Systemic JIA with Macrophage Activation Syndrome Complicated by Drug-Induced Liver Injury

Background Systemic juvenile idiopathic arthritis (sJIA) is an autoinflammatory condition that presents diagnostic and therapeutic challenges, especially when complicated by macrophage activation syndrome (MAS) - a life-threatening hyperinflammatory syndrome. Standard therapies for MAS secondary to sJIA include interleukin-1 (IL-1) inhibitors anakinra and canakinumab.[1] Reversible drug induced liver injury from anakinra and canakinumab has been reported, occurring in up to 10% of patients.[2] Specifically, with canakinumab, elevations in hepatic enzymes have been reported in up to 5% but rarely severe.[3] This case highlights the challenges of diagnosis and management for MAS in sJIA with concurrent drug-induced liver injury. Case Report A 16-year-old male, diagnosed with sJIA at age 13, initially presented with quotidian fever, evanescent rash, hepatosplenomegaly and polyarthritis, with no MAS... Initial treatment included prednisone, naproxen and tocilizumab. Due to persistent rash and arthritis, his therapy was changed to anakinra 100mg daily. One year later, he developed pharyngitis and fevers, progressing over 2 weeks into fulminant MAS with unremitting fevers, and supportive labs (Figure 1). His hepatic enzymes remained normal throughout. He stabilized with pulsed methylprednisolone and increasing anakinra to 200mg (3mg/kg). One month later, he developed significant liver injury, with transaminitis and mildly elevated unconjugated bilirubin. Workup revealed no concurrent infection, fever/sJIA flare, or other etiology. His presentation was most consistent with drug-induced liver injury, and anakinra was discontinued. Canakinumab started at 300 mg every 4 weeks. This allowed for prednisone tapering to 10mg over 3 months. However, a progressive transaminitis recurred, spiking 2-3 weeks following each canakinumab administration. During treatment, the patient had no symptoms of sJIA with normal CRP and cell counts. After 3 doses of canakinumab, he developed jaundice, elevated INR and elevated conjugated bilirubin with a peak ALT of 3000 U/L. Liver biopsy demonstrated features of drug-induced liver injury and hemophagocytosis, suggesting a possible mixed presentation with underlying sJIA disease activity and residual MAS. However, he remained afebrile with no signs of sJIA disease activity. Canakinumab was discontinued and 1 month later he started tofacitinib for breakthrough arthritis while on 10mg of prednisone. Two months later, he remains asymptomatic from sJIA and his liver injury has been resolved. His CRP is only mildly elevated on tofacitinib monotherapy. Conclusion This case represents the first detailed description of reversible severe liver injury associated with canakinumab in sJIA complicated with MAS. On tofacitinib, the patient was able to effectively recover from the liver injury and taper off corticosteroid. References [1.] Baldo F. Rheumatology 2025;64:32-44. [2.] Martins FR. Pediatr Rheumatol 2023;21:112. [3.] Ruperto N. Ann Rheum Dis 2018;77:1710-9.