Case 593 -- A 57 year old male with hepatitis C infection, lymphoma and renal disease

Contributed by Nidhi Aggarwal, MD and Bruce Rabin, MD, PhD


The patient is a 57 year old male who presented with chronic abdominal pain, ascites and swelling of both lower limbs. He was also being evaluated for liver transplant for cirrhosis associated with Hepatitis C infection since 1998. At that time he did not seek any treatment and remained relatively asymptomatic until 2002 when he developed swelling of the lower extremities bilaterally along with pruritus. He was then treated with interferon and responded. Investigations at that time revealed:

He underwent a bone marrow biopsy for evaluation of persistent anemia and thrombocytopenia which revealed a malignant B cell lymphoma which was treated with Rituxan, Fludarabine and Cytoxan. A liver biopsy in 2002 was consistent with chronic active hepatitis (Modified hepatitis activity index: 8/18, fibrosis on trichrome stain: 1/6). He had renal insufficiency with sub- nephrotic range proteinuria of 1.8 grams/24 hours, microscopic hematuria and hypoglobulinemia. Images from the kidney biopsy are shown below.

The biopsy revealed membranoproliferative glomerulonephritis with prominent circulating hyaline thrombi. There was global glomerulosclerosis involving about 25% of the glomeruli and moderate arteriosclerosis without significant tubular interstitial chronicity changes. Electron microscopy showed few subendothelium electron dense deposits with tubulofibularly substructure.

The virus has been undetectable on follow up quantitative hepatitis C PCR since 2003. Bone marrow aspiration and biopsy done in 2004 revealed no residual evidence of lymphoma. Alpha fetoprotein was 5ng/ml (normal <20ng/ml). In 2006 he presented again with complains of a rapidly worsening itchy rash which started on his extremity, spreading all over his body, and some swelling in the feet. In between 2006 and now the patient has been presenting to the hospital with variable complaints including abdominal pain, fall and rib fractures.

Past Medical History: Recreational drug use, Hypertension, Diverticulitis, Anemia, Bipolar disorder, low grade non- Hodgkin lymphoma, Portal hypertension, Esophageal varices, Splenic varices, GERD, status post exploratory laparotomy for gun shot wound over 20 years ago, encephalopathy.

Social History: He has two children and is divorced. He is currently unemployed. He smokes 15 cigarettes per day and drinks alcohol several times per month.

Family history: Mother had diabetes and father had Alzheimer's. He has two brothers and two sisters who are all healthy.

Physical examination was significant for a palpable liver two fingerbreadths below the costal margin and splenomegaly, palpable three to four fingerbreadths below the costal margin.

On Investigations:

AST, ALT, Bilirubin and Alkaline phosphatase were within normal limits. Urine examination showed 3+ proteinurea and 3+ hematurea. CT scan of the abdomen and pelvis showed cirrhosis, splenomegaly and portal hypertension.

Anti- SSA, Anti- SSB, ANCA (Anti- MPO, anti- proteinase 3) antibodies done at an earlier time were negative.

Serum electrophoresis showed a monoclonal band of IgM kappa. A serum sample was sent for cryoglobulin determination. A gelatinous precipitate was present after 3 days at 4C.The cryoglobulin was solubilized at 37C and immunoglobulin quantitation was:

IgG: 124.8 mg/dl
IgM: 410.66 mg/dl

The cryoglobulin was further characterized by immunofixation and the assessment showed the following results on repeated occasions including presently on 12/08.


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