Unveiling Mixed Cryoglobulinemia in Suspected Sepsis Without a Source

Cryoglobulinemia is an uncommon condition characterized by the presence of cryoprecipitable immune complexes in circulation, leading to clinical symptoms like purpura, muscle weakness, and joint pain. Specifically, mixed cryoglobulinemia involves the formation of these complexes due to rheumatoid factors, mainly IgM, occasionally IgG or IgA. Previously, Hepatitis C (HCV) was a common cause of mixed cryoglobulinemia, as the chronic HCV infection triggered immune responses that resulted in cryoglobulin formation. However, the emergence of direct-acting antivirals (DAAs) for HCV treatment has shifted the landscape, with autoimmune and lymphoproliferative disorders becoming more prominent etiological factors for mixed cryoglobulinemia. This case report features a 67-year-old woman with a history of Hepatitis C-related cirrhosis. She presented at the emergency department with signs of septic shock and widespread joint pain, particularly in the knees, shoulders, and neck. Effective sepsis management was achieved using antibiotics, albumin infusion, and midodrine. Nonetheless, significant cervical and bilateral knee pain persisted. Further examination uncovered hypocomplementemia and positive results for rheumatoid factors (IgA, IgM, IgG) and cryoglobulin agglutination, confirming the diagnosis of mixed cryoglobulinemia. This case emphasizes the importance of considering mixed cryoglobulinemia in chronic Hepatitis C patients displaying fatigue and joint pain, even in the absence of the traditional clinical manifestations. Moreover, the case underscores the dual benefits of DAA treatment for Hepatitis C in individuals with mixed cryoglobulinemia by achieving viral eradication and alleviating cryoglobulinemia-related symptoms, thus preventing further organ damage.