Case Presentation:
A 57 year‐old female with a history of seizure disorder and of recurrent urinary tract infections on nitrofurantoin suppression regimen presented with three day history of increasing confusion and jaundice. She had no history of alcohol abuse. Although she had not been on any new medications, the dose of nitrofurantoin was increased after a recent urinary tract infection. Her examination was notable for somnolence, scleral icterus, and asterixis. She was afebrile. Heart rate was 76/min, Blood pressure was 123/64mmHg. She had no cutaneous stigmata of chronic liver disease, abdominal distention, or hepatosplenomegaly. Admission labs were significant for an AST = 627, ALT = 574, Alkaline phosphatase = 303, total bilirubin = 10.6, direct bilirubin = 6.3, prothrombin time of 12.6, INR = 1.2. Complete blood count, electrolytes and Creatinine were within normal limits. CT scan of the abdomen/pelvis with contrast revealed mild intra and extrahepatic biliary duct dilation with no evidence of liver nodularity, no portal vein or hepatic vein thrombosis. Viral hepatitis panel was negative and an Epstein Barr Virus panel was diagnostic of a prior infection. Acetaminophen
Alpha‐1‐antitrypsin, ferritin and ceruloplasmin levels were within normal limits. Anti‐nuclear antibody was nonreactive. Actin antibody was positive at 31 units, and anti‐smooth muscle antibody was positive at 1:40. With the principal etiologies of liver failure excluded by laboratory and radiographic studies, the diagnosis of drug‐induced liver injury (DILI) was made. Nitrofurantoin was deemed to be the offending agent and discontinued in view of the recent dose adjustment dnd its strong association with DILI. She was treated with supportive care, lactulose and protein restriction. Her mental status, transaminitis and cholestasis gradually improved but then worsened on hospital day 7. An ultra‐sounded guided liver biopsy revealed marked portal, periportal and lobular lymphoplasmacytic inflammation without significant fibrosis, copper deposition or iron accumulation, consistent with autoimmune hepatitis. Additional data revealed Total IgG level of 1654. The combination of her worsening clinical status after a period of initial improvement, elevated autoimmune antibodies, and pathology suggestive of autoimmune hepatitis, lead to the unifying diagnosis of drug‐induced autoimmune hepatitis and she was started on prednisone 40 mg daily. Her transaminitis improved, asteixis and encephalopathy resolved and she was discharged on hospital day 14.
Discussion:
The patient’s elevated anti‐smooth muscle antibody titer, hypergammaglobulinemia, liver histology consistent with AIH, and absence of viral hepatitis predicts the diagnosis of AIH. The distinction between drug‐induced autoimmune hepatitis (DIAIH) and AIH presents a challenge to clinicians. This distinction is critical as discontinuation of the offending agent is necessary in DIAH. Additionally, unlike AIH, in DIAIH, there is no need for long‐term immunosuppression. The distinction between DIAIH and AIH is based on clinical acumen since there are no distinguishing pathognomonic clinical, laboratory or histological features. The common prinicpal causes of DIAH are nitrofurantoin and minocycline.
Conclusions:
Hospitalists should be aware of the distinction between DIAIH and AIH. The knowledge of DIAIH and its associated features is necessary to ensure a prompt diagnosis and thereby ensure better patient outcomes.