Deficiency of Il-1 Receptor Agonist (Il-1 RA) known as DIRA
DIRA is a newly classified and very rare auto inflammatory disease that is caused by an IL1RN gene mutation that is inherited from both carrier parents, since it is an autosomal recessive mutation. A person can carry the mutation, but it would take two carriers of the IL1RN gene mutation that have a child that inherits the mutation from both parents to lead to DIRA in the child. Parents that have one child with DIRA have a 1:4 chance of having another child with this condition. DIRA is a very rare disease, but it has been discovered that 2.5% of Puerto Ricans from the northwest part of the country carry mutation for DIRA, and it is estimated that this mutation could occur as frequently as 1: 6,300 patients in that region of the world. The mutation may also be more common in people with Dutch ancestry too.
IL1RN produces a protein called Interleukin-1 receptor Antagonist (Il-1RA) that helps to regulate inflammation, especially Interleukin 1 in the body that is a very strong messenger and part of the body's inflammatory response. In patients with DIRA, the IL1RN gene mutation causes the body to be deficient in IL-1 RA, and therefore the body is unable to properly regulate inflammation in the body.
DIRA causes severe skin and bone inflammation, and other organs in the body can also be affected. If left untreated, the child could develop disabling damage to their body, and die from this disease in early childhood.
Skin inflammation on DIRA patients is notable, with redness, putules of varying size and scaling skin. This inflammation can be all over the body, but injuries, and even intravenous canullae or lab draws can cause increased inflammation at the site of injury. Some patients with DIRA have deformed fingernails.
Inflammation in the bones can be very severe, with painful swelling of the bones anywhere in the body, and often is seen on many bones. The bone inflammation can cause the skin over the affected areas to become red and warm to the touch. The periosteum, the membrane that covers the bones in the body is affected by the inflammation from DIRA, and is extremely sensitive to pain.
The spaces between joints are not typically affected in DIRA patients, which is different than many other inflammatory bone conditions.
Children with DIRA are in a great deal of intense, chronic pain, and can be very irritable. The pain and suffering can lead to feeding challenges and growth delays.
Thankfully with the discovery of the genetic cause for DIRA, researchers have been able to treat DIRA patients with a medication that is a synthetic form of human Il-1RA in clinical trials. This medication is Kineret (anakinra), which is also used in off-label form for some CAPS patients in clinical trials. More information about Kineret is on our Treatments page.