Case report
A 31-year-old woman was diagnosed with AOSD in October 2013. The diagnosis was based on the presence of pyrexia, skin rash, sore throat, lymphadenopathy, leukocytosis, hyperferritinemia, and the lack of rheumatoid factor and antinuclear antibodies. The clinical findings met four major criteria (fever, arthralgia, typical rash, leukocytosis) and three minor criteria (sore throat, lymphadenopathy, negative test for antinuclear antibody and rheumatoid factor) for AOSD classification proposed by Yamaguchi et al.1 After the administration of 40 mg of prednisolone (PSL) per day, her symptoms improved and PSL was tapered. Prednisolone was maintained at 5–15 mg/day, depending on the severity of AOSD, but the patient’s symptoms sometimes relapsed because of drug discontinuation. In October 2015, 50 mg/day cyclosporine A (CyA) was started, and the dose was increased to 100 mg/day in February 2017. In July 2017, tocilizumab was started as persistent fever, lymphadenopathy, and hyperferritinemia (3944 ng/mL) persisted.
In October 2017, the patient was admitted to our hospital with liver dysfunction, which was the only finding, without any symptoms. Worsening of AOSD was not suspected as the C-reactive protein (CRP) concentration was almost normal and there was only mild hyperferritinemia (Table 1). Liver biopsy revealed the collapse of hepatocytes around the central vein (Figure 1), infiltration of eosinophils, Kupffer cell hyperplasia, and mild fibrosis around the Glisson’s capsule. We suspected liver dysfunction due to AOSD, acute-onset AIH, or drug-induced liver injury (DILI) caused by tocilizumab. We started methylprednisolone (mPSL) 125 mg/day for the first 3 days, followed by oral administration of PSL (50 mg/day) and CyA (100 mg/day). Prednisolone was gradually tapered and continued at 5 mg/day. However, in September 2020, both PSL and CyA were discontinued because of the patient’s strong desire to stop taking them.
Thereafter, she presented to our hospital in January 2021 with a history of fatigue, loss of appetite, and jaundice for 3 days. Physical examination revealed diffuse jaundice, but no lymphadenopathy or rash that suggested the worsening of AOSD. The laboratory findings are shown in Table 1. There were no specific results for other liver diseases, as of October 2017. Imaging revealed hepatosplenomegaly without tumorous or obstructive hepatobiliary diseases (Figure 2). Liver biopsy revealed interface hepatitis, hepatocyte rosette formation, periportal inflammation, plasma cell infiltrates, and emperipolesis; these are indicative of AIH (Figure 3). As her revised international AIH group score was 18, we diagnosed the patient with AIH complicated by AOSD. We started mPSL semi-pulse therapy (500 mg/day) for the first 3 days, followed by a maintenance dose of oral PSL 50 mg/day in combination with ursodeoxycholic acid 600 mg/day. Her symptoms and liver dysfunction improved gradually, but liver function was exacerbated on day 8. We therefore administered 100 mg of CyA, which improved liver function (Figure 4). Subsequently, PSL was tapered by 5–10 mg every 2 weeks. The patient’s liver function is currently normal on a dosage of PSL 3 mg/day and CyA 100 mg/day.