Systemic Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most common type of arthritis in kids and teens. About 10% to 20% of children with JIA have a rare and serious subtype called systemic juvenile idiopathic arthritis (SJIA). “Systemic” means it may affect not only the joints but other parts of the body, including the liver, lungs and heart. SJIA, sometimes referred to as Still’s disease, can occur any time during childhood, but it most commonly starts at about two years of age. Boys and girls are equally affected. SJIA also differs from other subtypes in that it’s the only one considered an autoinflammatory rather than autoimmune disease. SJIA is more severe and can be more challenging to diagnose and treat than other types of juvenile idiopathic arthritis. It is a lifelong disease for many patients and can continue into adulthood.

Exactly what causes SJIA isn't clear. The general theory is that a child has a genetic predisposition, and the disease onset is triggered by something in the environment. The word “idiopathic” means the cause or trigger is not known. Questions remain, but researchers are learning more about SJIA and why it’s different from other types of juvenile arthritis.

The body has two types of immunity — innate and adaptive. The innate immune system is active at birth and is the first line of defense against infection. The adaptive immune system develops throughout life. Its role is to target and help to destroy viruses and bacteria that slip past the innate immune system.

Most forms of JIA develop when the adaptive immune system becomes overactive and attacks healthy cells and tissues. These disorders are called autoimmune diseases. Research suggests that SJIA is different. It may be an autoinflammatory condition that causes the innate immune system to be activated even when there is no infection to fight. Several factors have led researchers to think that SJIA is an autoinflammatory disease. For one thing, children with SJIA usually don't have autoantibodies in their blood, as many kids with other forms of JIA do. Autoantibodies are formed when the adaptive immune system is overactive. Also, kids with SJIA have high blood levels of two inflammatory proteins (cytokines) called interleukin-1 (IL-1) and interleukin-6 (IL-6). These proteins are known to cause inflammation in other autoinflammatory diseases and are believed to trigger inflammation in SJIA.

Having systemic juvenile idiopathic arthritis (SJIA) affects different areas of the body and internal organs. At highest risk are kids whose symptoms aren't well controlled over time. But these conditions may occur in any child with SJIA.

Macrophage Activation Syndrome
The most serious potential complication of SJIA is a condition called macrophage activation syndrome (MAS). It has been described as a massive inflammatory response that overwhelms the whole body. Known triggers include viral infections, medication changes and flares — a spike in disease activity. MAS can occur in any rheumatic disease, but for reasons that aren't clear, an estimated 80% of cases are associated with SJIA. A review of data has shown that only about 10% of children with SJIA develop MAS, but some develop it more than once.

Lung and Heart Problems
Doctors have seen more cases of lung diseases, such as pulmonary artery hypertension and interstitial lung disease, in children with SJIA. Pulmonary artery hypertension is high blood pressure that affects the arteries in the lungs and the right side of the heart. In interstitial lung disease, lung tissue becomes scarred, making it harder to get oxygen into the bloodstream. Parents should be alert for any signs of breathing problems, especially shortness of breath, and notify their pediatric rheumatologist as soon as possible.

Bones and Joints
Persistent inflammation can slowly damage the joints, leading to reduced range of motion, loss of function, and sometimes the need for joint replacement early in life. SJIA, if not well controlled, is more likely than other types of juvenile arthritis to affect the jaw joint (the temporomandibular joint or TMJ), leading to a smaller-than-normal chin and changed appearance in some children. Fusion of the cervical spine (neck area) may also occur in kids with long-standing SJIA.

Long-lasting inflammation of the joint lining can also interfere with normal growth and bone development, causing one arm or leg to be longer than the other and slowing or stunting overall growth. Corticosteroids used to treat SJIA can also prevent kids from growing normally. Continued use of corticosteroids can cause osteoporosis (a disease of the bones that causes them to be weak and brittle) or osteopenia (lower than normal bone mass not low enough to be classified as osteoporosis). Having either condition may make kids more likely to experience fractures. Many doctors start kids with SJIA on calcium and vitamin D supplements from the beginning and encourage kids to get plenty of physical exercise and eat calcium-rich foods to foster strong, healthy bones.

High blood pressure (hypertension)
Hypertension can occur for at least two reasons. One is atherosclerosis — the buildup of fatty deposits on artery walls. When the arteries narrow, the heart must pump harder to move blood through them. Although atherosclerosis can develop in healthy children, it’s seen more often in SJIA — likely due to ongoing inflammation. A more frequent cause of high blood pressure is treatment with corticosteroids, which cause fluid retention and weight gain.

If the disease is undertreated, some kids may experience hair loss, anorexia, anemia, large, swollen glands and malaise (a generalized feeling of discomfort and illness).

Fever
A high, recurring fever, often with a rash, is one of the first signs of SJIA. The fever usually follows a pattern in which a child’s temperature reaches 103 degrees or higher, generally in the evening, and then drops within a few hours. Although a daily, spiking fever, typically in the evening, is one of the criteria for diagnosing SJIA, studies have shown that the pattern can vary. Sometimes the fever occurs in the morning or twice a day; occasionally, it may continue throughout the day. Over time, though, almost all children with untreated SJIA develop the typical pattern of daily fever that returns to normal.

Rash
A flat, pale or pink rash, depending on the child's skin color, often appears on the child’s trunk, arms or legs, although it can move from one part of the body to other parts. The rash may be itchy, but usually isn’t. It tends to last a few minutes to a few hours and is associated with fever spikes.

Joint Pain
Arthritis is the second most common early sign of SJIA. The symptoms of joint swelling, pain, stiffness and warmth that occur are worse in the morning and after a nap or prolonged stillness. However, unlike other forms of childhood arthritis, joint problems may develop weeks or even months after systemic symptoms. Children, especially very young ones, often don’t complain of joint pain with SJIA, but parents usually notice the onset of arthritis when a child starts to limp, seems stiff in the morning or suddenly becomes less active. Sometimes a single joint is affected, but more often several joints are involved, commonly the knees, wrists and ankles. Children with SJIA can also develop arthritis in the spine (in the neck area), jaw and hip joint.

SJIA symptoms may also come and go. Periods of lots of inflammation and worsening symptoms are called flares. A flare can last for days or months.

According to the SJIA diagnostic criteria developed by the International League of Associations for Rheumatology (ILAR), a diagnosis of SJIA requires a high fever for at least two weeks and arthritis (joint pain and inflammation) in one or more joints for at least six weeks. Fortunately, pediatric rheumatologists are skilled at identifying SJIA and handling the sometimes conflicting challenges of diagnosing the disease.

There are no specific tests for SJIA, so doctors rely on their experience and expertise as well as the child’s medical history and a comprehensive physical exam to identify the disease. Laboratory and other tests can help confirm an SJIA diagnosis and rule out conditions that cause similar symptoms.

Health History
Doctors take a medical history to learn about past illnesses and current medications as well as details of current symptoms, such as how long a child has had them. Knowing the length of time that SJIA symptoms have been present helps rule out infections and other problems that can affect the joints temporarily.

Physical Exam
Children who have a persistent fever and rash should have a thorough musculoskeletal exam, even if they don’t have obvious joint symptoms. During the physical exam, doctors look for tenderness, warmth, swelling and reduced range of motion, especially in the knees, wrists, ankles and hip joints — the ones most often affected by SJIA — as well as in the jaw and neck.

In some children, joint inflammation affects the growth centers in bones, causing them to be shorter than normal and possibly uneven from one side to another, so doctors assess limb length and overall growth. Doctors may also look for swollen lymph nodes behind the ears, in the neck or around the groin area.

Imaging Tests
X-rays are rarely helpful in diagnosing juvenile arthritis, but magnetic resonance imaging (MRI) and, occasionally, an ultrasound may be used to detect early joint inflammation or to look for complications. A chest X-ray can reveal lung inflammation, and an ultrasound of the heart can show inflamed tissue in and around the heart. These tests may also show if a liver or spleen is enlarged.

Laboratory Findings
Although SJIA can’t be diagnosed with blood tests, certain laboratory findings can help support or disprove the diagnosis. It’s common for kids with SJIA to have the following:

• Extremely high white blood cell and platelet counts.
• Severe anemia due to poor iron absorption.
• Extremely high levels of ferritin, an iron-storing protein.
• Elevated inflammation markers, including erythrocyte sedimentation (sed) rate and C-reactive protein.
• No sign of antinuclear antibodies or rheumatoid factor antibodies — both of which are often seen in the polyarticular form of juvenile idiopathic arthritis and other rheumatic diseases but rarely in SJIA.

There is no cure for SJIA but remission (little or no disease activity or symptoms) is possible. Early aggressive treatment is key to getting the disease under control as quickly as possible. The past few years have seen a revolution in treatments for SJIA. The introduction of targeted medications for SJIA has contributed to a change in the way many specialists approach therapy as well as its goals. Traditionally, a typical treatment goal for children with SJIA included relieving pain and controlling symptoms. But now, physicians also aspire to achieve disease remission with the ultimate hope of seeing the clinical signs and symptoms of the disease disappear.

The standard approach to treating SJIA is to start with nonsteroidal anti-inflammatory drugs (NSAIDs) and move up to stronger drugs over time, if necessary. If NSAIDs don't relieve SJIA symptoms within a week, the next step may include high doses of oral or IV corticosteroids , which can quickly improve fever and other systemic symptoms, as well as joint pain and swelling.

But long-term, high-dose use of corticosteroids can cause serious side effects in children, including osteoporosis , slowed growth, an increased risk of infections, weight gain and a change in facial appearance. When SJIA symptoms are under control, doctors gradually reduce the dose and eventually stop it completely. If symptoms return or a child can't tolerate corticosteroids, a different medication is often used.

Until recently, few treatment alternatives to corticosteroids existed for kids with SJIA. But in recent years the FDA has approved medications that target specific inflammatory proteins, including interleukin-1(IL-1) and interleukin-6 (IL-6), which are overactive in the disease.

These drugs, known as biologics , were once used only after other medications had been tried and failed. But because they can cause a dramatic improvement in some children with SJIA, some physicians now use biologics as a first-line therapy, avoiding corticosteroids and their side effects completely.

Once systemic symptoms of SJIA have disappeared, nonbiologic, conventional disease-modifying antirheumatic drugs (DMARDs) may be used alone or in combination with biologics for continued therapy for arthritis. Unlike NSAIDs or corticosteroids, conventional synthetic DMARDs may slow joint damage.

Although medication is the mainstay of SJIA treatment, a regular exercise program is an important part of therapy, too. Exercise helps to build muscle strength, increase energy, and reduce pain. It can also help kids feel more confident about their physical abilities, provide opportunities to interact with other children and help maintain joint function and flexibility.

Most kids can participate fully in physical activities and team sports when their symptoms are well controlled, but they may have to limit certain activities during disease flares. A rehabilitation or physical therapist will likely be part of a child's treatment team and can recommend the best activities.

Hear firsthand accounts of how juvenile arthritis affects lives. Warning: inspiration ahead!