A 56-year-old healthy man presented to the emergency department in the summer season with three days of fatigue and bilateral thigh pain. He was born in Puerto Rico but resided in the Northeast Region of the US, where he worked as a chef in a major metropolitan city. He had no sick contacts, recent travel, or alcohol or drug use.
Laboratory data on presentation demonstrated a creatinine (Cr) of 1.73 mg/dL, creatinine kinase (CK) of 3494 U/L and platelet count of 68x103/muL with initially normal liver function tests (LFTs). The patient was admitted for treatment of acute kidney injury from presumed rhabdomyolysis of unclear cause but subsequently developed low-grade fevers, leukocytosis, and worsening thrombocytopenia over the following days. His Cr worsened despite hydration and conservative management for which the patient underwent a renal biopsy on hospital day 4, with findings of acute tubular necrosis, interstitial hemorrhage, and capillaritis.
In addition to worsening renal function, he had an impressively rapid rise in his total and direct bilirubin with development of clinical jaundice over the subsequent days with laboratory values on hospital day 8 as follows: Cr of 4, total bilirubin of 41 mg/dL, and direct bilirubin of 38 mg/dL (Figure 1(a)). The GI consult service became involved in his care and on physical examination noted no evidence of chronic liver disease other than jaundice. The patient had no abdominal tenderness, hepatosplenomegaly, or asterixis. The bilirubin values were out of proportion to his other liver tests such as INR and albumin, which remained within normal values and AST/ALT and alkaline phosphatase values wavered between mildly elevated (<2 times the upper limit of normal) and normal values. Based on the kidney biopsy results and significant hyperbilirubinemia, testing was done for bacteremia, influenza, tuberculosis, HIV, tick-borne diseases, Hantavirus infection, acute viral hepatitis (A, B, C, E, CMV, EBV, and VZV) and vasculitis, which were all negative or normal.
An abdominal ultrasound and MRI liver protocol/MCRP showed a normal hepatobiliary system. Given his impressive rise in bilirubin out of proportion to other LFTs in combination with renal failure and rhabdomyolysis, the GI service recommended antibody testing for leptospirosis, for which serum IgM antibodies were checked on hospital day 5. The following day, he was started on empiric doxycycline in liaison with infectious disease consultation at 100 mg intravenously twice daily. In the interim, a liver biopsy was done showing liver parenchyma with marked canalicular and intracellular cholestasis, accentuated in perivenular zone, and rare foci of bile duct injury and ductular proliferation. There was no evidence of significant steatosis, fibrosis or intracellular iron deposition with trichrome, reticulin, PAS-D, and iron stains being unrevealing.
On hospital day 10, the Leptospira IgM returned positive, consistent with the diagnosis of icteric leptospirosis. He was continued on doxycycline 100 mg twice daily with subsequent normalization of leukocyte and platelet counts (Figure 1(b)). In view of the positive Leptospira IgM antibody results, the liver tissue obtained from biopsy was reevaluated for spirochete organisms with special staining; however no organisms were found.
The patient completed a 10-day course of doxycycline but unfortunately suffered from bile cast nephropathy from severe hyperbilirubinemia with continued rise in Cr (Figure 1(a)), for which he was treated with cholestyramine and ursodiol. His liver function tests and kidney laboratory results began to improve thereafter, and he was discharged on hospital day 26. At six-week follow-up, his renal function improved (Cr of 1.4 mg/dL) and his LFTs had normalized. It was later discovered that the restaurant where the patient had been working had a rodent infestation, which were the most likely source of his infection.