Occurs in 10 to 15% of patients with hepatitis C and has a spectrum of disease ranging from mild to life-threatening.
The large majority of patients with mixed cryoglobulinemic vasculitis are HCV positive.
Among patients with HCV related mixed cryoglobulinemia, 25 to 30% of patients remain asymptomatic, 40 to 45% have predominantly mild cutaneous manifestations and 20 to 30% present with significant organ damage, 7 to 12% progress to B cell eoplasms, and 2 to 5% will have rapidly progressive and life-threatening vasculitis.
Patients with with type III cryoglobulinemia usually have milder clinical manifestations than those with type two disease.
with the introduction of direct acting antiviral agents, a sustained virologic response is expected in more than 95% of the patients and has dramatically improved the prognosis of HCV relatedmixed cryoglobulinemia.
In a large perspective, study of patients with HCV related cryoglobulinemia vasculitis only 2.8% died after a median follow up of 15.3 months.
In a study of patients with type I cryoglobulinemia an estimated survival without clinical relapse, treatment complications, or death was 26% at five years.
Treatment approaches have involved different combinations of agents, including cortical, steroids, conventional immuno suppressant, plasma, exchange, all of which yielded inconsistent outcomes, and poor prognosis.
Alpha interferon yields a clinical, biochemical and virologic response in 40 to 60% of cases , however relapse within six months after completion of therapy is usual.
The addition of low to intermediate dose steroids mitigates vasculitic flares and provides symptomatic relief, however long term use of glucocorticoids should be avoided because of questionable effectiveness and long-term side effects.
High, pulsed doses of glucocorticoids may help manage severe vasculitic findings, including renal and neurologic involvement, and may prevent permanent organ damage.
Type I cryoglobulinemia is characterized as a hemostatic disorder, accompanied by multiple thromboses of small and median sized vessels, and sometimes by signs of vascular inflammation.
Types II and III mixed cryoglobulinemias are considered inflammatory small vessel vasculitis caused by complement mediated immune complex deposition.
Time I cryoglobulinemia involves IgG and IgM, whereas mixed cryoglobulinemia anemia comes mainly from HCV related vasculitis.
Skin involvement is present in most cases of mixed cryoglobulinemia and manifests primarily as vascular purpura that is sometimes necrotic.
In type I cryoglobulinemia, skin manifestations depend on ambient temperatures and cutaneous necrosis is much more marked than with mixed cryoglobulinemia.
Joint and muscle involvement is seen with most patients with mixed cryoglobulinemia with bilateral symmetric, non-destructive anrthralgia affecting large joints: frequently misdiagnosed as rheumatoid arthritis.
With type I arthralgias less frequently.
The most common neurologic impairment in mixed cryoglobulinemia is sensory-motor polyneuropathy.
Hyperviscosity symptoms can occur when the mono immunoglobin is present in large amounts and this typical type of type I cryoglobulinemia.
Approximately 1/3 of patients with mixed cryoglobulinemia have renal involvement, typically with membranoproliferative glomerulonephritis.