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Facts about the skin from DermNet New Zealand Trust. Topic index: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z



Cryoglobulinaemia

What is cryoglobulinaemia?

Cryoglobulinaemia is a rare disorder characterised by the presence of abnormal immunoglobulin proteins in the blood that can precipitate out into tissues at low temperatures and causing inflammation and damage.

Immunoglobulins are the class of proteins that make antibodies in response to foreign substances (antigens) introduced into the body. In the case of cryoglobulinaemia, the abnormal immunoglobulins form complexes (cryoglobulins) and precipitate (leach) out of the blood at cold temperatures. This causes restricted tissue blood flow and systemic inflammation, which leads to many clinical signs and symptoms including skin lesions, arthralgia (joint pain), arthritis, vascular purpura (purple skin marks), livedo (marbling pattern), and bleeding conditions.

Cryoglobulinaemia often occurs in association with other diseases, particularly autoimmune or infectious diseases (this is known as secondary cryoglobulinaemia). When it occurs without an associated disease it is called idiopathic or essential cryoglobulinaemia.

Types of cryoglobulinaemia

Cryoglobulinaemia is classified into 3 major types based on the make-up of the cryoglobulin complex. Each type has been found to be associated with certain diseases.

Cryoglobulin type Immunoglobulin composition Associated diseases
Type I: single monoclonal antibody Mainly IgM
Less often IgG and IgA
Waldenstrom's macroglobulinaemia
Chronic lymphocytic leukaemia
Multiple myeloma
Lymphadenopathy
Hairy cell leukaemia
Type II: mixed antibody with monoclonal rheumatoid factor (usually IgG or IgM) IgM-IgG
IgG-IgG
IgA-IgG
Waldenstrom macroglobulinaemia
Chronic lympocytic leukaemia
Multiple myeloma
Mixed essential cryoglobulinaemia
Type III: mixed antibody with polyclonal rheumatoid factor IgM-IgG
IgG-IgG-IgA
Systemic lupus erythematosus
Sjogren syndrome
Rheumatoid arthritis
Hepatitis A, B or C
Systemic sclerosis
Vasculitis
Glomerulonephritis

Who gets cryoglobulinaemia?

Cryoglobulinaemia is thought to be rare. Essential mixed cryoglobulinaemia occurs in about 1 in 100,000 people. Most cases of cryoglobulinaemia have an underlying cause. The type of cryoglobulinaemia found in patients is roughly 25% with type I, 25% with type II and 50% with type III.

It tends to develop between 40-60 years of age and affect females more than males by 3:1.

What are the clinical features of cryoglobulinaemia?

The clinical features of cryoglobulinaemia differ between the types as shown in the table below.

Features of Type I cryoglobulinaemia Features of Type II and III cryoglobulinaemia
  • Acrocyanosis (blueness of the hands and feet from the cold)
  • Retinal haemorrhage (bleeding)
  • Severe Raynaud phenomenon
  • Arterial thrombosis
  • Gangrene
  • Arthralgia and arthritis in the PIP and MCP joints (fingers, hands and toe joints), knees and ankles
  • Fatigue
  • Myalgias (muscle pains)
  • Renal (kidney) immune-complex disease
  • Cutaneous vasculitis
  • Peripheral neuropathy (numbness hands & feet)

Skin manifestations of cryoglobulinaemia

Skin problems are almost always present in patients with cryoglobulinaemia.

Skin problem Type I (%) Types II and III (%)
Ischaemic necrosis (skin and tissue damage due to lack of blood flow) 40 0-20
Palpable purpura 15 80
Livedoid vasculopathy 1 14 (in type III)
Cold-induced urticaria 15 10 (in type III)
Scarring of tip of nose, pinnae, fingertips and toes
Nailfold capillary abnormalities
Cryoglobulinaemia Cryoglobulinaemia Cryoglobulinaemia
Cryoglobulinaemia Cryoglobulinaemia Cryoglobulinaemia
Raynaud phenomenon
Cryoglobulinaemia

Other manifestations of cryoglobulinaemia

Many organs may be affected by cryoglobulinaemia.
Affected organ Signs and symptoms
Lungs Cough, shortness of breath, fluid in the lungs
Gastrointestinal Stomach pain, bleeding, enlarged liver and/or spleen
Kidneys Hypertension (high blood pressure), glomerulonephritis, nephrotic syndrome
Nervous system Visual disturbances, peripheral neuropathy

Fever may also occur.

What is the treatment for cryoglobulinaemia?

The main aim of therapy is to find and treat the underlying cause, and limit precipitation of cryoglobulins and the inflammation that results. Patients with cryoglobulinaemia should be advised to avoid cold environments to prevent triggering the precipitation of cryoglobulins.

Symptomatic treatment includes:

Identification and treatment of early symptoms such as skin lesions, fatigue or arthralgia, as a result of cryoglobulinaemia, will prevent further organ damage and improve patient outcomes.

Related information

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Author: Vanessa Ngan, staff writer

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