Drug-induced liver injury secondary to anakinra in a patient with systemic juvenile idiopathic arthritis-Case report and literature overview

Abstract

Background: Anakinra, an interleukin-1 receptor antagonist, is widely used to manage systemic juvenile idiopathic arthritis (sJIA) and related inflammatory conditions. While generally well tolerated, rare cases of drug-induced liver injury (DILI) have been reported.

Methods: In addition to a literature review, we present a pediatric case of severe DILI attributed to anakinra. The case is of a 14-year-old male with sJIA complicated by macrophage activation syndrome (MAS) who developed DILI following the initiation of anakrina.

Results: Anakrina was started after initial corticosteroid treatment. Following dose escalation, he developed a marked elevation in liver enzymes and cholestasis. Extensive workup, including a liver biopsy, excluded other causes and supported a diagnosis of anakinra-induced DILI. Discontinuation of anakinra led to the gradual normalization of liver function. Subsequent treatment with cyclosporine and tocilizumab was well tolerated.

Conclusions: Differentiating the liver enzyme elevation to MAS versus DILI is challenging but critical, as management strategies differ. Anakinra-induced liver injury appears to be an idiosyncratic, immune-mediated phenomenon that resolves on drug withdrawal. Our case highlights the importance of monitoring liver function during anakinra therapy and the role of liver biopsy in complex cases.

Keywords: anakinra; drug-induced liver injury (DILI); hepatotoxicity; interleukin-1 receptor antagonist; macrophage activation syndrome (MAS); pediatric rheumatology; systemic juvenile idiopathic arthritis (sJIA).

Figure 1:. Laboratory values at disease onset and resolution of transaminitis

Figure 2:. Lobular predominant hepatitis with zone 3 necrosis and parenchymal loss

Histologic findings include patchy chronic lobular inflammation with necrosis and parenchymal loss (*) surrounding a central vein (CV); relatively preserved hepatocytes are seen in the top left (#) (magnification 400×)