Complications

Complication
Timeframe
Likelihood
long term
medium

A diagnostic kidney biopsy is indicated. Follow-up should be performed with chemistries and urinalysis.[38]

Glomerulonephritis

long term
low

Thyroid disorders may be more prevalent in patients with hepatitis C virus-related mixed cryoglobulinemia. Autoimmune thyroid disease, subclinical hypothyroidism, and thyroid cancer have been observed more frequently in these patients, whereas hyperthyroidism is less common.[71]

Thyroid function testing is recommended.[4][71]

Overview of thyroid dysfunction

variable
low

Signs and symptoms include bleeding, visual disturbances, diplopia, ataxia, headache, and confusion. Signs of retinal hemorrhage and retinal vein thrombosis may be seen.[21][22][69] 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.[66]

Hyperviscosity syndrome may rarely complicate cryoglobulinemia. In type I cryoglobulinemia, symptoms of hyperviscosity may be due to high levels of cryoglobulins. Waldenstrom macroglobulinemia is a B-cell lymphoproliferative disorder characterized by autonomous production of IgM, which is sometimes accompanied by cryoglobulinemia.[67] Hyperviscosity syndrome occurs in 15% of patients with Waldenstrom macroglobulinemia and is thought to be related to the level of IgM. In mixed cryoglobulinemia, hyperviscosity syndrome is rare. Cryocrit levels are thought to contribute the most to plasma viscosity. Anemia may be protective.[40][70]

variable
low

Mixed cryoglobulinemia may present with small- to medium-vessel vasculitis. Symptoms and signs 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]

variable
low

There is an increased risk of lymphoproliferative disorders in mixed cryoglobulinemia (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]

variable
low

Central nervous system involvement is rare but is associated with cognitive dysfunction and periventricular white matter changes on magnetic resonance imaging.[34]

An electromyogram and/or nerve conductivity tests are indicated for diagnosis and monitoring of peripheral neuropathy.[4]

variable
low

Lower-extremity vascular testing is recommended to exclude vascular insufficiency.[4]

Use of this content is subject to our disclaimer