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Myeloma-associated systemic amyloidosis masquerading as NASH-associated cirrhosis and diabetic microvascular complications.

Pal P, Ray S, Patra SK, Das AK, Dey S, George R - Oxf Med Case Reports (2015)

Bottom Line: On evaluation, nephropathy, axonal neuropathy, carpal tunnel syndrome and decompensated cryptogenic liver disease with portal hypertension were found fitting with the diagnosis of diabetic nephropathy and neuropathy and nonalcoholic steato-hepatitis-associated cirrhosis, respectively.This case emphasizes the fact that due to nonspecific initial presentation and multisystem involvement, a high index of suspicion and prompt use of appropriate tests including tissue diagnosis may be required to diagnose amyloid light-chain amyloidosis, which may be a rare presenting feature of myeloma.It should be differentiated from a commoner multisystem disease like diabetes and its complications.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of General Medicine , Calcutta National Medical College and Hospital , Kolkata, West Bengal , India.

ABSTRACT
Authors describe the case of a 60-year-old diabetic man who presented with jaundice, ascites and significant weight loss over a period of 2 months. Physical examination revealed firm hepatomegaly with ascites. On evaluation, nephropathy, axonal neuropathy, carpal tunnel syndrome and decompensated cryptogenic liver disease with portal hypertension were found fitting with the diagnosis of diabetic nephropathy and neuropathy and nonalcoholic steato-hepatitis-associated cirrhosis, respectively. It was only after tissue diagnosis and serum protein electrophoresis that a definitive diagnosis of myeloma-related amyloidosis was made. This case emphasizes the fact that due to nonspecific initial presentation and multisystem involvement, a high index of suspicion and prompt use of appropriate tests including tissue diagnosis may be required to diagnose amyloid light-chain amyloidosis, which may be a rare presenting feature of myeloma. It should be differentiated from a commoner multisystem disease like diabetes and its complications.

No MeSH data available.


Related in: MedlinePlus

(A) Liver biopsy specimen showing amorphous eosinophilic deposit within the hepatic sinusioids (black arrows) [H&E, ×100] and (B) photomicrograph showing eosinophilic acellular material (arrow) positive for amyloid on Congo red stain (×200).
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OMV030F2: (A) Liver biopsy specimen showing amorphous eosinophilic deposit within the hepatic sinusioids (black arrows) [H&E, ×100] and (B) photomicrograph showing eosinophilic acellular material (arrow) positive for amyloid on Congo red stain (×200).

Mentions: A 60-year-old man presented with jaundice, ascites and weight loss over 2 months along with tingling and numbness in all extremities. He had been diagnosed with type 2 diabetes 6 years back and was fairly controlled with oral hypoglycemic agents. There was no history of fever, abdominal pain, alcoholism, hepatotoxic drug intake or any past or family history of jaundice. Physical examination revealed mild pallor, icterus, bipedal edema, firm non-tender hepatomegaly and ascites. There was no orthostatic hypotension and fundoscopy was normal. Complete blood count showed normocytic anemia (hemoglobin 10.2 g%, normal iron studies) and a raised erythrocyte sedimentation rate: 62 mm/first hour. Liver function test revealed a cholestatic pattern of liver involvement: conjugated hyperbilirubinemia (total bilirubin 2.9 mg/dl and direct 2 mg/dl), markedly raised alkaline phosphatase (1223 U/l), hypoalbuminemia (2.2 g/dl) with a globulin level of 3.5 mg/dl, mildly increased INR (1.5) and mildly raised transaminases (aspartate transaminase 54 U/l and alanine transaminase 44 U/l). Renal function tests showed azotemia and thyroid function tests were unremarkable. Serological tests for hepatitis B and C were negative. On ascitic fluid study, total cell count was 280 cells/cmm, most of them were lymphocytes. Serum ascites albumin gradient (SAAG) was 1.64 g/dl, indicating high SAAG ascites. Ultrasound of abdomen showed hepatomegaly with coarse echo-texture, ascites without any biliary obstruction and altered cortico-medullary differentiation in the kidney with normal kidney size. Stool for occult blood test was negative and upper gastrointestinal endoscopy revealed grade 2 esophageal varices. A contrast CT scan abdomen showed ascites and heterogeneously enhancing enlarged liver but no detectable mass lesion. Serum alpha fetoprotein was normal. So, NASH-associated cirrhosis on the background of type 2 diabetes was suspected. Echocardiography was normal. Urine examination revealed nephrotic range proteinuria (3 g/24 h) without any active sediment. Nephrotic range proteinuria in the absence of diabetic retinopathy prompted us to perform renal biopsy, which showed amyloid deposits (Fig. 1). Systemic amyloidosis was diagnosed and percutaneous liver biopsy was done to rule out other potential pathologies of cholestatic liver disease with portal hypertension considering the rarity of ascites and other stigmata of portal hypertension in hepatic amyloidosis and to complete the diagnostic assessment of cholestatic liver involvement. It revealed marked deposition of acellular amorphous eosinophilic deposit within the hepatic sinusoids (Fig. 2A), suggestive of hepatic amyloidosis. It was subsequently confirmed with Congo red staining (Fig. 2B). Serum protein electrophoresis showed hypoalbuminemia with monoclonal spike in gamma-globulin region. Serum immunofixation electrophoresis showed monoclonal IgG kappa light chain para-protein. Flow cytometric immunophenotyping of bone marrow aspirate specimen showed a population CD138 cells (Fig. 3A–C). Serum beta-2 microglobulin was raised: 10 600 µg/l. Bone marrow aspiration and later biopsy were performed which showed 20% plasma cells (Fig. 4A and B). Electro-diagnostic study of all four limbs showed absent sensory nerve action potentials and low amplitude compound motor action potentials with preserved motor conduction velocities suggestive of axonal neuropathy along with prolonged distal median motor latencies suggestive of CTS. The patient was referred to hematology department where he was started on combination induction therapy with thalidomide, dexamethasone and bortezomib. Unfortunately, after 6 weeks of treatment, the patient succumbed due to sepsis and progressive liver failure inspite of all supportive measures.Figure 1:


Myeloma-associated systemic amyloidosis masquerading as NASH-associated cirrhosis and diabetic microvascular complications.

Pal P, Ray S, Patra SK, Das AK, Dey S, George R - Oxf Med Case Reports (2015)

(A) Liver biopsy specimen showing amorphous eosinophilic deposit within the hepatic sinusioids (black arrows) [H&E, ×100] and (B) photomicrograph showing eosinophilic acellular material (arrow) positive for amyloid on Congo red stain (×200).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664849&req=5

OMV030F2: (A) Liver biopsy specimen showing amorphous eosinophilic deposit within the hepatic sinusioids (black arrows) [H&E, ×100] and (B) photomicrograph showing eosinophilic acellular material (arrow) positive for amyloid on Congo red stain (×200).
Mentions: A 60-year-old man presented with jaundice, ascites and weight loss over 2 months along with tingling and numbness in all extremities. He had been diagnosed with type 2 diabetes 6 years back and was fairly controlled with oral hypoglycemic agents. There was no history of fever, abdominal pain, alcoholism, hepatotoxic drug intake or any past or family history of jaundice. Physical examination revealed mild pallor, icterus, bipedal edema, firm non-tender hepatomegaly and ascites. There was no orthostatic hypotension and fundoscopy was normal. Complete blood count showed normocytic anemia (hemoglobin 10.2 g%, normal iron studies) and a raised erythrocyte sedimentation rate: 62 mm/first hour. Liver function test revealed a cholestatic pattern of liver involvement: conjugated hyperbilirubinemia (total bilirubin 2.9 mg/dl and direct 2 mg/dl), markedly raised alkaline phosphatase (1223 U/l), hypoalbuminemia (2.2 g/dl) with a globulin level of 3.5 mg/dl, mildly increased INR (1.5) and mildly raised transaminases (aspartate transaminase 54 U/l and alanine transaminase 44 U/l). Renal function tests showed azotemia and thyroid function tests were unremarkable. Serological tests for hepatitis B and C were negative. On ascitic fluid study, total cell count was 280 cells/cmm, most of them were lymphocytes. Serum ascites albumin gradient (SAAG) was 1.64 g/dl, indicating high SAAG ascites. Ultrasound of abdomen showed hepatomegaly with coarse echo-texture, ascites without any biliary obstruction and altered cortico-medullary differentiation in the kidney with normal kidney size. Stool for occult blood test was negative and upper gastrointestinal endoscopy revealed grade 2 esophageal varices. A contrast CT scan abdomen showed ascites and heterogeneously enhancing enlarged liver but no detectable mass lesion. Serum alpha fetoprotein was normal. So, NASH-associated cirrhosis on the background of type 2 diabetes was suspected. Echocardiography was normal. Urine examination revealed nephrotic range proteinuria (3 g/24 h) without any active sediment. Nephrotic range proteinuria in the absence of diabetic retinopathy prompted us to perform renal biopsy, which showed amyloid deposits (Fig. 1). Systemic amyloidosis was diagnosed and percutaneous liver biopsy was done to rule out other potential pathologies of cholestatic liver disease with portal hypertension considering the rarity of ascites and other stigmata of portal hypertension in hepatic amyloidosis and to complete the diagnostic assessment of cholestatic liver involvement. It revealed marked deposition of acellular amorphous eosinophilic deposit within the hepatic sinusoids (Fig. 2A), suggestive of hepatic amyloidosis. It was subsequently confirmed with Congo red staining (Fig. 2B). Serum protein electrophoresis showed hypoalbuminemia with monoclonal spike in gamma-globulin region. Serum immunofixation electrophoresis showed monoclonal IgG kappa light chain para-protein. Flow cytometric immunophenotyping of bone marrow aspirate specimen showed a population CD138 cells (Fig. 3A–C). Serum beta-2 microglobulin was raised: 10 600 µg/l. Bone marrow aspiration and later biopsy were performed which showed 20% plasma cells (Fig. 4A and B). Electro-diagnostic study of all four limbs showed absent sensory nerve action potentials and low amplitude compound motor action potentials with preserved motor conduction velocities suggestive of axonal neuropathy along with prolonged distal median motor latencies suggestive of CTS. The patient was referred to hematology department where he was started on combination induction therapy with thalidomide, dexamethasone and bortezomib. Unfortunately, after 6 weeks of treatment, the patient succumbed due to sepsis and progressive liver failure inspite of all supportive measures.Figure 1:

Bottom Line: On evaluation, nephropathy, axonal neuropathy, carpal tunnel syndrome and decompensated cryptogenic liver disease with portal hypertension were found fitting with the diagnosis of diabetic nephropathy and neuropathy and nonalcoholic steato-hepatitis-associated cirrhosis, respectively.This case emphasizes the fact that due to nonspecific initial presentation and multisystem involvement, a high index of suspicion and prompt use of appropriate tests including tissue diagnosis may be required to diagnose amyloid light-chain amyloidosis, which may be a rare presenting feature of myeloma.It should be differentiated from a commoner multisystem disease like diabetes and its complications.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of General Medicine , Calcutta National Medical College and Hospital , Kolkata, West Bengal , India.

ABSTRACT
Authors describe the case of a 60-year-old diabetic man who presented with jaundice, ascites and significant weight loss over a period of 2 months. Physical examination revealed firm hepatomegaly with ascites. On evaluation, nephropathy, axonal neuropathy, carpal tunnel syndrome and decompensated cryptogenic liver disease with portal hypertension were found fitting with the diagnosis of diabetic nephropathy and neuropathy and nonalcoholic steato-hepatitis-associated cirrhosis, respectively. It was only after tissue diagnosis and serum protein electrophoresis that a definitive diagnosis of myeloma-related amyloidosis was made. This case emphasizes the fact that due to nonspecific initial presentation and multisystem involvement, a high index of suspicion and prompt use of appropriate tests including tissue diagnosis may be required to diagnose amyloid light-chain amyloidosis, which may be a rare presenting feature of myeloma. It should be differentiated from a commoner multisystem disease like diabetes and its complications.

No MeSH data available.


Related in: MedlinePlus