Adalimumab Therapy and Granulomatous Hepatitis: A Rare Association

Abstract

Granulomatous hepatitis (GH) has been reported in approximately 5% of all liver biopsies, with the most common etiologies including sarcoidosis, tuberculosis, primary biliary cirrhosis (PBC), and druginduced. These four etiologies comprise 50-75% of all cases of granulomatous hepatitis. GH is characterized by accumulations of modified macrophages (epitheloid cells), which often fuse and form multinucleated giant cells in response to inflammation. This process is thought to occur as a type of delayed hypersensitivity reaction to some form of antigenic insult. Exceedingly rare are the etiologies attributed to rheumatologic/systemic inflammatory conditions not including sarcoidosis (˜9%), miscellaneous infections (5%), and lymphoma (2%). Upon literature review, only one case of GH associated with anti-TNF therapy has been reported, making the following case quite unique. We present a case of a 41-year-old female with past medical history of CREST syndrome who presented to our clinic after a CT chest revealed possible pancreatic mass, multiple liver masses, elevated CA19-9, amylase, lipase, ESR, and CRP. She was currently being treated with Humira. Endoscopy and MRI were ordered, however before they were performed, the patient was admitted to the hospital due to acute abdominal pain, nausea, and vomiting. CT abdomen was obtained with contrast and showed multiple hypodense lesions of the liver, no evidence of pancreatic mass, and mesenteric, retroperitoneal, and bilateral pelvic lymphadenopathy. Of note, liver enzymes and calcium levels were within normal limits. Liver biopsy revealed granulomatous hepatitis with fibrosis, possible focal central necrosis, and hemosiderin deposition. AFB smear, methenamine silver, and Ziehl Neelsen stains were all negative. With no evidence of sarcoidosis, PBC, or tuberculosis in this case, the exact etiology of the granulomatous hepatitis is not clear. Normal liver enzymes also obscure the clinical picture of hepatic involvement in our patient. Pathologic findings can aid in the determination of the cause, but often only narrow the differential. In this case, the possibility of necrotizing granulomas reported by Pathology suggests an infectious process vs lymphoma as the etiology of GH. Since the patient was afebrile and without leukocytosis, the likelihood of infection is minimal, leaving the possibility that her rheumatologic disorder and/or recent treatment with Adalimumab may have been the trigger leading to the GH.Figure 1Figure 2Figure 3