Cryoglobulin Levels Are a Marker of Clinical Improvement in Interferon and Ribavirin-Induced Symptomatic Cryoglobulinemia

Abstract

Introduction: Type II/Mixed cryoglobulinemia (MC) is a known manifestation of hepatitis C that presents with nonspecific vasculitis-related symptoms including neuropathy, glomerulonephritis and palpable purpura. Several studies support combined treatment with interferon and ribavirin as the standard treatment for hepatitis C-induced MC and paradoxically, a few case reports describe induced and exacerbated symptomatic MC secondary to ribavarin and interferon therapy. Case: A 58-year-old patient with chronic hepatitis developed symptomatic MC, manifested by acute renal failure secondary to membranoproliferative glomerulonephritis (peaking at glomerular filtration rate of 19 ml/min/1.73m2), purpuric rash (Figure 1), joint aches and extremity pain as well as large bilateral pleural effusions. The symptoms began approximately 4 hours after commencing combined antiviral treatment and resolution of all clinical symptoms including complete recovery of renal function was seen with plasma exchange followed by retuximab treatment. The cryoglobulin level peaked at 0.82 MG/ML (upper limit of normal 0.1) and returned to normal with plasma exchange therapy. Similarly, the complement levels which had nadired at 0.82 MG/ML for C4 (lower limit of normal 9.4 MG/ML) and 35.9 for C3 (lower limit of normal 71.3) were monitored during treatment and increased accordingly. Additionally, resolution of the purpuric rash and decrease of the rheumatoid factor level (peaked at 88.2 IU/mL, upper limit of normal being <20 IU/mL) were seen with plasma exchange therapy. Discussion: Occurrence of symptomatic cryoglobulinemia secondary to interferon and ribavirin therapy is limited to a few case reports. Consequently, little is known regarding treatment and monitoring of therapy in symptomatic MC. We show that cryoglobulin levels peak in interferon and ribavirin-induced cryoglobulinemia crisis and subsequently resolve with plasma exchange treatment.Figure: [1029] Right ankle rash.