Kawasaki Disease

Abstract

To the Editors: Previous studies have shown that 4.6% of patients with Kawasaki disease (KD) present with acute surgical abdomen.1 Although the etiology of KD is likely cytokine-associated disease, previous studies have not confirmed the cytokine characteristics in patients with acute surgical abdomen and KD. We describe the relationship between acute surgical abdomen and cytokine profile in a patient with KD. A 5-year-old boy was referred for suspected peritonitis on day 6 of treatment for persistent high fever, frequent diarrhea and abdominal pain. He was pyrexic (39.2°C) and dehydrated with diffuse abdominal tenderness and rigidity. At admission, a complete blood count revealed hemoglobin of 129 g/L, white blood cell count of 20.0 × 109/L with neutrophilia and platelet count of 153 × 109/L. Biochemical laboratory findings included hyponatremia (123 mEq/L), hypoalbuminemia (2.3 g/dL) and high C-reactive protein concentration (12.4 mg/dL). Chest radiographs and a computed tomography scan revealed ascites, ileus of the small bowel and colonic mucosal thickening. The patient received intravenous administration of albumin and intravenous antimicrobial treatment without improvement. Because the patient was suffering from severe abdominal pain, increased white blood cell count (15.9 × 109/L) and C-reactive protein (15.5 mg/dL), exploratory laparotomy was performed on day 8 that revealed marked serous ascites, mesenteric adenopathy and no bowel perforation. Because our surgeon chose a minimally invasive approach, lymph node biopsy was not performed. The appendix was removed, and pathological examination of the resected specimen confirmed a focal peritonitis. Cytology of the ascites showed increased cellularity (0.6 × 109/L, 50% neutrophils and 50% lymphocytes without malignant cells) consistent with exudative ascites and a total protein content of 28 g/L consistent with exudative and transudative ascites. Bacterial cultures of the ascitic fluid, blood and stool were negative. Serologic tests for antinuclear antibodies, antineutrophil cytoplasmic antibodies, C3, C4, Mycoplasma and Yersinia enterocolitica were negative. Polymerase chain reaction did not detect Epstein-Barr virus DNA in the blood, and cytomegalovirus antigen was not increased. On day 9, polymorphous exanthema developed on the patient’s hand which lasted for 1 day. The patient then developed oliguria, leg and palpebral edema and a gallop rhythm. Cardiomegaly with pleural effusion was seen on chest radiographs, and decreased ejection fraction of 51% with moderate mitral regurgitation and mild pericardial effusion was seen on echocardiography. We started anticongestive therapy with furosemide (0.5 mg/kg, 3 times daily), carperitide (0.05–0.2 μg/kg/min) and olprinone (0.3 μg/kg/min), and contractility improved (ejection fraction 56%). Intravenous methylprednisolone pulse therapy was instituted at 30 mg/kg/d on days 9, 10 and 11 to counteract abdominal pain and high grade fever, and these symptoms improved promptly. Echocardiography showed increased echo intensity in the coronary arterial wall and increased pericardial effusion. Intravenous immunoglobulin was begun (day 10, 1 g/kg; day 12, 2 g/kg) because of suspected atypical KD, and all effusions resolved. The patient developed desquamation of the fingers and toes on day 11. One month later, the patient’s mother reported that he had transient conjunctival congestion and reddening of the lips. Therefore, 5 of 6 principal symptoms and signs were satisfied for a diagnosis of KD. The patient had no cardiac deficits after 10 months. Elevated cytokines included serum interleukin (IL)-6 (day 9, 484 pg/mL; day 17, <1.6 pg/mL; normal, <4 pg/mL), IL-8 (day 9, 35.5 pg/mL; day 17, 16 pg/mL; normal, <2 pg/mL) and tumor necrosis factor (TNF)-α (day 9, 8.5 pg/mL; day 17, 2.4 pg/mL; normal, 0.6–2.8 pg/mL). Serum vascular endothelial growth factor also increased (day 9, 413 pg/mL; day 17, 911 pg/mL; normal, <459 pg/mL).2 In our patient with acute surgical abdomen and KD, a significantly increased IL-6 in the acute phase and later increased vascular endothelial growth factor were similar to previously reported elevations of these cytokines in KD resistant to initial intravenous immunoglobulin.3,4 Many reports have indicated that indurative edema develops by exudative mechanisms, caused by vasculitis in KD. Yasukawa et al2 showed that the exudative mechanism in KD was the direct result of increased serum vascular endothelial growth factor associated with cytokines (ie, IL-6) and reflected the severity of vascular hyperpermeability. In general, serum TNF-α is elevated in KD, with the highest values observed in patients who develop coronary artery aneurysm.5 Zulian et al1 reported that half of KD patients with acute surgical abdomen developed coronary artery aneurysm with cardiac involvement, whereas TNF-α with KD was not confirmed. In our patient, KD with cardiac involvement occurred with slightly increased serum TNF-α without coronary artery aneurysm. Kenji Miyamoto, MD Yuzuru Yamazaki, MD Department of Pediatrics, Dokkyo Medical University Kentaro Okamoto, MD Department of Pediatric surgery, Dokkyo Medical University Tatsuo Tsuboi, MD Jun-ichi Hirao, MD Osamu Arisaka, MD Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan