What is JIA?

Professor Tauny Southwood BM BS FRACP FRCP FRCPCH, Professor of Paediatric Rheumatology  20
at the University of Birmingham and Director of Research and Chair of the EULAR Standing Committee for Paediatric Rheumatology
Original article: 20/06/2002
Reviewed: 07/11/2010
Next review due: 07/11/2013


Juvenile Idiopathic Arthritis (JIA) is usually considered to be a rare disease of children and sometimes goes unrecognised for many weeks or even months. Even after diagnosis, many JIA patients and families feel isolated and alone. However, it is one of the commonest causes of physical disability that begins during childhood. In the UK, between 10,000 and 15,000 children under the age of 16 years are affected by the disease. There are many UK centres specialising in the clinical care of children with JIA. Most centres also provide teaching and training for medical students, doctors and other healthcare professionals, and support research programmes to improve understanding of the disease.

The aim of this article is to highlight some of the most important recent advances in knowledge about JIA. The article is divided into 3 sections:

1. Why is the diagnosis of JIA often delayed?

2. How are the effects of JIA measured?

3. What are the recent advances in JIA treatment?


Why is the diagnosis of JIA often delayed?
Arthritis means inflammation (swelling, pain and stiffness) of one or more joints such as the knees, hips or even the small joints of the fingers. JIA refers to persistent arthritis (lasting for more than 6 weeks), without an identified cause, which begins in a child before they become 16 years old. The earliest features of JIA are often non-specific, general symptoms of poor health such as reduced appetite, increased tiredness and irritability. Even when joint swelling occurs, it may not be noticed. Young children in particular may have difficulty in communicating symptoms of joint pain and joint stiffness. These factors contribute to the diagnostic delay which often occurs in children with JIA. General practitioners and paediatricians must be aware of the possibility of JIA in a child who appears unwell without any obvious cause.

The difficulty in diagnosis is compounded by the absence of a diagnostic test. Even the commonest laboratory abnormality associated with adult type rheumatoid arthritis, a positive rheumatoid factor test, is very rarely found in JIA. Most laboratory tests are only useful to rule out other causes of childhood arthritis, such as infection, injury or even leukaemia. There are over 100 diseases associated with arthritis in children, and exclusion of these can be quite a painstaking process. Most cases of JIA, however, present with typical patterns of clinical features, which make the diagnosis obvious to the experienced paediatric rheumatologist.

There are 7 relatively unique patterns of JIA, some of which carry an increased risk of poor outcome and justify more aggressive treatment approaches.

1. Persistent oligoarthritis: only ever affects 4 joints or less, and has the best outlook of all of the varieties.

2. Extended oligoarthritis: begins just like persistent oligoarthritis but then spreads to involve many joints.

3. Polyarthritis, rheumatoid factor negative: begins with many inflamed joints and testing for rheumatoid factor is negative.

4. Polyarthritis, rheumatoid factor positive: is more often seen in teenage girls and testing for rheumatoid factor is positive. This subtype carries one of the worst outlooks of all JIA.

5. Systemic arthritis: this subtype often has prominent clinical features such as fever, enlarged glands, and occasionally inflammation of the heart and other internal organs. Arthritis of many joints may be a major long term problem.

6. Psoriatic arthritis: this may be difficult to diagnose in children as the typical rash of psoriasis may be relatively hidden (in the scalp, the belly button, behind the ears or in the groin) and may not occur until many years after the onset of arthritis.

7. Enthesitis Related Arthritis (ERA): this form of arthritis affects mainly older boys and teenagers. As well as arthritis, there may be inflammation and pain in the soles of the feet, behind the heels and around the hips. This subtype of JIA may evolve to ankylosing spondylitis during the adult years.

There are many possible complications which may occur in JIA. Growth may be reduced, and osteoporosis may occur. “Silent” inflammation of the eyes (chronic anterior uveitis) can be a difficult problem, as it can only be detected using “slit lamp” equipment and may cause blindness if not detected early enough. Other body systems can also be affected, including the skin, heart, lungs and abdomen.


How are the effects of JIA measured?
It is often difficult to judge if a child with JIA is improving or deteriorating, yet this judgement is very important for decisions about treatment. The affected child and their parents can give an opinion on whether they are getting better, and the healthcare professional can gain an impression of progression of clinical features on physical examination, comparing the findings with previous documentation in the patient’s notes. These subjective means of measurement are not ideal for comparing response between visits, or between patients, or indeed between groups of patients. Even images of the joints using x-rays or MRI scans may not be ideal, as the results may lag behind the clinical stage of the disease.

To improve the objectivity of measurement, a score can be calculated from 6 standardised “outcome” measurements. This is particularly useful for research, as the “core outcome variables” can be used to judge success or failure of a particular treatment. The core outcome variables are:

1. Parent’s or child’s global assessment of well-being: This is the parent’s or child’s judgement of how well they are. It is recorded as a mark along a 10cm line ranging from “the worst ever” at one end to “the best ever” at the other.

2. Physician’s global assessment of disease activity: A similar scale to 1, except that the physician assesses the activity of the arthritis.

3. Number of joints affected by active arthritis: How many joints are affected by acute inflammation with swelling, heat and redness?

4. Number of joints with restricted range of movement: How many joints are unable to move through their expected range.

5. The function of the child: Usually assessed by a questionnaire (eg childhood health assessment questionnaire, CHAQ).

6. A blood test measurement of inflammation: Either a CRP or ESR.

A more recent set of outcome measures, the Juvenile Arthritis Disease Activity Score (JADAS), has been proposed and tested. This has the advantage of being a useful guide of treatment response for individual patients from one clinic visit to the next and may be useful for comparisons of disease activity between individual patients. Of course, JIA affects many other aspects of health, such as growth, appetite, energy levels, pain, and stiffness. Any of these can be used to judge improvement, but they may be quite variable and difficult to standardise.

What are the recent advances in JIA treatment?

It is now widely accepted that the treatment of JIA should involve a well-trained, experienced multidisciplinary team of clinicians, including paediatric rheumatologists and other doctors (eg eye specialists, dentists, orthopaedic surgeons), nurses, physiotherapists, occupational therapists, social workers, psychologists and community healthcare workers. In addition, it is accepted that children and adolescents affected by JIA, and their families, deserve thorough disease education and counselling early in the disease process, and a programme of transition as they move towards rheumatology care in their adult years.  The British Society for Paediatric and Adolescent Rheumatology (BSPAR) has recently proposed Standards of Care for children and adolescents with JIA and their families.

The drug treatment of JIA has become more aggressive over the last few years, as it has been recognised that early control of the inflammation probably improves the prognosis of the illness. Early drug treatment includes the use of simple analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) by mouth, intra-articular corticosteroids, and methotrexate, often by subcutaneous injection, although the optimal dose of this drug is still debated. Even with this approach, however, up to 30% of children with JIA will continue to have disease that is not well controlled. There have been some recent attempts to find out why some children with JIA do not respond or develop side effects to methotrexate.  It is possible that children with a longer duration of uncontrolled arthritis respond poorly, and it may be possible to predict side effects from the genetic background of the patient.  It has also been difficult to know when to stop methotrexate in a child who has responded to the treatment.  Recent research has suggested that disease control for 6 months may be sufficient and the chances of remaining in remission may be higher if there are no, or at least very low, signals of inflammation in the blood as well.

Over the last 10 years, new drugs and treatment approaches have been tested in children with JIA who have either failed to respond completely to standard treatment, or had unacceptable side effects.

A wide variety of drugs have now been synthesised to mimic naturally occurring biological chemicals in the body, hence the term “biologics”. Several drugs block chemicals called “cytokines” such as TNF, IL-1 and IL-6, all of which contribute towards inflammation.

Etanercept (Enbrel) was the first TNF blocker to be tested in JIA and the most recent studies have indicated that it appears to be relatively safe and effective in the medium to long term.  Other TNF blockers, infliximab (Remicade), and adalimumab (Humira) also appear to be effective in treating  children with JIA affecting many joints.  There have been some recent concerns that there may be an increased risk of cancer in JIA patients treated with TNF blockers, although recently published studies have suggested that the risk is very low and may be due to the disease of JIA itself rather than the etanercept treatment.

The IL-1 blocker anakinra (Kinaret) and IL-6 blocker tocilizumab (RoActemra) appear to be useful in treating children with systemic arthritis and are still being tested in randomised controlled trials. Abatacept (Orencia) interferes with cells of the immune system which normally help the body to deal with infection. It has been used effectively to treat children with JIA.

Long-term follow-up studies for all of these new drugs are being conducted to be sure that the new treatments are safe. A major disadvantage, however, is the expense of the drugs. This currently limits its availability in the UK. It should be remembered that there are many other “biologic agents” being developed and tested at present, and it is likely that these will have important benefits for children with JIA in the future.

For the most severe cases of JIA, which are not controlled by any currently available drugs, the last resort is to use a procedure called “autologous stem cell transplantation”. For this treatment, some of the patients own immune system cells are saved, cleared of the cells that cause the chronic inflammation of JIA, and then used to “rescue” the patient after inflammation their immune system is “wiped out” with anti-cancer type doses of chemotherapy drugs. This has  been effective in JIA, but is a risky procedure too, as it places the patient at great risk of infection temporarily.

In summary, the understanding and treatment of JIA is better than it has ever been. Important breakthroughs have been made over the last 5 years and many more exciting possibilities for effective treatment are on the horizon.

References available on request