Definition of Cryopyrin-Associated Periodic Syndrome

Cryopyrin-Associated Periodic Syndrome (CAPS) also known as Hereditary Periodic Fever Syndrome is an extremely rare autosomal arthritis disease. It affects approximately 1 in every 1,000,000 population group. Autosomal dominant heredity means that inheriting a copy of the mutated gene from one parent is enough to manifest the disease in the individual.

CAPS is an auto-inflammatory disease that is made of three rare arthritic diseases:

  • Neonatal-Onset Multisystem Inflammatory Disease (NOMID)
  • Familial Cold Autoinflammatory Syndrome (FCAS)
  • Muckle-Wells Syndrome (MWS)

Causes of Cryopyrin-Associated Periodic Syndrome

A defect in gene expression is the pathological basis of all three diseases found under CAPS. Therefore, the main cause of CAPS is familial. It runs in families that have the mutated gene called cryopyrin. This gene is responsible for regulating the body’s inflammatory response.

Symptoms of Cryopyrin-Associated Periodic Syndrome

The clinical manifestations of CAPS are grouped into syndromes. CAPS being a collection of three main auto-inflammatory diseases, which are largely associated with arthritis, arthralgia or arthropathy, tend to exhibit a multi-systemic symptomatology. Each of the three diseases has a distinct presentation of signs and symptoms that make it easy to distinguish.  However, there are overlapping symptoms which often pose a diagnostic challenge to the clinician.

  • Neonatal-Onset Multisystem Inflammatory Disease (NOMID): Onset of the disease is from birth or from 6 months of age. However, the disease begins to clinically show manifestation at the age of 1 year. Arthritis is the most common symptom, and the knee joint is the primary site. The infant may become inconsolably irritable and refuse to stand or move his/her legs. The knee develops structural changes such as abnormal fusion of joint structures causing calcified masses to build up in the joint. These cause abnormally large joints which often result in joint deformity and functional disability. Other symptoms include:
    • Non-itchy rash
    • Recurrent vomiting
    • Neurological symptoms e.g. headache, loss of hearing etc.
  • Familial Cold Autoinflammatory Syndrome (FCAS): Its hallmark is the presence of an aggravating factor which is exposure to cold. Cold triggers exacerbation of symptoms. Involvement of large joints is common especially the knee joints. Other symptoms include:
    • Extreme thirst
    • Nausea
    • Vomiting
    • fever
  • Muckle-Wells Syndrome (MWS): this is an on and off variant of CAPS. Each exacerbation episode lasts about 2 – 3 days. It has a predilection for teenagers. Knee joint is also the most common site of arthritis. Joint pain is often described as intense and sharp. Other associated symptoms include:
    • Headache
    • Nausea and vomiting
    • Deafness
    • Renal failure symptoms

Treatment of Cryopyrin-Associated Periodic Syndrome

Treatment of CAPS is now being improved with the discovery of new trial therapies to not only abate symptoms but eradicate the cause of CAPS. The use of medical and surgical interventions is to prevent or halt the progression of permanent debilitating effects of CAPS. The role of Orthopedic involvement in management of CAPS is extremely crucial. Dr. Burke, our orthopedic specialist is fully updated on the recent treatment formulas available. His sharp clinical acumen enables him to selectively determine, based on a host of factors, what patients with CAPS need.  He uses the following approach:

  • Pharmacological therapy:
    • Interleukin-1 receptor blockers
    • NSAIDS
    • Steroids
    • Methotrexate
  • Surgical intervention including joint replacement