Complications
A diagnostic kidney biopsy is indicated. Follow-up should be performed with chemistries and urinalysis.[38]
Thyroid disorders may be more prevalent in patients with hepatitis C virus-related mixed cryoglobulinaemia. Autoimmune thyroid disease, subclinical hypothyroidism, and thyroid cancer have been observed more frequently in these patients, whereas hyperthyroidism is less common.[69]
Signs and symptoms include bleeding, visual disturbances, diplopia, ataxia, headache, and confusion. Signs of retinal haemorrhage and retinal vein thrombosis may be seen.[21][22][67] Plasma or serum viscosity should be measured.[40] Plasmapheresis may reverse the complications of hyperviscosity acutely but needs to be followed by treatment of the underlying cause.[64]
Hyperviscosity syndrome may rarely complicate cryoglobulinaemia. In type I cryoglobulinaemia, symptoms of hyperviscosity may be due to high levels of cryoglobulins. Waldenstrom's macroglobulinaemia is a B-cell lymphoproliferative disorder characterised by autonomous production of IgM, which is sometimes accompanied by cryoglobulinaemia.[65] Hyperviscosity syndrome occurs in 15% of patients with Waldenstrom's macroglobulinaemia and is thought to be related to the level of IgM. In mixed cryoglobulinaemia, hyperviscosity syndrome is rare. Cryocrit levels are thought to contribute the most to plasma viscosity. Anaemia may be protective.[40][68]
Mixed cryoglobulinaemia may present with small- to medium-vessel vasculitis. Signs and symptoms include the presence of purpura, acute onset sensory neuropathy, mononeuritis multiplex, or glomerulonephritis.[23] Patients in whom vasculitis is suspected will require a detailed workup, with particular attention to multiple organ function.[24]
There is an increased risk of lymphoproliferative disorders in mixed cryoglobulinaemia (MC). Malignancy is commonly extranodal. Hepatitis C virus (HCV) infection may be an independent risk factor for lymphoproliferative malignancies.[35]
Clinical monitoring for malignancy should be carried out in patients with MC with or without HCV. A total body CT-scan, and lymph node/bone marrow biopsies, may be required in some patients.[4]
Lower-extremity vascular testing is recommended to exclude vascular insufficiency.[4]
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