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BMJ Case Rep. 2010; 2010: bcr06.2009.1974.
Published online 2010 May 19. doi:  10.1136/bcr.06.2009.1974
PMCID: PMC3047012
Rare disease

Primary amyloidosis presenting as cholestatic jaundice

Abstract

This case report describes a rare but fatal presentation of amyloidosis. Multiple organs and systems can be affected by the condition. Cholestatic jaundice is a infrequent manifestation of amyloidosis. An 80-year-old patient died within a month after onset of jaundice as a result of irreversible damage caused by deposition of amyloid. The relatively short period of time did not allow a tissue sample to be obtained from the patient and the final diagnosis was made postmortem.

Background

Amyloidosis is a group of sporadic, familial and inherited, degenerative and infectious disease processes, linked by the common theme of abnormal protein folding and extracellular deposition of a protein in an abnormal fibrillar form.1 Amyloid deposits enlarge and displace normal tissue structures causing further disruption of tissue function.

Obstructive jaundice is the condition with yellowish staining of the skin and mucous membranes that is due to impaired bile flow in the biliary tract, such as intra- or extra-hepatic cholestasis.

The liver is a common site of amyloid deposition, both in primary and secondary amyloidosis. Hepatocellular failure and portal hypertension are rare, with cholestasis and jaundice found in only approximately 5% of cases of amyloidosis.2 In total there have been 25 cases of cholestatic jaundice caused by primary amyloidosis published in the English literature.3 Amyloid deposits are confirmed with positive staining with Congo red and light chain deposits show apple-green birefringence under polarised light.4

Case presentation

An 80-year-old woman presented to our department with a 3 week history of worsening jaundice accompanied by pruritus, lower abdominal pain, vomiting, darkening in urine colour and pale stools, with no change in bowel habit. Two months before admission, the patient was investigated for right upper quadrant pain associated with vomiting. A computed tomography (CT) scan (figs 1 and and2)2) at this time showed a mesenteric mass and lymphadenopathy at the porta hepatis; biopsy revealed a mesenteric haematoma. A repeat CT scan a month later (fig 3) failed to show any improvement of the haematoma. However, enlarged (3 cm) lymph nodes at porta hepatis, a dilated common bile duct (23 mm), a 3 cm mass adjacent to sigmoid colon, and gallstones were all visualised.

Figure 1
Axial computed tomography (CT) image following the administration of intravenous contrast medium demonstrating a soft tissue mass at the porta hepatis (long arrow), compressing and possibly invading the portal vein (short arrow).
Figure 2
Axial CT image following the administration of intravenous contrast medium demonstrating a soft tissue mass within the sigmoid mesentery (arrow).
Figure 3
Axial CT image following the administration of intravenous contrast medium demonstrating biliary dilatation.

Raised inflammatory markers and positive examination findings pointed to a diagnosis of common bile duct obstruction. A percutaneous transhepatic cholangiogram was performed and a stent was successfully placed through a distal common bile duct obstruction (fig 4). The patient deteriorated following the procedure and was presumed to have cholangitis and septic shock secondary to biliary stent insertion.

Figure 4
Final position of metal biliary stent inserted percutaneously with contrast medium flowing into the duodenum.

Investigations

A postmortem examination revealed the underlying cause of death to be amyloidosis which could have been a prime, or a contributing, factor to the development of jaundice, liver failure, soft tissue haemorrhage and pancreatitis. Macroscopic examination of the pancreas demonstrated areas of pronounced fibrosis in the pancreas indicative of chronic pancreatitis, and no evidence of tumour. Both the pancreas and the surrounding fat contained widespread deposits of amorphous proteinaceous material typical of amyloidosis. The amyloid deposits were confirmed by Congo red positivity and immunoreactivity for amyloid P protein. Amyloid A was not strongly positive and potassium permanganate treatment showed preservation of birefringence consistent with amyloidosis of light chain derivation. Amyloid deposits were found in the pancreas, soft tissue (peri-pancreatic, porta hepatis, retroperitoneal), spleen, liver and lung.

Outcome and follow-up

On the 15th day after admission, the patient died as a result of multiorgan failure.

Discussion

In this case report we present a patient with cholestatic jaundice, abdominal pain and vomiting, which was caused by an acute exacerbation of chronic pancreatitis and an organising thrombus in the porta hepatis. The underlying cause of these events revealed at postmortem examination was light chain amyloidosis, which may have been caused by a B lymphocyte dyscrasia (including multiple myeloma). The most common form of amyloidosis is the primary form, where the deposits consist of AL type protein (comprised of immunoglobulin light chains, mainly λ). In up to 15% of cases, this type of deposit coexists with multiple myeloma. The second most common form is called reactive or secondary amyloidosis. In this condition, the AA type deposits are derived from serum amyloid protein synthesised in the liver. This form is related to infectious and non-infectious chronic inflammatory conditions (ie, connective tissue disorders, Crohn’s disease, tuberculosis).5,6

The liver is a common site of amyloid deposition in both primary (AL) and secondary (AA) amyloidosis.7 According to multiple studies it can be affected in up to 92% of cases, but clinical manifestations of liver amyloidosis are less frequent and often mild.6 The symptoms of hepatic involvement may include right upper quadrant fullness and discomfort due to hepatomegaly, feeling of early satiety, chronic nausea, dyspepsia, and weight loss. Other common organs and systems affected by amyloid deposition are kidneys, heart and the peripheral nervous system. Therefore, patients may present with renal insufficiency or nephritic syndrome, congestive heart failure, or autonomic or peripheral neuropathy. Carpal tunnel syndrome can be observed in some cases. The gastrointestinal tract can also be affected by the deposition of the β pleated sheet protein causing gastroparesis, haematemesis and pseudo-obstruction—to name just a few of many possible presentations.1,6

Biochemical markers of liver involvement are present in approximately every fourth case of amyloidosis. The incidence of elevated alkaline phosphatase (ALP) values ranges from 16–86% of cases of amyloidosis.1,3,6,7 Elevated serum bilirubin values occurred in 4–8% of reported cases.5 Decreased values of albumin are also reported, the aetiology of which can be nephritic syndrome or reduced synthesis by the affected liver.3 The deposition of protein in the liver can indirectly affect the hepatocytes and cause atrophy, degeneration and necrosis with subsequent regenerative changes.5,8 Mentioned histopathologic changes can contribute to the biochemical changes in liver enzymes serum activity. Large quantities of amyloid in the space of Disse interfere with bile and blood flow giving the appearance of cholestatic jaundice and rarely occurring portal hypertension.1 The deposits of amyloid have also been reported in large intrahepatic and extrahepatic ducts, causing their dilatation and manifesting as obstructive jaundice,6 which occurred in our case.

Diagnosis of amyloidosis requires a tissue biopsy. In the case of hepatomegaly, the material can be acquired via percutaneous liver biopsy. This procedure carries a risk of liver rupture and life threatening haemorrhage in up to 5% of cases.6 Other possible sites for obtaining histological material are the rectum, subcutaneous fat and bone marrow.3 The dye Congo red gives the deposits a pink or red appearance, which under polarised light has a green birefringence.5 Serum and urine electrophoresis, immunofixation electrophoresis, CT and ultrasound scans are also used in the diagnostic process, but none of them are sufficient for definite diagnosis of amyloidosis.

The only biochemical marker related to prognosis is the elevated serum bilirubin concentration, in which case the survival time varies from 0.5 to 15 months. The median survival time in primary amyloidosis is below 2 years. Heart failure, multiple myeloma and hepatomegaly associated with light chain proteinuria significantly affect survival time.3 To date, no curative therapy for amyloidosis has been developed. Some improvement in symptoms and prolonged survival can be achieved with chemotherapy.6

This case is particularly interesting due to the patient’s presentation with obstructive jaundice and right upper quadrant pain. Also, subsequent CT scans failed to demonstrate the peritoneal amyloid deposits found at postmortem examination. Interestingly the cause of this woman’s obstructive jaundice was due to either extrinsic compression of the common bile duct by an organising mesenteric thrombus at the porta hepatis or amyloid deposits within the pancreas. This mesenteric thrombus was likely to have been reactive in origin secondary to a hypercoaguable state induced by systemic amyloidosis.

Learning points

  • Amyloidosis is not a single entity but a group of conditions, which have in common the deposition of protein in various organs of the body.
  • The presentation of amyloidosis with jaundice is very rare but also has a very poor prognostic value.

Footnotes

Competing interests: None.

Patient consent: Patient/guardian consent was obtained for publication.

REFERENCES

1. Culafic D, Perisic M, Ivan Boricic I, et al. Primary amyloidosis presenting with cholestasis and hyperkinetic portal hypertension. J Gastrointestinal Liver Dis 2007; 16: 201–4. [PubMed]
2. Rubinow A, Koff RS, Cohen AS. Severe intrahepatic cholestasis in primary amyloidosis. A report of four cases and a review of the literature. Am J Med 1978; 64: 937–46. [PubMed]
3. Peters RA, Koukoulis G, Gimson A. Primary amyloidosis and severe intrahepatic cholestatic jaundice. Gut 1994; 35: 1322–5. [PMC free article] [PubMed]
4. Jaudol M, Dodé C, Cosyns JP. Autosomal-dominant periodic fever with AA amyloidosis: Novel mutation in tumor necrosis factor receptor 1 gene. Kidney Int 2001; 59: 1677–82. [PubMed]
5. Kumar V, Abbas AK, Fausto N. Robbins and Cotran pathologic basis of disease, 7th edn Elsevier Saunders, 2005: 258–64.
6. Liu CJ, Chien RN, Huang SF, et al. Severe intrahepatic cholestasis in an elderly patient with primary amyloidosis and colon adenocarcinoma. Chang Gung Med J 2004; 27: 74–9. [PubMed]
7. Park MA, Mueller PS, Kyle RA, et al. Primary (AL) hepatic amyloidosis: clinical features and natural history in 98 patients. Medicine 2003; 82: 291–8. [PubMed]
8. Chopra S, Rubinow A, Koff RS, et al. Hepatic amyloidosis. A histopathologic analysis of primary (AL) and secondary (AA) forms. Am J Pathol 1984; 115: 186–93. [PubMed]

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