Case Presentation: A 56 year-old woman with a history of untreated Hepatitis C, anal cancer status post chemotherapy and radiation, current IV heroin use, and MRSA tricuspid valve endocarditis presented with lethargy, jaundice, abdominal pain, oliguria, fevers and lower extremity swelling and rash. On arrival, she initially had fluid-responsive hypotension and fever up to 102. Physical exam revealed jaundice, abdominal tenderness, lower extremity petechiae, and non-pitting edema. Initial lab values showed a creatinine of 7.16, sodium of 124, anion gap of 18, direct bilirubin of 9.9. total bilirubin of 16.7, and moderate transminitis. Urinalysis showed pyuria and significant proteinuria. CBC, Lipase, Ammonia, INR, Lactate, BNP, and troponin were all normal. CT abdomen/pelvis showed diffuse edema of the gallbladder wall, and US of the abdomen showed a stable dilated common bile duct. Renal, ID and GI were consulted. The patient was initially started on broad spectrum antibiotics, but her fevers subsided and both blood and urine cultures grew Klebsiella, antibiotics were narrowed. TTE showed no vegetations and lower extremity doppler was negative for DVT. Muddy brown casts were seen in the urine and her AKI was thought to be secondary to ATN from hypotension. A Hep C viral load was 7000. C3 was mildly low and C4, ANCA, and ANA were not drawn due to error prior to discharge. Cryoglobulins were drawn and pending at time of discharge. The patient’s kidney function and clinical status improved over several days, and she was discharged with close follow-up. Following discharge, her cryoglobulin labwork came back positive and showed monoclonal IgM kappa and IgG-lambda typing. The patient had passed away, prior to the positive findings.
Discussion: Type II mixed cryoglubulinemia is most often associated with HCV infection. Symptoms can be variable but include Metlzer’s triad of purpura, fatigue, and arthralgias, as well as liver failure, renal failure, vasculitis and pulmonary involvement. Renal involvement, usually glumerulonephritis, is seen in about 20% of those who initially present with cryoglobunemia and may be due to HCV mediated immune complexes, though the mechanism is not well elucidated. The onset to renal involvement in Type II cryoglobulinemia is usually measured in years, but in more severe cases it can occur more rapidly, and these patients have worse short term prognosis. Studies have shown that immunosuppressive therapy can be beneficial in treating acute renal dysfunction and other end organ manifestations of HCV cryoglobulinemia. Antiviral therapy for HCV is usually started several months following immunosuppressive treatment in these patients, though studies are ongoing.
Conclusions: Patients with HCV associated mixed cryoglobulinemia and evidence of severe or progressing disease such as glomerulonephritis will often benefit from initial immunosuppression followed by treatment of the underlying HCV.