Arthritis and Rheumatology Conditions and Diagnoses

Background | How common is JRA? | How is JRA Diagnosed? | What happens to the joints? | What the cause? | Is it genetic? | Will it spread or get worse? | Will it persist or recur? | What lab tests diagnose it? | Types of JRA | Diary / Personal Record | Treatment

Children with Juvenile Rheumatoid Arthritis (JRA) have swelling or pain ranging from very mild limited joint involvement to severe systemic disease associated with high fever, rash and lymph node enlargement. There are several types of JRA. The three major subtypes include:

1. Systemic
2. Polyarticular
3. Pauciarticular

In other countries, these diseases may be called "juvenile arthritis" or "juvenile chronic arthritis" which omits the "rheumatoid." The name of the diagnosis could change again in a few years as the pediatric rheumatologists around the world discuss and learn more about the disease.

How common is Juvenile Rheumatoid Arthritis (JRA)?

Juvenile rheumatoid arthritis is the most common type of arthritis in children. It is a chronic disease. This means it will probably last a long time. About 1 in 1,000 children have JRA. The number of new cases per year is estimated at 9 per 100,000 population. These numbers would tell us that about 40-50 children in the Cincinnati Tri-state area will be diagnosed with JRA each year.

How is JRA Diagnosed?

Juvenile rheumatoid arthritis (JRA) 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 resemble JRA. 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 JRA, arthritis must be present for at least 6 weeks in a row in the same joint. The arthritis may be present in one or more joints. Some children with systemic JRA may have high fever, rash, lymph node enlargement and other features with no 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 the arthritis is present.

There are several blood tests that help to evaluate your child or exclude other diseases. The tests do not make the diagnosis. Tests help categorize and identify internal markers or signs of arthritis, such as anemia or inflammation. Some children have positive blood tests but do not have arthritis.

The physical exam and the history are just as important as the blood tests. X-rays of the affected joints are helpful in the diagnosis; however, they are also helpful to exclude other diseases or to help follow the progress of disease as it can affect the cartilage and bone.

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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 lining, or synovium (si-no-ve-um). The synovium makes fluid that provides nutrition to the cartilage, or cushion, of the joint. When the synovium gets inflamed, it makes more fluid and the synovium becomes swollen. This causes the swelling that you can feel and see on the outside of the joint. The swelling can be painful and causes stiffness with lack of mobility of the affected joints.

There is a complex process going on in the synovium with different kinds of white blood cells and chemicals released by the white blood cells which cause the inflammation. This process could eventually affect the cartilage and underlying bone.

The rest of the body can also be affected by the inflammation. Patients with JRA are usually tired or fatigued. This is part of the effect on the entire body. Some patients also have fevers, rashes, lymph node enlargement and weight problems.

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 the
doctors will still check for it. Some patients 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.

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What causes JRA?

The exact cause of Juvenile Rheumatoid Arthritis is unknown. JRA 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 systems, especially in people who are predisposed because of genetic factors. The genetic factors seem to play the most significant role in pauciarticular JRA, with many genes being involved. Environmental factors appear to be more important in systemic JRA. Environmental factors may be an infection that is virus-related but other germs may be involved in different patients.

The main symptom of JRA is inflammation in the joints. In general, inflammation is necessary to protect us against germs, and it normally subsides when infection is cleared. In JRA, 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 JRA, are antiinflammatory drugs of different strengths. Some of them, in fact, have the ability to suppress the "over-reacting" immune system.

Although we still do not understand the exact cause of JRA, we have recently learned a great deal about what is responsible for chronic inflammation. We now know that two molecules called Tumor Necrosis Factor alpha (TNF-alpha) and Interlukin-1 (IL-1) are the major factors that keep inflammation in the joints active. This has led to the development of two new very effective drugs such as: Etanercept and Anakinra. These drugs selectively neutralize (work against) TNF-alpha and IL-1. Since they act selectively on the inflammation, they are very effective and relatively safe. We expect that more drugs like these will be developed in the near future.

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Is there a chance other family members, particularly other children in the family, will also get the arthritis?

JRA is not contagious. Even though we have mentioned infection and genetic factors, it is not common for other people in the family to develop this arthritis. Of course, there are occasional cases of JRA occurring in families, but this is extremely rare. As a matter of fact, one part of our ongoing research is to have a National Registry of all the brothers and sisters with JRA so that we can conduct a more organized approach to finding out why their families were affected in that way.

You may ask how this relates to other family members who already have some type of arthritis. Arthritis is one of the most widespread chronic conditions. The most common form of arthritis is osteoarthritis. Most people have family members, particularly in the older generations, who have osteoarthritis. In all likelihood, osteoarthritis does not relate to the JRA 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 JRA. There are certain genes that are more common in different types of diseases. However, the genetic component of arthritis is not yet fully understood.

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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 or have a way to offer a firm prognosis.

Some children will have only one joint affected throughout the entire course of their JRA. 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. Most children do not become "crippled" from this disease. This, however, is based on early aggressive medical therapy as well as a continuous physical therapy program for the joints (usually done at home each day).

As we gain more experience and follow our patients for 20-30 years, we find that the young children with JRA grow into productive adults. This does not necessarily mean there isn't some residual deformity or even active arthritis; however, this does show that the children do finish high school, pursue college educations and have productive careers, marriage and parenthood.

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Will the disease persist or recur in adulthood?

There is some information available about the persistence or recurrence of arthritis in adulthood. Approximately half of the patients 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. Exact numbers are not available on how many patients will have this disease during adulthood. Overall, however, we should remain optimistic as treatment options are constantly improving. We are also optimistic that the functional outcome of the children, as they become adults, will still be good and perhaps even better over time.

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What are the laboratory tests that you order for my child to help make the diagnosis?

There are several important points about laboratory tests. The first is that none of the tests confirm diagnosis of arthritis. That means that the diagnosis 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 prognosis and exclude other illnesses or conditions. In addition, lab tests can help us to follow your child for important measures of inflammation and for side effects from medications.

1. The first test that is often discussed is the erythrocyte sedimentation rate, ESR, or "sed rate." The sed rate is not diagnostic of any particular disease. The sed rate reflects inflammation in the system or tissue injury. 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. The sed rate has to be used in the context of each individual patient.
2. 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 rheumatoid arthritis. It is often called the "lupus" test. However, in children it is more common for patients with a positive ANA to have juvenile rheumatoid arthritis, since lupus is uncommon in young children. The ANA test is positive in about 2/3 of children with pauciarticular JRA Type I and about 1/3 (or more) of children with polyarticular JRA. Also, the ANA is a marker for patients at higher risk for development of eye inflammation.
3. The rheumatoid factor is a test that is commonly positive in adult 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 indicates "seropositive" polyarticular JRA. Seropositive polyarticular JRA is quite similar to 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.
4. Other common tests include a survey of the complete blood count, liver function, kidney function and muscle enzymes. 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 JRA 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.
5. Another test that may done is HLA-B27. This is a gene that is present in about 70-90% of patients with arthritis that affects the spine. Other tests include the complement proteins. The complement proteins usually decrease (or go down) when there is inflammation present in diseases such as lupus and other diseases causing inflammation in the small blood vessels. They are not usually decreased in JRA.
6. X-rays are often ordered to evaluate the structure of the bones. Remember that synovium and fluid cannot be evaluated on x-rays. Initially, the bones are evaluated for fracture, infection, or tumor. Later 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 on your child, the doctor will explain why the x-rays are being done.

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Types of JRA

Pauciarticular Jra (Type I)

Pauciarticular JRA is the most common form of juvenile rheumatoid arthritis. "Pauci" means few. By definition, this form of JRA has 4 or less joints involved during the first 6 months of disease. Approximately 40% of patients with pauciarticular JRA will go on to develop more than 4 joints over the course of the next few months to years. This is sometimes called extended pauciarticular JRA. This is because the arthritis went on to involve more than the original few joints and involve many joints.

Patients with pauciarticular JRA are generally divided into 2 categories which are quite distinct. The categories are "Type I" and "Type II" pauciarticular JRA. Type II occurs mostly in boys who have the onset of arthritis during late school age or adolescence.

The first group, Type I, is a group with onset of arthritis commonly before 5 years of age. The majority of these children are girls. The most common joint to be involved is the knee. However, ankles, wrists and elbows can also be affected. It is unusual, at least early in the course of this type of JRA, to have hip, neck, jaw, shoulder, or finger involvement. The most common blood test to be positive in this subgroup is the antinuclear antibody test or 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. 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 7 years of developing the arthritis. Visits to the eye doctor are usually 3 to 4 times per year, even if no symptoms affect the eyes.

Iridocyclitis – Uveitis, Iritis

Children and adolescents with JRA 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; pauciarticular onset JRA, Type I. The ANA, or antinuclear antibody test, is usually positive in this group. Most children will develop eye disease within 7 years of the onset of their arthritis if eye involvement is going to occur.

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 (Uveitis). The treatment for the eyes is separate therapy 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 problems. The slit lamp needs to be performed every 4-6 months for several years depending on which subtype of JRA your child has. The rheumatologist will inform you how often to get the slit lamp test.

Importantly, 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 tract of the eye examinations so we have a 5 year calendar to project the schedule for the upcoming slit lamp examinations.

Pauciarticular Jra (Type Ii)

Pauciarticular JRA is the most common form of juvenile rheumatoid arthritis. "Pauci" means few. By definition, this form of JRA has 4 or less joints involved during the first 6 months of disease. The first form of pauciarticular JRA Type I, affects young children, mostly girls, before five years of age. This second type of pauciarticular JRA, Type II, occurs mostly in boys who have the onset of arthritis during late school age or adolescence.

It is believed that there is a link between this group of children with pauciarticular JRA Type II and a family of arthritic conditions called spondyloarthropathies. "Spondylo" means spine; "arthropathy" means affecting the joint. Together these mean 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 pauciarticular JRA, Type II, 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. 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 bowel. 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.

Polyarticular Jra

Polyarticular JRA by definition involves 5 or more joints in the first 6 months. "Poly" means many. Patients with polyarticular JRA commonly 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 JRA 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.

Most children who have polyarticular JRA do not have a positive rheumatoid factor blood test like many adults with arthritis. The presence of rheumatoid factor, however, suggests that these children may have disease that is very similar to adult rheumatoid arthritis. These youngsters (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 blood vessels. We will talk with you more about these features if they occur.

Polyarticular patients are at less risk for developing eye inflammation than patients with pauciarticular JRA. Inflammation in the eye can occur in about 5 out of 100 polyarticular patients. This means that slit lamp examinations by the ophthalmologist need to be done every 6 months for the first few years of disease.

Systemic Jra

Systemic JRA is the form of juvenile rheumatoid arthritis which affects the entire body or "system," often before it affects the joints. The most common symptom is a high fever which usually occurs 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 will likely be a rash. This rash comes and goes. Only about 1 in 20 children will complain of any itching with the rash. The rash is not contagious. You will soon find that the rash is present wherever 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 lymph nodes, liver, and spleen are organs which react to the inflammation and can become somewhat enlarged in about 6 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. This can be a very difficult form of arthritis or 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 JRA 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. We will need to monitor the anemia for any changes over time.

Usually the systemic features of systemic JRA 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 JRA. However, only in a small group of children does it becomes 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. Luckily, involvement of the heart muscle is rare.

Patients with systemic JRA can also have growth problems and lack of weight gain. Specific attention to the nutritional needs and to close monitoring of your child's growth is necessary. Poor appetite is common and frustrating for many families. The nutritionist has great techniques to offer parents to help in this area.

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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 as an aid to understanding. 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 recall problems or questions when discussing your child's disease with doctor and nurse.

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What can be done to treat the arthritis?

The treatment approach for Juvenile Rheumatoid Arthritis (JRA) is multifaceted. 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. Each team member, including the family, rheumatologist, nurse educator, physical therapist, occupational therapist, nutritionist, ophthalmologist, orthopedist and psychologist, plays a special part in the treatment. Not all patients need each of the health care professionals. However, children with multiple affected joints usually see these health care providers intermittently through the course of their disease.

Briefly, we start with medication that works against pain and inflammation. This is usually a nonsteroidal antiinflammatory drug (NSAID), such as Ibuprofen, Naprosyn, or Tolmetin. Some patients need additional medications.

Many people have questions about deletions or additions to the diet that can be helpful in treating the pain and the inflammation. Some research has been done regarding the effect of diet on arthritis. However, there is no definite diet for treating arthritis. We are always strongly supportive of a well-balanced, nutritious diet. If there are questions regarding different types of diets that you may have learned or heard about, please discuss these with the physician, nurse, or nutritionist.

Some medications require some changes in your child's dietary needs. These would be discussed separately and recommended if your child is thought to need one of those medications. Sometimes there are special concerns about the growth of children with different types of JRA. Your child's growth, both height and weight gain, may need special nutritional evaluation and treatment.

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Treatment Goals of Family-Centered Care Team for Child with Juvenile Rheumatoid Arthritis (JRA)

• 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
• Cooperate and advocate with financial resources, i.e., insurance companies

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 often need to consult with other subspecialists, such as Orthopedics, Cardiology, Gastroenterology and Nephrology to address special needs of the children.

The strategy operates with the family in the center. This is called family-centered care. This requires careful evaluation of many areas of care and a sharing of information.

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How should we treat our child in terms of playing sports, attending school, restrictions and discipline?

School is very important, both academically and socially. The majority of children attend school regularly; however, special arrangements may need to be made in order to maximize the school experience. We will work closely to help you work with the counselors and school personnel in order to make your child's school experience rich and rewarding.

All of these issues are important to discuss with the health care team. Occasionally some restrictions are imposed during times of increased inflammation. We encourage regular school attendance and even participation in physical activities. Impact-loading or contact sports, such as basketball or football, may be too rigorous and potentially harmful for your child's joints. The age of your child and intensity of the sports program are also important factors. Swimming, bicycling, walking, and other strengthening exercises are all low impact activities and are strongly encouraged. Physical education is likewise important and can be modified if necessary so that your child can participate. These options will be discussed in more detail by the physical therapist and occupational therapist.

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Drug Treatment

Drug treatment is divided into several separate groups of medications (listed below) which have different effects, adverse reactions and strengths.

1. Nonsteroidal antiinflammatory drugs NSAID's
2. Slow-acting antiinflammatory drugs
3. Corticosteroids
4. Immunosuppressive drugs
5. Biological agents
6. 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 adverse reactions (or side-effects)
• allergies to medications

Nonsteroidal Antiinflammatory Drugs (Nsaid's)

The nonsteroidal antiinflammatory drugs (NSAID's) have 3 major purposes:

• decrease inflammation (antiinflammatory)
• 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 1-2 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 irritation. The central nervous system irritation means that children can become very irritable or "hyper." Most children tolerate the medications indefinitely, but talk with your nurse or doctor or pharmacist if you have concerns. The specific side-effects of each of the NSAID's will be explained.

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The most commonly used NSAID's are the following:

• Naproxen (Naprosyn)
• Tolmetin (Tolectin)
• Ibuprofen (Advil, Motrin, etc.)
• Indomethacin (Indocin)

Other NSAID's that may be used:

• Nabumetone (Relafen)
• Sulindac (Clinoril)
• Diclofenac (Voltaren)
• Celecoxib (Celebrex)

Slow-Acting Antiinflammatory Drugs

These are called slow-acting because the onset of action or benefit is usually several weeks or months. These medications tend to be stronger but also have more potential for side-effects.

The list of these medications may include the following:

• Methotrexate
• Hydroxychloroquine (Plaquenil)

This drug has become one of the best treatment options for a child whose disease is not well controlled by a NSAID's alone.

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The Corticosteroids Or "Steroids"

The corticosteroids are potent antiinflammatory drugs. These are not the same type of steroids used by body builders. We can give them either by mouth, infusion. 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.

Another way to give steroids is quite different, however. This is local injection of a long-acting corticosteroid put directly into a joint (or several individual joints) which gives prompt antiinflammatory action in the joint alone. This is a safe and routine procedure and can be done without significant discomfort.

Biological Agents

The biological agents have been used over the past few years in the treatment of arthritis. These drugs include:

• IVIG (intravenous gamma globulin)
• Etanercept (Enbrel)
• Infliximab (Remicade)
• Anakinra (Kineret)

These would be discussed in detail before administering these products to your child.

Immunosuppressive Drugs

This group is rarely used but may be necessary for severe unresponsive disease. These drugs include:

• Cyclophosphamide (Cytoxan)
• Azathioprine (Imuran)

These are in the "chemotherapy" family. There are many side effects which need to be carefully explained before starting these drugs. We will give you all of the necessary details if the situation arises for the use of one of these drugs.

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Investigational Drugs

We are a major center for research in pediatric rheumatology. Cincinnati Children's is the coordinating center for the Pediatric Rheumatology Collaborative Study Group. We are involved in research to test the use of medicines / products in the treatment of JRA. There are always protocols (or rules) and thoughtful attention paid to safety and effectiveness. If there is a product 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.

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Written 6/05