Still's Disease

A salmon-colored rash may be a sign of juvenile RA.

Still's disease, a disorder featuring inflammation, is characterized by high spiking fevers, salmon-colored rash that comes and goes, and arthritis. Still's disease is also referred to as systemic-onset juvenile idiopathic arthritis. Still's disease was first described in children, but it is now known to occur, much less commonly, in adults (in whom it is referred to as adult-onset Still's disease or AOSD). Still's disease is named after the English physician Sir George F. Still (1861-1941).

Still's disease accounts for 10%-20% of all cases of JIA. It affects about 25,000-50,000 children in the United States. It is rare in adults, a majority of whom are 20-35 years of age at the onset of symptoms.

There have been a number of schools of thought regarding the cause (or causes) of Still's disease. One concept is that Still's disease is due to infection with a microbe. Another idea is that Still's disease is an autoimmune disorder. In fact, the precise cause of Still's disease is not yet known.

There are no specific known risk factors for the development of Still's disease.

Still's disease is one type of juvenile idiopathic arthritis (JIA) and is also known as systemic-onset JIA. It is referred to as "juvenile" because it typically affects children under 16 years of age. By systemic, it is meant that along with joint inflammation it typically begins with symptoms and signs of systemic (body-wide) illness, such as high fevers, gland swelling, and internal organ involvement. By idiopathic, it is meant that the disease has no known cause.

Systemic-onset JIA was formerly known as systemic-onset juvenile rheumatoid arthritis (JRA) and is the same disease. Several years ago, the naming system for all types of JRA changed, and JRA is now called juvenile idiopathic arthritis or JIA.

Still's disease usually begins with systemic (body-wide) symptoms.

• Extreme fatigue can accompany waves of high fevers that rise daily to 102 F (39 C) or even higher and rapidly return to normal levels or below.
• Fever spikes often occur at approximately the same time every day.
• A faint salmon-colored skin rash characteristically comes and goes and does not itch.

Other Still's disease symptoms and signs include the following:

• Poor appetite, nausea, and weight loss are common.
• There is also commonly swelling of the lymph glands, enlargement of the spleen and liver, and sore throat.
• Some patients develop inflammation around the heart (pericarditis) and lungs (pleuritis), with occasional fluid accumulation around the heart (pericardial effusion) and lungs (pleural effusion).
• Arthritis, with joint swelling, often occurs after rash and fevers have been present for some time.
• Although arthritis may initially be overlooked because of the impressive nature of the systemic symptoms, everyone with Still's disease eventually develops joint pain and swollen joints.
• This usually involves many joints (polyarticular arthritis). Any joint can be affected, although there are preferential patterns of joint involvement in Still's disease.

Of all patients with Still's disease, 100% have high intermittent fever, and 100% have joint inflammation and pain, muscle pain with fevers, and develop persistent chronic arthritis. Approximately 95% of Still's disease patients have the faint salmon-colored skin rash, 85% have swelling of the lymph glands or enlargement of the spleen and liver, 85% have a marked increase in the white blood cell count, 60% have inflammation of the lungs (pleuritis) or around the heart (pericarditis), 40% have severe anemia, and 20% have abdominal pain.

Still's disease is diagnosed purely on the basis of the typical clinical features of the illness.

• These features include high intermittent fever, joint inflammation and pain, muscle pain, faint salmon-colored skin rash, swelling of the lymph glands or enlargement of the spleen and liver, and inflammation around the heart (pericarditis) or lungs (pleuritis).
• Persistent arthritis (arthritis lasting at least six weeks) is required to make a firm diagnosis of Still's disease.
• Other diseases (especially infections, cancers, and other types of arthritis) must be excluded.

Many patients with Still's disease develop markedly elevated white blood cell counts, as if they have a serious infection, but no infection is found.

• Low red blood counts (anemia) and elevated blood tests that indicate inflammation (such as erythrocyte sedimentation rate or ESR, C-reactive protein, and ferritin) are common.
• However, the classic blood tests for rheumatoid arthritis (rheumatoid factor) and systemic lupus erythematosus (antinuclear antibodies) are usually negative.

Still's disease is treated by primary care physicians, including pediatricians, internists, general practice, and family practice physicians.

• Typically, these primary care doctors work with either pediatric or adult rheumatologists in caring for these patients.
• Depending on organs affected, other specialists who can be involved in the care of patients with Still's disease include
  • cardiologists,
  • pulmonologists,
  • orthopedic surgeons,
  • physical therapists, and
  • occupational therapists.

Still's disease can cause serious damage to the joints, particularly the wrists. It can also impair the function of the heart and lungs. Treatment of Still's disease is directed toward the individual areas of inflammation. Many symptoms are often controlled with anti-inflammatory drugs such as aspirin or other nonsteroidal drugs (NSAIDs). It has been reported that some patients with Still's disease can frequently have elevations of liver function blood tests as a side effect of aspirin and sometimes other anti-inflammatory medications. Cortisone medications (steroids) such as prednisone are used to treat more severe features of illness.

For patients with persistent illness, medications that affect the inflammatory aspects of the immune system are used. Medications now being used are analogous to the classic "second-line" therapies used for patients with rheumatoid arthritis. These include hydroxychloroquine (Plaquenil), etanercept (Enbrel), penicillamine (Cuprimine, Depen), adalimumab (Humira), azathioprine (Imuran), canakinumab (Ilaris), methotrexate (Rheumatrex, Trexall), infliximab (Remicade), and cyclophosphamide (Cytoxan).

Recently, because Still's disease has been found to involve a specific chemical messenger of inflammation known as interleukin 1 (IL-1), the injectable biologic medication anakinra (Kineret), which blocks IL-1, has been found to be a very effective treatment for Still's disease. Still's disease also involves interleukin 6 (IL-6). Tocilizumab (Actemra), an intravenous treatment that blocks IL-6, is approved to treat systemic JIA in children.

The fever and other systemic features tend to run their course within several months. The arthritis can be a long-term problem. It usually stays on after the systemic features have gone.

• The arthritis can then become chronic and persist into adulthood.
• Persisting arthritis of the wrists, with eventual fusion, is common, especially if not treated aggressively.
• Newer biologic treatments are likely to be beneficial in stopping the progressive joint damage.

There is no prevention for Still's disease.