Adult Onset Still's Disease

Juan Javier Lichauco, M.D., Jayashree Sinha, M.D.,, and Peter Barland, M.D.

Drs. Lichauco and Sinha are Fellows in Rheumatology, Department of Medicine, Montefiore Medical Center and the Albert Einstein College of Medicine, New York.

It's mysterious and it's rare. A form of rheumatoid arthritis, Still's Disease mainly affects children. But there's even a rarer form which strikes adults -- Adult Onset Still's Disease (AOSD).

AOSD is an inflammatory condition that attacks internal organs, joints and other parts of the body. It can appear and disappear suddenly. In very severe cases, AOSD becomes chronic and extremely debilitating, causing terrible pain and stiffness. After many years, the disease cripples vital organs such as the heart and lungs.

There are treatments, mainly anti-inflammatory drugs, that help with most AOSD symptoms. Until recently, we have known little about its causes but medical researchers are starting to learn more about AOSD. With this knowledge comes the promise of new and better treatments.

AOSD gets its name from Dr. Still, a renowned British pediatrician, who first identified the childhood form of the disease. Though rare, it is found worldwide and predominantly affects young adults between 16 and 35.

AOSD does not seem to run in families. The disease can be difficult to diagnose, as it is difficult to distinguish from a number of other conditions that cause unexplained fever as well as other forms of rheumatoid arthritis, as well as from a number of other diseases.

Symptoms of AOSD
Common symptoms of AOSD include those on the following list. It is important to remember that there is no definite pattern that AOSD symptoms follow. In some cases, only one or two symptoms occur immediately; others may follow later. Aside from fever and joint pain, which are almost always among the first signs of AOSD, some of the symptoms on this list may not appear for weeks, or even at all.

Fever
The first sign that someone may be coming down with AOSD is a high spiking fever of 103 degrees or above. The fever usually rises rapidly in the evening and then subsides to or near normal by the next morning. Occasionally, an unusual pattern of two fever spikes in a day is seen in one-fifth of AOSD sufferers.

Rash
The typical Still's rash is salmon pink in color and comes and goes unpredictably, although it sometimes occurs at the same time as high fever. It is most common on the chest and thigh, although it may also appear on the face, hands and feet. In some cases, the rash becomes itchy.

Joint and Muscle Pain
At some point, every AOSD sufferer experiences intense joint pain, often in the hand. This can be accompanied by severe muscle pain as well. Both may become worse during a fever spike.

Sore Throat
Most AOSD sufferers come down with a sore throat that is usually described as a severe, constant burning pain in the area around the pharynx.²

Heart and Lung Symptoms
These include pain, difficulty breathing and other problems that can be mistaken for an infection of tissue within the heart.

Abdominal Pain
This can be caused by swollen lymph nodes, as well as enlargement of the spleen or liver. These symptoms are also sometimes attributed to other causes.

Abnormal White Blood Cell Count and Other Blood Abnormalities
These can be easily detected using a variety of blood tests. Most patients with AOSD have greatly elevated white blood cell counts which may lead their doctors to suspect an underlying infection or even leukemia. However, the cultures of the blood and other sites are always negative and the blood and bone marrow do not show the abnormal cells found in leukemia. A group of tests referred to as "acute phase reactants" are almost always abnormally elevated in AOSD. The two most commonly associated with AOSD are an elevated sedimentation rate (ESR) and a high blood ferritin level.

Diagnosis of AOSD
While there is no simple test for AOSD, most doctors will make the diagnosis if a person has five or more of the criteria below, including two or more from the first (major criteria) list:⁷

Major AOSD Criteria

1. High fever lasting one week or longer
2. Joint pain lasting two weeks or longer
3. Rash
4. Abnormal white blood cell count and other blood problems

Minor AOSD Criteria

1. Sore throat
2. Swelling of the lymph nodes or spleen
3. Liver problems
4. Absence of rheumatoid arthritis

Joint and Muscle Change
Occasionally the diagnosis of AOSD may be supported by the finding of soft tissue swelling, bone loss and damage to the wrist, hand, hip, knee and spinal joints. These changes, however, are diagnostic.

Diseases that Mimic AOSD Symptoms
An important part of detecting AOSD is ruling out other diseases that can cause similar symptoms. Some of the prime suspects are:

• Infections such as hepatitis, rubella, parvovirus,coxsackie, EBV (Epstein-Barr virus) CMV (cytomegalo virus) and HIV (AIDS)
• Infective endocarditis (an infection of the heart tissue)
• Tuberculosis
• Lyme disease
• Ehrlichiosis
• Sarcoidosis
• Hepatitis
• Crohn's disease
• Cancer, including leukemia and lymphoma
• Connective tissue disease, such as SLE (Lupus)

Causes of AOSD
We do not know the exact cause AOSD but researchers are currently investigating a number of possibilities:

• Infection
  The abrupt appearance of high fever, sore throat, rash, lymph node swelling and abnormal white blood cell counts suggest some kind of infectious trigger.
  
  While no particular cause of infection has been found, the rubella (German Measles) virus has been detected in many people with AOSD cases. Researchers have also found some association between AOSD and EB, CMV, mumps, parainfluenza, and other viruses.
• Immune Disorder
• Genetics
• Hormonal Influences
  Pregnant women are slightly more likely to come down with AOSD or to have a relapse. On the other hand, if the female hormones associated with pregnancy played a role, we would expect AOSD to be more common in one sex or the other. Unlike lupus or rheumatoid arthritis, however, which are more common in women, AOSD seems to affect both sexes equally.

Treatment and Prognosis
The most widely used treatment for AOSD symptoms is non-steroidal anti-inflammatory drugs (NSAIDs). A good early indication of how well an AOSD sufferer will do in the long term is their initial response to these drugs. Statistically, 20-25% of AOSD sufferers improve with NSAIDs. Many of these find that their symptoms clear up quickly, sometimes for good. NSAIDs are normally taken until 1-3 months after the symptoms are gone.

In particularly acute or severe cases, doctors sometimes also prescribe corticosteroids to address heart, blood, and other life-threatening problems that AOSD can cause. Anti-TNF therapy, aimed at a component of the immune system, may be a promising treatment.¹⁰

Some AOSD sufferers do not respond well to NSAIDs and go on to develop the chronic (long term) form of the disease. Because corticosteroids have serious side effects, they cannot be used to treat AOSD over a period of years. Instead, depending on the individual case, doctors prescribe drugs such as methotrexate, IM gold, D-penicillamine, hydroxychloroquine and azathioprine. For safety reasons, cyclophosphamide is reserved only for the most difficult cases.

Summary
Though not common, AOSD is a serious and potentially debilitating disease that can cause serious damage and other problems to the joints, heart, lungs, liver and spleen. While some AOSD sufferers have only a mild form of the disease that responds well to safe NSAID drugs, others come down with a severe, chronic form that is more difficult to treat that can cause long term pain and disability or even death. While we have a lot to learn about how AOSD works and how to treat it, some progress is being made.

References
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