A case of trisomy 18 with Kawasaki disease

A 3-year-old boy with trisomy 18 (T18) who underwent corrective surgery for atrial and ventricular septal defects and patent ductus arteriosus was receiving angiotensin-converting enzyme inhibitors for left ventricular noncompaction. He had a 3-day history of fever and rash prior to admission. At admission, his temperature was 39.3°C, blood pressure was 95/62 mmHg, heart rate was 141 bpm, and oxygen saturation was 95% (O2 1.5 L/min), which decreased the following day. Notable physical features included cracked red lips, bilateral nonexudative conjunctivitis, cervical lymphadenopathy, indurative edema of the hands, polymorphous rashes on the trunk and extremities, and redness at the Bacille Calmette–Guérin vaccine inoculation site (Figure 1). Laboratory analysis revealed an elevated leukocyte count (12,600/μL; 76.4% neutrophils), increased C-reactive protein (CRP; 9.4 mg/dL), high brain natriuretic peptide (139 pg/mL) level, and decreased serum sodium (135 mEq/L). Coagulation factor abnormalities were also noted (fibrinogen: 595 mg/dL, fibrin degradation product: 7.9 μg/mL, and D-dimer: 1.4 μg/mL). Blood bacterial cultures were negative. Differential diagnoses such as sepsis, other vasculitides, and autoinflammatory diseases were excluded. Chest radiography revealed infiltrative shadows. Although Kawasaki disease (KD) was clinically suspected, bacterial pneumonia could not be excluded due to the patient's respiratory condition and history of recurrent aspiration pneumonia. The patient was administered Sulbactam/Ampicillin (SBT/ABPC). In addition to persistent fever, all six principal clinical features of KD were observed, including red cracked lips, bilateral nonexudative conjunctivitis, cervical lymphadenopathy, indurative edema of the hands, and polymorphous rash. Based on these findings, KD was strongly suspected. A pediatric cardiologist performed echocardiography on Day 4 of illness (hospital day 2). Mild left main coronary artery dilation (LMT; Z-score + 2.0) was observed, confirming the diagnosis. The Kobayashi score for intravenous immunoglobulin (IVIG) resistance was 3 (days ≤ 4, platelet count < 300 × 109/L). Therefore, the patient was treated with IVIG (1 g/kg/day for 2 days) and oral aspirin (30 mg/kg/day), with dobutamine (3 μg/kg/min) administered for heart failure. Figure S1 presents the patient's clinical course. On Day five, the patient was afebrile and all major symptoms improved. The rapid defervescence achieved by IVIG treatment inhibited the progression of LMT dilation. The aspirin dose was reduced to 5 mg/kg on Day 10. CRP levels decreased to 0.1 mg/dL on Day 14. Although a spike was detected on Day 19, no major KD symptoms were observed. The patient was diagnosed with aspiration pneumonia based on the infiltrative shadows on radiography. Subsequently, the patient was treated with SUL or AMP and discharged on Day 32 after improvement of pneumonia. Currently, the patient is 5 years and being followed up at the outpatient clinic without any recurrence of KD or coronary artery dilation. KD is an acute febrile illness of unknown etiology that causes vasculitis in medium-sized arteries and primarily affects children <5 years.1 To date, no large-scale studies or case reports on T18 patients with KD have been published. To the best of our knowledge, this is the first reported case of T18 with KD.1, 2 T18 has a poor prognosis, with a 1-year survival rate of 5%–10% and a median survival of 14.5 days.3 The lack of reports on T18 KD is possibly due to the limited number of patients with T18 surviving to the typical age of KD onset and the low birth prevalence of T18. A nationwide survey in Japan reported that Down syndrome (DS) is a rare comorbidity of KD. Although incomplete KD appears to occur more frequently in patients with DS.4 A definitive causal link has not been established; however, this trend may reflect underlying immune abnormalities commonly observed in DS, such as T- and B-cell lymphopenia, impaired antibody responses, and cytokine imbalances, which may contribute to diagnostic challenges and a higher prevalence of difficult-to-diagnose cases, possibly associated with immune deficiency.2, 4, 5 In T18, although less well-studied, similar immune dysfunctions were reported, including impaired T-cell function and dysregulated cytokine production.5 This suggests comparable mechanisms underlying KD's presentation in T18. Immunological abnormalities may contribute to KD's pathogenesis and presentation, underscoring the importance of the careful evaluation of patients with chromosomal disorders. Although our patient responded well to IVIG, immune dysregulation with T18,5 including cytokine imbalances, may influence disease progression and treatment response. Mild coronary artery dilatation was observed at diagnosis, suggesting that earlier echocardiographic evaluation enables timely intervention and improved outcomes. Recent advancements in medical technology and treatment interventions have improved the survival rate of patients with T18,3 potentially increasing KD incidence. This report highlights early KD diagnosis in T18 patients for effective treatment and survival. M.I. collected and analyzed the data, constructed the figure, and drafted the manuscript. K.S. and H.S. reviewed and revised the manuscript. S.K., F.T., S.S., J.I., and K.S. managed the patients. K.S. coordinated and supervised the data collection process, and reviewed and revised the manuscript. All the authors have read and approved the final version of the manuscript. Informed consent was obtained from the parents for publication of the data. We extend our thanks to Editage (www.editage.com) for the English-language editing services. We are grateful to our colleague, Dr. Clyde Fumiaki Ito, for his guidance and valuable advice in drafting the English abstract of this article. The authors declare no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Figure S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.