A Case Report of Atypical Kawasaki Disease Presenting with Persistent Fever and Hepatic Dysfunction

A Case Report of Atypical Kawasaki Disease Presenting with Persistent Fever and Hepatic Dysfunction | 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 A Case Report of Atypical Kawasaki Disease Presenting with Persistent Fever and Hepatic Dysfunction Yong-Xing Zhong, Jian Xu, Zheng Zhang, Qi Zheng, Fang-Yan Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6672592/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Kawasaki disease (KD) is an acute vasculitis of unknown etiology, primarily involving the coronary arteries. IVIG-resistant KD is associated with a significantly higher risk of coronary artery aneurysm (CAA), necessitating prompt treatment to suppress systemic inflammation. This report presents a case of IVIG-resistant KD complicated by cholestatic hepatitis, successfully managed with infliximab, though progression to a giant coronary aneurysm was observed. Case Presentation This case report describes a two-year-old male patient with Kawasaki disease (KD) who developed cholestatic hepatitis, a complication of the disease. Following the failure of both IVIG and corticosteroids, infliximab was administered, resulting in a notable clinical improvement. Nevertheless, despite treatment, a giant coronary artery aneurysm ultimately developed. Conclusion Infliximab was found to be an effective treatment for reducing systemic inflammation in this case of IVIG-resistant Kawasaki disease. Further studies are required to determine the optimal timing for infliximab administration in order to prevent severe cardiovascular complications. Kawasaki disease IVIG resistance infliximab cholestatic hepatitis case report Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that primarily affects medium-sized arteries, particularly the coronary arteries [ 1 , 2 ] . It is the primary cause of acquired heart disease in children in developed countries, with significant long-term implications for cardiovascular health. Kawasaki disease (KD) frequently manifests as an acute, self-limiting illness [ 1 ] . However, its capacity to induce coronary artery involvement, including the formation of coronary artery aneurysms (CAA), represents the most significant concern. Beyond the coronary arteries, the systemic vascular damage associated with KD can lead to broader cardiovascular risks, such as premature atherosclerosis and myocardial ischemia. This underscores the critical importance of early diagnosis and intervention [ 3 , 4 ] . The precise pathogenesis of KD remains unclear. However, it is postulated that an exaggerated immune response to an environmental trigger in genetically predisposed individuals is a key factor [ 5 ] . This aberrant immune activation results in widespread endothelial dysfunction and inflammatory infiltration of the vascular wall, which ultimately leads to the characteristic vasculitis observed in KD. Nevertheless, the precise molecular and cellular mechanisms that underpin the disease remain poorly understood. The objective of treatment for Kawasaki disease (KD) is to suppress systemic inflammation, halt the progression of vasculitis, and minimize damage to the coronary arteries. The standard first-line therapy is high-dose intravenous immunoglobulin (IVIG) combined with aspirin. IVIG has been demonstrated to be efficacious in reducing the incidence of coronary complications when administered early in the disease course. Nevertheless, 15–20% of patients demonstrate resistance to IVIG [ 6 ] , which is characterized by the persistence or recurrence of fever following its administration. IVIG-resistant cases are associated with a markedly elevated risk of CAA formation. Studies have reported a ninefold increased incidence of CAA in these cases compared to IVIG-responsive cases [ 7 ] . The management of IVIG-resistant KD presents a significant clinical challenge, as there is currently no universally accepted set of treatment guidelines for this subset of patients [ 8 ] . The current therapeutic strategies include the administration of additional IVIG doses or alternative agents, such as corticosteroids, cyclosporine A, methotrexate, and biologic therapies, including infliximab. In cases of greater refractory nature, plasma exchange may be a potential avenue for consideration. Among these options, corticosteroids are often employed as a second-line therapy; however, concerns remain about potential adverse effects, such as delayed coronary healing. Biologic therapies targeting key inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), have demonstrated efficacy in this patient population. Infliximab, a monoclonal antibody that targets TNF-α [ 9 ] , has emerged as a valuable therapeutic option for patients with KD who do not respond to IVIG [ 10 ] . Tumor necrosis factor-α (TNF-α) plays a pivotal role in the inflammatory cascade of Kawasaki disease (KD). Elevated levels of this cytokine have been linked to disease severity and resistance to standard therapy. Clinical studies have demonstrated that infliximab is an effective treatment for reducing fever and inflammatory markers in a relatively short period of time, while also demonstrating a favorable safety profile. Furthermore, some evidence indicates that infliximab may exert protective effects on the coronary arteries [ 11 ] . However, the precise role of infliximab in preventing CAA formation remains an area of active investigation. This report elucidates the intricacies of managing IVIG-resistant KD and the potential role of infliximab in such cases. While infliximab effectively resolves systemic inflammation in many patients, further research is required to ascertain the optimal timing, patient selection, and long-term outcomes of this treatment. Early identification of IVIG resistance and the strategic use of second-line therapies like infliximab may prove pivotal in improving outcomes and minimizing the risk of long-term cardiovascular complications in children with KD. Case Presentation A previously healthy two-year-old Han Chinese boy from Zhejiang Province presented with a one-day history of fever. Upon admission, the patient's body temperature was 38.1°C, and no other significant clinical findings were observed at that time. However, his condition subsequently deteriorated rapidly. On the second day of hospitalization, the patient developed a generalized erythematous rash. By the third day, additional clinical features had emerged, including cervical lymphadenopathy, erythematous and cracked lips, and edema of the hands and feet that was noticeable upon examination. These findings were consistent with the diagnostic criteria for Kawasaki disease (KD), thus necessitating further investigation. Laboratory evaluations revealed (Fig. 1 ) marked systemic inflammation and hepatic dysfunction, including a white blood cell (WBC) count of 28.23 × 10⁹/L, a C-reactive protein (CRP) level of 162.31 mg/L, and elevated liver enzymes (alanine aminotransferase [ALT] 161.53 U/L, aspartate aminotransferase [AST] 370.90 U/L). Biliary involvement was indicated by elevated alkaline phosphatase (ALP) at 324.62 U/L, gamma-glutamyl transferase (GGT) at 85.52 U/L, total bilirubin at 51.18 µmol/L, direct bilirubin at 30.35 µmol/L, and total bile acids (TBA) at 116.44 µmol/L. Additionally, the presence of hypoalbuminemia (27.06 g/L) further substantiated the diagnosis of systemic inflammation. These laboratory findings, when considered alongside the patient's clinical presentation, served to confirm the diagnosis of classic KD complicated by cholestatic hepatitis. On hospital day 3 (illness day 4), intravenous immunoglobulin (IVIG) at a dose of 2 g/kg, in conjunction with clopidogrel (1 mg/kg/day), was initiated as a course of treatment. Notwithstanding the administration of the aforementioned standard therapy, the patient continued to experience a persistent high-grade fever (Fig. 1 ), which may be indicative of IVIG resistance. On hospital day 5 (illness day 6), a second IVIG infusion at 1 g/kg was administered, in conjunction with three doses of high-dose methylprednisolone pulse therapy (13 mg/kg, 20 mg/kg, and 20 mg/kg, administered sequentially). Unfortunately, this intensified treatment regimen proved ineffective in controlling the fever or reducing inflammatory markers, underscoring the refractory nature of the disease. In view of the lack of response to first- and second-line therapies, a 5 mg/kg dose of infliximab, a tumor necrosis factor-alpha (TNF-α) inhibitor, was administered on hospital day 8 (illness day 9) as a rescue therapy. Notably, the patient's fever abated within 24 hours of the infusion of infliximab. Subsequent laboratory tests demonstrated normalization of inflammatory markers (Fig. 1 ), including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as a significant improvement in liver function parameters (alanine transaminase (ALT), aspartate transaminase (AST), bilirubin levels, and total bilirubin (TBA)). Furthermore, the patient's bile acid levels returned to normal, and they exhibited clinical improvement without any adverse reactions to infliximab. Despite the resolution of systemic inflammation, echocardiographic evaluation revealed (Fig. 2 – 4 ) the development of a giant coronary artery aneurysm (CAA). This troubling outcome underscores the aggressive nature of the patient's disease and highlights the limitations of current therapeutic strategies in completely preventing vascular damage in cases of refractory KD. The persistence of vascular complications despite achieving clinical remission with infliximab underscores the necessity for further investigation into optimal treatment strategies and timing for IVIG-resistant KD. This case study demonstrates the potential efficacy of infliximab in managing IVIG-resistant KD, particularly in reducing systemic inflammation and preventing further hepatic dysfunction. Nevertheless, it also gives rise to significant queries regarding the optimal timing of infliximab administration and its capacity to safeguard against severe coronary complications. Further research is required to elucidate the long-term outcomes of infliximab therapy and its potential to improve the prognosis of patients with refractory KD. Discussion This case meets the diagnostic criteria for classic Kawasaki disease (KD) [ 12 ] , which is characterized by persistent fever and significant liver dysfunction that were unresponsive to standard treatments, including intravenous immunoglobulin (IVIG) and corticosteroids. Although hepatic involvement in Kawasaki disease (KD) is uncommon, cholestatic hepatitis represents a particularly rare manifestation. The precise mechanisms remain unclear, although several hypotheses have been put forth. One potential mechanism involves the aggregation of natural killer (NK) cells in hepatic sinusoids, as observed during the acute phase of KD [ 13 ] . This can result in localized inflammation and hepatocellular injury. An alternative hypothesis posits that small-vessel vasculitis within the liver and bile ducts contributes to impaired bile flow and resultant hepatobiliary dysfunction. Elevated levels of pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), during the acute phase may contribute to further exacerbation of liver damage through immune-mediated injury [ 14 ] . In this case, treatment with infliximab, a monoclonal antibody targeting TNF-α, effectively controlled systemic inflammation, leading to resolution of fever and normalization of inflammatory markers, including liver function tests. Since its initial documented use in 2004 [ 15 ] for a child with refractory KD, infliximab has been increasingly [ 16 – 19 ] recognized as a viable treatment option for patients who have not responded to IVIG. A number of studies have demonstrated the efficacy of this treatment in reducing the duration of fever, lowering inflammatory markers, and potentially mitigating coronary artery damage. Its mechanism of action [ 20 ] , primarily through the inhibition of TNF-α, a key mediator in KD-associated vascular inflammation, highlights its potential for addressing the immune dysregulation observed in this disease. However, despite the apparent clinical and biochemical response to infliximab in this patient, a giant coronary artery aneurysm (CAA) developed, underscoring the compl!exity of KD pathology and the challenges in completely preventing severe vascular complications. The formation of CAAs represents a recognized risk in IVIG-resistant KD, particularly in cases with prolonged inflammation. This remains a significant contributor to long-term cardiovascular morbidity and mortality. Although studies such as those conducted by Tremoulet et al . have indicated a potential protective effect of infliximab on coronary arteries, the evidence remains inconclusive. The timing of infliximab administration, disease severity, and individual patient response are likely to influence outcomes, and further investigation is required in order to elucidate these variables. This case highlights the dual role of infliximab, which not only has anti-inflammatory properties but also plays a crucial role in managing refractory Kawasaki disease (KD). However, the fact that treatment did not entirely prevent the formation of a coronary artery aneurysm (CAA) in this patient suggests that current treatment regimens may require further refinement. The optimal timing and indications for infliximab remain key areas for future research. Literature has suggested that early administration of infliximab during the inflammatory phase may offer enhanced vascular protection and reduce the risk of CAA formation [ 11 ] . However, this hypothesis needs to be validated through randomized controlled trials. As our understanding of the pathophysiology of KD continues to evolve, personalized approaches that integrate biomarkers and imaging studies may provide valuable insights for treatment decisions, potentially improving outcomes and reducing the burden of coronary artery complications. Conclusion This case highlights the effectiveness of infliximab in managing systemic inflammation in a patient with IVIG-resistant Kawasaki disease (KD) complicated by cholestatic hepatitis. While infliximab successfully controlled the inflammatory response, leading to the resolution of fever and normalization of inflammatory markers, the development of a giant coronary artery aneurysm (CAA) underscores the challenges in fully preventing severe vascular complications. This suggests that the timing of infliximab administration is crucial, and earlier intervention, particularly during the acute inflammatory phase, may offer better protection against coronary artery damage and aneurysm formation. Further randomized controlled trials are needed to establish the optimal timing and patient selection for infliximab therapy, and incorporating biomarkers and advanced imaging techniques could help personalize treatment strategies, improving outcomes and reducing long-term cardiovascular risks. Declarations Clinical trial number: Not applicable. Ethics approval and consent to participate This study was approved by Shaoxing Maternity and Child Health Care Hospital. Consent for publication Written informed consent was obtained from the patient’s parents for publication of this case report and any accompanying images. A copy of the written consent is available for review. Availability of data and materials All data generated or analyzed during this study are included in the article. Competing interests The authors declare that they have no competing interests. Funding Shaoxing Health Science and Technology Plan Project (2022KY039，2023SKY049) Authors' contributions YXZ and ZZ were involved in the data collection process and the study coordination. FYY and JXwere involved in the writing of the manuscript and in the interpretation of the results. ZZ and QZ participated in the collection of literature and other related contentAll authors read and approved the final manuscript. Acknowledgements This study was partially supported by Shaoxing Maternity and Child Health Care Hospital. Authors' information YXZ [email protected] XJ [email protected] ZZ [email protected] QZ [email protected] FYY [email protected] References MCCRINDLE B W, ROWLEY A H, NEWBURGER J W, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association [J]. Circulation, 2017, 135(17): e927-e99. NEWBURGER J W, TAKAHASHI M, BURNS J C. Kawasaki Disease [J]. J Am Coll Cardiol, 2016, 67(14): 1738-49. FUKAZAWA R. Long-term prognosis of Kawasaki disease: increased cardiovascular risk? [J]. Curr Opin Pediatr, 2010, 22(5): 587-92. NOVAL RIVAS M, ARDITI M. Kawasaki disease: pathophysiology and insights from mouse models [J]. Nat Rev Rheumatol, 2020, 16(7): 391-405. AGARWAL S, AGRAWAL D K. Kawasaki disease: etiopathogenesis and novel treatment strategies [J]. Expert Rev Clin Immunol, 2017, 13(3): 247-58. NAKAMURA Y, YASHIRO M, UEHARA R, et al. Epidemiologic features of Kawasaki disease in Japan: results of the 2009-2010 nationwide survey [J]. J Epidemiol, 2012, 22(3): 216-21. CAMPBELL A J, BURNS J C. Adjunctive therapies for Kawasaki disease [J]. J Infect, 2016, 72 Suppl: S1-5. XUE L J, WU R, DU G L, et al. Effect and Safety of TNF Inhibitors in Immunoglobulin-Resistant Kawasaki Disease: a Meta-analysis [J]. Clin Rev Allergy Immunol, 2017, 52(3): 389-400. BROGAN R J, ELEFTHERIOU D, GNANAPRAGASAM J, et al. Infliximab for the treatment of intravenous immunoglobulin resistant Kawasaki disease complicated by coronary artery aneurysms: a case report [J]. Pediatr Rheumatol Online J, 2009, 7: 3. PAN Y, FAN Q, HU L. Treatment of immunoglobulin-resistant kawasaki disease: a Bayesian network meta-analysis of different regimens [J]. Front Pediatr, 2023, 11: 1149519. HUR G, SONG M S, SOHN S, et al. Infliximab Treatment for Intravenous Immunoglobulin-resistant Kawasaki Disease: a Multicenter Study in Korea [J]. Korean Circ J, 2019, 49(2): 183-91. Correction to: Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association [J]. Circulation, 2019, 140(5): e181-e4. OHSHIO G, FURUKAWA F, FUJIWARA H, et al. Hepatomegaly and splenomegaly in Kawasaki disease [J]. Pediatr Pathol, 1985, 4(3-4): 257-64. HACHIYA A, KOBAYASHI N, MATSUZAKI S, et al. Analysis of biomarker serum levels in IVIG and infliximab refractory Kawasaki disease patients [J]. Clin Rheumatol, 2018, 37(7): 1937-43. WEISS J E, EBERHARD B A, CHOWDHURY D, et al. Infliximab as a novel therapy for refractory Kawasaki disease [J]. J Rheumatol, 2004, 31(4): 808-10. BURNS J C, BEST B M, MEJIAS A, et al. Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease [J]. J Pediatr, 2008, 153(6): 833-8. SON M B, GAUVREAU K, BURNS J C, et al. Infliximab for intravenous immunoglobulin resistance in Kawasaki disease: a retrospective study [J]. J Pediatr, 2011, 158(4): 644-9 e1. SONG M S, LEE S B, SOHN S, et al. Infliximab treatment for refractory kawasaki disease in korean children [J]. Korean Circ J, 2010, 40(7): 334-8. YOUN Y, KIM J, HONG Y M, et al. Infliximab as the First Retreatment in Patients with Kawasaki Disease Resistant to Initial Intravenous Immunoglobulin [J]. Pediatr Infect Dis J, 2016, 35(4): 457-9. TREMOULET A H, JAIN S, JAGGI P, et al. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial [J]. Lancet, 2014, 383(9930): 1731-8. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6672592","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":474360224,"identity":"a9f478d4-9b08-450c-92c0-40650e7073e0","order_by":0,"name":"Yong-Xing Zhong","email":"","orcid":"","institution":"Shaoxing Maternity and Child Health Care Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yong-Xing","middleName":"","lastName":"Zhong","suffix":""},{"id":474360226,"identity":"b9804461-343f-48c2-acc3-58c16d46a2fc","order_by":1,"name":"Jian Xu","email":"","orcid":"","institution":"Shaoxing Research Institute of Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Xu","suffix":""},{"id":474360227,"identity":"eefb0573-17ad-4aec-ab78-6e36019fa138","order_by":2,"name":"Zheng Zhang","email":"","orcid":"","institution":"Shaoxing Maternity and Child Health Care Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zheng","middleName":"","lastName":"Zhang","suffix":""},{"id":474360228,"identity":"c00d9933-8d5a-4ed3-a99f-553338f4684e","order_by":3,"name":"Qi Zheng","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Zheng","suffix":""},{"id":474360230,"identity":"9093daf4-da27-4b5c-b876-80813eb2f967","order_by":4,"name":"Fang-Yan Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYBAC+2bG9h8fDCTk+NkbiNRiwM58QHJGhY2xZM8BYrXwsyVIc5xJSzS4kUCkFnNmHgNjxrbDCQw3H2+8wVBjE01Qi2Uzj0FyYdvhPMbZacUWDMfSchsI6jnMY3B4ZtvhYmbpHDMJxobDRGkxbOZtO5zYJnmGSC0Gh9mSmXmA3u+R4CFSi2Qz8zFGUCBL8AD9kkCMX/j5D7YxgKLS/vjhjTc+1NgQ4RdkR0okkKIcooVUHaNgFIyCUTAyAACA5T5zhmqchAAAAABJRU5ErkJggg==","orcid":"","institution":"Shaoxing Maternity and Child Health Care Hospital","correspondingAuthor":true,"prefix":"","firstName":"Fang-Yan","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2025-05-15 12:23:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6672592/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6672592/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85270172,"identity":"f8f72a7d-678f-4896-b2eb-09b68a026527","added_by":"auto","created_at":"2025-06-24 06:21:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":52052,"visible":true,"origin":"","legend":"\u003cp\u003eBody temperature, ALT, TBA, and medication duration\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6672592/v1/0c3199c05892465b7db3ae0d.png"},{"id":85270174,"identity":"8a0e86ad-bd8e-43ed-922a-867b9b183f26","added_by":"auto","created_at":"2025-06-24 06:21:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":80165,"visible":true,"origin":"","legend":"\u003cp\u003eEchocardiography on the 4th day of hospitalization shows a Z-value of 2.06 in the right coronary artery\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6672592/v1/ed6fdefc38db6977925615f8.png"},{"id":85270180,"identity":"bc09ea13-1177-4450-9dad-3acbc9d18c0f","added_by":"auto","created_at":"2025-06-24 06:21:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":65096,"visible":true,"origin":"","legend":"\u003cp\u003eEchocardiography of the left coronary artery (left anterior descending branch) on the 11th day of hospitalization. Z-value: 8.46\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6672592/v1/b64c7985d1066ddb7b323296.png"},{"id":85270175,"identity":"a82cc9e2-d040-4421-9587-1d86bda3a7d7","added_by":"auto","created_at":"2025-06-24 06:21:52","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":103563,"visible":true,"origin":"","legend":"\u003cp\u003eEchocardiography on the 24th day of hospitalization shows a Z-value of 10.51 for the left coronary artery (left anterior descending branch) and 10.00 for the right coronary artery\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6672592/v1/9903d1ae2294b3f8db4fbea8.png"},{"id":88521153,"identity":"6d1d4ee8-d6d5-4a62-b3b2-169a56907bc6","added_by":"auto","created_at":"2025-08-07 09:47:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":618913,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6672592/v1/0cf5d348-3b7d-4f77-99d7-73228bf42ba4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Case Report of Atypical Kawasaki Disease Presenting with Persistent Fever and Hepatic Dysfunction","fulltext":[{"header":"Background","content":"\u003cp\u003eKawasaki disease (KD) is a systemic vasculitis of unknown etiology that primarily affects medium-sized arteries, particularly the coronary arteries\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. It is the primary cause of acquired heart disease in children in developed countries, with significant long-term implications for cardiovascular health. Kawasaki disease (KD) frequently manifests as an acute, self-limiting illness\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. However, its capacity to induce coronary artery involvement, including the formation of coronary artery aneurysms (CAA), represents the most significant concern. Beyond the coronary arteries, the systemic vascular damage associated with KD can lead to broader cardiovascular risks, such as premature atherosclerosis and myocardial ischemia. This underscores the critical importance of early diagnosis and intervention\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe precise pathogenesis of KD remains unclear. However, it is postulated that an exaggerated immune response to an environmental trigger in genetically predisposed individuals is a key factor\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. This aberrant immune activation results in widespread endothelial dysfunction and inflammatory infiltration of the vascular wall, which ultimately leads to the characteristic vasculitis observed in KD. Nevertheless, the precise molecular and cellular mechanisms that underpin the disease remain poorly understood.\u003c/p\u003e \u003cp\u003eThe objective of treatment for Kawasaki disease (KD) is to suppress systemic inflammation, halt the progression of vasculitis, and minimize damage to the coronary arteries. The standard first-line therapy is high-dose intravenous immunoglobulin (IVIG) combined with aspirin. IVIG has been demonstrated to be efficacious in reducing the incidence of coronary complications when administered early in the disease course. Nevertheless, 15\u0026ndash;20% of patients demonstrate resistance to IVIG\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e, which is characterized by the persistence or recurrence of fever following its administration. IVIG-resistant cases are associated with a markedly elevated risk of CAA formation. Studies have reported a ninefold increased incidence of CAA in these cases compared to IVIG-responsive cases\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe management of IVIG-resistant KD presents a significant clinical challenge, as there is currently no universally accepted set of treatment guidelines for this subset of patients\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. The current therapeutic strategies include the administration of additional IVIG doses or alternative agents, such as corticosteroids, cyclosporine A, methotrexate, and biologic therapies, including infliximab. In cases of greater refractory nature, plasma exchange may be a potential avenue for consideration. Among these options, corticosteroids are often employed as a second-line therapy; however, concerns remain about potential adverse effects, such as delayed coronary healing. Biologic therapies targeting key inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), have demonstrated efficacy in this patient population.\u003c/p\u003e \u003cp\u003eInfliximab, a monoclonal antibody that targets TNF-α\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, has emerged as a valuable therapeutic option for patients with KD who do not respond to IVIG\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Tumor necrosis factor-α (TNF-α) plays a pivotal role in the inflammatory cascade of Kawasaki disease (KD). Elevated levels of this cytokine have been linked to disease severity and resistance to standard therapy. Clinical studies have demonstrated that infliximab is an effective treatment for reducing fever and inflammatory markers in a relatively short period of time, while also demonstrating a favorable safety profile. Furthermore, some evidence indicates that infliximab may exert protective effects on the coronary arteries\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. However, the precise role of infliximab in preventing CAA formation remains an area of active investigation.\u003c/p\u003e \u003cp\u003eThis report elucidates the intricacies of managing IVIG-resistant KD and the potential role of infliximab in such cases. While infliximab effectively resolves systemic inflammation in many patients, further research is required to ascertain the optimal timing, patient selection, and long-term outcomes of this treatment. Early identification of IVIG resistance and the strategic use of second-line therapies like infliximab may prove pivotal in improving outcomes and minimizing the risk of long-term cardiovascular complications in children with KD.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA previously healthy two-year-old Han Chinese boy from Zhejiang Province presented with a one-day history of fever. Upon admission, the patient's body temperature was 38.1\u0026deg;C, and no other significant clinical findings were observed at that time. However, his condition subsequently deteriorated rapidly. On the second day of hospitalization, the patient developed a generalized erythematous rash. By the third day, additional clinical features had emerged, including cervical lymphadenopathy, erythematous and cracked lips, and edema of the hands and feet that was noticeable upon examination. These findings were consistent with the diagnostic criteria for Kawasaki disease (KD), thus necessitating further investigation.\u003c/p\u003e \u003cp\u003eLaboratory evaluations revealed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) marked systemic inflammation and hepatic dysfunction, including a white blood cell (WBC) count of 28.23 \u0026times; 10⁹/L, a C-reactive protein (CRP) level of 162.31 mg/L, and elevated liver enzymes (alanine aminotransferase [ALT] 161.53 U/L, aspartate aminotransferase [AST] 370.90 U/L). Biliary involvement was indicated by elevated alkaline phosphatase (ALP) at 324.62 U/L, gamma-glutamyl transferase (GGT) at 85.52 U/L, total bilirubin at 51.18 \u0026micro;mol/L, direct bilirubin at 30.35 \u0026micro;mol/L, and total bile acids (TBA) at 116.44 \u0026micro;mol/L. Additionally, the presence of hypoalbuminemia (27.06 g/L) further substantiated the diagnosis of systemic inflammation. These laboratory findings, when considered alongside the patient's clinical presentation, served to confirm the diagnosis of classic KD complicated by cholestatic hepatitis.\u003c/p\u003e \u003cp\u003eOn hospital day 3 (illness day 4), intravenous immunoglobulin (IVIG) at a dose of 2 g/kg, in conjunction with clopidogrel (1 mg/kg/day), was initiated as a course of treatment. Notwithstanding the administration of the aforementioned standard therapy, the patient continued to experience a persistent high-grade fever (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), which may be indicative of IVIG resistance. On hospital day 5 (illness day 6), a second IVIG infusion at 1 g/kg was administered, in conjunction with three doses of high-dose methylprednisolone pulse therapy (13 mg/kg, 20 mg/kg, and 20 mg/kg, administered sequentially). Unfortunately, this intensified treatment regimen proved ineffective in controlling the fever or reducing inflammatory markers, underscoring the refractory nature of the disease.\u003c/p\u003e \u003cp\u003eIn view of the lack of response to first- and second-line therapies, a 5 mg/kg dose of infliximab, a tumor necrosis factor-alpha (TNF-α) inhibitor, was administered on hospital day 8 (illness day 9) as a rescue therapy. Notably, the patient's fever abated within 24 hours of the infusion of infliximab. Subsequent laboratory tests demonstrated normalization of inflammatory markers (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as a significant improvement in liver function parameters (alanine transaminase (ALT), aspartate transaminase (AST), bilirubin levels, and total bilirubin (TBA)). Furthermore, the patient's bile acid levels returned to normal, and they exhibited clinical improvement without any adverse reactions to infliximab.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eDespite the resolution of systemic inflammation, echocardiographic evaluation revealed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) the development of a giant coronary artery aneurysm (CAA). This troubling outcome underscores the aggressive nature of the patient's disease and highlights the limitations of current therapeutic strategies in completely preventing vascular damage in cases of refractory KD. The persistence of vascular complications despite achieving clinical remission with infliximab underscores the necessity for further investigation into optimal treatment strategies and timing for IVIG-resistant KD.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThis case study demonstrates the potential efficacy of infliximab in managing IVIG-resistant KD, particularly in reducing systemic inflammation and preventing further hepatic dysfunction. Nevertheless, it also gives rise to significant queries regarding the optimal timing of infliximab administration and its capacity to safeguard against severe coronary complications. Further research is required to elucidate the long-term outcomes of infliximab therapy and its potential to improve the prognosis of patients with refractory KD.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case meets the diagnostic criteria for classic Kawasaki disease (KD)\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e, which is characterized by persistent fever and significant liver dysfunction that were unresponsive to standard treatments, including intravenous immunoglobulin (IVIG) and corticosteroids. Although hepatic involvement in Kawasaki disease (KD) is uncommon, cholestatic hepatitis represents a particularly rare manifestation. The precise mechanisms remain unclear, although several hypotheses have been put forth. One potential mechanism involves the aggregation of natural killer (NK) cells in hepatic sinusoids, as observed during the acute phase of KD\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. This can result in localized inflammation and hepatocellular injury. An alternative hypothesis posits that small-vessel vasculitis within the liver and bile ducts contributes to impaired bile flow and resultant hepatobiliary dysfunction. Elevated levels of pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), during the acute phase may contribute to further exacerbation of liver damage through immune-mediated injury\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this case, treatment with infliximab, a monoclonal antibody targeting TNF-α, effectively controlled systemic inflammation, leading to resolution of fever and normalization of inflammatory markers, including liver function tests. Since its initial documented use in 2004\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e for a child with refractory KD, infliximab has been increasingly\u003csup\u003e[\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e recognized as a viable treatment option for patients who have not responded to IVIG. A number of studies have demonstrated the efficacy of this treatment in reducing the duration of fever, lowering inflammatory markers, and potentially mitigating coronary artery damage. Its mechanism of action\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e, primarily through the inhibition of TNF-α, a key mediator in KD-associated vascular inflammation, highlights its potential for addressing the immune dysregulation observed in this disease.\u003c/p\u003e \u003cp\u003eHowever, despite the apparent clinical and biochemical response to infliximab in this patient, a giant coronary artery aneurysm (CAA) developed, underscoring the compl!exity of KD pathology and the challenges in completely preventing severe vascular complications. The formation of CAAs represents a recognized risk in IVIG-resistant KD, particularly in cases with prolonged inflammation. This remains a significant contributor to long-term cardiovascular morbidity and mortality. Although studies such as those conducted by Tremoulet \u003cem\u003eet al\u003c/em\u003e. have indicated a potential protective effect of infliximab on coronary arteries, the evidence remains inconclusive. The timing of infliximab administration, disease severity, and individual patient response are likely to influence outcomes, and further investigation is required in order to elucidate these variables.\u003c/p\u003e \u003cp\u003eThis case highlights the dual role of infliximab, which not only has anti-inflammatory properties but also plays a crucial role in managing refractory Kawasaki disease (KD). However, the fact that treatment did not entirely prevent the formation of a coronary artery aneurysm (CAA) in this patient suggests that current treatment regimens may require further refinement. The optimal timing and indications for infliximab remain key areas for future research. Literature has suggested that early administration of infliximab during the inflammatory phase may offer enhanced vascular protection and reduce the risk of CAA formation\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. However, this hypothesis needs to be validated through randomized controlled trials. As our understanding of the pathophysiology of KD continues to evolve, personalized approaches that integrate biomarkers and imaging studies may provide valuable insights for treatment decisions, potentially improving outcomes and reducing the burden of coronary artery complications.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case highlights the effectiveness of infliximab in managing systemic inflammation in a patient with IVIG-resistant Kawasaki disease (KD) complicated by cholestatic hepatitis. While infliximab successfully controlled the inflammatory response, leading to the resolution of fever and normalization of inflammatory markers, the development of a giant coronary artery aneurysm (CAA) underscores the challenges in fully preventing severe vascular complications. This suggests that the timing of infliximab administration is crucial, and earlier intervention, particularly during the acute inflammatory phase, may offer better protection against coronary artery damage and aneurysm formation. Further randomized controlled trials are needed to establish the optimal timing and patient selection for infliximab therapy, and incorporating biomarkers and advanced imaging techniques could help personalize treatment strategies, improving outcomes and reducing long-term cardiovascular risks.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eClinical trial number: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study was approved by Shaoxing Maternity and Child Health Care Hospital.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient\u0026rsquo;s parents for publication of this case report and any accompanying images. A copy of the written consent is available for review.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in the article.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eShaoxing Health Science and Technology Plan Project (2022KY039，2023SKY049)\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u003c/p\u003e\n\u003cp\u003eYXZ and ZZ were involved in the data collection process and the study coordination. FYY and JXwere involved in the writing of the manuscript and in the interpretation of the results. ZZ and QZ participated in the collection of literature and other related contentAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was partially supported by Shaoxing Maternity and Child Health Care Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYXZ [email protected]\u003c/p\u003e\n\u003cp\u003eXJ \u003cu\[email protected]\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eZZ [email protected]\u003c/p\u003e\n\u003cp\u003eQZ [email protected]\u003c/p\u003e\n\u003cp\u003eFYY [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMCCRINDLE B W, ROWLEY A H, NEWBURGER J W, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association [J]. Circulation, 2017, 135(17): e927-e99.\u003c/li\u003e\n\u003cli\u003eNEWBURGER J W, TAKAHASHI M, BURNS J C. Kawasaki Disease [J]. J Am Coll Cardiol, 2016, 67(14): 1738-49.\u003c/li\u003e\n\u003cli\u003eFUKAZAWA R. Long-term prognosis of Kawasaki disease: increased cardiovascular risk? [J]. Curr Opin Pediatr, 2010, 22(5): 587-92.\u003c/li\u003e\n\u003cli\u003eNOVAL RIVAS M, ARDITI M. Kawasaki disease: pathophysiology and insights from mouse models [J]. Nat Rev Rheumatol, 2020, 16(7): 391-405.\u003c/li\u003e\n\u003cli\u003eAGARWAL S, AGRAWAL D K. Kawasaki disease: etiopathogenesis and novel treatment strategies [J]. Expert Rev Clin Immunol, 2017, 13(3): 247-58.\u003c/li\u003e\n\u003cli\u003eNAKAMURA Y, YASHIRO M, UEHARA R, et al. Epidemiologic features of Kawasaki disease in Japan: results of the 2009-2010 nationwide survey [J]. J Epidemiol, 2012, 22(3): 216-21.\u003c/li\u003e\n\u003cli\u003eCAMPBELL A J, BURNS J C. Adjunctive therapies for Kawasaki disease [J]. J Infect, 2016, 72 Suppl: S1-5.\u003c/li\u003e\n\u003cli\u003eXUE L J, WU R, DU G L, et al. Effect and Safety of TNF Inhibitors in Immunoglobulin-Resistant Kawasaki Disease: a Meta-analysis [J]. Clin Rev Allergy Immunol, 2017, 52(3): 389-400.\u003c/li\u003e\n\u003cli\u003eBROGAN R J, ELEFTHERIOU D, GNANAPRAGASAM J, et al. Infliximab for the treatment of intravenous immunoglobulin resistant Kawasaki disease complicated by coronary artery aneurysms: a case report [J]. Pediatr Rheumatol Online J, 2009, 7: 3.\u003c/li\u003e\n\u003cli\u003ePAN Y, FAN Q, HU L. Treatment of immunoglobulin-resistant kawasaki disease: a Bayesian network meta-analysis of different regimens [J]. Front Pediatr, 2023, 11: 1149519.\u003c/li\u003e\n\u003cli\u003eHUR G, SONG M S, SOHN S, et al. Infliximab Treatment for Intravenous Immunoglobulin-resistant Kawasaki Disease: a Multicenter Study in Korea [J]. Korean Circ J, 2019, 49(2): 183-91.\u003c/li\u003e\n\u003cli\u003eCorrection to: Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association [J]. Circulation, 2019, 140(5): e181-e4.\u003c/li\u003e\n\u003cli\u003eOHSHIO G, FURUKAWA F, FUJIWARA H, et al. Hepatomegaly and splenomegaly in Kawasaki disease [J]. Pediatr Pathol, 1985, 4(3-4): 257-64.\u003c/li\u003e\n\u003cli\u003eHACHIYA A, KOBAYASHI N, MATSUZAKI S, et al. Analysis of biomarker serum levels in IVIG and infliximab refractory Kawasaki disease patients [J]. Clin Rheumatol, 2018, 37(7): 1937-43.\u003c/li\u003e\n\u003cli\u003eWEISS J E, EBERHARD B A, CHOWDHURY D, et al. Infliximab as a novel therapy for refractory Kawasaki disease [J]. J Rheumatol, 2004, 31(4): 808-10.\u003c/li\u003e\n\u003cli\u003eBURNS J C, BEST B M, MEJIAS A, et al. Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease [J]. J Pediatr, 2008, 153(6): 833-8.\u003c/li\u003e\n\u003cli\u003eSON M B, GAUVREAU K, BURNS J C, et al. Infliximab for intravenous immunoglobulin resistance in Kawasaki disease: a retrospective study [J]. J Pediatr, 2011, 158(4): 644-9 e1.\u003c/li\u003e\n\u003cli\u003eSONG M S, LEE S B, SOHN S, et al. Infliximab treatment for refractory kawasaki disease in korean children [J]. Korean Circ J, 2010, 40(7): 334-8.\u003c/li\u003e\n\u003cli\u003eYOUN Y, KIM J, HONG Y M, et al. Infliximab as the First Retreatment in Patients with Kawasaki Disease Resistant to Initial Intravenous Immunoglobulin [J]. Pediatr Infect Dis J, 2016, 35(4): 457-9.\u003c/li\u003e\n\u003cli\u003eTREMOULET A H, JAIN S, JAGGI P, et al. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial [J]. Lancet, 2014, 383(9930): 1731-8.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Kawasaki disease, IVIG resistance, infliximab, cholestatic hepatitis, case report","lastPublishedDoi":"10.21203/rs.3.rs-6672592/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6672592/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003cbr\u003e\nKawasaki disease (KD) is an acute vasculitis of unknown etiology, primarily involving the coronary arteries. IVIG-resistant KD is associated with a significantly higher risk of coronary artery aneurysm (CAA), necessitating prompt treatment to suppress systemic inflammation. This report presents a case of IVIG-resistant KD complicated by cholestatic hepatitis, successfully managed with infliximab, though progression to a giant coronary aneurysm was observed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation\u003c/strong\u003e\u003cbr\u003e\nThis case report describes a two-year-old male patient with Kawasaki disease (KD) who developed cholestatic hepatitis, a complication of the disease. Following the failure of both IVIG and corticosteroids, infliximab was administered, resulting in a notable clinical improvement. Nevertheless, despite treatment, a giant coronary artery aneurysm ultimately developed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003cbr\u003e\nInfliximab was found to be an effective treatment for reducing systemic inflammation in this case of IVIG-resistant Kawasaki disease. Further studies are required to determine the optimal timing for infliximab administration in order to prevent severe cardiovascular complications.\u003c/p\u003e","manuscriptTitle":"A Case Report of Atypical Kawasaki Disease Presenting with Persistent Fever and Hepatic Dysfunction","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-24 06:21:47","doi":"10.21203/rs.3.rs-6672592/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"802512ed-1b1d-4fac-8076-0dbd573a2b36","owner":[],"postedDate":"June 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-07T09:39:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-24 06:21:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6672592","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6672592","identity":"rs-6672592","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}