Cryopyrin-Associated Periodic Syndrome (CAPS)

CAPS includes three diseases that were previously thought to be different syndromes:

  1. Muckle Wells syndrome (MWS)
  2. familial cold urticaria (FCU)
  3. chronic infantile neurological cutaneous and articular syndrome (CINCA) (also known in USA as neonatal onset multisystem inflammatory disease, NOMID)

These three diseases are part of a single spectrum.

FCU is the mildest and causes attacks of itchy rash, red eyes and fever within hours of exposure to cold. Most affected patients come from North America.

Typical CAPS rash in a patient before canakinumab treatment. The picture at the bottom of this page shows the same patient’s skin after canakinumab treatment

MWS is the type most often seen in the UK. It causes daily episodes of generalised ‘nettle’ rash, red eyes and fever. These usually present soon after birth and are worst in the evenings. About a quarter of patients will become deaf later in childhood.

CINCA (NOMID) is the most severe and causes chronic inflammation of the lining of the brain resulting in loss of hearing, poor vision and learning difficulties. Children with CINCA can also have problems with their bone growth, and also have the rash and fever seen in the other two conditions.

As in all the inherited fever syndromes there are raised levels of inflammatory markers. If they are not treated, patients with CAPS may develop severe long term disabilities such as blindness, deafness and, in about 1 in 4 cases, amyloidosis.

Inheritance of MWS and FCU is autosomal dominant. As with the other fever syndromes some patients will have no affected relatives.

Although CINCA is due to mutations in the same gene, these mutations usually develop for the first time in the affected individual and so other family members are usually not affected.

The patient shown in the picture above, showing how the rash disappeared after  treatment with canakinumab,

The patient shown in the picture above. The rash disappeared after treatment with canakinumab,

The physicians at the NAC have been managing patients with CAPS for over 14 years. In 2001 they discovered that CAPS is caused by mutations in a gene known as NLRP3or CIAS1. This leads to production of a protein known as NALP3 or cryopyrin. This protein is involved in controlling inflammation. This leads to excessive production of an inflammatory messenger called interleukin 1β (IL-1β). IL-1β is also responsible for many of the symptoms healthy people experience when they have flu.

The role of IL-1β production in causing the symptoms of CAPS was discovered at the NAC. Over the last 10 years the NAC team have helped to develop a new and profoundly effective treatment for CAPS called canakinumab. Canakinumab is the only licensed treatment for CAPS.

Canakinumab is a type of drug called a monoclonal antibody. When administered by injection under the skin every 8 weeks it leads to complete resolution of the symptoms and signs of CAPS. Since they began receiving this treatment, patients with CAPS have experienced a remarkable turnaround in their lives. Canakinumab blocks the activity of IL-1β and thereby simply “switches off” the excessive inflammation that is the hallmark of CAPS. Canakinumab has only become standard treatment for CAPS relatively recently, so information is not yet available regarding the long term. But it is believed that prolonged treatment with canakinumab will completely prevent the long term deformities and complications that were previously seen in patients with CAPS.

The side effects of cankinumab include:

  • stinging
  • skin redness at the injection site, in some people
  • increased risk of infection.

In general the infections reported have been mild but all patients should be screened for tuberculosis and asked about a history of other infections before starting such drugs.

Children with CAPS under age 4

There are no licensed drugs for children under age 4 with CAPS at present, although there is an ongoing trial of canakinumab.
Children in this age group may be prescribed off label canakinumab or anakinra, another drug of the same class.

 

 

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