What is Cryoglobulinemic Vasculitis?
Cryoglobulinemic vasculitis is caused by abnormal antibodies that clump together at low temperatures and block or inflame small blood vessels. It typically causes a purple rash on the legs, joint pain, fatigue and nerve damage, and it is strongly associated with hepatitis C infection — treating which often treats the vasculitis.
Also called: Cryoglobulinaemia
Who gets Cryoglobulinemic Vasculitis?
Most often adults over 40. The dominant association worldwide is chronic hepatitis C infection, which accounts for the majority of mixed cryoglobulinaemia. Other causes include B-cell lymphoproliferative disorders, Sjögren's syndrome, lupus and other chronic infections.
What are the symptoms of Cryoglobulinemic Vasculitis?
Not everyone has every symptom below, and having one does not confirm the diagnosis. These are the features that most often lead to assessment:
- Purple spots on the lower legs, often triggered or worsened by cold or prolonged standing
- Joint pain, typically without swelling
- Profound fatigue
- Numbness, tingling or burning in the feet and hands
- Skin ulcers, particularly around the ankles
- Raynaud's phenomenon
- Blood or protein in the urine, swelling, or high blood pressure where the kidneys are affected
- Enlarged liver or spleen
How is Cryoglobulinemic Vasculitis diagnosed?
Cryoglobulin testing requires specific handling: the sample must be kept at body temperature from collection to laboratory, otherwise the result is falsely negative. This is the commonest reason the diagnosis is missed.
Low C4 complement with normal or near-normal C3 is a characteristic and useful clue. Rheumatoid factor is often positive.
Hepatitis C testing is essential in every case. Where negative, investigation for a B-cell disorder follows.
Skin biopsy confirms the vasculitis; nerve conduction studies and urine testing assess nerve and kidney involvement.
How is Cryoglobulinemic Vasculitis treated?
Where hepatitis C is the cause, direct-acting antiviral therapy is the treatment, and clearing the virus resolves the vasculitis in most patients — a genuine cure rather than suppression.
Severe disease affecting the kidneys or nerves needs immunosuppression alongside antiviral therapy, usually rituximab, with plasma exchange in life-threatening cases.
Where the cause is a B-cell disorder, treatment is directed at that.
Supportive measures include keeping warm, avoiding prolonged standing, and compression stockings.
Living with Cryoglobulinemic Vasculitis
Outcomes have transformed since direct-acting antivirals for hepatitis C became available, and most virus-associated disease now resolves. Nerve damage recovers slowly and may be incomplete. Follow-up continues after viral clearance because a minority relapse, and because there is a small associated lymphoma risk.
When should you see a rheumatologist?
A purple rash on the legs with fatigue, joint pain and numbness, particularly with a history of hepatitis C or a low C4 level, should be assessed for cryoglobulins — with the sample handled warm.
Common questions about Cryoglobulinemic Vasculitis
Why was my cryoglobulin test negative when the doctor was sure?
Cryoglobulins precipitate as the sample cools, so the blood must be kept warm from the moment it is drawn until it reaches the laboratory. Incorrect handling is the commonest cause of a false negative, and the test is often repeated with proper handling.
Will treating hepatitis C cure the vasculitis?
In most patients, yes. Direct-acting antivirals clear the virus in the great majority of cases, and the vasculitis usually resolves with it. Severe kidney or nerve involvement may need immunosuppression at the same time.
Why does cold make it worse?
The abnormal proteins clump at temperatures below body heat, which is why symptoms concentrate in the legs, hands and feet and worsen in cold weather.
This page is general information to support a consultation. It is not a diagnosis, and it does not replace an assessment by a doctor who has examined you.