Systemic Juvenile Idiopathic Arthritis (sJIA)/Adult Onset Still’s Disease (AOSD)
What is sJIA/AOSD?
Systemic Juvenile Idiopathic Arthritis (sJIA).
Systemic means that multiple organs in the body are affected.
Juvenile = starts before the age of 16 years
Idiopathic = we do not yet have a clear cause
Arthritis = inflammation of the joints
In adults, the disease is called Adult Onset Still’s Disease (AOSD)
Systemic JIA and Adult Onset Still’s Disease are autoinflammatory diseases. This means that the innate immune system starts producing inflammation without there being a reason for it. The disease is characterized by high, spiking fevers, a salmon-pink coloured rash and inflammation of the joints. In addition, patients usually have an enlarged liver and spleen, enlarged lymph nodes in the neck and a sore throat. Most patients are very sick and blood tests shows high levels of inflammation. The exact cause of the disease is still unknown. Treatment consists of anti-inflammatory medication such as NSAIDs, prednisone and recently biologics such as anti IL-1 and anti IL-6.
Where does the name come from?
In 1897, the English paediatrician George Still first described the combination of prolonged inflammation of the joints, enlarged lymph nodes, an enlarged spleen, and serositis (inflammation of serous membranes, such as the peritoneum, pericardium or pleura). If children are affected, the disease is called systemic JIA. In adults, we use the term Adult Onset Still’s Disease.
Systemic JIA occurs in about 1 per 100,000 children. The condition can occur at any age, but is relatively more common in pre-schoolers and in young people between the ages of 15-25. Boys and girls are equally affected. The disease is rarely seen in adults (0.16-0.4 per 100,000 adults) with a peak between the ages of 35-45. In adults, slightly more women seem to be affected by the disease.
The main symptoms of the disease are a high spiking fever in the evening-night (up to >38.5 degrees Celsius) with often a return to a normal temperature in the morning or even a low temperature, and inflammation of one or more joints. The arthritis may be present at the onset of the disease, but sometimes occurs later in the disease course, and may also move from one joint to another. In addition, lymphadenopathy (enlarged lymph nodes), enlargement of the liver or spleen, serositis (inflammation of serous membranes, such as the peritoneum, pericardium or pleura) and a skin rash are common. The rash is often salmon-coloured, develops during a fever episode and disappears when the fever subsides. The rash may also appear when the child experiences emotional stress or is in bath. General symptoms have also been reported, such as a sore throat, fatigue, irritability, and weight loss due to decreased appetite and increased energy consumption of the body. Some patients have severe inflammation of the joints, while others have less joint pain but suffer more from inflammation in the rest of the body.
How does our immune system work?
The immune system protects us from potential pathogens: without it, we would die from an infection very quickly. The immune system is roughly divided into two parts: the innate and the acquired immune system.
The innate immune system
White blood cells of the innate immune system respond to warning signals in the blood. An example of a warning signal is lipopolysaccharide (LPS), a substance found on the cell wall of all kinds of bacteria. The pattern recognition is fast, but is nonspecific (not directed at one specific bacterium). When white blood cells ‘encounter’ LPS, they will start producing a variety of inflammatory substances, including interleukin 1 (IL-1). IL-1 in turn activates other white blood cells, causing an inflammatory response. Through binding to its receptor, IL-1 also triggers a reaction in the temperature system in the brain, which causes fever. Examples of types of white blood cells that play a role in the innate immune system are monocytes and neutrophil granulocytes. In autoinflammatory diseases, the innate immune system is overactive.
The acquired immune system
The acquired immune system tends to react a little slower, but because it causes the production of specific antibodies, it is a more specific and longer-lasting response. An example of how the acquired immune system works is vaccination: because your body makes specific antibodies after a vaccination, you have long-term protection against these diseases. Types of white blood cells that play a role in the acquired immune system are T-cells and B-cells. In autoimmune diseases such as rheumatoid arthritis, the acquired immune system plays an important role. For instance, T-cells generate an autoimmune response to the body’s own proteins or antibodies are made to fight parts of the body.
What causes systemic JIA/AOSD?
Systemic JIA/Still was previously classified under the group of autoimmune disorders, but now falls under the group of autoinflammatory disorders. The cause of the disease is not yet fully known, but recent research has brought more clarity. According to scientific research, sJIA/Still involves an uncontrolled innate immune system, which makes too many inflammatory proteins. This error in the immune system leads to an
inflammatory response in the body without there being any clear evidence of infection. This error in the immune system differs from an autoimmune disorder.
The diagnosis is made based on the whole clinical picture, meaning the patient’s history, physical examinations, but also blood tests. There are no specific tests to diagnose systemic JIA and therefore it often takes some time before a definitive diagnosis can be made. If the symptoms are less clear, it may sometimes be necessary to do additional tests to rule out other causes of fever.
Treatment consists of inhibiting the over-active immune system. It is common to start first with non-steroidal anti inflammatory drugs (NSAID), such as diclofenac or indomethacin. Up to 10% of patients respond to this, with the disappearance of fever and a gradual improvement of the inflammatory parameters and arthritis. However, most patients require more treatment. Instead of corticosteroids (such as prednisolone), it is common today to immediately start with biologics, such as Anakinra (short-acting IL-1 receptor antagonist) and Tocilizumab (anti-IL-6). Anakinra seems to work especially well when this medication is started quickly. The biologics intervene at a more specific location in the over-active immune system. Prednisolone has a broader mechanism of action and therefore shuts down a larger part of the immune system, which is not always desirable. Also, when compared to the biologics, prednisolone has more side effects, including long-term side effects.
Disease course / long-term prognosis
It is difficult to predict how the disease will develop in each patient. Before the introduction of biologics, many patients continued to have symptoms or had recurring symptoms after reducing the prednisone or stopping with it all together. Currently, a large group of patients is responding well to the biologics and some patients can even stop with the biologics after a few months. Studies for this have been mainly conducted with children and less well with adult patients. Unfortunately, it is still difficult to control the disease in some children and sometimes it is necessary to give multiple medications and sometimes prednisone as well. Also, after a long period of remission (no symptoms), the disease may come back.
A serious complication that may occur in children with systemic JIA is macrophage activation syndrome (MAS). When this happens, the macrophages and T-cells work so hard and multiply so fast that they can’t be controlled anymore. This causes the production of high levels of cytokines (inflammatory proteins), which also trigger further actions. With serious consequences. The macrophages eat the new blood cells in the bone marrow, causing the patient to have a shortage of red and white blood cells and platelets. This can result in a high fever and anaemia, increased susceptibility to infections and blood clotting problems. The liver also stops working properly, which can cause serious clotting problems.
Researchers believe that the disease is multifaceted. That is: the result of a combination of genetic predisposition and exposure to environmental factors (such as inflammation). However, even if genetic predisposition is a factor, it is very rare for two children within the same family to have the disease.