What is Juvenile Idiopathic Arthritis (JIA)?
Children with juvenile idiopathic arthritis (JIA) have inflammation of the joints that is called arthritis. This arthritis causes swelling pain with movement and possible decreased motion in the joint. This ranges from very mild limited joint involvement to severe systemic disease associated with high fever, rash and lymph node enlargement. There are seven types of JIA. The three major types include:
- Oligoarticular JIA (arthritis in four joints or less)
- Polyarticular JIA (arthritis in five or more joints)
- Systemic JIA (arthritis plus fever, rash and large lymph nodes)
In the past, these diseases were called “juvenile rheumatoid arthritis,” or “JRA,” "juvenile arthritis" or "juvenile chronic arthritis."
Juvenile idiopathic arthritis (JIA) is the most common type of arthritis in children. It is a chronic disease. This means it will probably last a long time. About one in 1,000 children have JIA in the United States. The number of new cases per year is estimated at nine per 100,000 people. These numbers tell us that about 40-50 children in the Cincinnati area will be diagnosed with JIA each year.
How is JIA Diagnosed?
Juvenile idiopathic arthritis (JIA) is a "diagnosis of exclusion." This means that we have to exclude or make sure your child does not have any other conditions or types of arthritis that could look like JIA. This exclusion process requires a comprehensive history, with a review of symptoms and a thorough head-to-toe physical exam. It is also important to review your child's and family's past medical history.
Arthritis is defined as swelling or painful loss of motion in one or more joints. In order to diagnose JIA, arthritis must be present for at least six weeks in a row in the same joint. Some children with systemic JIA may start out with high fever, rash, lymph node enlargement and other features but without joint involvement. Those children may go on to develop the arthritis at a later time; however, the systemic features (meaning those elsewhere in the body) usually come before or at the same time as the arthritis.
There are several blood tests that help to evaluate your child or exclude other diseases. These tests do not make the diagnosis of JIA as some children with arthritis will have completely normal blood tests. However, if they are abnormal, these. Tests help categorize and identify internal markers or signs of arthritis, like anemia or inflammation. It is also important to that some children may have positive or abnormal blood tests but do not actually have arthritis.
The physical exam and the history are just as important as the blood tests. X-rays or other imaging studies (ultrasound, MRI) of the affected joints cam be helpful in making a diagnosis. They can also helpful to exclude other diseases, or to help follow the effects of JIA on cartilage and bone.
What Happens to the Joints?
The word "arthritis" means inflammation in the joints. The target of the inflammation in arthritis is the lining of the joint. This lining is called synovial tissue, or the synovium (si-no-ve-um). In all of us the synovium makes fluid that provides nutrition to the cartilage, and cushions the joint. This is normal. When the synovium gets inflamed, it makes more fluid, so the joint gets swollen and the synovium becomes thicker. The swelling can be painful and causes stiffness and can make the joint hard to move.
All of us have synovial tissue in our joints but with JIA there is a complex process going on in the synovium with lots of different kinds of extra white blood cells gathering in the synovial tissue that release chemicals that cause even more inflammation. This process could eventually cause damage to cartilage and underlying bone.
The rest of the body can also be affected by the inflammation. Patients with JIA are usually tired and may have less appetite. This is part of the effect of the disease on the entire body. Some patients also have fevers, rashes, lymph node enlargement and weight problems.
Some patients with JIA are at higher risk for inflammation in the front of the eye, called the anterior chamber. This inflammation in the eye is called uveitis or iritis (see below). Occasionally, other parts of the body, such as the kidneys, lungs, gastrointestinal tract or heart may be affected by the inflammation. This is not common, but your rheumatologist will still check for it.
What Causes JIA?
The exact cause is unknown. JIA is believed to be caused by a combination of genetic and environmental factors. Researchers think that something in the environment impacts or 'triggers' the immune system, especially in people who have genetic factors that make them more likely to get arthritis. The genetic factors seem to play the most significant role in oligoarticular JIA, with many genes being involved. Environmental factors appear to be more important in systemic JIA. Environmental factors may be an infection that is virus-related but other germs may be involved in different patients.
The main symptom of JIA is inflammation in the joints. In general, inflammation is necessary to protect us against germs, and it normally goes away when infection is cleared. In JIA, however, the inflammation "gets out of control" and becomes persistent in the joints. Some researchers believe that the immune system (that is supposed to react against germs), becomes confused in this disease and starts reacting against our own body.
As we discuss later in the list of questions, the goal of medical treatment is to limit the inflammation. The medications used to treat JIA specifically work against inflammation (anti-inflammatory). Some of them have the ability to quiet down the "over-reacting" immune system.
Although we still do not understand the exact cause of JIA, we have recently learned a great deal about what is responsible for chronic inflammation. We now know that three molecules called Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-6 (IL-6) and Interleukin-1 (IL-1) are the major factors that keep inflammation in the joints active. This has led to the development of several new, very effective drugs such as: Etanercept, Adalimumab, Infliximab, Anakinra, Canakinumab, and Tocilizumab. These drugs selectively neutralize (work against) TNF-alpha, IL-1 and IL-6. Since they act selectively, only on TNF alpha, IL-1 or IL-6, they are very effective and relatively safe. Another effective drug, Abatacept, attaches to the surface of inflammatory cells and blocks the communication between these cells. We expect that more drugs like these will be developed in the near future.
Will Family Members Get Arthritis?
Is there a chance other family members, particularly other children in the family, will also get the arthritis?
JIA is not contagious. Even though we have mentioned infection and genetic factors, it is rare for other people in the family to develop this arthritis.
You may ask how this relates to other family members who already have some type of arthritis. There are many types of arthritis and it is one of the most common widespread chronic conditions. The most common form of arthritis in adults is osteoarthritis. Most people have family members, particularly in the older generations, who have osteoarthritis. Osteoarthritis is a different type of arthritis not related to the JIA that your child has developed. There may be a connection if there is lupus or rheumatoid arthritis in other family members, but it is still unclear how this directly links to your child with JIA. There are certain genes that are more common in different types of diseases. However, the genetic component of arthritis is not yet fully understood.
Will It Spread, Get Worse, or Cause Crippling?
This is probably one of the most common questions to be asked. Unfortunately, we cannot accurately predict how the disease is going to progress nor have a way to offer a firm prognosis.
Some children will have only one joint affected throughout the entire course of their JIA. Other children will start with one joint and it will spread to affect several additional joints or perhaps even spread to involve large and small joints. In some patients the disease remains mild and easy to control. In other patients, it is more severe and difficult to control.
Some of the blood tests help us to understand the possibility of more aggressive disease; however, these tests are not exact. In the past many children developed some degree of disability. However, the medical treatments developed and tested for use in children with JIA in the last 20 years have dramatically changed that for almost all children with JIA. This improvement in outcome for children with JIA is based on early and effective control of the inflammation in the joints as well as a continuous physical and/or occupational therapy program for the joints (usually done at home each day).
We have gained more experience and have followed children with JIA for 20-30 years. We find that the young children with JIA grow into very productive adults. This does not necessarily mean there aren't some residual effects on the joints or even active arthritis. However, we know that children with JIA do finish high school, pursue college educations, and have productive careers, marriage and families of their own as frequently as children without JIA. We want your child to live a healthy, full life like other children without JIA.
Will the Disease Persist or Recur in Adulthood?Approximately half of the patients with JIA will still have active disease after 10 years. We also know that the disease may come back in adulthood or persist into adulthood, especially in those patients who have developed the disease during late school age or adolescent years. It is thought that about 30-50% of children with JIA will continue to have active arthritis in adulthood. However, given the excellent response to treatment seen in almost all children with JIA, you should remain optimistic about the functional outcome for your child, as they become adults, will still be good and perhaps even better over time.
What Tests Help Make the Diagnosis?
There are several important points about laboratory tests. Lab tests do not determine if the joint is inflamed, that is done by physical exam or imaging (X-rays, ultrasounds, MRI or CT). There is no single lab test that if it is positive or if it is negative that can say your child has JIA. That means that the diagnosis of JIA cannot be made by laboratory tests alone. The diagnosis is made by history and physical examination. The lab tests help to categorize the type of arthritis, identify markers for how a person will do in the future (called prognosis) and exclude other illnesses or conditions. In addition, lab tests can help us to follow your child for important measures of inflammation to see how well the disease is controlled and also for side effects from medications.
- The first test that is often discussed is the erythrocyte sedimentation rate, ESR, or "sed rate." The sed rate is not used to find out if a patient has a particular disease. The sed rate shows inflammation in the system or tissue injury but this can be caused by many causes. The sed rate will vary from patient to patient. Some patients have normal sed rates but still have arthritis. Other patients may have very high sed rates, but do not appear to be seriously ill. If the sed rate is high and if it is thought to be due to the JIA, then it can be a valuable way to see if the treatment is working. A very similar lab, the C-reactive protein, or CRP, may be sent to monitor inflammation in the same way as the sed rate.
- Another common test is the antinuclear antibody test or ANA. The ANA is a screening test. It is a protein which is made by the white blood cells. The ANA test is the most common test to be positive in children with juvenile idiopathic arthritis. It is often called the "lupus" test. However, in children it is more common for patients with a positive ANA to have JIA, since lupus is uncommon in young children. The ANA test is positive in about 2/3 of children with oligoarticular JIA and about 1/3 (or more) of children with polyarticular JIA. Also, the ANA is a marker for patients at higher risk for development of eye inflammation.
- The rheumatoid factor is a test that is commonly positive in adults with rheumatoid arthritis. This is also a protein (or an immunoglobulin) which is made by the white blood cells. This test is rarely positive in children. When the rheumatoid factor is positive, it usually means the child has "seropositive" polyarticular JIA. Seropositive polyarticular JIA is a lot like adult rheumatoid arthritis. The rheumatoid factor can also be positive in other diseases. Sometimes, it is positive in patients with chronic infections. Again, the rheumatoid factor must be used along with the history and physical exam.
- Other common tests include a survey of the complete blood count, liver function, and kidney function. These are selected based on your child's signs, symptoms, or which medications he/she is taking. The complete blood count (CBC) helps to look for anemia (low red blood cell count). Patients with JIA or chronic inflammation can frequently have anemia. These tests are a way to watch for any problems that cannot be detected by physical examination or by history.
- Another test that may be done is HLA-B27. This is a gene that is present in about 70-90% of patients with a subtype of arthritis that affects the spine. It is also positive in about 5-7% of the healthy people so to have a positive HLA-B27 test does not mean a person will always get arthritis.
- X-rays are often ordered to evaluate the structure of the bones. Synovium (lining of the joint) does not show up on x-rays. Initially, x-rays of the bones are done to check for fracture, infection, or tumor that can look like JIA. Later, if your child has JIA, then x-rays can help as a way to follow whether there is any damage to the bone or loss of cartilage due to the arthritis. When x-rays are ordered for your child, the doctor will explain why the x-rays are being done.
- Ultrasound is the use of sound waves to look inside joints. Ultrasound exams are completely safe and painless. They can show fluid or inflammation of the synovium or tendons around joints.
- Magnetic resonance image (MRI) or computerized tomography (CT) are tests done in radiology to look at the joints. They can detect inflammation but also provide 3 dimensional (3D) pictures of the joints in fine detail.
Types of JIA
Oligoarticular JIA is the most common form of juvenile idiopathic arthritis. Oligo means few in Latin. By definition, this form of JIA has four or less joints involved during the first six months of disease. About 40% of patients with oligoarticular JIA will go on to develop arthritis in more than four joints over the course of the next few months to years. This is sometimes called extended oligoarticular JIA.
Oligoarticular JIA usually occurs with young girls (1-5 years old) or in boys in late school age or adolescence. For young girls with oligoarticular JIA, onset is often before the age of 5. The most common joint to be involved is the knee, and these patients usually have a positive ANA. These young girls with limited joint involvement and positive ANA are in the group of patients at highest risk to develop inflammation in the eye (up to 30%). The eye inflammation is called iritis or iridocyclitis (ear-ri-do-si-cli-tis). For this reason, this group of children is checked by the ophthalmologist more frequently for possible inflammation in the eye. The highest risk of getting eye inflammation is within seven years of developing the arthritis. Visits to the eye doctor are usually three to four times per year, even if no symptoms affect the eyes. For these boys with oligoarticular JIA it is believed that there is a link between this group of children and a family of arthritic conditions called spondyloarthropathies. "Spondylo" means spine; "arthropathy" means affecting the joint. Together these mean male children or adolescents can develop arthritis in the back or spine area. In patients who have arthritis in the spine, the disease is called juvenile ankylosing spondylitis. If there is not arthritis in the spine, then that diagnosis cannot be made yet. The common link is a gene called HLA-B27. Patients with a spondyloarthropathy commonly have HLA-B27. About 60-80% of the young boys with oligoarticular JIA have the HLA-B27 gene. Not all of these boys (sometimes girls) will go on to develop ankylosing spondylitis however.
These patients can have joint inflammation in the hips, knees, ankles, toes and shoulders. Involvement in the hands, wrists and elbows is much less common. Inflammation may also occur in the heels and tendons (sometimes called enthesitis related arthritis where an enthesis is a tendon or ligament). Some of these patients could develop inflammation in the small intestine or colon. It is important for this group of children to be aware of symptoms related to their bowels. If abdominal pain and diarrhea occur, attention can be directed to proper diagnosis and treatment. The other symptom to watch for is sudden inflammation in the eye. This form of eye inflammation is quite painful and is usually brought promptly to the attention of the doctor.
Iridocyclitis – Uveitis, Iritis
Children and adolescents with JIA are susceptible to developing inflammation in the eye as well as the joints. The children at highest risk are the little girls with the fewest joints involved. Most children who get eye disease get it within seven years of the onset of their arthritis.
The inflammation is located in the front of the eye in the part called the iris (colored part of the eye) and in the ciliary body. The term for the eye inflammation is called iridocyclitis or Uveitis. In over 80% of children with JIA who get uveitis there are absolutely no symptoms and the only way it can be found is by the eye doctor looking at the eyes. If the child does have symptoms then it is blurry vision, pink eye, squinting, or pain. Since few or no symptoms happen we must check for the inflammation on a regular basis before the eye is damaged and there are changes in vision. If there is inflammation the ophthalmologist will prescribe eye drops. Treatment for the eyes is separate from the treatment for the joints.
A slit lamp examination by the ophthalmologist is a brief, easy, painless test to perform even on young children and is the best way to detect the eye inflammation seen in children with JIA. The slit lamp needs to be done at regular intervals for several years, depending on which type of JIA your child has. The rheumatologist will tell you how often to get the slit lamp test.
The eye inflammation is independent or separate from the arthritis. This means one symptom can be active and the other can be in remission or not present. It is important for you to help keep track of the eye examinations.
Polyarticular JIA, by definition, involves five or more joints in the first six months. "Poly" means many. Patients with polyarticular JIA usually have involvement of both large and small joints. This means that any joint (the neck, jaws, fingers, toes and all the other large joints) can get inflammation. Arthritis in the low and mid-back would be uncommon. However, the neck (or cervical spine) is commonly involved in this subtype. Patients with polyarticular JIA can have some systemic features, such as low-grade fever, weight loss, reduced appetite, mild lymph node enlargement and low-grade anemia. Problems of the heart, lung, and kidney are rare. However, we will watch for involvement in other areas of the body in addition to the joints.
At most one out of 10 (10%) children who have polyarticular JIA will have a positive rheumatoid factor blood test. Most adults with rheumatoid arthritis do have a positive rheumatoid factor. The presence of rheumatoid factor in a child with polyarticular JIA suggests that these children may have disease that is very similar to adult rheumatoid arthritis. These children (mostly girls with onset of disease during late school age or adolescence) may have the other features of adult rheumatoid arthritis. These would include rheumatoid nodules and the potential for inflammation in small joints. We will talk with you more about these features if they occur.
Polyarticular JIA patients are at less risk for developing eye inflammation than patients with oligoarticular JIA. Inflammation in the eye can occur in about five out of 100 polyarticular JIA patients. This means that slit lamp examinations by the ophthalmologist need to be done every 6-12 months for the first few years of disease.
Systemic JIA is the form of juvenile idiopathic arthritis which affects the entire body or "system," often before it affects the joints. The most common symptom is a high fever which usually happens once or twice a day. The fever is usually quite high with temperatures 103° or higher. This fever typically occurs in the late afternoon or the evening. During the fever, your child can look quite ill. When your child is not feverish, there will be fewer signs or symptoms of the disease.
During the times of fever, there is often a rash. This rash comes and goes. Only about one in 20 children will complain of any itching with the rash. The rash is not contagious. The rash is often present when there is pressure on the skin. An example is under the elastic of the undergarments or where the skin has been scratched. The rash also comes out whenever the skin is hot from exercise or environmental temperature. Even getting a warm bath and drying off with the towel may bring out the rash. The rash lasts only a short time and then goes away completely or moves to another part of the body. The rash does not cause any damage or permanent changes to the skin.
The lymph nodes, liver, and spleen are organs which react to the inflammation. They can become enlarged in about six out of 10 children. The enlargement is not dangerous. However, it is part of the disease and needs to be understood.
Eventually, most children will develop arthritis in at least a few joints. At the beginning of the illness it can come and go with the systemic features. It is not possible to project a prognosis regarding the joints until some time has gone by and the course of your child's disease becomes apparent.
Most patients with systemic JIA become quite anemic over the course of the first few weeks of inflammation. This anemia can be severe in some patients but rarely requires transfusion. Usually, the white blood count and the platelets are very high.
Usually the systemic features of systemic JIA last for several weeks to several months. It is unusual for the systemic features to last indefinitely; however, this does occur in rare cases.
Inflammation of the outer lining of the heart, the pericardium, occurs in some children with systemic JIA. However, only in a small group of children does it become serious with chest pain, shortness of breath, and pressure in the chest. If this would occur, it is important to notify the doctor or nurse as soon as possible so that it can be evaluated and treatment can be started if necessary. Fortunately, involvement of the heart muscle is rare.
Diary / Personal Record
Sometimes your doctor or nurse will ask you to keep a diary or personal record for your child. This is usually used to help understand your child’s symptoms. It is often kept to record fever, rash, pain, stiffness, limping, abdominal pain, headache, or other symptoms on a day-to-day basis. A diary may also be kept to record possible side effects of medicines or to record when other medications, such as antibiotics or pain medicine, are prescribed.
Such a diary can be easily created (or a regular calendar can be used). The diary should be brought to each clinic visit. This can help you remember problems or questions when discussing your child's disease with your doctor and nurse.
Treatment Goals for JIA
- Educate patient and family
- Help families learn how to manage disease on a daily basis
- Control inflammation
- Reduce pain and stiffness
- Prevent deformity and maintain joints in a position which gives normal function
- Reduce any deformities that may have already developed, such as loss of motion
- Maximize strength and function (children lose strength around the affected joints because of the inflammation)
- Promote normal growth and development, both physical (height and weight) and psychosocial (emotional, social, intellectual)
- Minimize side effects of therapy
All of these goals are accomplished by the team of family, doctor, advanced practice nurse, clinic nurse, occupational therapist, physical therapist, nutritionist, social worker, psychologist and ophthalmologist. We may need to consult with other subspecialists, such as Orthopedics, Cardiology, Gastroenterology and Nephrology to address special needs.
The focus is on the family and meeting your needs. This is called family centered care. This requires careful evaluation in many areas of care and sharing of information. Think of you and your child as the center of the spokes on a wheel on a bicycle. You share information back and forth with each member of the team.
Drug treatment is divided into several separate groups of medications (listed below) that have different effects, adverse reactions and strengths.
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Slow-acting anti-inflammatory drugs
- Biological agents
- Experimental or investigational agents
The decision to select a medication for your child will involve several factors:
- Age of your child
- Previous medicines that have worked or failed
- Duration of disease (or how long they have had the disease)
- Severity of disease
- Potential or past adverse reactions (or side effects)
- Allergies to medications
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
The nonsteroidal anti-inflammatory drugs (NSAIDs) have three major purposes:
- Decrease inflammation (anti-inflammatory)
- Provide pain relief (analgesic)
- Reduce fever (antipyretic)
The effect on inflammation can be mild to moderate and can occur quickly. The medicine can work as soon as one to two weeks, but the full benefit may not be seen for up to 12 weeks.
The main side effects are stomach upset and occasional central nervous system symptoms. The stomach upset can cause nausea, abdominal pain or decreased appetite. The central nervous system symptoms can mean that children can become very irritable or "hyper." Or they can get very sleepy or have headaches. If your child experiences any of the central nervous system symptoms they usually show up soon after starting the medication (in the first few weeks) and resolve quickly once the medicine is stopped. Most children tolerate the medications without any problems, but talk with your nurse, doctor or pharmacist if you have concerns. The specific side effects of each of the NSAIDs will be explained. It is best to take NSAIDs with food or milk to help prevent stomach upset.
The most commonly used NSAIDs are:
- Naproxen (Naprosyn)
- Meloxicam (Mobic)
- Ibuprofen (Advil, Motrin)
- Nabumetone (Relafen)
- Celecoxib (Celebrex)
Slow-Acting Anti-inflammatory Drugs (Disease Modifying Anti-Rheumatic Drugs, DMARDs)
These are called slow-acting because the onset of action or benefit is usually not for several weeks or months. These medications tend to be stronger than NSAIDs but also have more potential for side-effects.
The list of these medications may include:
- Leflunomide (Arava)
Methotrexate is also sometimes classified as immunosuppressive or cytotoxic, but in reality it is more anti-inflammatory in the doses used for arthritis. The drug has become one of the best treatment options for a child whose disease is not well controlled by NSAIDs alone. Methotrexate has been used for over 35 years in children with JIA all over the world. There are over 2000 articles in the medical literature about the use of methotrexate in JIA.
The Corticosteroids or "Steroids"
The corticosteroids are potent anti-inflammatory drugs. These are not the same type of steroids used by body builders. We can give them three different ways:
- By mouth
- By intravenous infusion
- By local injection into the joint
These medications are given only for specific situations. Serious problems can be promptly treated by these medications but the use is weighed carefully for benefit versus possible side effects.
The local injection is of a long-acting corticosteroid put directly into a joint (or several individual joints). This gives prompt anti-inflammatory action in the joint alone. This is a safe and routine procedure and can be done without significant discomfort. Almost all the steroid stays inside the joint so there are few steroid side effects.
Biological agents have been used over the past 20 years in the treatment of children with JIA. The biological agents are designed to block a very specific step in the inflammation process. They have been shown to be extremely effective in controlling the JIA in the vast majority of children with JIA. In fact, these medications have dramatically decreased the impact of the JIA on child and improved long-term outcomes for these children. They are able to prevent or stop the worsening of joint damage in many patients. The biological agents work by controlling the overactive inflammatory response seen in children with JIA. Because they are stronger drugs than the others on this list, they can be associated with more severe side effects. However, the vast majority of children treated with biological agents tolerate them without side effects. Many new biological drugs are being developed and tested for use in children with JIA so new treatments will become available for the treatment of your child. The biologic agents commonly used for JIA treatment are:
- Etanercept (Enbrel)
- Adalimumab (Humira)
- Infliximab (Remicade)
- Anakinra (Kineret)
- Canakinumab (Ilaris)
- Tocilizumab (Actemra)
- Abatacept (Orencia)
These would be discussed in detail before administering these products to your child.
We are a major center for research in pediatric rheumatology. Cincinnati Children's is the coordinating center for the Pediatric Rheumatology Collaborative Study Group which is an international group of pediatric rheumatology centers working together to develop and test new treatments for children with JIA. We are involved in research to test the use of medicines / products in the treatment of JIA. There are always protocols (or rules) and thoughtful attention paid to safety and effectiveness. If there is a new medicine that could be potentially helpful for your child, this may be discussed as a trial or research study. All the specific details would be thoroughly explained and permission is always obtained before any study medication would be used.