Despite ongoing research into rare periodic fevers, this area of medicine is complex and not fully understood – even by scientists! In this section of the website, we present some of our current understanding of the science behind the tiny DNA change(s) that lead to rare periodic fevers, and we describe some of the diseases themselves – CAPS, SJIA, FMF, TRAPS, and HIDS/MKD. Explore to find out more.
A healthy immune system: Your body’s defence against germs
We all know that a healthy immune system is essential to fight off invading germs that can cause illnesses or disease. This includes common viruses that cause colds or flu every winter, bacteria such as streptococcus, which can cause a very sore throat, and other germs such as those responsible for stomach flu.
The skin and mucosa (inner lining of the nose) act as frontline barriers to prevent germs from entering the body. They are coupled with our saliva, sweat and tears (the bodie's "chemical" defences), which contain substances such as enzymes that can kill germs.
If germs manage to enter the body, the immune system forms the next line of defence to prevent them from growing and multiplying. The immune defence system consists of patrolling cells and messenger substances (cytokines) that circulate in the blood, which detect and fight invading germs.
Infection: When germs invade
Find out now how some immune system defences become active even without outside invaders, causing “friendly fire” that can harm people with autoinflammatory conditions.
When germs invade the body causing an infection, two parts of the immune system work together to fight the invaders:
Development of a healthy immune response to germs
Autoinflammatory diseases are conditions where the inflammatory response appears to occur automatically or “on its own,” instead of as a response to invading germs. This autoinflammation involves the nonspecific innate immune system and occurs periodically in some people or continuously (chronically) in others.
During an autoinflammatory response, the innate immune system is activated even though no germs are present in the body. (This means that the immune cells act as if they were fighting germs, resulting in an inflammatory response that affects the entire body.) This causes a disease flare with typical symptoms including fever, rash, joint swelling, pain, and fatigue.
Why does this happen?
There are various causes of autoinflammatory diseases:
|Other conditions with autoinflammatory causes||
CAPS: Cryopyrin-associated periodic syndromes, FMF: Familial Mediterranean fever, TRAPS: Tumour necrosis factor receptor associated periodic syndrome, HIDS/MKD: Hyperimmunoglobulinemia D syndrome/mevalonate kinase deficiency, SJIA: Systemic Juvenile Idiopathic Arthritis
The culprit: IL-1β
Interleukin-1 beta (IL-1β) is a messenger of the nonspecific innate immune system that can play a special role in many autoinflammatory diseases, including promotion of the inflammatory response. What do we mean by messenger? These are signals to immune cells to come to the site where invaders are.
IL-1β has different effects on various parts of the body
Effects of IL-1β
Periodic fever syndromes
Periodic fever syndromes are rare diseases; they affect a very small percentage of people in the general population – for example, fewer than 5 out of 10,000 people. They are usually hereditary and may be caused by a change to the genetic recipe (DNA) of the nonspecific innate immune system that causes the system to be switched on even without invaders to fight. Periodic fever syndromes include (but are not limited to) cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), tumour necrosis factor receptor associated periodic syndrome (TRAPS) and hyperimmunoglobulinemia D syndrome/mevalonate kinase deficiency (HIDS/MKD).
The symptoms involve the repeated occurrence of fever lasting more than 24 hours and are often accompanied by rashes and joint pain. They can also involve other symptoms, and sometimes further damage may occur due to the effects of continuous (chronic) inflammation.
Diagnosis of CAPS, FMF, TRAPS or HIDS/MKD can be a challenge. This is because these diseases occur only rarely and have symptoms common to many other diseases. Doctors may have to rule out many possible conditions and order laboratory or genetic tests in order to make a diagnosis.
So what are autoimmune diseases?
Autoimmune conditions involve the acquired immune system. The acquired immune system includes immune cells that following initial contact, fight only a specific type of germ. Autoimmune diseases often involve the formation of antibodies that are mistakenly directed against parts of the body. Well-known autoimmune diseases include Crohn’s disease, psoriasis, and rheumatoid arthritis.
But there is some overlap
Some diseases of the immune system cannot be strictly categorized as either autoinflammatory or autoimmune. For example, some forms of arthritis involve the innate and acquired immune systems and can be considered both autoinflammatory and autoimmune conditions.
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