Case Presentation: Introduction: Mixed Cryoglobulinemia (MC) is a rare subtype of the Cryoglobulinemia disorders which are caused by precipitation of immune complexes in the serum at cold temperature. MC involves more than one immunoglobulin component, i.e. IgM, rheumatoid factor (RF) and can be classified further as Type II or III. MC has associations with both Hepatitis C Virus (HCV) and Membranoproliferative Glomerulonephritis (MPGN). Case presentation: A 61 y/o Caucasian male with history of diastolic heart failure, rheumatoid arthritis, untreated HCV infection, and biopsy confirmed MPGN presents with 2 weeks of worsening SOB and orthopnea, productive cough, and bilateral ankle/feet swelling. Patient also complains of fatigue, arthralgias, and hematuria. On exam he was hypoxic, lungs had bilateral crackles and lower extremities showed 2+ edema with extensive petechial rash bilaterally. CXR revealed bilateral infiltrates and CBC showed moderate normocytic anemia. Patient was admitted and treated for pneumonia, and acute on chronic heart failure. He also noticed to have intermittent gross hematuria which was initially attributed to MPGN. Based on the history and clinical presentation including petechial rash there was also a concern for development of mixed cryoglobulinemia, for which patient underwent diagnostic work up. Results included positive Rheumatoid Factor (RF). Complement panel showed normal C3 and low C4. Additionally, high levels of free  light chain, free  light chain, and / free ratio were resulted. IgG immunoglobulin level reported low. Cryoglobulins were detected. Patient was diagnosed with mixed cryoglobulinemia with cryoglobulinemic vasculitis that was most likely induced by HCV. Patient was placed on prednisone. Rituximab was not initiated due to high risk of liver failure. Patient was noncompliant with follow-up to begin direct antiviral treatment for HCV and readmitted for worsening symptoms and died of complications.

Discussion: Discussion:This patient exhibited Meltzer’s Triad, which indicates a diagnosis of MC. Symptoms include purpura, weakness, and arthralgia. An important clinical manifestation of MC is vasculitis; however, of the 45% of HCV infected population that have detectable cryoglobulins, only 15% display vasculitis. It is important to note that in the absence of clinical signs, serum testing for low C4, positive RF, high / free ratio, and low IgG have diagnostic capability, which this patient exhibited. Prognosis of HCV infected patients with cryoglobulinemic vasculitis is poor with an estimated 5-year mortality rate of 25% and is dependent of vasculitic involvement of kidney, CNS, heart, and GI. Recently, lower mortality rates have been reported using antiviral combinations with greater efficacy and better tolerance.

Conclusions: Conclusion:Diagnosing MC can be difficult as it is a rare disorder and often can present asymptomatically. It is important to have high clinical suspicion when symptoms including weakness, arthralgia, and petechial rash presents in HCV infected individuals. Treatment of Hepatitis C is imperative to decreasing patient mortality by preventing HCV induced cryoglobulinemic vasculitis.