title: Troxis necrosis, a novel mechanism for drug-induced hepatitis secondary to immunomodulatory therapy.
abstract: OBJECTIVE
  A case of drug-induced hepatitis mediated by troxis necrosis, a form of autoimmune hepatitis, is described.
  
  
  METHODS
  Clinical data, light and electron microscopy of an ultrasound-guided core needle liver biopsy specimen, were examined to investigate the cause of transaminitis in a 26year old male patient on Cellcept and Plaquenil for the treatment of lupus erythematosus. A systematic PUBMED review of troxis necrosis as the underlying mechanism for drug-induced hepatitis was performed.
  
  
  RESULTS
  Liver function tests (LFTs) were significant for elevated AST (305) and ALT (174); the autoimmune workup was significant for anti-ANA positivity and α-SMA negativity. On light microscopy, the liver biopsy shows focal areas of lymphocytic infiltrates surrounding and forming immunologic synapses with lobular hepatocytes, indicating lobular hepatitis of autoimmune nature. Electron microscopy confirmed the presence of immunologic synapses. Upon cessation of the offending medications, the LFTs returned to baseline with no further intervention. Literature search yielded 7 previously reported cases of drug-induced hepatitis mediated by troxis necrosis.
  
  
  CONCLUSIONS
  Troxis necrosis is a novel mechanism for drug-induced hepatitis, including immunomodulatory medications including a monoclonal anti-TWEAK antibody and Cellcept and Plaquenil, two widely used immunosuppression/anti-rejection medications.
authors: Department of Pathology and Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States.
authors: Christina H
authors: CH
authors: Wei
authors: Department of Pathology and Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States.
authors: Andrew
authors: A
authors: Penunuri
authors: Department of Medicine, Division of Rheumatology, Harbor-UCLA Medical Center, Torrance, CA 90509, United States.
authors: George
authors: G
authors: Karpouzas
authors: Department of Pathology and Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States.
authors: Wayne
authors: W
authors: Fleishman
authors: Department of Medicine, Division of Rheumatology, Harbor-UCLA Medical Center, Torrance, CA 90509, United States.
authors: Anuj
authors: A
authors: Datta
authors: Department of Pathology and Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States.
authors: Samuel W
authors: SW
authors: French
mesh_terms: D000328:Adult; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000009:adverse effects; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects*; D056747:Immunomodulation; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy*; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008297:Male; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D009336:Necrosis
chemical_list: D004791:Enzyme Inhibitors; D006886:Hydroxychloroquine; D009173:Mycophenolic Acid
keywords: Drug induced hepatitis; Immunologic synapse; Troxis necrosis