Cryoglobulinemic vasculitis is a small- and medium-sized vasculitis characterized by immune complex deposition in various tissues. Cryoglobulins (CGs) are cold precipitable immunoglobulins that redissolve upon heating. Causes of cryoglobulinemia include infections with hepatitis C virus as the leading cause, autoimmune diseases, and lymphoproliferative disorders. Many mechanisms contribute to its pathogenesis, among which there are roles for microorganisms with their molecular mimicry, the rheumatoid factor, and host gene mutations. Other factors reported include adaptive and innate immunity dysregulation, epigenetics, as well as the physicochemical properties of cryoglobulins like hyperviscosity and self-aggregation in type І CG. Clinical manifestations are attributed to hyperviscosity in the monoclonal type І. The mixed types II, III can have cutaneous, musculoskeletal, neurological, renal, cardio-pulmonary, and other organ manifestations. There is an increased risk of malignancy with non-Hodgkin lymphoma being the classical complication. The differential diagnosis includes a wide array of disease entities that need to be considered. Diagnosis requires many modalities: laboratory, imaging, and microscopic. Treatment should be tailored based on disease severity and the underlying cause. Following the successful introduction of direct-acting anti-HCV drugs, autoimmune and lymphoproliferative disorders substituted HCV as the leading cause of CGs. Relapse of Cryoglobulinemic vasculitis was however reported following successful virus eradication.
