A 4-year-old boy was admitted to our hospital because of markedly high level of transaminase. The patient had been well until 3 days before admission, when a runny nose and fever were noted. On the day of symptom onset, the patient was evaluated by his primary care pediatrician and was diagnosed as having bronchitis. After which, the patient experienced nausea and vomiting and was taken to the emergency department at another hospital. At the other hospital, the patient did not appear ill but had redness in the pharynx and cervical lymphadenopathy. The blood test results showed high transaminase level, after which he was transferred to our hospital.
On arrival, the patient was ill-appearing and febrile, with a body temperature of 40.4 ºC. His blood pressure was 97/48 mmHg, pulse rate was 148 beats per minute, respiratory rate was 28 breaths per minute, with oxygen saturation of 96% while breathing ambient air. Physical examination revealed bilateral conjunctival congestion, erythema around the navel, reddening and indurative edema of palms, and cervical lymphadenopathy. There was no evidence of reddening of the lips, strawberry tongue, and redness at the site of Bacille Calmette-Guèrin (BCG) inoculation. The blood test results showed markedly high level of transaminase with acute inflammatory response (white blood cell count: 16,400 /µL; erythrocyte sedimentation rate: 50 mm/h; C-reactive protein: 15.7 mg/dL; aspartate aminotransferase (AST): 5,323 U/L; alanine aminotransferase (ALT): 1,554 U/L; total bilirubin: 1.5 mg/dL; gamma-glutamyl transpeptidase: 149 U/L; and total bile acid: 381.1 µmol/L). There was no evidence of viral hepatitis (negative results of hepatitis A virus antibody, hepatitis B surface antigen, hepatitis C virus antibody, and polymerase chain reaction for Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1 and 2, and human herpes virus 6) or autoimmune hepatitis. No bacterial growth was detected in any of the cultures. Some cytokines were measured using cytokine bead assay (BD™ CBA kit); IL-6 level increased to 87.7 pg/mL, IL-10 increased to 32.0 pg/mL, whereas IL-1β and TNFα levels were normal. Although the echocardiogram showed normal cardiac function with no evidence of valve regurgitation, slight dilatation of left main trunk was observed (Fig. 1). Ultrasonographic evaluation of cervical lymph nodes revealed multiple hypoechoic-enlarged nodes, which resembled a cluster of grapes (Fig. 2A). An abdominal ultrasound showed thickening of the gallbladder wall, increased periportal echogenicity throughout the liver parenchyma, and dilatation of the CBD with the maximum diameter of 6.6 mm at the intrapancreatic region (4-year-old standard value: 2.3 mm, upper limit: 3.7 mm)10 (Fig. 2B-2D). No evidence of biliary calculus and pancreatitis was observed.
After admission, intravenous administration of cefotaxime was initiated; however, it was ineffective. The next day of hospitalization (day 4 of fever), reddening of lips was observed and the patient was diagnosed with KD based on the presence of five principal symptoms.5 Intravenous immunoglobulin (IVIG) (2 g/kg) was administered as initial therapy. Oral aspirin (ASA) was not administered owing to high transaminase level. Kobayashi score of 8 suggested that the patient was at high risk of IVIG resistance.11 Viral hepatitis could not be completely ruled out at this point; therefore, steroid administration was avoided. The patient defervesced rapidly with the initiation of treatment, and transaminase level gradually improved. However, the patient’s fever relapsed on day 6; therefore IVIG (2 g/kg) and intravenous prednisolone (PSL) (2 mg/kg/day) were administered as second-line therapy. Flurbiprofen, which is used as an alternative to ASA in Japan when high transaminase levels are observed,12 was also administered because transaminase level remained to be high (AST, 171 IU/L; ALT, 468 IU/L). The patient maintained a defervesced state after second-line therapy. Oral medication was switched from flurbiprofen to ASA (5 mg/kg/day) on day10 (AST, 45 IU/L; ALT, 171 IU/L), and PSL administration was simultaneously changed from intravenous to oral because the patient’s C-reactive protein level normalized. Following which, PSL administration was tapered as 5-day step—from 2 mg/kg/day to 1 mg/kg/day to 0.5 mg/kg/day. Membranous desquamation appeared on the fingertips on day 15.
The maximum diameter of the CBD reduced from 6.6 mm on day 4 to 3.1 mm on day 8. Although re-dilatation was observed, it gradually diminished and normalized (4.3 mm on day 28, 4.0 mm on day 63, 3.3 mm on day 105, and 2.8 mm on day 182). The thickening of the gallbladder wall was persistent on day 8; however, it improved after day 28. All abdominal ultrasound tests were performed in a fasting state (Fig. 2D). No exacerbation of coronary lesions was observed.