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[Conditions](https://durgical.com/en/conditions/) · [Rheumatology](https://durgical.com/en/conditions/)

# Cryoglobulinemic vasculitis

A small-vessel vasculitis caused by proteins that clump in the cold, most often due to hepatitis C, with leg purpura, joint pain and kidney damage.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Skin](https://durgical.com/en/anatomy/skin/)
- [Kidneys](https://durgical.com/en/anatomy/kidney/)
- [Vessels inside the kidney](https://durgical.com/en/anatomy/intrarenal-arteries-and-veins/)
- [Liver](https://durgical.com/en/anatomy/liver/)
- [Spleen](https://durgical.com/en/anatomy/spleen/)
- [Sural nerves](https://durgical.com/en/anatomy/sural-nerve/)
- [Common fibular nerve](https://durgical.com/en/anatomy/common-fibular-nerve/)
- [Digital arteries](https://durgical.com/en/anatomy/palmar-digital-arteries/)

## Why it happens

- [Hemorrhage: petechiae, purpura, ecchymosis, hematoma, and what blood loss does](https://durgical.com/en/general-pathology/hemorrhage-petechiae-purpura-ecchymosis-hematoma-and-what-blood-loss-does/)
- [Immunoglobulins (antibodies)](https://durgical.com/en/biochemistry/enzymes/immunoglobulins/)
- [Blood vessels: artery, vein and capillary layers](https://durgical.com/en/histology/blood-vessels-artery-vein-and-capillary-layers/)

## What it is

A small-vessel vasculitis in which cryoglobulins (immunoglobulins that precipitate below body temperature) form immune complexes that deposit in vessel walls. Mixed cryoglobulinaemia (types II and III) is the form that causes vasculitis and is strongly linked to chronic hepatitis C infection.

## Who gets it

Rare in the general population, but cryoglobulins are found in many people with chronic hepatitis C, and a minority develop vasculitis. Most patients are middle-aged, and women are affected more often. In Colombia and Latin America, hepatitis C and HIV coinfection are the main causes to look for.

## Causes

- Chronic hepatitis C infection (the majority of mixed cryoglobulinaemia)
- Hepatitis B and HIV infection
- Autoimmune disease, especially Sjögren disease and lupus
- B-cell lymphoproliferative disorders (lymphoma, Waldenström macroglobulinaemia, myeloma for type I)
- Idiopathic (essential) cryoglobulinaemia

## Risk factors

- Chronic hepatitis C, especially long-standing infection
- Injection drug use or past unsafe transfusion
- Sjögren disease
- Female sex and age over 50

## Pathophysiology

Chronic antigen stimulation (for example by hepatitis C) drives clonal B-cell expansion that produces IgM rheumatoid factor. This binds polyclonal IgG to form cryoprecipitable immune complexes that deposit in small vessels, activate complement (consuming C4 especially) and cause vasculitis of skin, kidney and nerves. Type I (single monoclonal immunoglobulin) mainly causes hyperviscosity and vessel occlusion rather than vasculitis.

## Classification

- Type I: monoclonal immunoglobulin only, linked to myeloma or Waldenström; hyperviscosity and thrombosis
- Type II: monoclonal IgM rheumatoid factor plus polyclonal IgG; mixed, usually hepatitis C
- Type III: polyclonal IgM and IgG; mixed, hepatitis C or autoimmune disease

## Symptoms and signs

- Meltzer triad: palpable purpura, arthralgia and weakness
- Purpura on the legs that comes in crops and may leave brown pigment or ulcers
- Numbness, tingling or burning in the feet from peripheral neuropathy
- Raynaud phenomenon and skin ulcers or necrosis of fingers or toes
- Oedema, foamy or dark urine and high blood pressure from kidney involvement
- Dry eyes and mouth (sicca symptoms)

## Red flags

- Rapidly rising creatinine or nephrotic-range proteinuria
- Digital gangrene or skin necrosis
- Abdominal pain with signs of intestinal ischaemia
- Haemoptysis or breathlessness (rare alveolar haemorrhage)
- New lymph node enlargement or weight loss suggesting lymphoma

## Diagnosis

**Clinical**
Suspected with recurrent leg purpura, arthralgia and neuropathy, especially in a person with hepatitis C. Diagnosis combines clinical features, detection of serum cryoglobulins and low complement, and biopsy when needed.

**Tests**
Serum cryoglobulins (blood must be kept at 37 °C until it clots, or false negatives occur); very low C4 with normal or mildly low C3; positive rheumatoid factor; hepatitis C antibody and RNA, hepatitis B and HIV tests; serum protein electrophoresis; creatinine and urinalysis. [Skin](https://durgical.com/en/anatomy/skin/) biopsy shows leukocytoclastic vasculitis; [kidney](https://durgical.com/en/anatomy/kidney/) biopsy typically shows membranoproliferative glomerulonephritis.

**Imaging**
Not diagnostic; [liver](https://durgical.com/en/anatomy/liver/) ultrasound for chronic hepatitis and cirrhosis, and imaging to look for lymphoma when suspected.

## Differential diagnosis

- IgA vasculitis (Henoch–Schönlein purpura)
- Hypersensitivity (drug-induced) leukocytoclastic vasculitis
- Lupus and Sjögren disease
- ANCA-associated vasculitis
- Infective endocarditis
- Hyperviscosity from myeloma or Waldenström macroglobulinaemia

## Goal of treatment

Treat the underlying cause (above all hepatitis C), control vasculitis to protect the kidneys, nerves and skin, and avoid cold exposure.

## Treatment

**Medical**
Hepatitis C-related disease: direct-acting antiviral therapy, which clears the virus in most patients and often resolves vasculitis.

**Medical**
Severe or organ-threatening vasculitis: rituximab, with or without short-course corticosteroids; immunosuppression for autoimmune or idiopathic forms.

**Procedure**
Plasma exchange for life-threatening disease (rapidly progressive kidney failure, digital ischaemia, hyperviscosity).

**Follow-up**
Monitoring of kidney function, complement and cryoglobulins, neuropathy and skin ulcers; patient education to keep warm, protect the hands and feet and care for leg ulcers.

## Complications

- Membranoproliferative glomerulonephritis and chronic kidney disease
- Chronic painful neuropathy
- Leg ulcers and digital gangrene
- B-cell non-Hodgkin lymphoma
- Progression of the underlying liver disease to cirrhosis

## Prognosis

Mild skin and joint disease has a good outlook, especially when hepatitis C is cured. Kidney involvement, intestinal vasculitis and lymphoma determine survival; relapses can occur even after viral cure.

## Prevention

- Prevention, screening and treatment of hepatitis C
- Hepatitis B vaccination and safe injection and transfusion practices

## Test yourself

Think of the answer, then tap the question to see it.

## Which infection causes most mixed cryoglobulinaemic vasculitis?

Chronic hepatitis C.

## What is the Meltzer triad?

Palpable purpura, arthralgia and weakness.

## Which complement pattern is typical?

Markedly low C4 with normal or slightly low C3.

## Which glomerular lesion is typical on kidney biopsy?

Membranoproliferative glomerulonephritis.

## Why must the blood sample for cryoglobulins be kept warm?

Because cryoglobulins precipitate in the cold and would be lost with the clot, giving a false negative.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/cryoglobulinemic-vasculitis/)

## Related conditions

- [Viral hepatitis](https://durgical.com/en/conditions/viral-hepatitis/)
- [HIV infection and AIDS](https://durgical.com/en/conditions/hiv-infection-and-aids/)
- [Sjögren disease](https://durgical.com/en/conditions/sjogren-disease/)
- [Systemic lupus erythematosus](https://durgical.com/en/conditions/systemic-lupus-erythematosus/)
- [Non-Hodgkin lymphoma](https://durgical.com/en/conditions/non-hodgkin-lymphoma/)
- [Membranoproliferative glomerulonephritis](https://durgical.com/en/conditions/membranoproliferative-glomerulonephritis/)
- [Peripheral neuropathy (diabetic and other)](https://durgical.com/en/conditions/peripheral-neuropathy/)
- [Raynaud phenomenon](https://durgical.com/en/conditions/raynaud-phenomenon/)
- [IgA vasculitis (Henoch–Schönlein purpura)](https://durgical.com/en/conditions/iga-vasculitis/)
- [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Cryoglobulinemia](https://medlineplus.gov/ency/article/000540.htm) (MedlinePlus (U.S. National Library of Medicine), 2025); [Cryoglobulinemia](https://www.hopkinsvasculitis.org/types-vasculitis/cryoglobulinemia/) (Johns Hopkins Vasculitis Center, 2026).

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Source: https://durgical.com/en/conditions/cryoglobulinemic-vasculitis/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/cryoglobulinemic-vasculitis/