Cryoglobulinemia
Cryoglobulinemia is the presence of immunoglobulins that precipitate below 37 degrees Celsius, classified as type I (monoclonal, driven by a lymphoproliferative disorder, causing hyperviscosity) or mixed types II/III (immune-complex, driven mainly by hepatitis C virus infection, causing small-vessel vasculitis). Type I is treated by targeting the underlying clonal disorder; mixed disease is treated with direct-acting antiviral therapy for hepatitis C, escalating to glucocorticoids plus rituximab for organ-threatening vasculitis.
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What this article covers
- Overview
Definition: cryoglobulins are immunoglobulins that reversibly precipitate below 37.0 degrees Celsius (98.6 degrees Fahrenheit) and redissolve on rewarming; cryoglobulinemia is their presence in the…
- Epidemiology
Mixed cryoglobulinemia is rare: estimated prevalence is about 1 in 100,000, and mixed disease (types II and III) accounts for 75% to 90% of all cryoglobulinemic vasculitis.
- Risk factors
Chronic hepatitis C virus infection, the leading identifiable cause of mixed cryoglobulinemia (hepatitis c virus hcv infection).
- Pathophysiology
Type I mechanism: a single monoclonal immunoglobulin, usually IgM but sometimes IgG or IgA, is overproduced by a clonal B-cell or plasma cell population; at sufficient concentration it precipitates…
- Clinical features
Type I, occlusive/hyperviscosity pattern: headache, visual disturbance, and other neurologic symptoms from hyperviscosity, plus Raynaud phenomenon, livedo reticularis, digital cyanosis, ulceration…
- Differential diagnosis
IgA vasculitis (Henoch-Schonlein purpura): also causes palpable purpura in dependent areas, but occurs mainly in children after an upper respiratory infection, adds prominent abdominal pain, and is…
- Diagnosis
The diagnosis is established by detecting circulating cryoglobulins in a properly handled serum sample, classifying the cryoglobulin by immunofixation as type I, II, or III, and correlating with a…
- Management
First, identify and treat the driving disorder, since the two types are treated causally.
- Complications
Chronic kidney disease and end-stage kidney disease: more than 50% of patients with immune-complex MPGN progress to end-stage kidney disease within 15 years without treatment of the cause.
- Prognosis
Cause-directed treatment changes the trajectory: direct-acting antiviral regimens cure hepatitis C in more than 90% of patients and improve the vasculitis.
- Prevention
Hepatitis C virus screening in any patient with unexplained purpura, glomerulonephritis, or peripheral neuropathy, given a global prevalence of 2% to 3%, higher than 10% in endemic regions.
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