Clinical Course and Management of Kawasaki Disease Complicated with Duodenal Bleeding: A Two-Stage Case Review and Literature Analysis

Clinical Course and Management of Kawasaki Disease Complicated with Duodenal Bleeding: A Two-Stage Case Review and Literature Analysis | 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 Research Article Clinical Course and Management of Kawasaki Disease Complicated with Duodenal Bleeding: A Two-Stage Case Review and Literature Analysis Wu Bin, HongHua Lin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6623778/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 Objective: To explore the clinical characteristics, diagnostic process, treatment measures, and prognosis of Kawasaki disease (KD) combined with duodenal bleeding and to improve the understanding of this rare but serious complication. Methods: We analyzed retrospectively the comprehensive clinical data of a child diagnosed with KD who was admitted to our hospital with duodenal bleeding. In addition to this case, three similar instances identified through a literature review were included. We summarized and compared the clinical manifestations, laboratory tests, imaging and endoscopic findings, treatment strategies, and prognoses. Results: All four children were male, aged 2.5-11 years old, and the types of KD included typical, atypical, and Kawasaki disease shock syndrome(KDSS). All clinical manifestations of KD, such as fever, rash, and conjunctival congestion, followed by gastrointestinal bleeding, such as melena, hematemesis, or hemorrhagic shock. Gastroscopy confirmed that duodenal bulb ulcer or perforation was the source of bleeding. Some children had intravenous immunoglobulin (IVIG) non-response or severe cardiovascular complications (such as coronary artery aneurysm). Treatment is mainly IVIG, antiplatelet or anticoagulant drugs, proton pump inhibitors, endoscopic hemostasis, or surgical repair. Most children have a good prognosis, and heart disease does not progress further. Conclusion: Duodenal bleeding is a rare but serious complication of Kawasaki disease that requires vigilance, especially when there is no response to IVIG, KDSS, or severe inflammatory response. Timely gastrointestinal evaluation act,ive hemostasis, and supportive treatment measures can help improve the prognosis. Pediatrics Kawasaki Disease Shock Duodenal Ulcer Gastrointestinal Hemorrhage Immunoglobulins Intravenous Figures Figure 1 Figure 2 1. Introduction Kawasaki disease (KD) is a systemic vasculitis that mainly affects small and medium-sized blood vessels in children and is one of the leading causes of acquired heart disease in children. Its typical clinical manifestations include persistent fever, skin and mucosal changes, changes in the extremities, lymphadenopathy, and bilateral conjunctival congestion[1]. Although the etiology of KD has not been fully clarified, its inflammatory response can affect multiple systems, especially the cardiovascular system[2]. With the deepening of the understanding of KD, atypical manifestations and multisystem complications have gradually attracted clinical attention[3]. Among these cases, the prognosis for KD combined with toxic shock syndrome is particularly complex, especially in instances where patients do not respond to intravenous immunoglobulin (IVIG) treatment[4]. Additionally, complications affecting the digestive system—recognized as atypical manifestations of KD—have received increasing attention. These may include symptoms such as abdominal pain, vomiting, diarrhea, gallbladder enlargement, and abnormal liver function[5]. However, reports of KD combined with severe gastrointestinal bleeding, especially duodenal bleeding, are still rare, and clinical diagnosis and treatment are challenging[6]. The duodenal bulb is the most vulnerable part of the digestive tract to ulcer bleeding. It may be directly or indirectly damaged by pathology under the background of strong inflammation of KD, especially in the process of using therapeutic drugs such as aspirin and glucocorticoids, which is more likely to aggravate the destruction of the gastrointestinal mucosal barrier[7]. This article reviews the detailed medical history of a child with Kawasaki disease and duodenal bleeding admitted to our hospital. It analyzes its clinical characteristics, pathological mechanisms, diagnostic ideas, and treatment strategies in combination with three similar cases reported at home and abroad. It aims to provide a reference for clinicians and improve their ability to identify and deal with this rare complication. 2. Materials and methods The case in this study is an 11-year-old boy admitted to XXX in December 2024. The collected clinical data included the patient's initial symptoms, physical examination results, laboratory test results (complete blood count, C-reactive protein, erythrocyte sedimentation rate, liver and kidney function tests, and myocardial enzyme levels), imaging examinations (chest CT, echocardiography, and coronary CT angiography), and endoscopic examination results confirming active duodenal bleeding. The patient received IVIG, aspirin, corticosteroid pulse therapy, proton pump inhibitors, and blood transfusion. Follow-up assessments will be performed at 3, 6, and 12 months, including cardiac ultrasound, laboratory index tests, and gastrointestinal symptom assessments. All data were extracted and verified independently by two researchers. This study was approved by the Ethics Committee of XXX (approval number: AF-HEC-007-010), and written informed consent was obtained from the patient's legal guardian. We systematically searched PubMed, Embase, Web of Science, and Google Scholar until April 2025 using the following search terms: "Kawasaki disease" AND ("duodenal bleeding" OR "duodenal bleeding" OR "gastrointestinal bleeding") AND ("case report" OR "case series"). We manually screened relevant references. We ultimately identified three reports in English that met the inclusion criteria. The inclusion and exclusion criteria were as follows: Inclusion criteria: (1) Kawasaki disease diagnosis by the 2017 American Heart Association (AHA) guidelines, requiring ≥ 5 of the six main clinical features or fewer features supported by relevant laboratory and imaging test results; (2) Presence of IVIG resistance, defined as persistent or recurrent fever (≥ 38°C) ≥ 36 hours after the initial IVIG (2 g/kg) administration; (3) KDSS diagnosis, characterized by hypotension (age-adjusted) or clinical signs of poor perfusion requiring intensive care; (4) Detection of coronary artery aneurysm, defined as an echocardiographic Z score > + 2.5; (5) Confirmation of duodenal bleeding was based on a sharp drop in hemoglobin, a positive fecal occult blood test, or endoscopic or surgical confirmation of duodenal bleeding. Exclusion criteria: (1) gastrointestinal bleeding in non-duodenal sites; (2) incomplete clinical or diagnostic information; (3) articles not published in peer-reviewed journals or written in languages other than English. Due to the limited sample size (n = 4), descriptive statistics were used. Categorical variables (sex, clinical type of Kawasaki disease, presence of gastrointestinal symptoms, and treatment) were summarized using frequencies and proportions. Continuous variables (including hemoglobin level, white blood cell count, C-reactive protein, erythrocyte sedimentation rate, and liver function indicators) were reported directly and presented in comparison tables. Due to the insufficient sample size and heterogeneity of clinical manifestations, no inferential statistics or hypothesis testing were performed. 3. Results This study analyzes a rare KD case complicated by duodenal bleeding and systematically reviews three similar cases reported in the literature. The clinical features, laboratory findings, imaging and endoscopic evaluations, treatment strategies, and prognoses were summarized for comparative analysis. 3.1. Case from Our Institution 3.1.1. Patient Demographics An 11-year-old boy was admitted on December 19, 2024, due to persistent fever and cough for 3 days. The highest recorded temperature was 39.8°C, accompanied by cough, pharyngeal erythema, and rhinorrhea, without evident dyspnea. The patient was alert upon admission, though fever fluctuated despite antipyretic use. 3.1.2. Clinical Course Day 3 (December 21, 2024): The patient developed persistent high fever (> 39°C), generalized rash, dry and cracked lips, bilateral conjunctival congestion, and swelling of the distal extremities. These signs met the diagnostic criteria for classic KD.IVIG(2 g/kg) and high-dose aspirin (30–50 mg/kg/day) were initiated on December 22. Day 4 (December 22, 2024): The fever rebounded after a brief temperature decline. The patient exhibited lethargy, hypotension (85/37 mmHg), and tachycardia (140 bpm), prompting transfer to the Pediatric Intensive Care Unit (PICU). Echocardiography revealed coronary artery dilation (LAD: 5.8 mm, Z-score = 8.43), consistent with moderate coronary artery aneurysm (CAA). Laboratory findings showed oliguria, metabolic acidosis, elevated lactate, and liver dysfunction (ALT: 189.7 U/L↑; albumin: 22.3 g/L↓), leading to a diagnosis of KDSS and IVIG-resistant KD. Day 19 (January 7, 2025): The patient experienced hematemesis and melena. Hemoglobin dropped from 92 g/L to 84 g/L, with signs of hypovolemic shock (BP: 80/40 mmHg; pallor). Emergency upper endoscopy showed active duodenal bulb ulcer bleeding. Hemostasis was achieved via titanium clip placement and hemostatic powder application. No recurrent bleeding was observed. Discharge (January 16, 2025): The patient recovered well with stable vital signs, no fever or gastrointestinal bleeding, and normal blood pressure (110/70 mmHg). Echocardiography showed no further progression of the aneurysm (Left Anterior Descending artery(LAD): 4.7 mm; Z = 4.83). The patient was discharged on low-dose aspirin (3–5 mg/kg/day), with scheduled follow-up echocardiography and blood tests at 3, 6, and 12 months. 3.1.3. Laboratory and Imaging Findings 1) Hematology: December 19, 2024: WBC count 31.15×10⁹/L↑, neutrophil count 93.9%↑, hemoglobin 120 g/L↓, platelet count 341×10⁹/L December 21, 2024: WBC count 24.24×10⁹/L↑, hemoglobin 116 g/L↓, platelet count 370×10⁹/L January 3, 2025: WBC count 17.06×10⁹/L↑, neutrophil count 11.04×10⁹/L↑, hemoglobin 92 g/L↓, platelet count 874×10⁹/L↑ 2) Inflammatory markers: CRP: peak 146.35 mg/L↑ ESR: 66 mm/h↑ PCT: mildly elevated on multiple measurements 3) Biochemistry: ALT: 189.7 U/L↑, AST: 42.0 U/L↑, TBil: 85.8 µmol/L↑, DBil: 68.3 µmol/L↑, Albumin: 22.3 g/L↓ Electrolyte abnormalities: Na 130–134 mmol/L↓, K 3.3–3.9 mmol/L↓, Ca 2.01–2.04 mmol/L↓, P 0.76–1.02 mmol/L↓ 4) Cardiac markers: NT-proBNP: 583.8 pg/mL↑ CK-MB and Troponin I: within or mildly above reference ranges 5) Imaging and Endoscopy: Chest CT (December 20): patchy bilateral pulmonary infiltrates and mild pleural effusion Echocardiography (Jan 3): LAD 4.7 mm (Z = 4.83)↑, RCA 4.3 mm (Z = 4.39)↑, AV groove 5.8 mm (Z = 8.43)↑, small pericardial effusion Gastroscopy (January 7): Active duodenal bulb ulcer with bleeding, successfully treated endoscopically 3.2. Literature Cases of Duodenal Complications in KD A systematic review identified three published cases of KD complicated by duodenal bleeding or perforation. 3.2.1. Case 1 : Duodenal Perforation [ 8 ] Patient: 2.5-year-old boy with fever and rash, developed melena on day 8 and abdominal pain on day 11 Findings: X-ray showed free air; Hb 6.5 g/dL↓; WBC 12×10⁹/L↑; ESR 109 mm/h↑ Treatment: IVIG, aspirin (later substituted with dipyridamole due to G6PD deficiency), laparotomy with perforation repair Prognosis: Good postoperative recovery; no cardiac complications 3.2.2. Case 2 : Duodenal Ulcer Bleeding[ 9 ] Patient: 4-year-old boy with abdominal pain, fever, vomiting of coffee-ground material, and melena Findings: Hb 108 g/L↓; PLT 65×10⁹/L↓; CRP 31 mg/L↑; ALT 54 U/L↑ Treatment: IVIG, omeprazole, clopidogrel (instead of aspirin); endoscopic hemostasis Prognosis: No rebleeding within 1 month; coronary dilation resolved after 8 weeks 3.2.3. Case 3 : Atypical KD with GI Bleeding [ 10 ] Patient: 4.5-year-old boy with prolonged fever (2 months), GI symptoms (nausea, vomiting, diarrhea, bloody stool), and jaundice Findings: Hb 53 g/L↓; PLT 20×10⁹/L↓; WBC 21.7×10⁹/L↑; hyperbilirubinemia Treatment: IVIG, massive blood transfusion (5200 mL), surgical repair of duodenal ulcer Prognosis: Healing of duodenal erosion and improvement in coronary dilation, but chronic gastritis persisted 3.3 Comparative Analysis of Four Kawasaki Disease Cases with Duodenal Hemorrhage The clinical characteristics, treatments, and prognosiss of four cases of KD complicated by duodenal hemorrhage are summarized in Table 1 and Figs. 1 and 2 . Table 1 Clinical Characteristics of Four KD Cases with Duodenal Hemorrhage Feature Current Case (11 years) Case 1 (2.5 years) Case 2 (4 years) Case 3 (4.5 years) Gender Male Male Male Male KD Type Typical KD, IVIG-resistant, KDSS Typical KD Complete KD Atypical KD Gastrointestinal Symptoms Melena, hematemesis Melena, vomiting, abdominal pain Tarry stool, vomiting Bloody stool, vomiting, abdominal pain Bleeding Onset Day 19 of treatment Day 8 post-onset Day 5 post-onset 2 months post-onset Blood Count Hb: 92 g/L↓, WBC: 31.15×10⁹/L↑ Hb: 65 g/L↓, WBC: 12×10⁹/L↑ Hb: 108 g/L↓, WBC: 11.5×10⁹/L↑ Hb: 53 g/L↓, WBC: 21.7×10⁹/L↑ Inflammatory Markers CRP: 146.35 mg/L↑, ESR: 66 mm/h↑ CRP↑, ESR: 109 mm/h↑ CRP: 31 mg/L↑ Not reported Biochemistry ALT: 189.7 U/L↑, Albumin: 22.3 g/L↓ ALT: 51 U/L↑, AST: 79 U/L↑ ALT: 54 U/L↑, Albumin: 21.3 g/L↓ Total bilirubin: 67 µmol/L↑ Imaging Findings Coronary artery dilation, pleural effusion Free abdominal gas Mild coronary artery dilation Hepatomegaly, splenomegaly Endoscopy/Surgery Duodenal ulcer, endoscopic hemostasis (titanium clips, hemostatic powder) Duodenal perforation, surgical repair Duodenal ulcer, endoscopic hemostasis Duodenal ulcer, surgical repair Treatment IVIG (2 g/kg × 2), methylprednisolone (30 mg/kg/day × 3 days), aspirin, clopidogrel, PPI IVIG, aspirin, surgery, PPI IVIG, clopidogrel, endoscopic hemostasis, PPI IVIG, transfusion, surgery, PPI Prognosis No recurrence, stable coronary aneurysm (LAD: 4.7 mm, Z = 4.83) No cardiac complications Coronary arteries normalized Chronic gastritis, improved coronary arteries Note : KD = Kawasaki disease; KDSS = Kawasaki disease shock syndrome; IVIG = intravenous immunoglobulin; Hb = hemoglobin; WBC = white blood cell count; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; ALT = alanine aminotransferase; AST = aspartate aminotransferase; PPI = proton pump inhibitor; LAD = left anterior descending artery; ↓ = decreased; ↑ = increased. 3.3.1 Comparative Analysis of Bleeding Onset and Anemia Severity in Four KD Cases This comparative analysis highlights the variability in KD presentation, bleeding onset, and treatment approaches. The current case and Case 2 showed milder anemia and responded to endoscopic hemostasis, while Cases 1 and 3 required surgical intervention due to severe complications such as perforation or profound anemia. Prognosis varied, with stabilization or regression of coronary artery lesions in most cases, but case 3 developed chronic gastritis. 3.3.2 Treatment Response and Prognosis Current Case Following the second dose of IVIG and methylprednisolone pulse therapy, the patient exhibited a gradual decline in inflammatory markers, including white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT), with body temperature returning to normal. After endoscopic hemostasis, hemoglobin levels increased to 98 g/L, and no further gastrointestinal bleeding occurred. Follow-up echocardiography revealed stable coronary artery aneurysm morphology and an ejection fraction (EF) was restored to 60%. Literature Cases Case 1 experienced gastrointestinal perforation during KD. After surgical repair, inflammatory markers significantly decreased, and no cardiac complications were reported. Case 2 responded rapidly to endoscopic hemostasis, with complete resolution of coronary artery dilation within 8 weeks. Case 3 underwent surgical intervention and blood transfusion, resulting in significant relief of gastrointestinal symptoms and improvement in coronary artery dilation. However, the patient continued to exhibit chronic gastritis. All four patients had severe gastrointestinal bleeding during the acute or subacute phase of Kawasaki disease, with the bleeding site limited to the duodenum. Each patient had a significant systemic inflammatory response and varying degrees of liver dysfunction. This patient was an older (11 years old) patient with KDSS and was resistant to IVIG, suggesting that his clinical course was more complicated. In terms of hemostatic intervention, endoscopic hemostasis was successfully applied in this case and case 2 , while case 1 and case 3 required surgical intervention. All patients survived after timely and comprehensive treatment, with short-term clinical relief and a good prognosis. However, because coronary artery lesions may progress, long-term follow-up is required, especially echocardiographic evaluation, to monitor cardiac function and recovery. 4. Discussion KD is a systemic vasculitis that manifests with complex clinical symptoms and can affect multiple organ systems during the acute phase. Recent research has drawn increasing attention to the gastrointestinal involvement in KD, infrequent but severe complications such as duodenal hemorrhage. Clinical observations suggest that KD complicated by duodenal bleeding is often characterized by rapidly progressing symptoms and severe clinical courses, necessitating prompt recognition and intervention. The underlying pathophysiological mechanisms of KD involve a cascade of immune-mediated inflammatory responses predominantly mediated by T-cells and macrophages. These immune cells infiltrate both coronary artery endothelium and the gastrointestinal microvasculature, increasing vascular permeability and contributing to microvascular thrombosis[ 11 ]. The resulting ischemia and tissue necrosis contribute to ulcer formation. Elevated levels of proinflammatory markers such as TNF-α, IL-6, and MMP-9, especially in IVIG-resistant patients, further compromise gastrointestinal barrier integrity, increasing the risk of mucosal injury and bleeding [ 12 ]. The duodenal bulb is particularly vulnerable to such injury due to its rich blood supply and susceptibility to stress-induced ulceration. While high-dose aspirin (ASA) and corticosteroids are commonly used to control inflammation in KD, they are known to compromise mucosal integrity. ASA reduces prostaglandin synthesis, impairing mucosal protection and elevating ulcer risk, while corticosteroids delay healing[ 13 ]. Moreover, in KDSS, tissue hypoperfusion and ischemia-reperfusion injury can further damage the gastrointestinal mucosa [ 14 ], as illustrated in the current case where duodenal bulb ulcer and bleeding were evident following KDSS onset. Effective treatment of KD with gastrointestinal hemorrhage necessitates controlling systemic inflammation, preventing coronary artery lesions, and achieving rapid hemostasis. In our clinical case, two doses of IVIG (2 g/kg) and methylprednisolone pulse therapy (30 mg/kg/day for 3 days) were administered, along with dual antiplatelet therapy (aspirin and clopidogrel). Endoscopic hemostasis using titanium clips and hemostatic powder successfully controlled the bleeding and avoided the need for surgical intervention. This aligns with Hu et al. (2020), who demonstrated the efficacy of early endoscopic hemostasis in similar KD cases, with surgical intervention being required only in cases involving perforation or hemodynamic instability. The optimization of antiplatelet therapy remains a central clinical challenge. Aspirin is routinely used in KD to prevent coronary thrombosis but increases gastrointestinal bleeding risk. In this case, clopidogrel was introduced following duodenal hemorrhage to maintain antiplatelet efficacy while minimizing bleeding risk, resulting in complete resolution of coronary artery dilation. This supports the findings of Hu et al. (2020) and suggests that clopidogrel may serve as a safer alternative in high-risk patients. Adjunctive use of proton pump inhibitors (PPIs), such as omeprazole, was consistent across all cases, in line with McCrindle et al. (2017) recommendations to protect the gastrointestinal mucosa[ 15 ]. From a prognostic perspective, timely intervention was associated with survival in all reported cases. However, coronary prognoses varied. Case 2 had complete resolution of coronary dilatation within eight weeks; Case 1 had no cardiac complications; and Case 3 showed partial improvement and developed chronic gastritis. These prognostic results emphasize the importance of early intervention for improved gastrointestinal and cardiovascular prognosis. The observed differences in coronary and gastrointestinal recovery among patients may be due to differences in systemic inflammatory responses and microvascular damage. Elevated levels of proinflammatory cytokines such as TNF-α and IL-6, especially in IVIG-resistant or KDSS cases, compromise mucosal integrity and contribute to coronary artery damage and gastrointestinal involvement[ 5 ]. In addition, ischemia-reperfusion injury, which results in impaired intestinal mucosal microcirculation, may exacerbate mucosal erosions and ulcers, potentially affecting the severity and duration of gastrointestinal and cardiac complications[ 16 ]. These pathophysiological insights support that the gastrointestinal and cardiovascular prognoses of Kawasaki disease are closely related through standard inflammatory and ischemic mechanisms, reinforcing the clinical need for timely, systemic anti-inflammatory therapy and personalized treatment. Recent genetic studies have highlighted polymorphisms in genes such as ITPKC and CASP3 that may contribute to abnormal immune responses and gastrointestinal complications in patients with KD[ 17 ]. These genetic variants are thought to modulate T-cell activation and apoptotic pathways, amplifying systemic inflammation and leading to microvascular damage in coronary arteries and gastrointestinal tissues. Their presence may help explain why some patients with KD experience severe gastrointestinal symptoms, including duodenal ulcers and bleeding, even in the absence of traditional risk factors. These findings highlight the need for future studies investigating the genetic basis of gastrointestinal involvement in KD, particularly in immune regulation and endothelial integrity. A better understanding of gene-environment interactions could enable risk stratification, guide personalized treatment strategies, and ultimately improve short-term management and long-term prognosis for patients with KD with gastrointestinal involvement. Incorporating genetic analysis into clinical practice may provide opportunities for the early identification of high-risk patients and for the prevention of severe complications. Unfortunately, our patient did not undergo genetic testing, and genetic studies are warranted in future work. 5. Conclusion This study highlights that duodenal bleeding, although rare, is a serious and potentially life-threatening complication in patients with KD, especially for those with IVIG resistance or KDSS. Our results suggest that systemic vasculitis and immune-mediated endothelial damage, combined with ischemia, aspirin, and corticosteroid use, lead to gastrointestinal mucosal fragility and bleeding. Timely recognition of gastrointestinal symptoms, such as melena and abdominal pain, and prompt endoscopic intervention are essential to prevent adverse outcomes. Importantly, this study highlights the clinical application of personalized antiplatelet therapy (i.e., replacing aspirin with clopidogrel in high-risk patients), a safer and more effective approach to balance antithrombotic efficacy and gastrointestinal safety. The successful application of endoscopic hemostasis techniques such as titanium clip placement and hemostatic powder has demonstrated a minimally invasive and highly effective treatment strategy for gastrointestinal bleeding in Kawasaki disease. In addition, immune-related genes such as ITPKC and CASP3 suggest a potential mechanistic link between genetic susceptibility to Kawasaki disease and gastrointestinal involvement. These findings have opened up new avenues for studying the immunogenetic basis of gastrointestinal complications, with the ultimate goal of developing precision medicine tools for early risk stratification and targeted intervention. References Owens AM, Plewa MC (2023) Kawasaki disease. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK537163/ Houska N, Albertz M, Ing RJ (2025) Update on diagnosis and management of Kawasaki disease: A scientific statement from the American Heart Association. J Cardiothorac Vasc Anesth 39(5):1103–1105. https://doi.org/10.1053/j.jvca.2025.02.007 Conte C, Sogni F, Rigante D, Esposito S (2023) An Update on Reports of Atypical Presentations of Kawasaki Disease and the Recognition of IVIG Non-Responder Children. Diagnostics (Basel Switzerland) 13(8):1441. https://doi.org/10.3390/diagnostics13081441 Pilania RK, Bhattarai D, Singh S (2018) Controversies in diagnosis and management of Kawasaki disease. World J Clin Pediatr 7(1):27–35. https://doi.org/10.5409/wjcp.v7.i1.27 Tao E, Lang D (2024) Unraveling the gut: the pivotal role of intestinal mechanisms in Kawasaki disease pathogenesis. Front Immunol 15:1496293. https://doi.org/10.3389/fimmu.2024.1496293 Hu C, Yu Y (2020) Gastrointestinal hemorrhage before anticoagulant therapy in Kawasaki disease: a case report. BMC Pediatr 20(1):32. https://doi.org/10.1186/s12887-020-1916-6 Bindu S, Mazumder S, Bandyopadhyay U (2020) Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol 180:114147. https://doi.org/10.1016/j.bcp.2020.114147 Masoumi K et al (2015) Spontaneous duodenal perforation as a complication of Kawasaki disease. Case Reports in Pediatrics , 2015, 689864. https://doi.org/10.1155/2015/689864 Hu C, Yu Y (2020) Gastrointestinal hemorrhage before anticoagulant therapy in Kawasaki disease: a case report. BMC Pediatr 20(1):32. https://doi.org/10.1186/s12887-020-1916-6 Singh R et al (2007) Atypical Kawasaki disease and gastrointestinal manifestations. Paediatr Child Health 12(3):235–237. https://doi.org/10.1093/pch/12.3.235 Wang Y, Li T (2022) Advances in understanding Kawasaki disease-related immuno-inflammatory response and vascular endothelial dysfunction. Pediatr Invest 6(4):271–279. https://doi.org/10.1002/ped4.12341 Galeotti C, Kaveri SV, Cimaz R, Koné-Paut I, Bayry J (2016) Predisposing factors, pathogenesis and therapeutic intervention of Kawasaki disease. Drug Discovery Today 21(11):1850–1857. https://doi.org/10.1016/j.drudis.2016.08.004 Malik TF, Gnanapandithan K, Singh K (2023) Peptic ulcer disease. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK534792/ Gamez-Gonzalez LB, Moribe-Quintero I, Cisneros-Castolo M, Varela-Ortiz J, Muñoz-Ramírez M, Garrido-García M, Yamazaki-Nakashimada M (2018) Kawasaki disease shock syndrome: Unique and severe subtype of Kawasaki disease. Pediatr Int 60(9):781–790. https://doi.org/10.1111/ped.13614 McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu M-H, Saji TT, Pahl E (2017) Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation 135(17):e927–e999. https://doi.org/10.1161/CIR.0000000000000484 Kvietys PR (2010) The gastrointestinal circulation. In Gastrointestinal circulation and mucosal pathology I: Ischemia/Reperfusion (Chap. 10). Morgan & Claypool Life Sciences. https://www.ncbi.nlm.nih.gov/books/NBK53095/ Markandran K, Clemente KNM, Tan E, Attal K, Chee QZ, Cheung C, Chen CK (2024) The Future of Kawasaki Disease Diagnosis: Liquid Biopsy May Hold the Key. Int J Mol Sci 25(15):8062. https://doi.org/10.3390/ijms25158062 Additional Declarations The authors declare no competing interests. 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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-6623778","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":454003518,"identity":"aeca7224-d8aa-49f5-b039-dc374a6ea893","order_by":0,"name":"Wu Bin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIie3PMWsCMRTA8TxuTXHNLfUrBAqlg+AH6RIXJyOFLilYeyDERfcTxH4Fu9z8jgfnEup6xcVPUApdXArNdSzoXbeC+Q9veLwfJIyFQv8yzpAZ8dRqb/cojF9EUdKAuI6KUw544yoC9YSB7StZ8ggfbLWpIbLUOd05GrLdHPFt9XjbmnpyMNkJMlSUGrqH5avKF9lGpwQJzNzuKLkuB5K4I5gwJSnOCp14EoGtIReWwFbka1no54ak35uJgcQ4Gel1Hem6d+Uf1rkSvFAoCtQvnuSn/hJPNX1yIy67mwl9iNFYr7aU7w/mOPkd/UxsfO8b/+U4FAqFzqRvCatqZF66oNsAAAAASUVORK5CYII=","orcid":"","institution":"Anhui Provincial Children's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Wu","middleName":"","lastName":"Bin","suffix":""},{"id":454003519,"identity":"432defbb-613a-4b2e-9114-636f8a7b9baa","order_by":1,"name":"HongHua Lin","email":"","orcid":"","institution":"Anhui Provincial Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"HongHua","middleName":"","lastName":"Lin","suffix":""}],"badges":[],"createdAt":"2025-05-08 23:15:49","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6623778/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6623778/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82608549,"identity":"eb4a733a-71f0-4dbe-81d2-be978fb142d0","added_by":"auto","created_at":"2025-05-13 10:24:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":90443,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of Bleeding Onset Time in Four Cases\u003c/p\u003e\n\u003cp\u003eNote: The x-axis represents days post-onset of KD, with bar length indicating the time of bleeding onset. Case 3, an atypical\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6623778/v1/a7f58ff7eef8944313ebb256.png"},{"id":82608552,"identity":"d85bc595-b310-42fa-bc8a-d069ab4a3471","added_by":"auto","created_at":"2025-05-13 10:24:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":85530,"visible":true,"origin":"","legend":"\u003cp\u003eHemoglobin Levels in Four Cases\u003c/p\u003e\n\u003cp\u003eNote: The x-axis represents the lowest hemoglobin level (g/L), with bar length reflecting the severity of anemia. The current case and Case 2 exhibited milder anemia compared to Cases 1 and 3.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6623778/v1/27a0e2a4118ece059bfed2ed.png"},{"id":82609747,"identity":"8faa298a-c00a-4533-afba-e63714df85d9","added_by":"auto","created_at":"2025-05-13 10:31:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":814909,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6623778/v1/5ab82892-110c-4449-ad13-3b6e47ccf413.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eClinical Course and Management of Kawasaki Disease Complicated with Duodenal Bleeding: A Two-Stage Case Review and Literature Analysis\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eKawasaki disease (KD) is a systemic vasculitis that mainly affects small and medium-sized blood vessels in children and is one of the leading causes of acquired heart disease in children. Its typical clinical manifestations include persistent fever, skin and mucosal changes, changes in the extremities, lymphadenopathy, and bilateral conjunctival congestion[1]. Although the etiology of KD has not been fully clarified, its inflammatory response can affect multiple systems, especially the cardiovascular system[2]. With the deepening of the understanding of KD, atypical manifestations and multisystem complications have gradually attracted clinical attention[3]. Among these cases, the prognosis for KD combined with toxic shock syndrome is particularly complex, especially in instances where patients do not respond to intravenous immunoglobulin (IVIG) treatment[4].\u003c/p\u003e\n\u003cp\u003eAdditionally, complications affecting the digestive system—recognized as atypical manifestations of KD—have received increasing attention. These may include symptoms such as abdominal pain, vomiting, diarrhea, gallbladder enlargement, and abnormal liver function[5]. However, reports of KD combined with severe gastrointestinal bleeding, especially duodenal bleeding, are still rare, and clinical diagnosis and treatment are challenging[6]. The duodenal bulb is the most vulnerable part of the digestive tract to ulcer bleeding. It may be directly or indirectly damaged by pathology under the background of strong inflammation of KD, especially in the process of using therapeutic drugs such as aspirin and glucocorticoids, which is more likely to aggravate the destruction of the gastrointestinal mucosal barrier[7].\u003c/p\u003e\n\u003cp\u003eThis article reviews the detailed medical history of a child with Kawasaki disease and duodenal bleeding admitted to our hospital. It analyzes its clinical characteristics, pathological mechanisms, diagnostic ideas, and treatment strategies in combination with three similar cases reported at home and abroad. It aims to provide a reference for clinicians and improve their ability to identify and deal with this rare complication.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cp\u003eThe case in this study is an 11-year-old boy admitted to XXX in December 2024. The collected clinical data included the patient's initial symptoms, physical examination results, laboratory test results (complete blood count, C-reactive protein, erythrocyte sedimentation rate, liver and kidney function tests, and myocardial enzyme levels), imaging examinations (chest CT, echocardiography, and coronary CT angiography), and endoscopic examination results confirming active duodenal bleeding. The patient received IVIG, aspirin, corticosteroid pulse therapy, proton pump inhibitors, and blood transfusion. Follow-up assessments will be performed at 3, 6, and 12 months, including cardiac ultrasound, laboratory index tests, and gastrointestinal symptom assessments. All data were extracted and verified independently by two researchers. This study was approved by the Ethics Committee of XXX (approval number: AF-HEC-007-010), and written informed consent was obtained from the patient's legal guardian. We systematically searched PubMed, Embase, Web of Science, and Google Scholar until April 2025 using the following search terms: \"Kawasaki disease\" AND (\"duodenal bleeding\" OR \"duodenal bleeding\" OR \"gastrointestinal bleeding\") AND (\"case report\" OR \"case series\"). We manually screened relevant references. We ultimately identified three reports in English that met the inclusion criteria. The inclusion and exclusion criteria were as follows:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eInclusion criteria:\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e(1) Kawasaki disease diagnosis by the 2017 American Heart Association (AHA) guidelines, requiring\u0026thinsp;\u0026ge;\u0026thinsp;5 of the six main clinical features or fewer features supported by relevant laboratory and imaging test results;\u003c/p\u003e \u003cp\u003e(2) Presence of IVIG resistance, defined as persistent or recurrent fever (\u0026ge;\u0026thinsp;38\u0026deg;C)\u0026thinsp;\u0026ge;\u0026thinsp;36 hours after the initial IVIG (2 g/kg) administration;\u003c/p\u003e \u003cp\u003e(3) KDSS diagnosis, characterized by hypotension (age-adjusted) or clinical signs of poor perfusion requiring intensive care;\u003c/p\u003e \u003cp\u003e(4) Detection of coronary artery aneurysm, defined as an echocardiographic Z score\u0026thinsp;\u0026gt;\u0026thinsp;+\u0026thinsp;2.5;\u003c/p\u003e \u003cp\u003e(5) Confirmation of duodenal bleeding was based on a sharp drop in hemoglobin, a positive fecal occult blood test, or endoscopic or surgical confirmation of duodenal bleeding.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eExclusion criteria:\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e(1) gastrointestinal bleeding in non-duodenal sites;\u003c/p\u003e \u003cp\u003e(2) incomplete clinical or diagnostic information;\u003c/p\u003e \u003cp\u003e(3) articles not published in peer-reviewed journals or written in languages other than English.\u003c/p\u003e \u003cp\u003eDue to the limited sample size (n\u0026thinsp;=\u0026thinsp;4), descriptive statistics were used. Categorical variables (sex, clinical type of Kawasaki disease, presence of gastrointestinal symptoms, and treatment) were summarized using frequencies and proportions. Continuous variables (including hemoglobin level, white blood cell count, C-reactive protein, erythrocyte sedimentation rate, and liver function indicators) were reported directly and presented in comparison tables. Due to the insufficient sample size and heterogeneity of clinical manifestations, no inferential statistics or hypothesis testing were performed.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eThis study analyzes a rare KD case complicated by duodenal bleeding and systematically reviews three similar cases reported in the literature. The clinical features, laboratory findings, imaging and endoscopic evaluations, treatment strategies, and prognoses were summarized for comparative analysis.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003e3.1. Case from Our Institution\u003c/h2\u003e\n\u003cdiv id=\"Sec4\" class=\"Section3\"\u003e\n\u003ch2\u003e3.1.1. Patient Demographics\u003c/h2\u003e\n\u003cp\u003eAn 11-year-old boy was admitted on December 19, 2024, due to persistent fever and cough for 3 days. The highest recorded temperature was 39.8\u0026deg;C, accompanied by cough, pharyngeal erythema, and rhinorrhea, without evident dyspnea. The patient was alert upon admission, though fever fluctuated despite antipyretic use.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section3\"\u003e\n\u003ch2\u003e3.1.2. Clinical Course\u003c/h2\u003e\n\u003cp\u003eDay 3 (December 21, 2024): The patient developed persistent high fever (\u0026gt;\u0026thinsp;39\u0026deg;C), generalized rash, dry and cracked lips, bilateral conjunctival congestion, and swelling of the distal extremities. These signs met the diagnostic criteria for classic KD.IVIG(2 g/kg) and high-dose aspirin (30\u0026ndash;50 mg/kg/day) were initiated on December 22.\u003c/p\u003e\n\u003cp\u003eDay 4 (December 22, 2024): The fever rebounded after a brief temperature decline. The patient exhibited lethargy, hypotension (85/37 mmHg), and tachycardia (140 bpm), prompting transfer to the Pediatric Intensive Care Unit (PICU). Echocardiography revealed coronary artery dilation (LAD: 5.8 mm, Z-score\u0026thinsp;=\u0026thinsp;8.43), consistent with moderate coronary artery aneurysm (CAA). Laboratory findings showed oliguria, metabolic acidosis, elevated lactate, and liver dysfunction (ALT: 189.7 U/L\u0026uarr;; albumin: 22.3 g/L\u0026darr;), leading to a diagnosis of KDSS and IVIG-resistant KD.\u003c/p\u003e\n\u003cp\u003eDay 19 (January 7, 2025): The patient experienced hematemesis and melena. Hemoglobin dropped from 92 g/L to 84 g/L, with signs of hypovolemic shock (BP: 80/40 mmHg; pallor). Emergency upper endoscopy showed active duodenal bulb ulcer bleeding. Hemostasis was achieved via titanium clip placement and hemostatic powder application. No recurrent bleeding was observed.\u003c/p\u003e\n\u003cp\u003eDischarge (January 16, 2025): The patient recovered well with stable vital signs, no fever or gastrointestinal bleeding, and normal blood pressure (110/70 mmHg). Echocardiography showed no further progression of the aneurysm (Left Anterior Descending artery(LAD): 4.7 mm; Z\u0026thinsp;=\u0026thinsp;4.83). The patient was discharged on low-dose aspirin (3\u0026ndash;5 mg/kg/day), with scheduled follow-up echocardiography and blood tests at 3, 6, and 12 months.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section3\"\u003e\n\u003ch2\u003e3.1.3. Laboratory and Imaging Findings\u003c/h2\u003e\n1) Hematology:\u003cbr /\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eDecember 19, 2024: WBC count 31.15\u0026times;10⁹/L\u0026uarr;, neutrophil count 93.9%\u0026uarr;, hemoglobin 120 g/L\u0026darr;, platelet count 341\u0026times;10⁹/L\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eDecember 21, 2024: WBC count 24.24\u0026times;10⁹/L\u0026uarr;, hemoglobin 116 g/L\u0026darr;, platelet count 370\u0026times;10⁹/L\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eJanuary 3, 2025: WBC count 17.06\u0026times;10⁹/L\u0026uarr;, neutrophil count 11.04\u0026times;10⁹/L\u0026uarr;, hemoglobin 92 g/L\u0026darr;, platelet count 874\u0026times;10⁹/L\u0026uarr;\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n2) Inflammatory markers:\u003cbr /\u003e\n\u003cp\u003eCRP: peak 146.35 mg/L\u0026uarr;\u003c/p\u003e\n\u003cp\u003eESR: 66 mm/h\u0026uarr;\u003c/p\u003e\n\u003cp\u003ePCT: mildly elevated on multiple measurements\u003c/p\u003e\n\u003cp\u003e3) Biochemistry:\u003c/p\u003e\n\u003cp\u003eALT: 189.7 U/L\u0026uarr;, AST: 42.0 U/L\u0026uarr;, TBil: 85.8 \u0026micro;mol/L\u0026uarr;, DBil: 68.3 \u0026micro;mol/L\u0026uarr;, Albumin: 22.3 g/L\u0026darr;\u003c/p\u003e\n\u003cp\u003eElectrolyte abnormalities: Na 130\u0026ndash;134 mmol/L\u0026darr;, K 3.3\u0026ndash;3.9 mmol/L\u0026darr;, Ca 2.01\u0026ndash;2.04 mmol/L\u0026darr;, P 0.76\u0026ndash;1.02 mmol/L\u0026darr;\u003c/p\u003e\n\u003cp\u003e4) Cardiac markers:\u003c/p\u003e\n\u003cp\u003eNT-proBNP: 583.8 pg/mL\u0026uarr;\u003c/p\u003e\n\u003cp\u003eCK-MB and Troponin I: within or mildly above reference ranges\u003c/p\u003e\n\u003cp\u003e5) Imaging and Endoscopy:\u003c/p\u003e\n\u003cp\u003eChest CT (December 20): patchy bilateral pulmonary infiltrates and mild pleural effusion\u003c/p\u003e\n\u003cp\u003eEchocardiography (Jan 3): LAD 4.7 mm (Z\u0026thinsp;=\u0026thinsp;4.83)\u0026uarr;, RCA 4.3 mm (Z\u0026thinsp;=\u0026thinsp;4.39)\u0026uarr;, AV groove 5.8 mm (Z\u0026thinsp;=\u0026thinsp;8.43)\u0026uarr;, small pericardial effusion\u003c/p\u003e\n\u003cp\u003eGastroscopy (January 7): Active duodenal bulb ulcer with bleeding, successfully treated endoscopically\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003e3.2. Literature Cases of Duodenal Complications in KD\u003c/h2\u003e\n\u003cp\u003eA systematic review identified three published cases of KD complicated by duodenal bleeding or perforation.\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\n\u003ch2\u003e3.2.1. Case \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e: Duodenal Perforation [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/h2\u003e\n\u003cp\u003ePatient: 2.5-year-old boy with fever and rash, developed melena on day 8 and abdominal pain on day 11\u003c/p\u003e\n\u003cp\u003eFindings: X-ray showed free air; Hb 6.5 g/dL\u0026darr;; WBC 12\u0026times;10⁹/L\u0026uarr;; ESR 109 mm/h\u0026uarr;\u003c/p\u003e\n\u003cp\u003eTreatment: IVIG, aspirin (later substituted with dipyridamole due to G6PD deficiency), laparotomy with perforation repair\u003c/p\u003e\n\u003cp\u003ePrognosis: Good postoperative recovery; no cardiac complications\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\n\u003ch2\u003e3.2.2. Case \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e: Duodenal Ulcer Bleeding[\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/h2\u003e\n\u003cp\u003ePatient: 4-year-old boy with abdominal pain, fever, vomiting of coffee-ground material, and melena\u003c/p\u003e\n\u003cp\u003eFindings: Hb 108 g/L\u0026darr;; PLT 65\u0026times;10⁹/L\u0026darr;; CRP 31 mg/L\u0026uarr;; ALT 54 U/L\u0026uarr;\u003c/p\u003e\n\u003cp\u003eTreatment: IVIG, omeprazole, clopidogrel (instead of aspirin); endoscopic hemostasis\u003c/p\u003e\n\u003cp\u003ePrognosis: No rebleeding within 1 month; coronary dilation resolved after 8 weeks\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section3\"\u003e\n\u003ch2\u003e3.2.3. Case \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e: Atypical KD with GI Bleeding [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/h2\u003e\n\u003cp\u003ePatient: 4.5-year-old boy with prolonged fever (2 months), GI symptoms (nausea, vomiting, diarrhea, bloody stool), and jaundice\u003c/p\u003e\n\u003cp\u003eFindings: Hb 53 g/L\u0026darr;; PLT 20\u0026times;10⁹/L\u0026darr;; WBC 21.7\u0026times;10⁹/L\u0026uarr;; hyperbilirubinemia\u003c/p\u003e\n\u003cp\u003eTreatment: IVIG, massive blood transfusion (5200 mL), surgical repair of duodenal ulcer\u003c/p\u003e\n\u003cp\u003ePrognosis: Healing of duodenal erosion and improvement in coronary dilation, but chronic gastritis persisted\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003e3.3 Comparative Analysis of Four Kawasaki Disease Cases with Duodenal Hemorrhage\u003c/h2\u003e\n\u003cp\u003eThe clinical characteristics, treatments, and prognosiss of four cases of KD complicated by duodenal hemorrhage are summarized in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eClinical Characteristics of Four KD Cases with Duodenal Hemorrhage\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFeature\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCurrent Case (11 years)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCase \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e (2.5 years)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCase \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e (4 years)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCase \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e (4.5 years)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGender\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKD Type\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTypical KD, IVIG-resistant, KDSS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTypical KD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eComplete KD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAtypical KD\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGastrointestinal Symptoms\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMelena, hematemesis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMelena, vomiting, abdominal pain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTarry stool, vomiting\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBloody stool, vomiting, abdominal pain\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBleeding Onset\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDay 19 of treatment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDay 8 post-onset\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDay 5 post-onset\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 months post-onset\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBlood Count\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHb: 92 g/L\u0026darr;, WBC: 31.15\u0026times;10⁹/L\u0026uarr;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHb: 65 g/L\u0026darr;, WBC: 12\u0026times;10⁹/L\u0026uarr;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHb: 108 g/L\u0026darr;, WBC: 11.5\u0026times;10⁹/L\u0026uarr;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHb: 53 g/L\u0026darr;, WBC: 21.7\u0026times;10⁹/L\u0026uarr;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInflammatory Markers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCRP: 146.35 mg/L\u0026uarr;, ESR: 66 mm/h\u0026uarr;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCRP\u0026uarr;, ESR: 109 mm/h\u0026uarr;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCRP: 31 mg/L\u0026uarr;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBiochemistry\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT: 189.7 U/L\u0026uarr;, Albumin: 22.3 g/L\u0026darr;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT: 51 U/L\u0026uarr;, AST: 79 U/L\u0026uarr;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT: 54 U/L\u0026uarr;, Albumin: 21.3 g/L\u0026darr;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal bilirubin: 67 \u0026micro;mol/L\u0026uarr;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eImaging Findings\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCoronary artery dilation, pleural effusion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFree abdominal gas\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMild coronary artery dilation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHepatomegaly, splenomegaly\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEndoscopy/Surgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDuodenal ulcer, endoscopic hemostasis (titanium clips, hemostatic powder)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDuodenal perforation, surgical repair\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDuodenal ulcer, endoscopic hemostasis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDuodenal ulcer, surgical repair\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTreatment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIVIG (2 g/kg \u0026times; 2), methylprednisolone (30 mg/kg/day \u0026times; 3 days), aspirin, clopidogrel, PPI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIVIG, aspirin, surgery, PPI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIVIG, clopidogrel, endoscopic hemostasis, PPI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIVIG, transfusion, surgery, PPI\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePrognosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo recurrence, stable coronary aneurysm (LAD: 4.7 mm, Z\u0026thinsp;=\u0026thinsp;4.83)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo cardiac complications\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCoronary arteries normalized\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChronic gastritis, improved coronary arteries\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e\u003cstrong\u003eNote\u003c/strong\u003e: KD\u0026thinsp;=\u0026thinsp;Kawasaki disease; KDSS\u0026thinsp;=\u0026thinsp;Kawasaki disease shock syndrome; IVIG\u0026thinsp;=\u0026thinsp;intravenous immunoglobulin; Hb\u0026thinsp;=\u0026thinsp;hemoglobin; WBC\u0026thinsp;=\u0026thinsp;white blood cell count; CRP\u0026thinsp;=\u0026thinsp;C-reactive protein; ESR\u0026thinsp;=\u0026thinsp;erythrocyte sedimentation rate; ALT\u0026thinsp;=\u0026thinsp;alanine aminotransferase; AST\u0026thinsp;=\u0026thinsp;aspartate aminotransferase; PPI\u0026thinsp;=\u0026thinsp;proton pump inhibitor; LAD\u0026thinsp;=\u0026thinsp;left anterior descending artery; \u0026darr; = decreased; \u0026uarr; = increased.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\n\u003ch2\u003e3.3.1 Comparative Analysis of Bleeding Onset and Anemia Severity in Four KD Cases\u003c/h2\u003e\n\u003cp\u003eThis comparative analysis highlights the variability in KD presentation, bleeding onset, and treatment approaches. The current case and Case \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e showed milder anemia and responded to endoscopic hemostasis, while Cases \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e required surgical intervention due to severe complications such as perforation or profound anemia. Prognosis varied, with stabilization or regression of coronary artery lesions in most cases, but case \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e developed chronic gastritis.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section3\"\u003e\n\u003ch2\u003e3.3.2 Treatment Response and Prognosis\u003c/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eCurrent Case\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eFollowing the second dose of IVIG and methylprednisolone pulse therapy, the patient exhibited a gradual decline in inflammatory markers, including white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT), with body temperature returning to normal. After endoscopic hemostasis, hemoglobin levels increased to 98 g/L, and no further gastrointestinal bleeding occurred. Follow-up echocardiography revealed stable coronary artery aneurysm morphology and an ejection fraction (EF) was restored to 60%.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eLiterature Cases\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eCase 1\u0026nbsp;\u003c/strong\u003eexperienced gastrointestinal perforation during KD. After surgical repair, inflammatory markers significantly decreased, and no cardiac complications were reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 2\u0026nbsp;\u003c/strong\u003eresponded rapidly to endoscopic hemostasis, with complete resolution of coronary artery dilation within 8 weeks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 3\u0026nbsp;\u003c/strong\u003eunderwent surgical intervention and blood transfusion, resulting in significant relief of gastrointestinal symptoms and improvement in coronary artery dilation. However, the patient continued to exhibit chronic gastritis.\u003c/p\u003e\n\u003cp\u003eAll four patients had severe gastrointestinal bleeding during the acute or subacute phase of Kawasaki disease, with the bleeding site limited to the duodenum. Each patient had a significant systemic inflammatory response and varying degrees of liver dysfunction. This patient was an older (11 years old) patient with KDSS and was resistant to IVIG, suggesting that his clinical course was more complicated. In terms of hemostatic intervention, endoscopic hemostasis was successfully applied in this case and case \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, while case \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and case \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e required surgical intervention. All patients survived after timely and comprehensive treatment, with short-term clinical relief and a good prognosis. However, because coronary artery lesions may progress, long-term follow-up is required, especially echocardiographic evaluation, to monitor cardiac function and recovery.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eKD is a systemic vasculitis that manifests with complex clinical symptoms and can affect multiple organ systems during the acute phase. Recent research has drawn increasing attention to the gastrointestinal involvement in KD, infrequent but severe complications such as duodenal hemorrhage. Clinical observations suggest that KD complicated by duodenal bleeding is often characterized by rapidly progressing symptoms and severe clinical courses, necessitating prompt recognition and intervention.\u003c/p\u003e \u003cp\u003eThe underlying pathophysiological mechanisms of KD involve a cascade of immune-mediated inflammatory responses predominantly mediated by T-cells and macrophages. These immune cells infiltrate both coronary artery endothelium and the gastrointestinal microvasculature, increasing vascular permeability and contributing to microvascular thrombosis[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The resulting ischemia and tissue necrosis contribute to ulcer formation. Elevated levels of proinflammatory markers such as TNF-α, IL-6, and MMP-9, especially in IVIG-resistant patients, further compromise gastrointestinal barrier integrity, increasing the risk of mucosal injury and bleeding [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The duodenal bulb is particularly vulnerable to such injury due to its rich blood supply and susceptibility to stress-induced ulceration. While high-dose aspirin (ASA) and corticosteroids are commonly used to control inflammation in KD, they are known to compromise mucosal integrity. ASA reduces prostaglandin synthesis, impairing mucosal protection and elevating ulcer risk, while corticosteroids delay healing[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Moreover, in KDSS, tissue hypoperfusion and ischemia-reperfusion injury can further damage the gastrointestinal mucosa [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], as illustrated in the current case where duodenal bulb ulcer and bleeding were evident following KDSS onset.\u003c/p\u003e \u003cp\u003eEffective treatment of KD with gastrointestinal hemorrhage necessitates controlling systemic inflammation, preventing coronary artery lesions, and achieving rapid hemostasis. In our clinical case, two doses of IVIG (2 g/kg) and methylprednisolone pulse therapy (30 mg/kg/day for 3 days) were administered, along with dual antiplatelet therapy (aspirin and clopidogrel). Endoscopic hemostasis using titanium clips and hemostatic powder successfully controlled the bleeding and avoided the need for surgical intervention. This aligns with Hu et al. (2020), who demonstrated the efficacy of early endoscopic hemostasis in similar KD cases, with surgical intervention being required only in cases involving perforation or hemodynamic instability. The optimization of antiplatelet therapy remains a central clinical challenge. Aspirin is routinely used in KD to prevent coronary thrombosis but increases gastrointestinal bleeding risk. In this case, clopidogrel was introduced following duodenal hemorrhage to maintain antiplatelet efficacy while minimizing bleeding risk, resulting in complete resolution of coronary artery dilation. This supports the findings of Hu et al. (2020) and suggests that clopidogrel may serve as a safer alternative in high-risk patients. Adjunctive use of proton pump inhibitors (PPIs), such as omeprazole, was consistent across all cases, in line with McCrindle et al. (2017) recommendations to protect the gastrointestinal mucosa[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFrom a prognostic perspective, timely intervention was associated with survival in all reported cases. However, coronary prognoses varied. Case \u003cspan refid=\"FPar4\" class=\"InternalRef\"\u003e2\u003c/span\u003e had complete resolution of coronary dilatation within eight weeks; Case \u003cspan refid=\"FPar3\" class=\"InternalRef\"\u003e1\u003c/span\u003e had no cardiac complications; and Case \u003cspan refid=\"FPar5\" class=\"InternalRef\"\u003e3\u003c/span\u003e showed partial improvement and developed chronic gastritis. These prognostic results emphasize the importance of early intervention for improved gastrointestinal and cardiovascular prognosis. The observed differences in coronary and gastrointestinal recovery among patients may be due to differences in systemic inflammatory responses and microvascular damage. Elevated levels of proinflammatory cytokines such as TNF-α and IL-6, especially in IVIG-resistant or KDSS cases, compromise mucosal integrity and contribute to coronary artery damage and gastrointestinal involvement[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In addition, ischemia-reperfusion injury, which results in impaired intestinal mucosal microcirculation, may exacerbate mucosal erosions and ulcers, potentially affecting the severity and duration of gastrointestinal and cardiac complications[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. These pathophysiological insights support that the gastrointestinal and cardiovascular prognoses of Kawasaki disease are closely related through standard inflammatory and ischemic mechanisms, reinforcing the clinical need for timely, systemic anti-inflammatory therapy and personalized treatment.\u003c/p\u003e \u003cp\u003eRecent genetic studies have highlighted polymorphisms in genes such as ITPKC and CASP3 that may contribute to abnormal immune responses and gastrointestinal complications in patients with KD[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. These genetic variants are thought to modulate T-cell activation and apoptotic pathways, amplifying systemic inflammation and leading to microvascular damage in coronary arteries and gastrointestinal tissues. Their presence may help explain why some patients with KD experience severe gastrointestinal symptoms, including duodenal ulcers and bleeding, even in the absence of traditional risk factors. These findings highlight the need for future studies investigating the genetic basis of gastrointestinal involvement in KD, particularly in immune regulation and endothelial integrity. A better understanding of gene-environment interactions could enable risk stratification, guide personalized treatment strategies, and ultimately improve short-term management and long-term prognosis for patients with KD with gastrointestinal involvement. Incorporating genetic analysis into clinical practice may provide opportunities for the early identification of high-risk patients and for the prevention of severe complications. Unfortunately, our patient did not undergo genetic testing, and genetic studies are warranted in future work.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis study highlights that duodenal bleeding, although rare, is a serious and potentially life-threatening complication in patients with KD, especially for those with IVIG resistance or KDSS. Our results suggest that systemic vasculitis and immune-mediated endothelial damage, combined with ischemia, aspirin, and corticosteroid use, lead to gastrointestinal mucosal fragility and bleeding. Timely recognition of gastrointestinal symptoms, such as melena and abdominal pain, and prompt endoscopic intervention are essential to prevent adverse outcomes. Importantly, this study highlights the clinical application of personalized antiplatelet therapy (i.e., replacing aspirin with clopidogrel in high-risk patients), a safer and more effective approach to balance antithrombotic efficacy and gastrointestinal safety. The successful application of endoscopic hemostasis techniques such as titanium clip placement and hemostatic powder has demonstrated a minimally invasive and highly effective treatment strategy for gastrointestinal bleeding in Kawasaki disease. In addition, immune-related genes such as ITPKC and CASP3 suggest a potential mechanistic link between genetic susceptibility to Kawasaki disease and gastrointestinal involvement. These findings have opened up new avenues for studying the immunogenetic basis of gastrointestinal complications, with the ultimate goal of developing precision medicine tools for early risk stratification and targeted intervention.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOwens AM, Plewa MC (2023) Kawasaki disease. In StatPearls. StatPearls Publishing. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK537163/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/books/NBK537163/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHouska N, Albertz M, Ing RJ (2025) Update on diagnosis and management of Kawasaki disease: A scientific statement from the American Heart Association. J Cardiothorac Vasc Anesth 39(5):1103\u0026ndash;1105. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1053/j.jvca.2025.02.007\u003c/span\u003e\u003cspan address=\"10.1053/j.jvca.2025.02.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConte C, Sogni F, Rigante D, Esposito S (2023) An Update on Reports of Atypical Presentations of Kawasaki Disease and the Recognition of IVIG Non-Responder Children. Diagnostics (Basel Switzerland) 13(8):1441. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/diagnostics13081441\u003c/span\u003e\u003cspan address=\"10.3390/diagnostics13081441\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePilania RK, Bhattarai D, Singh S (2018) Controversies in diagnosis and management of Kawasaki disease. World J Clin Pediatr 7(1):27\u0026ndash;35. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5409/wjcp.v7.i1.27\u003c/span\u003e\u003cspan address=\"10.5409/wjcp.v7.i1.27\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTao E, Lang D (2024) Unraveling the gut: the pivotal role of intestinal mechanisms in Kawasaki disease pathogenesis. Front Immunol 15:1496293. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fimmu.2024.1496293\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2024.1496293\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu C, Yu Y (2020) Gastrointestinal hemorrhage before anticoagulant therapy in Kawasaki disease: a case report. BMC Pediatr 20(1):32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12887-020-1916-6\u003c/span\u003e\u003cspan address=\"10.1186/s12887-020-1916-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBindu S, Mazumder S, Bandyopadhyay U (2020) Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol 180:114147. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bcp.2020.114147\u003c/span\u003e\u003cspan address=\"10.1016/j.bcp.2020.114147\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMasoumi K et al (2015) Spontaneous duodenal perforation as a complication of Kawasaki disease. \u003cem\u003eCase Reports in Pediatrics\u003c/em\u003e, 2015, 689864. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2015/689864\u003c/span\u003e\u003cspan address=\"10.1155/2015/689864\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu C, Yu Y (2020) Gastrointestinal hemorrhage before anticoagulant therapy in Kawasaki disease: a case report. BMC Pediatr 20(1):32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12887-020-1916-6\u003c/span\u003e\u003cspan address=\"10.1186/s12887-020-1916-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh R et al (2007) Atypical Kawasaki disease and gastrointestinal manifestations. Paediatr Child Health 12(3):235\u0026ndash;237. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/pch/12.3.235\u003c/span\u003e\u003cspan address=\"10.1093/pch/12.3.235\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Li T (2022) Advances in understanding Kawasaki disease-related immuno-inflammatory response and vascular endothelial dysfunction. Pediatr Invest 6(4):271\u0026ndash;279. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/ped4.12341\u003c/span\u003e\u003cspan address=\"10.1002/ped4.12341\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaleotti C, Kaveri SV, Cimaz R, Kon\u0026eacute;-Paut I, Bayry J (2016) Predisposing factors, pathogenesis and therapeutic intervention of Kawasaki disease. Drug Discovery Today 21(11):1850\u0026ndash;1857. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.drudis.2016.08.004\u003c/span\u003e\u003cspan address=\"10.1016/j.drudis.2016.08.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalik TF, Gnanapandithan K, Singh K (2023) Peptic ulcer disease. In StatPearls. StatPearls Publishing. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK534792/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/books/NBK534792/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGamez-Gonzalez LB, Moribe-Quintero I, Cisneros-Castolo M, Varela-Ortiz J, Mu\u0026ntilde;oz-Ram\u0026iacute;rez M, Garrido-Garc\u0026iacute;a M, Yamazaki-Nakashimada M (2018) Kawasaki disease shock syndrome: Unique and severe subtype of Kawasaki disease. Pediatr Int 60(9):781\u0026ndash;790. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/ped.13614\u003c/span\u003e\u003cspan address=\"10.1111/ped.13614\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu M-H, Saji TT, Pahl E (2017) Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation 135(17):e927\u0026ndash;e999. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1161/CIR.0000000000000484\u003c/span\u003e\u003cspan address=\"10.1161/CIR.0000000000000484\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKvietys PR (2010) The gastrointestinal circulation. In Gastrointestinal circulation and mucosal pathology I: Ischemia/Reperfusion (Chap. 10). Morgan \u0026amp; Claypool Life Sciences. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK53095/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/books/NBK53095/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarkandran K, Clemente KNM, Tan E, Attal K, Chee QZ, Cheung C, Chen CK (2024) The Future of Kawasaki Disease Diagnosis: Liquid Biopsy May Hold the Key. Int J Mol Sci 25(15):8062. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ijms25158062\u003c/span\u003e\u003cspan address=\"10.3390/ijms25158062\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Anhui Provincial Children's Hospital","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, Shock, Duodenal Ulcer, Gastrointestinal Hemorrhage, Immunoglobulins, Intravenous","lastPublishedDoi":"10.21203/rs.3.rs-6623778/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6623778/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eTo explore the clinical characteristics, diagnostic process, treatment measures, and prognosis of Kawasaki disease (KD) combined with duodenal bleeding and to improve the understanding of this rare but serious complication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe analyzed retrospectively the comprehensive clinical data of a child diagnosed with KD who was admitted to our hospital with duodenal bleeding. In addition to this case, three similar instances identified through a literature review were included. We summarized and compared the clinical manifestations, laboratory tests, imaging and endoscopic findings, treatment strategies, and prognoses.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAll four children were male, aged 2.5-11 years old, and the types of KD included typical, atypical, and Kawasaki disease shock syndrome(KDSS). All clinical manifestations of KD, such as fever, rash, and conjunctival congestion, followed by gastrointestinal bleeding, such as melena, hematemesis, or hemorrhagic shock. Gastroscopy confirmed that duodenal bulb ulcer or perforation was the source of bleeding. Some children had intravenous immunoglobulin (IVIG) non-response or severe cardiovascular complications (such as coronary artery aneurysm). Treatment is mainly IVIG, antiplatelet or anticoagulant drugs, proton pump inhibitors, endoscopic hemostasis, or surgical repair. Most children have a good prognosis, and heart disease does not progress further.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eDuodenal bleeding is a rare but serious complication of Kawasaki disease that requires vigilance, especially when there is no response to IVIG, KDSS, or severe inflammatory response. Timely gastrointestinal evaluation act,ive hemostasis, and supportive treatment measures can help improve the prognosis.\u003c/p\u003e","manuscriptTitle":"Clinical Course and Management of Kawasaki Disease Complicated with Duodenal Bleeding: A Two-Stage Case Review and Literature Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 10:23:24","doi":"10.21203/rs.3.rs-6623778/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":"bba02cec-275d-47be-a63a-953bd54a0de4","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":48280253,"name":"Pediatrics"}],"tags":[],"updatedAt":"2025-05-13T10:23:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 10:23:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6623778","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6623778","identity":"rs-6623778","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}