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Treatment of Childhood and Teenage Arthritis

Special Report

Thomas J.A. Lehman, MD
Pediatric Rheumatology, Hospital for Special Surgery
  1. Understanding Juvenile Idiopathic Arthritis (JIA)
  2. Oligoarthritis
  3. Extended oligoarthritis
  4. Polyarthritis - rheumatoid factor negative (RF-)
  5. Polyarthritis - rheumatoid factor positive (RF+)
  6. Systemic onset arthritis
  7. Arthritis associated with psoriasis
  8. Arthritis associated with enthesitis
  9. Arthritis associated with infection, or reactive arthritis
  10. Reactive Arthritis
  11. Understanding NSAIDs
  12. Considering Alternative Therapies

Understanding Juvenile Idiopathic Arthritis (JIA)

Pediatric rheumatologists have an important goal when they treat children with arthritis. We want to assure the best possible functional outcome - that means that children are able to function well in daily life, going to school every day and ultimately holding jobs and raising families like everyone else. To accomplish this, we must assure that we do our best to prevent underlying damage to their joints, bones, eyes, and other organs that can be damaged by the various types of arthritis that afflict children.

In the past all children with arthritis were lumped together under the name "juvenile rheumatoid arthritis" or JRA. Today, JRA is no longer an appropriate name because we know that there are many different causes of arthritis in children, just as there are in adults. Almost all of the different rheumatic diseases seen in adults also occur in childhood. So what we now call juvenile idiopathic arthritis (idiopathic means of unknown cause) or "juvenile inflammatory arthritis" - or JIA - has been divided into eight subtypes and in the future will probably be divided even further:

  • oligoarthritis;
  • extended oligoarthritis;
  • rheumatoid factor negative (RF-) polyarthritis;
  • rheumatoid factor positive (RF+) polyarthritis (also called early onset rheumatoid arthritis);
  • systemic onset arthritis;
  • arthritis associated with psoriasis;
  • arthritis associated with enthesitis;
  • arthritis associated with infection (also known as reactive arthritis).

Even this list doesn't cover every cause of childhood arthritis. There are many other causes of arthritis in childhood. These include systemic lupus erythematosus, dermatomyositis, scleroderma, Kawasaki's disease, and systemic onset vasculitis. (Of all the arthritic diseases seen in adults, only gout and temporal arteritis do not truly occur in childhood.)

Treatment Goals

The new names for different types of JIA are important because they enable physicians to recognize that they are dealing with different diseases in different groups of children. This is critical because each has its own best therapy and its own different prognosis (outlook). And what we expect for the future of these children differs depending on the disease. This also allows us to adjust our treatment appropriately.

It is very important to have the right diagnosis in order to assure that your child receives the best treatment and, therefore, the best possible outcome. That's why it's so important that any child with joint pains be seen promptly by a physician experienced in caring for children with arthritis - ideally a pediatric rheumatologist. Delay in proper diagnosis and treatment may lead to permanent damage to the joints, eyes or other organs. Mistaking a type of arthritis which is serious for a mild arthritis may delay proper treatment, while mistaking a mild arthritis for a severe one may lead to unnecessary medications and side effects.

Treatments for Severe Forms of Arthritis in Children

For children with the more severe forms of arthritis, it is crucial to see a physician who is experienced in children and in using the more the potent medications required to help change the course of the disease. Over time continuing arthritis damages the joints. We now know it is very important to stop this joint damage as soon as possible. Using medications which will stop joint damage is difficult because we must tamp down the immune system sufficiently to quiet the inflammation - but not so severely that your child is placed at serious risk for infection. It can be a difficult balancing act for a physician who is unfamiliar with these medicines. As a parent you need to be alert for any exposure to or signs of infection in your child - such as a high fever or rash - and report them to your child's doctor immediately. In some cases, the drug may have to be temporarily discontinued, especially if the child has been exposed to a potentially serious infection, such as chicken pox.

Types of Arthritis in Children


"Oligo" is the Latin word for "few." Typically, oligoarthritis is seen in young children with fewer than five joints involved during the first six months of disease. Characteristically, this disease affects large joints - almost exclusively the knees and ankles, rarely the wrists or elbows. True oligoarthritis never starts with finger or hip involvement, even though there may be less than five joints involved.

An interesting part of this disease is that it always comes on very slowly and subtly. Parents can almost never remember when it started. They recall that 'for a while' the child has looked funny when he or she first starts walking in the morning. However, it always got better after 30 or 40 minutes, and the parents usually say, "We just thought she must have slept on it wrong."

It is far more frequent in girls than boys. Usually, it starts between one and five years of age. (If oligoarthritis occurs over the age of nine, begins in the hips, or begins with involvement of a finger, it is not oligo JIA; rather, it is likely to be enthesitis-associated arthritis or another type of arthritis. This is important because the best therapy and the normal outcome are different).

Blood tests often reveal that children with oligoarthritis are positive for a marker called anti-nuclear antibodies (ANA). This indicates that they are at increased risk for an eye disease called uveitis. All children with oligoarthritis need to be monitored regularly by an ophthalmologist who is familiar with this disorder.

Outlook: True oligoarthritis is one of the types of arthritis that children usually do outgrow. With proper care, most children can escape the side effects of this disease. However some children are left with a difference in their leg lengths, which proper treatment may help prevent and/or eye disease. The eye disease may cause permanent damage and even blindness if not properly detected and treated. Unfortunately the eye disease is not painful and parents may not be aware of the problem until long after the child has developed permanent eye damage. This is just one of the many reasons why it is essential that every child with oligoarthritis be properly evaluated and treated and not simply dismissed as having growing pains.

Treatment: Therapy is usually very simple. Nonsteroidal anti-inflammatory drugs (NSAIDs) are almost invariably effective for these children. Injections of corticosteroid drugs directly into inflamed joints (intra-articular steroids) may help prevent a leg length discrepancy, although it won't help every child. These children should not need oral steroids or immunosuppressive drugs, such as methotrexate.

Some children with oligoarthritis can have a significant anemia (a hemoglobin of less than 11) or an elevated sedimentation rate (higher than 40). These children most likely will turn out to have a more serious polyarthritis over time. Children with oligoarthritis should not have a rash nor fever associated with their arthritis. Those who do are more likely to have an infection or another cause for their arthritis. These signs can also be seen with serious polyarthritis - which must be treated much more aggressively.

Extended oligoarthritis

Children with this extended form of oligoarthritis start out with four or fewer joints involved during the first six months of disease but, over time, more joints become involved.

Outlook: Children with this form are at high risk of having long-lasting, permanent arthritis that they don’t grow out of and requiring more aggressive therapy.

Treatment: While treatment starts with NSAIDs, your physician will likely prescribe more potent medications as soon as it becomes clear that your child has extended oligoarthritis. These children need disease-modifying anti-rheumatic drugs (DMARDs) that help suppress the immune system and limit damage to the bones and joints. Helpful drugs include hydroxychloroquine (brand-named Plaquenil), sulfasalazine (Azulfidine), and methotrexate (Rheumatrex). The good news is that 80 to 90% of this group will respond to one of these drugs and not need anything further. For those who don't respond, biologic drugs such as etanercept (Enbrel), infliximab (Remicade) or other immunosuppressive medications, such as azathioprine (Imuran) or cyclosporine (Neoral or Sandimmune), may be necessary. Oral steroids are virtually never necessary in this age group.

Polyarthritis - Rheumatoid Factor Negative (RF-)

"Poly" means "many," and rheumatoid factor (abbreviated RF) is a marker found in blood tests. Thus, in this type of childhood arthritis, the child does not have RF (i.e. is "negative") and has more than four joints are involved during the first six months of disease. Blood tests also may reveal that they have high sedimentation rates.

This form of arthritis distinguishes itself from others by:

  • The involvement of more than four joints (Poly) during the first six months of the disease;
  • The absence of rheumatoid factor (RF) marker in the blood, (noted as RF-);
  • The absence of a rash;
  • It afflicts girls more often than boys;
  • High sedimentation rates of the blood

Symptoms develop gradually over a number of weeks. (When symptoms develop explosively in multiple joints, it is most likely arthritis associated with infection or another type - not RF- polyarthritis.) Although it does not typically occur in very young children, it can occur in any age group.

Outlook: RF- polyarthritisis a chronic recurrent condition and a much more aggressive disease than oligoarthritis. Although from time to time it may seem to be "gone," it often will come back again.

Treatment: Although NSAIDs help ease pain, your physician will likely move forward to DMARDs, such as hydroxychloroquine, sulfasalazine, methotrexate, or etanercept in order to limit permanent damage to the joints as much as possible.

Note: There are many subgroups of children within the RF- polyarthritis category. This category should still be viewed as "under construction." Many children with RF- polyarthritis actually have psoriasis-associated arthritis (described below). However, because so many people are confused between the definitions of psoriasis and seborrhea - two totally different skin conditions - the committee working on the proper names requires that you have physician-diagnosed psoriasis in order to be included in the psoriasis-associated arthritis category.

If there is a family history of psoriasis, the child should not be included in the RF- polyarthritis category. That leaves a lot of children without a definite label. It doesn't mean these children don't have the disease -- only that our system of names is still "under construction". Fortunately, the name does not matter because, at the present time, we use the same set of medications for children with psoriatic arthritis, psoriasis-associated arthritis, and RF- polyarthritis.

Polyarthritis - Rheumatoid Factor Positive (RF+)

As the name indicates, the child has RF (is "positive" on this blood test). When this type of arthritis occurs in teenagers, it represents the early onset of adult type rheumatoid arthritis and should be treated aggressively. When children under age ten are RF+, it more likely signals a different rheumatic disorder, such as mixed connective tissue disease, hepatitis or bacterial endocarditis.

This form of arthritis distinguishes itself from others by:

  • The involvement of more than four joints (Poly) during the first six months of the disease;
  • The presence of rheumatoid factor (RF) marker in the blood, (noted as RF+);
  • It afflicts girls more often than boys;
  • ANA positive test reading;
  • High sedimentation rates in the blood.

Outlook: This is a serious form of chronic disease that can cause progressive joint destruction over time.

Treatment: Aggressive treatment should be initiated as early as possible to prevent damage. In addition to NSAIDs, these children need immunosuppressive therapy to try to alter the course of the disease. Typical DMARDs used include hydroxychloroquine, sulfasalazine, methotrexate, etanercept, infliximab and other biologics. If severe bone damage occurs, joint replacement surgery may be necessary.

Systemic Onset Arthritis

Systemic Onset Arthritis affects not only the joints but the whole body. Children with this form of disease typically have fevers and rashes, which is why it is called systemic. In fact, the arthritis in the joints may not even be obvious at the outset. However, in contrast to all other forms of childhood arthritis, joint problems may begin with the hips. (Remember, the actual hip joint is in the groin; so that's where the pain will be - not on the outer side of the buttocks, which many think of as their hips.)

Children with this disease often start with unexplained high fevers - even over 104 - although the fever falls back to normal at least once a day. Girls and boys are equally affected, and it can occur at any age. Initially, there can be marked elevation of the white count and platelet count.

Outlook: The course of systemic onset arthritis is highly variable. Some of these children recover completely. Others, especially teenage boys, seem to be left with some mild wrist involvement and occasional rash with exertion. Other children have a very severe, chronic, destructive course and do poorly.

Treatment: Although therapy begins with NSAIDs, aggressive treatment with DMARDs is often required to get the disease under control and prevent progression and bone damage. It is important to begin aggressive therapy as soon as it is clear that the child is not going to quickly respond to NSAIDs. Commonly used drugs include hydroxychloroquine, sulfasalazine, methotrexate, azathioprine, and cyclosporine. None of these medications will work for every patient every time. However, one is likely to work for your child. If not, your physician may try one of the new biologics, such as etanercept (Enbrel), infliximab (Remicade), or anakinra (Kineret). The newest medication shown to be very effective for these children is thalidomide (Thalomid).

Note: When children are in such severe pain that they cry out simply from being touched or if they have a low white count or a low platelet count, the problem is most likely not arthritis. Such children should be carefully evaluated for other disorders, such as infection, leukemia, lymphoma, or other types of cancer.

Treatments under Research for Children with Systemic Onset Arthritis:

Etanercept has yielded some extraordinarily dramatic outcomes. It doesn't work for every child every time, but it looks to be a very good drug for children who have failed first line therapy, although there is a risk of reduced efficacy over time. In some instances, it may be used in conjunction with methotrexate. It is given as an injection at home, just as people with diabetes self-inject. In addition to the risk of serious infection, etanercept has been associated with drug-induced lupus and possibly some clotting abnormalities. Fortunately, these side effects are very rare. Runny nose, pain at the injection site, mild bruising, and occasional headache have all been reported; for a child who is doing dramatically better on the drug, these are not significant side effects.

Infliximab is given as an intravenous (IV) infusion in the hospital, clinic, or doctor's office at period ranging from once every four to eight weeks. It has also been used extensively with success in adult rheumatoid arthritis. Although it has been used in children, it seems to be associated with an increased risk of infection, especially in the higher doses that have been tried in some children with systemic onset disease. However, it has been of great benefit for some children.

The newest biologic is anakinra (Kineret), also successful in adults and now being tried in children. Unfortunately this drug requires injections every day. On the horizon is yet another biologic, adalimumab. It has been used in some children in preliminary studies, appears to be a very effective drug, and only requires one injection every two weeks. Again, both of these are injected at home.

Doxycycline, an antibiotic that also has anti-inflammatory benefits, may help this type of arthritis. It can't be used in children under the age of 10, because it will permanently stain their teeth. However, it has been shown to be a good agent for the long term in teenagers. Unfortunately, although many take it for acne, teenagers don't tolerate doxycycline well; they often report stomach upset and only about 25% will stay on it. It is important to realize that doxycycline has been linked to drug-induced lupus.

Combinations of Immunosuppressives

Researchers are also exploring the use of combinations of immunosuppressives; the use in children of other medications used in adults, such as leflunomide (Arava) and mycophenolate mofetil (CellCept); and thalidomide (Thalomid). Although thalidomide caused terrible birth defects when given to pregnant women, it has proven of great benefit for selected diseases related to the immune system. In many children with very severe arthritis that was not responding to any other medications, thalidomide has provided relief. However, it must be used with great caution to avoid exposure to women who are or might become pregnant and their partners. Like all of these medications it should only be used by physicians with experience using it in children with chronic disease.

Bone Marrow Transplants

You may have read in the newspapers about physicians using autologous bone marrow transplantation to treat serious rheumatic diseases. The initial results were very promising, but when the number of children transplanted increased to 24, four deaths occurred. For a while this program was halted for careful reassessment. Transplants have now begun again very carefully. This should be done only in an experienced center and only as a last resort when all medications have failed.

Arthritis associated with psoriasis

It's important to understand that a child does not need to have psoriasis in order to have the arthritis associated with psoriasis. This arthritis follows the same pattern that is seen in people who have arthritis with clear cut psoriasis, also known as psoriatic arthritis. Further, when these children are followed for a long period of time, many of the children who do not have psoriasis at the onset of their arthritis develop psoriasis ten to 20 years later. That is how we know these two conditions are associated with each other. Plus these children often have a family history of psoriasis in a first degree relative.

The initial symptom in these children may be dactylitis, which is a swollen finger or sausage digit. Typically it appears as a very swollen finger or toe. In blood tests, children with arthritis associated with psoriasis are often ANA positive, which can be a marker for risk of eye disease. Therefore,children should be checked regularly by an ophthalmologist to minimize the risk of permanent eye damage by detecting and treating it early.

Outlook: Often the original joint responds very nicely to therapy with NSAIDs and the arthritis disappears - but the arthritis often returns months or years later. The disease is recurrent and chronic, so the child should be monitored carefully. Aggressively treated, children can do well. The biggest risk for children with arthritis associated with psoriasis comes from parents who don't want to admit that the arthritis is back. As a result, they delay returning to the doctor until the arthritis has a good head start and bone damage has already occurred.

Treatment: NSAIDs may be sufficient in the initial stages. But when the disease progressively recurs, these children often need sulfasalazine. If they are allergic to sulfa drugs, hydroxychloroquine may be substituted. Many require methotrexate. Others may require etanercept, another biologic, or cyclosporine.

Arthritis Associated with Enthesitis

Enthesitis is inflammation of the entheses - the points where tendons attach to bone. Thus, although these children may have swollen joints, the key symptom is pain around the joint (periarticular pain) where the tendons insert. This is often misdiagnosed as a child who is clumsy, with recurrent sport injuries, frequent strains or sprains. The most common symptoms are heel pain, Achilles tendon pain, and/or wrist pain. Often these children also have back stiffness or hip stiffness, although they may angrily deny it, focusing instead on the joint problem. They are typically misdiagnosed as 'injuries' by physicians unfamiliar with arthritis.

Enthesitis-associated arthritis typically occurs in teenagers, boys more often than girls. About half are positive for a marker in the blood called HLA-B27. About 25% of them may develop arthritis that significantly affects the back, and they may evolve into a disorder called ankylosing spondylitis later in life. Often there is a family history of back pain, frequently chalked up to an "old athletic injury" and typically in fathers and uncles, that turns out to be the same disease.

Outlook: There is a mixed prognosis for children with arthritis associated with enthesitis. Many find it only a chronic inconvenience. However a few go on to develop ankylosing spondylitis. Children who have sacroiliac joint involvement on X-ray, are likely to need significant DMARD therapy, especially those who are HLA-B27 positive. Children who have a normal sedimentation rate at diagnosis tend to do well.

Treatment: Therapy starts with NSAIDs. For those who need DMARDs, drugs commonly prescribed include sulfasalazine, hydroxychloroquine, and methotrexate, and most patients get well with one of these agents. When first line drugs fail, etanercept works well. Experience with other biologics is limited.

Arthritis Associated with Infection, or Reactive Arthritis

Arthritis associated with infection, or reactive arthritis, is probably the most common cause of arthritis in childhood. It usually follows a bacterial or viral infection. Although it may be severe at the beginning, most of the children with this condition recover completely over time.

Reactive Arthritis

Reactive arthritis, also known as Reiter's Syndrome, is rare in children and distinguished by the occurrence of arthritis, urethritis, and conjunctivitis. Children will sometimes have rashes, particularly on their hands and feet. They may also have severe, painful, acute anterior uveitis (swelling and irritation of the uvea, the middle layer of the eye.)

Diagnosis: For a diagnosis of reactive arthritis, arthritis, urethritis, and conjunctivitis do not have to all be present on the same day. They may occur one after the other without ever overlapping in time.

Treatment: The most important step in the treatment of children with infection-associated arthritis, including Lyme disease and Reiter’s syndrome, involves making sure the infection is properly treated. Once it is clear that the infection associated with the arthritis is no longer active, children should be treated just like other children with spondyloarthropathies.

Most respond well to easily tolerated NSAIDs, but some may require indomethacin during the early phase of their arthritis. In most cases, the illness resolves completely over a period of a few months. Second-line agents are rarely required, but some children benefit from the addition of sulfasalazine. Although intra-articular injection of corticosteroids may be useful if a single joint remains troublesome after the infection has been fully treated, oral corticosteroids are rarely necessary.

Physical therapy to maintain strength and range of motion is often necessary during the acute phase of the reiter's syndrome. Surgery should not be necessary for a child with infection-associated arthritis unless it is necessary for treatment of the infection.

Once the infection is properly treated and has resolved, the long-term prognosis for children with infection-associated arthritis is very good. Occasionally, children have recurrent episodes of arthritis with subsequent infections. Rarely, children may have an episode of infection-associated arthritis, recover, and then develop persistent spondyloarthropathy years later.

Understanding NSAIDs

In the early 1970s, medical scientists discovered how aspirin works to help arthritis: by inhibiting an enzyme called cyclooxygenase (COX) that is involved with pain and inflammation. Subsequently, more than two dozen nonsteroidal anti-inflammatory drugs (NSAIDs) were developed to inhibit COX. Some are sold over the counter, such as ibuprofen (Advil, Motrin) and naproxen (Aleve). Others are available by prescription only and may be more efficacious.

However, in the early 1980s, it was discovered that there were two COX enzymes. COX-2 was believed to be responsible for pain, fever and inflammation, but COX-1 was found to have the positive effect of protecting the gastrointestinal tract.

That finding resulted in a new generation of pain and inflammation relievers called COX-2 inhibitors. These newest NSAIDs selectively neutralize only COX-2, but largely ignore COX-1, thus lowering that risk of stomach ulcers and gastrointestinal bleeding traditionally associated with NSAIDs. However, they are not any more effective than the older NSAIDs - and are a lot more expensive. The COX-2 inhibitors include celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra).

If your a child is well controlled on a regular NSAID and does not have gastrointestinal symptoms, there is no reason to switch over to a COX-2 inhibitor.

Considering Alternative Therapies

Glucosamine and Chondroitin Sulfate
Many people have heard that the dietary supplements glucosamine and chondroitin sulfate can help arthritis. However, they have only been shown to help osteoarthritis, a non-inflammatory type of arthritis that afflicts older adults. The benefits are relatively mild, and it may increase the incidence of stomach upset. No beneficial effect in childhood arthritis has ever been shown.

Fish Oils
Fish oils (the Omega-3 fatty acids) have been extensively studied in inflammatory arthritis. Although they may help inflammation, significant benefit is only achieved through the consumption of a large number of capsules. Further, according to large studies conducted in the 1980s, the benefit is only temporary. By six months, the body readjusts and the same inflammatory state reappears.

Other Alternative Therapies
Virtually every other alternative therapy - from device, to procedure, to supplement - is worthless. Any short-term benefit they provide is likely due to the placebo effect. That is, if you take something and believe it will help, it may help temporarily. That's how powerful our minds are. Thus, magnets have been shown not to work; you can give people black plastic discs that are not magnetized and you get the same response rate. Copper bracelets don't work. No special diets work; if you put people on a "no nightshades" diet, about 30% will feel better, but so will 30% of those given extra tomatoes, potatoes, mushrooms, etc. It doesn't make a difference.

If you are considering a "dietary supplement" for your child, it's important to remember that they are manufactured in facilities without any kind of government supervision. There is no proof that these dietary supplements are safely made, contain the ingredients they claim they contain, or are safe to give to children. When analyzed, some have even been found to be contaminated with heavy metals and other substances that none of us would want our children to have. They are best avoided.


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