Lambda-AL Amyloidosis Masquerading as Severe Obstructive Painless Jaundice, a case study

Authors: Ashruth C.P Azad, M.D., Vandana Gambhir, M.D., Rickmeet Bains, Anisha Bhangav, Kermun Sihota, Ranvir Singh Rathore, M.D., Kewal K. Mahajan, M.D., Riaz N. Chaudhary, M.D.

Institution: Mercy Saint Vincent Medical Center

Introduction: Primary amyloidosis has a varying spectrum of presentation, depending upon the degree of system involvement. Hepatic involvement is frequently reported, but in contrast, the presence of intrahepatic cholestasis is exceedingly rare. A study of 490 cases of hepatic amyloidosis only 4.7 presented with cholestatic jaundice. We present a case of primary amyloidosis presenting as severe progressive painless jaundice.

Case Descriptions: A 60 year-old female with past medical history of diabetes, end stage renal disease on peritoneal dialysis, presented with a 3 week history of jaundice, pale colored stools, dark urine and nausea. She denied any other symptoms. Patient was found to be deeply jaundiced, had hepatomegaly and spider angiomas. Her labs revealed, total bilirubin of 6.41 mg/dL (0.3-1.2 mg/dL), direct bilirubin of 5.32 mg/dL (0-0.3 mg/dL), alkaline phosphatase (ALP) of 531 U/L (25-100 U/L), aspartate aminotransferase of 85 U/L (8-36 U/L), and alanine aminotransferase of 41 U/L (4-40 U/L), International Normalized Ratio of 3.5 Amylase, lipase, hepatitis panel, pertinent tumor marker and autoimmune antibodies were negative. Given her direct bilirubinemia and increased ALP, an investigation to into the causes of obstructive jaundice was initiated. Abdominal ultrasound, computed tomography, Magnetic resonance Cholangio-Pancreatography, and Endoscopic Ultrasound- Endoscopic Retrograde Cholangio-Pancreatography, revealed numerous stones in the gallbladder, but normal common bile duct and pancreas. A trans-jugular liver biopsy revealed, no cirrhosis but Congo red stain was positive for amyloidosis. Bone marrow biopsy confirmed primary amyloidosis without evidence of multiple myeloma or lymphoma. Immunohistochemical staining showed kappa:lambda plasma cell ratio of 1:3%. Patient was treated with dexamethasone, but her direct bilirubin continued to elevate to 17.16 mg/dL, leading to multi-organ failure and death.

Discussion: Liver is frequently involved by amyloidosis, but jaundice and liver failure are uncommon features. Our patient presented with progressive painless direct hyperbilirubinemia, which initially led us to believe that the jaundice was primarily of the obstructive kind. The presence of jaundice is a poor prognostic indicator, with death usually resulting within 3 months of onset. The pathophysiology is due to the peri-portal deposition of amyloid leading to bile duct distortion and a decrease in functioning hepatocytes. Liver biopsy is the most reliable method of diagnosing amyloidosis. Immunohistochemical staining provides further detail of the type of protein involved. Some patients benefit from systemic chemotherapy; however, multi-organ failure is a contraindication for chemotherapy, this was the case in our patient.

Conclusion: The diagnosis of primary amyloidosis is often missed due to nonspecific findings. Amyloidosis should always be considered in patient with unexplained intrahepatic cholestasis, and liver tissue should be stained with Congo red and viewed under polarized microscopy to make the diagnosis.