Case Presentation: A 56-year-old healthy man who presents with three days of fatigue and bilateral thigh pain. He was born in Puerto Rico but lives in Boston and had no recent travel. He denies alcohol or drug use. He works as a cook at an urban restaurant. Admission vitals and physical exam are unremarkable. Initial laboratory data demonstrates creatinine of 1.73 mg/dL, CK of 3494 U/L and platelets of 68000/μL. The liver function tests are normal. Over the next three days, creatinine, total bilirubin and direct bilirubin rapidly increase to 3.76 mg/dL, 11.4 mg/dL and 9.9 mg/dL, respectively. Other liver function tests remain normal. Blood cultures, HIV, CMV, EBV, influenza, viral hepatitis, TB, tick-borne diseases and hematologic workup is unremarkable. A renal biopsy shows acute tubular necrosis, interstitial hemorrhage and capillaritis, without evidence of glomerulonephritis, thrombotic microangiopathy and vasculitis. Over the next four days, the creatinine stabilizes, but the total bilirubin rises to 41 mg/dL; AST, ALT and ALP increase only slightly. Abdominal ultrasound and MCRP show no structural abnormalities. Leptospirosis is considered given the disproportionate rise of bilirubin, and doxycycline is empirically started. Three days later, Leptospora IgM returns positive, and doxycycline is continued for total of ten days. Over the next five days, the total bilirubin levels plateau at 35 mg/dL, but the patient develops worsening creatinine to 7 mg/dL and is diagnosed with bile cast nephropathy. Chloestyramine and ursidoil are initiated, and the bilirubin and creatinine levels begin to decrease. The patient is discharged after 22 days in the hospital. Three weeks post-discharge, his creatinine is improved to 1.4 mg/dL, and his liver function tests are normal. It is later discovered that the restaurant where the patient works was infested with rodents, the most likely source of his infection.
Discussion: Caused by the spirochete bacteria Leptospira, leptospirosis is one of the most prevalent zoonotic diseases globally, but is rare and often under recognized in developed countries. Sporadic cases of leptospirosis are seen in urban areas where the disease is spread through the urine of rodents and domestic animals. While some will only experience self-limited symptoms such as mild fever, myalgia and fatigue, others suffer more severe disease states called Weil’s disease, as with this patient. Weil’s disease is characterized by injury to major organs such as liver failure, renal failure and pulmonary hemorrhage. Other clinical manifestations include CNS, cardiac and ocular involvements. Intra-hepatic cholestasis is a unique feature of leptospirosis and presents as disproportionally elevated bilirubin levels. High bilirubins can lead to bile cast nephropathy, a less well documented complication of leptospirosis, causing AKI independently from direct bacterial toxicity. Severe manifestations of leptospirosis are treated with antibiotics such as penicillin or doxycycline. Early treatment for Weil’s disease is crucial as the median mortality rate of leptospirosis is 2.2% and is much higher in those with jaundice (19.1%) or renal failure (12.1%).
Conclusions: The diagnosis of the leptospirosis is challenging as it can present with a broad range of clinical manifestations and is not commonly seen in the U.S. It is important to recognize key features of leptospirosis such as rhabdomyolysis, intra-hepatic cholestasis and multi-organ involvement (Weil’s disease) to arrive at early diagnosis and treatment.