outcomes after the multisystem inflammatory syndrome in children study. JAMA Pediatr. 2025;179(3):293–301. Visi G, Spina F, Del Duca F, et al. Autoptic findings in cases of sudden death due to Kawasaki disease. Diagnostics (Basel). 2023;13(11):1831. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 29 Nov, 2025 Read the published version in International Journal of Emergency Medicine → Version 1 posted Editorial decision: Revision requested 23 Oct, 2025 Reviews received at journal 12 Oct, 2025 Reviewers agreed at journal 12 Oct, 2025 Reviewers agreed at journal 12 Oct, 2025 Reviewers invited by journal 07 Oct, 2025 Editor assigned by journal 25 Sep, 2025 Submission checks completed at journal 25 Sep, 2025 First submitted to journal 08 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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13:56:17","extension":"png","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":11496048,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure5Leftventriculemuslefibres.png","url":"https://assets-eu.researchsquare.com/files/rs-7567526/v1/25ac6d1c4e56571df634aa87.png"},{"id":93942338,"identity":"8b0b1f3e-bcf8-4292-b859-278c5286110b","added_by":"auto","created_at":"2025-10-20 13:48:17","extension":"xml","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":58179,"visible":true,"origin":"","legend":"","description":"","filename":"b8bdd3b9945d4b0d8dbd90d1b4fc41001structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7567526/v1/037e43911d54e61b91eeb00e.xml"},{"id":93942344,"identity":"314d7862-f233-4ebd-89aa-c1421c28e154","added_by":"auto","created_at":"2025-10-20 13:48:17","extension":"html","order_by":24,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":66520,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7567526/v1/78409eac8146d549dde1fbf9.html"},{"id":93942334,"identity":"7de21b37-1fdf-4868-a586-e96954ac138e","added_by":"auto","created_at":"2025-10-20 13:48:17","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":6779217,"visible":true,"origin":"","legend":"\u003cp\u003eEKG strip - ST segment depression in I, II, III, aVF, V5 and V6 ECG leads\u003c/p\u003e","description":"","filename":"Figure1ECGstrip.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7567526/v1/5ff1ca340569ee9f7a05e980.jpg"},{"id":93942329,"identity":"6278e6c9-5a6e-431b-86c1-e29c62beb57a","added_by":"auto","created_at":"2025-10-20 13:48:17","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1539208,"visible":true,"origin":"","legend":"\u003cp\u003eCT scan image - Aneurysm (red arrow) of the proximal third of LAD with mural thrombosis, which causes occlusion of the further course of the dilated artery (green arrow)\u003c/p\u003e","description":"","filename":"Figure2Aneurysmoftheproximalthirdofleftanteriordescendingartery.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7567526/v1/c2cfef6b1f63b6fa243b1e18.jpg"},{"id":93942330,"identity":"f52801c3-7423-4566-b89a-6bfdc7ba3f78","added_by":"auto","created_at":"2025-10-20 13:48:17","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":232022,"visible":true,"origin":"","legend":"\u003cp\u003eMural thrombus within an aneurysmal segment of the LAD.\u003c/p\u003e","description":"","filename":"Figure3Muralthrombus.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7567526/v1/3ab49e8a4caed2880f499608.jpg"},{"id":93944106,"identity":"23b936a7-886c-427b-b7f1-a79b2a20636b","added_by":"auto","created_at":"2025-10-20 14:04:17","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":6074627,"visible":true,"origin":"","legend":"\u003cp\u003eMicroscopic image - CA with chronic inflammatory infiltration of the vessel wall (blue arrow). Marked thickening of the tunica intima with secondary regressive changes (red arrow)\u003c/p\u003e","description":"","filename":"Figure4Coronaryartery.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7567526/v1/ae267949b455b499ef55ee1d.jpg"},{"id":93942342,"identity":"6f1c58ab-9b1d-4342-8ce2-58619efa22c7","added_by":"auto","created_at":"2025-10-20 13:48:17","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":7978289,"visible":true,"origin":"","legend":"\u003cp\u003eMicroscopic image - Multiple areas of myocardial fibrosis in the wall of the left ventricle with compensatory hypertrophy of cardiomyocytes (blue arrows)\u003c/p\u003e","description":"","filename":"Figure5Leftventriculemuslefibres.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7567526/v1/247485ee5b5aac7f0f7208e2.jpg"},{"id":97179664,"identity":"a7d174de-cf3f-49a8-9d1e-e327d888ab5c","added_by":"auto","created_at":"2025-12-01 16:16:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":23047339,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7567526/v1/30841c07-7feb-4006-9317-c6b8b8bf4eba.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Fatal late cardiovascular sequelae of previously unrecognized Kawasaki disease in 12-year- old child","fulltext":[{"header":"Introduction/Background","content":"\u003cp\u003eKawasaki disease (KD), formerly called mucocutaneous lymph node syndrome, is one of the most common vasculitides of childhood. The syndrome is characterized by vasculitis of the medium-sized arteries. The acute illness is self-limited and includes high fever, non-exudative conjunctivitis, inflammation of the oral mucosa, rash, cervical adenopathy and findings in the extremities (edema of hands and feet) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Kawasaki disease mainly affects infants and children under five years of age. The incidence is higher in Japan (\u0026gt;\u0026thinsp;200/100,000) than in Western countries (5\u0026ndash;22/100,000) and males are more commonly affected (1.5:1) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe cause of KD is unknown, although it is suspected to be triggered by an unidentified infectious pathogen in genetically predisposed children. KD might not be a normal immune response to an unusual environmental stimulus, but rather a genetically determined unusual and uncontrolled immune response to a common stimulus [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. KD is the leading cause of acquired heart disease among children and unrecognized and untreated children are at risk for serious cardiovascular sequelae, particularly abnormalities of the coronary arteries (CA). The article presents a fatal case of late cardiovascular complication of previously unrecognized KD in a 12-year-old boy. He remained virtually asymptomatic from the age of five, when he experienced myocarditis of unknown origin, most likely representing an unrecognized case of incomplete Kawasaki disease.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eWe present the case report of a 12-year-old Ukrainian boy with a history of myocarditis of unknown etiology at the age of 5.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe patient was admitted at the age of 5 to a local pediatric infectious disease department for 1 week of fever, cervical lymphadenopathy and pharyngitis. At the time of admission, he was on oral amoxicillin/clavulanic acid for 5 days. On admission, his labs showed leukocytosis 20, ESR 26, CRP 20mg/L, ALT 89 U/L (1,48 ukat/L), AST 39 U/L (0,65 ukat/L). After the admission, the serology for viruses was negative (EBV, CMV, adenovirus, HHV6). Throat swab was positive for Streptococcus pneumoniae. The antibiotic was changed do 3rd- generation cephalosporin (ceftazidime). For persisting fever and epigastric pain, CXR and abdominal CT scan were performed, both without pathological findings. Due to an increase of Troponin-I 114 ng/mL (normal range 0-0,04 ng/mL) and CK-MB 187 U/L (normal range 5-25 U/L) and suspicion of acute myocarditis, he was transferred to the pediatric cardiology department. The initial echocardiogram showed mildly decreased left ventricular function (EF 52%) without structural defects. The echo report did not mention examination of coronary arteries. One dose of intravenous immunoglobulin (IVIG) was given (1g/kg) and methylprednisolone (4mg/day) was started, tapered off within 2 weeks. Follow-up echocardiogram showed improvement in left ventricular function (EF 65%). The values of Troponin-I 0,326ng/L a CK-MB 22U/L normalized. He was dismissed with no medication and the condition was concluded as myocarditis of unclear etiology. He was followed by the cardiologist with several echocardiograms showing normal function, the examination of coronary arteries was not mentioned in either of the reports. The follow-up was completed at the age of 8 years. In the next period, the patient was in good condition. He actively played football with a good tolerance for physical activity. He occasionally described feeling a brief pressure on the chest that spontaneously subsided within minutes. Since discharge from cardiology follow-up, he had not been monitored by a cardiologist.\u003c/p\u003e\n\u003cp\u003eThe patient was recently admitted at the age of 12 years to our pediatric department with a short episode (several hours) of mild chest pain localized in the lower left sternal border with no recent history of acute respiratory tract infection or fever. On admission, there were no clinical signs of respiratory or circulatory compromise. Changes in repolarization were evident on the ECG (\u003cstrong\u003efigure\u003c/strong\u003e 1), with only a mild elevation of high sensitive troponin T = 51 ng/L (\u0026lt;14 ng/L), NT pro BNP 110 ng/L (\u0026lt;14 ng/L) and normal levels of CK of 1.76 μkat/L (1.1-4.8 μkat/L). An interstitial pattern was visualized on the X-ray of the lungs. The chest pain resolved spontaneously within admission to the ward.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eShortly after admission, the patient developed progressive tachypnea and increased work of breathing. Our differential diagnoses included pulmonary embolism, myocarditis, primary pulmonary pathology, aortic dissection, acute coronary syndrome and multisystem inflammatory syndrome in children (MIS-C). CT angiography was indicated.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA brief improvement in his clinical status was followed by a sudden deterioration, circulatory and respiratory collapse, and the need for intubation with rapid progression to cardiac arrest.The initial rhythm was pulseless ventricular tachycardia. After the first shock, pulseless electrical activity refractory to treatment and ultimately resulted in death. At the time of ongoing resuscitation, the result of CT angiography was not available. Due to the unavailability of extracorporeal resuscitation in our institution, resuscitation was terminated after 40 minutes. Nasopharyngeal and tracheal Covid-19 Multiplex RT-PCR Kit\u0026nbsp;(DIANA Biotechnologies, Czech Republic) was negative, as patient had no recent signs of respiratory infection.\u003c/p\u003e\n\u003cp\u003eCT angiography subsequently revealed diffuse pulmonary congestion with thickened interstitium and severe\u0026nbsp;dilatation of the proximal\u0026nbsp;left anterior descending artery (LAD) with thrombotic occlusion (\u003cstrong\u003efigure 2\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAutopsy of lungs and heart\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLungs\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Both lungs were heavy and edematous (right 740 g, left 660 g), with frothy, blood-tinged fluid on the cut surface. Microscopically, marked pulmonary edema and congestion with areas of intra-alveolar hemorrhage. No hyaline membranes, no interstitial fibrosis. Bronchioles contained focal blood, pulmonary vessels were patent without thrombi.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Findings consistent with acute cardiogenic pulmonary edema due to left-sided heart failure. No features of diffuse alveolar damage or COVID-19-related pneumonia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHeart\u003c/strong\u003e\u003cbr\u003eAneurysm of the left ventricular wall (40 × 20 × 15 mm) filled with organized, adherent thrombus (\u003cstrong\u003efigure\u003c/strong\u003e 3). Several well-demarcated foci of myocardial softening (6–10 mm) in the anterior septum and left ventricular wall, consistent with old infarcts.\u003cbr\u003e\u0026nbsp;Coronary arteries (LAD, circumflex, RCA) showed marked intimal thickening, focal calcification, and severe luminal narrowing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMicroscopy:\u003c/strong\u003e Chronic inflammatory infiltrate with fibrous intimal thickening and focal calcifications in coronary arteries; loss of elastic fibers. Myocardium with cardiomyocyte hypertrophy and areas of replacement fibrosis. (\u003cstrong\u003efigure\u003c/strong\u003e \u003cstrong\u003e4 and 5\u003c/strong\u003e)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Chronic coronary disease with advanced vascular changes, myocardial ischemic injury with old infarcts and aneurysm formation, complicated by coronary thrombosis.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eKD is an inflammatory disorder of young children, associated with vasculitis of CA with subsequent aneurysm formation in up to one-third of untreated patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTypical KD is diagnosed when fever lasting more than 4\u0026ndash;5 days is associated with \u0026ge;\u0026thinsp;4 principal clinical criteria (bilateral non-exudative conjunctivitis, changes of lips and oral mucosa, cervical lymphadenopathy, polymorphous exanthema, changes of the extremities and perineal region). Incomplete KD, mostly seen in children younger than 12 months, is suggested if a fever lasting for more than 5 days is associated with \u0026lt;\u0026thinsp;4 (2\u0026ndash;3/5) principal clinical features, compatible laboratory or echocardiographic findings and other febrile illnesses have been excluded. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. We assume that the myocarditis seen in our patient at the age of 5 was most likely an incomplete form of KD. According to the parents and available medical records, our patient presented with fever, pharyngitis and neck lymphadenopathy at that time. No coronary pathology had been diagnosed on echocardiography scans and the patient had been treated for myocarditis (insufficient immunosuppressive therapy had been initiated). In our opinion, the coronary artery aneurysm (CAA) in our patient developed due to inflammatory involvement at the age of 5.\u003c/p\u003e\u003cp\u003eCAA may regress, remain stable or enlarge over time. Fortunately, up to half of CAA regress spontaneously within the first 2 years of disease onset. Predicting the risk of developing CAA remains challenging [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. CA complications are the primary cause of morbidity and mortality related to KD and have become the leading form of acquired heart disease in children in developed countries [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A standardized imaging protocol supervised by an experienced pediatric echocardiographer, including a specific sequence of imaging views to clearly delineate all segments of the CA, is necessary for an accurate and complete assessment. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Serial echocardiographic studies in acute KD show that CA dilatation may be visible early in the illness, but maximal development is usually in the second and third week of the acute illness [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The initial CA diameter is a factor determining the risk of CA [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The proximal LAD and the proximal right CA are the most frequent locations of CAA, and the posterior descending artery is the least common. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This corresponds to the findings in our patient.\u003c/p\u003e\u003cp\u003ePatients with CAA might develop thrombosis or stenotic lesions of CA leading to myocardial ischemia, infarction, or death. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] The risk of aneurysm thrombosis is greatest in the first 2 years after the acute episode but persists lifelong. Despite the 3-year follow-up in the cardiac center, no CA pathology had been diagnosed at the time of the acute illness or during the follow-up period in our patient. The presence of an aneurysm of the LAD artery had most likely been overlooked. No chronic antithrombotic therapy was initiated. Our patient had presented no episodes of severe chest pain, shortness of breath or other severe clinical symptoms despite the regular intensive physical activity (club soccer player). Only occasionally he reported a short feeling of tightness in the chest, which always resolved spontaneously within minutes, and which did not limit his physical activity.\u003c/p\u003e\u003cp\u003eThe main goal of treatment in the acute phase of KD is to suppress systemic inflammation to minimize the risk of CAA development. The highest risk reduction of CAA development is achieved when the treatment is initiated as early as possible within the first 7 days of illness and no later than 10 days after disease onset. The rate of CA aneurysm development increases significantly after days 8\u0026ndash;9. Numerous international treatment guidelines have been published [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAspirin and IVIG are two drugs that are conventionally used to treat KD. The early single transfusion of IVIG (2g/kg) is currently the most effective anti-inflammatory treatment of KD, substantially reducing the prevalence of persistent CA lesions [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Historically, high dosages of aspirin were used during the acute phase of KD for anti-inflammatory effects, but there is no evidence of a benefit with high versus low dose aspirin when considering coronary vascular damage. Aspirin treatment does not reduce the risk of coronary aneurysms but risk of CA thrombosis [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The duration of antiplatelet therapy is determined by the extent of CA involvement. In the absence of CA involvement, aspirin is administered for a total of 6\u0026ndash;8 weeks, in the transient involvement of CA up to complete regression and in the presence of CAA for life.\u003c/p\u003e\u003cp\u003eChildren diagnosed with incomplete KD are at an increased risk of cardiac complications. The lack of recognition and subsequent absence of appropriate anti-inflammatory and antithrombotic treatments significantly elevate the likelihood of thrombotic events, as illustrated in the case of our patient. Aneurysm size is the strongest predictor of major cardiac events. Our patient developed a giant aneurysm and met the criteria for combined anticoagulation and antiplatelet therapy. However, this treatment was not initiated as the diagnosis was not recognized [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eInflammatory vasculopathy resembling acute KD affecting children who had prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged recently. The term MIS-C associated with COVID-19 has been used to describe the condition. As MIS-C shares clinical features with acute KD, this condition must be included in differential diagnosis of acute KD [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. As our patient did not present with signs and symptoms corresponding to MIS-C, and PCR was negative from nasopharyngeal and tracheal sample. There were also no signs of inflammation corresponding to MIS-C or Covid-19 infection in the histology of the lungs. Recent evidence shows that the outcome regarding coronary arteries in patients with MIS-C is generally excellent [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe development of critical myocardial ischemia and malignant arrhythmia are among the most serious complications of long-term CA disease. When compared with the incidence of KD, only a limited number of cases described in the literature suffered from sudden death, underwent autoptic and histologic examination as this condition is rarely fatal [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePediatric services are largely unfamiliar with the detection and management of myocardial ischemia due to its rarity in children. Patients with a previous history of KD presenting with acute chest pain should be urgently transported to the tertiary pediatric cardiac surgical center as clinical features cannot reliably determine the underlying etiology. Patients with STEMI (ST elevation myocardial infarction) require urgent catheter re-vascularization or surgical revascularization. Thrombolysis is initiated in cases of CAA occluded by a thrombus [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe diagnostic methods of choice for non-STEMI (non-ST- elevation myocardial infarction), as demonstrated in our patient\u0026rsquo;s case, is ECG, serial high sensitive troponin levels, echocardiography and coronary imaging with CT or coronary angiography.\u003c/p\u003e\u003cp\u003eDue to possible development of significant coronary collaterals over time, serial ECG and high sensitive Troponin levels may be unremarkable, even with significant myocardial ischemia [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The level of Troponin (hsTnT) in our patient was in the grey zone and the immediate correct interpretation of CT angiography was crucial and would have allowed timely initiation of therapy (systemic thrombolysis), which may potentially reduce risk of a fatal outcome.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eKD is the leading cause of acquired coronary disease in children, and patients with CAA remain at lifelong risk of myocardial infarction, arrhythmia, and sudden death. Early recognition and prompt initiation of appropriate therapy are essential to prevent long-term complications. Emergency physicians should be aware, that clinical symptoms of patients with late CA complications may be subtle, and patients with a previous history of KD or previous unexplained myocarditis presenting with suspected cardiac emergency require timely referral to a pediatric congenital cardiac center.\u003c/p\u003e"},{"header":"List of Abbreviations","content":"\u003cp\u003eCA Coronary artery\u003c/p\u003e\u003cp\u003eCAA Coronary artery aneurysm\u003c/p\u003e\u003cp\u003eCOVID-19 Coronavirus Disease 2019\u003c/p\u003e\u003cp\u003eCT Computed Tomography\u003c/p\u003e\u003cp\u003eECG Electrocardiogram\u003c/p\u003e\u003cp\u003eEF Ejection fraction\u003c/p\u003e\u003cp\u003eIVIG Intravenous immunoglobulin\u003c/p\u003e\u003cp\u003eKD Kawasaki disease\u003c/p\u003e\u003cp\u003eLAD Left anterior descending (artery)\u003c/p\u003e\u003cp\u003eMIS-C Multisystem Inflammatory Syndrome in Children\u003c/p\u003e\u003cp\u003eRT-PCR Reverse transcription polymerase chain reaction\u003c/p\u003e\u003cp\u003eSARS-CoV-2 Severe acute respiratory syndrome coronavirus 2\u003c/p\u003e\u003cp\u003eSTEMI ST-elevation myocardial infarction\u003c/p\u003e\u003cp\u003enon-STEMI non-ST- elevation myocardial infarction\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis work was supported by Charles University under the Cooperatio Program. The funding body had no role in study design, data collection, interpretation, or writing of the manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eFJ, FT - original draft preparation; writing – review and editing, HM, KA, SJ, BJ, HL contributed to clinical evaluation, imaging, and post-mortem analysis. All authors critically revised the manuscript and approved the final version\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBurns JC, Glod\u0026eacute; MP. Kawasaki syndrome. Lancet. 2004;364:533\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eElakabawi K, Lin J, Jiao F, Guo N, Yuan Z. Kawasaki disease: global burden and genetic background. Cardiol Res. 2020;11(1):9\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNoval Rivas M, Arditi M. Kawasaki disease: pathophysiology and insights from mouse models. Nat Rev Rheumatol. 2020;16(7):391\u0026ndash;405.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRajasekaran K, Duraiyarasan S, Adefuye M, Manjunatha N, Ganduri V. Kawasaki disease and coronary artery involvement: a narrative review. Cureus. 2022;14(8):e28358.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJone PN, Tremoulet A, Choueiter N, et al. Update on diagnosis and management of Kawasaki disease: a scientific statement from the American Heart Association. Circulation. 2024;150(23):e481\u0026ndash;500.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJone PN, Tremoulet A, Choueiter N, et al. Correction to: Update on diagnosis and management of Kawasaki disease. Circulation. 2025;151(13):e863.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim SH. Diagnosis of coronary artery abnormalities in Kawasaki disease: recent guidelines and z score systems. Clin Exp Pediatr. 2022;65(9):430\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcCrindle BW, Cifra B. The role of echocardiography in Kawasaki disease. Int J Rheum Dis. 2018;21(1):50\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEleftheriou D, Levin M, Shingadia D, Tulloh R, Klein NJ, Brogan PA. Management of Kawasaki disease. Arch Dis Child. 2014;99(1):74\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrogan P, Burns JC, Cornish J, et al. Lifetime cardiovascular management of patients with previous Kawasaki disease. Heart. 2020;106(6):411\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFukazawa R, Kobayashi J, Ayusawa M, et al. JCS/JSCS 2020 guideline on diagnosis and management of cardiovascular sequelae in Kawasaki disease. Circ J. 2020;84(8):1348\u0026ndash;407.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede Graeff N, Groot N, Ozen S, et al. European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease \u0026ndash; the SHARE initiative. Rheumatology (Oxford). 2019;58(4):672\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eResearch Committee of the Japanese Society of Pediatric Cardiology and Cardiac Surgery. Guidelines for medical treatment of acute Kawasaki disease: 2012 revised version. Pediatr Int. 2014;56(2):135\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSuzuki T, Michihata N, Hashimoto Y, et al. Association between aspirin dose and outcomes in patients with acute Kawasaki disease: a nationwide retrospective cohort study in Japan. Eur J Pediatr. 2024;183(1):415\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHayashi K, Miyakoshi C, Hoshino S, et al. Initial intravenous immunoglobulin therapy without aspirin for acute Kawasaki disease: a retrospective cohort study with Bayesian inference. BMJ Paediatr Open. 2024;8(1):e002312.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCannon L, Campbell MJ, Wu EY. Multisystemic inflammatory syndrome in children and Kawasaki disease: parallels in pathogenesis and treatment. Curr Allergy Asthma Rep. 2023;23(6):341\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNetea SA, Biesbroek G, van Stijn D, et al. Kawasaki disease diagnosis and treatment in over 1000 patients: a continuum of dysregulated inflammatory responses. Biomedicines. 2024;12(9):2014.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCem E, B\u0026ouml;nc\u0026uuml;oğlu E, Kıymet E, et al. Which findings make multisystem inflammatory syndrome in children different from the pre-pandemic Kawasaki disease? Pediatr Cardiol. 2023;44(2):424\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTruong DT, Trachtenberg FL, Hu C, et al. Six-month outcomes in the long-term outcomes after the multisystem inflammatory syndrome in children study. JAMA Pediatr. 2025;179(3):293\u0026ndash;301.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVisi G, Spina F, Del Duca F, et al. Autoptic findings in cases of sudden death due to Kawasaki disease. Diagnostics (Basel). 2023;13(11):1831.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijem","sideBox":"Learn more about [International Journal of Emergency Medicine](https://intjem.biomedcentral.com/)","snPcode":"12245","submissionUrl":"https://submission.nature.com/new-submission/12245/3","title":"International Journal of Emergency Medicine","twitterHandle":"@IntJEmergMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Kawasaki disease, incomplete Kawasaki disease, coronary aneurysm, myocardial infarction, pediatric cardiac arrest, case report","lastPublishedDoi":"10.21203/rs.3.rs-7567526/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7567526/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eKawasaki disease (KD), previously termed mucocutaneous lymph node syndrome, is a childhood vasculitis affecting medium-sized arteries and is the leading cause of acquired heart disease in children. It primarily affects children under five years of age. If left untreated, KD can lead to serious cardiovascular complications, particularly coronary artery aneurysms (CAA) and thrombosis. Incomplete KD presents with fewer clinical criteria, making it more difficult to diagnose. Importantly, long-term sequelae such as CAA may remain clinically silent for years. This case highlights the critical need for awareness that even minimal or transient symptoms can be the only warning sign of life-threatening complications in adolescents with a remote history of incomplete or unrecognized KD.\u003c/p\u003e\u003ch2\u003eCase presentation\u003c/h2\u003e\u003cp\u003eWe describe a fatal case of a 12-year-old boy with a history of presumed myocarditis at age five, which retrospectively fulfilled criteria for incomplete KD but remained undiagnosed. From age five to twelve, he was asymptomatic except for occasional, brief chest tightness. At twelve, he presented with mild chest pain followed by rapid clinical deterioration, cardiac arrest, and death. Post-mortem imaging and autopsy revealed a thrombosed giant aneurysm of the left anterior descending coronary artery, consistent with chronic coronary disease.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThis case illustrates the potentially fatal long-term cardiovascular sequelae of unrecognized and untreated incomplete KD. Early recognition and treatment with IVIG are critical to reduce coronary complications. Healthcare providers must maintain clinical vigilance for patients with a history of KD. Even subtle or transient symptoms in patients with a history of KD should prompt immediate evaluation to prevent fatal outcomes\u003c/p\u003e","manuscriptTitle":"Fatal late cardiovascular sequelae of previously unrecognized Kawasaki disease in 12-year- old child","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-20 13:48:12","doi":"10.21203/rs.3.rs-7567526/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-23T16:58:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-13T00:52:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"275426592455656640691052192927280949864","date":"2025-10-12T23:57:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"4384286852889212199904384573109436184","date":"2025-10-12T11:45:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-07T18:24:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-26T03:01:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-26T03:00:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Emergency Medicine","date":"2025-09-08T21:02:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijem","sideBox":"Learn more about [International Journal of Emergency Medicine](https://intjem.biomedcentral.com/)","snPcode":"12245","submissionUrl":"https://submission.nature.com/new-submission/12245/3","title":"International Journal of Emergency Medicine","twitterHandle":"@IntJEmergMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fc920efd-1285-4c94-9df8-36168b95f99f","owner":[],"postedDate":"October 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T16:12:39+00:00","versionOfRecord":{"articleIdentity":"rs-7567526","link":"https://doi.org/10.1186/s12245-025-01079-9","journal":{"identity":"international-journal-of-emergency-medicine","isVorOnly":false,"title":"International Journal of Emergency Medicine"},"publishedOn":"2025-11-29 15:58:45","publishedOnDateReadable":"November 29th, 2025"},"versionCreatedAt":"2025-10-20 13:48:12","video":"","vorDoi":"10.1186/s12245-025-01079-9","vorDoiUrl":"https://doi.org/10.1186/s12245-025-01079-9","workflowStages":[]},"version":"v1","identity":"rs-7567526","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7567526","identity":"rs-7567526","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}