STILL’S DISEASE

Introduction…Still's disease, sometimes referred to as Adult-Onset Still’s Disease (AOSD) is a rare systemic inflammatory disease characterized by the classic triad of

persistent high spiking fevers,

joint pain, and…

a distinctive salmon-colored bumpy rash.

The disease is considered a diagnosis of exclusion and sadly is idiopathic.

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

What causes Still's disease?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.

Some say it is of viral mutation leading back to autoimmune disorders. In fact, the precise cause of Still's disease is not yet known but with constant research and promising advancements, the future looks bright.

Pathophysiology

However, as the cause remains unknown, it presumably involves interleukin-1 (IL-1), since drugs that block the action of IL-1β are effective treatments. Interleukin-18 is expressed at high levels.

In regards to that, other anti-IL1β drugs are being developed

How does Still's disease relate to Juvenile Idiopathic Arthritis?

Still's disease is one type of Juvenile Idiopathic Arthritis (JIA) and is also known as systemic-onset JIA. Still's disease accounts for 10%-20% of all cases of JIA.

Other types of JIA include

• Oligoarticular JIA

• Polyarticular JIA

Systemic-onset JIA was formerly known as systemic-onset juvenile rheumatoid arthritis (JRA) and is the same disease.

It occurs mostly in adolescence typically affecting children under 16 years of agehence ‘juvenile’

There is a bimodal age distribution with one peak incidence between ages 15–25 and a second peak between ages of 36–46 years.

Signs and Symptoms

Articular.Arthritis occurs after rash and fevers have been present for some time.

There is eventual development of joint pain and swollen joints. This usually involves many joints (poly-articular arthritis). Any joint can be affected.

Extra- ArticularStill's disease usually begins with systemic symptoms as such:

Extreme fatigue.

High fevers that rise daily to 39 degree Celcius 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.

Poor appetite, nausea, and weight loss may occur.

Lymphadenopathy, splenomegaly, hepatomegaly, and sore throat are also common.

Pericarditis, pleuritis, pericardial effusion and pleural effusion may occur but is less likely. They present as underlying complications.

How is Still's disease diagnosed?Diagnosis is hardly based upon serology but on the basis of the typical aforementioned clinical features of the illness. However, many patients with Still's disease develop markedly elevated white blood cell counts.Typically, low red blood counts indicating anemia is present.Elevated ESR, C-reactive protein and ferritin are common. However, tests for rheumatoid factor and antinuclear antibodies are usually negative.

Criteria for Diagnosis Yamaguchi criteria for classification of Still's disease

There should be presence of 5 or more criteria, of which at least 2 are Major.

Major CriteriaFever of >39°C for >1 weekLeukocytosis >10,000/microL with >80% polymononuclear leukocytes (predominating granulocytes)Salmon colored rash (usually over the trunk or extremities, non-pruritic)Arthralgia and/or Arthritis >2 week

Minor CriteriaSore throatLymphadenopathyHepatomegaly and/or SplenomegalyLiver dysfunction (high AST/ALT)Negative Anti Nuclear Antibodies and Rheumatoid Factor

Cush criteria for classification of Still's diseaseRequires all of the following:

Fever > 39 degrees

Arthralgia and/or arthritis

Rheumatoid factor < 1:80

Anti Nuclear Antibodies < 1:100

In addition, any two of the following is sited for:

WBC count > 15,000

Stills rash

Pleuritis or Pericarditis

Hepatomegaly, Splenomegaly, or Lymphadenopathy

TREATMENT

Treatment of Still's disease is directed toward the individual areas of inflammation.Still's disease is treated with anti-inflammatory drugs. Steroids such as prednisone are used to treat severe symptoms. 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), penicillamine(Cuprimine, Depen), azathioprine (Imuran), methotrexate (Rheumatrex, Trexall), 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 which blocks IL-6, has been approved to treat systemic JIA in children.

I appreciate your attention.Adighibenma S.O.S