Adult-onset Still's disease (patient information)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Overview

Adult onset Still's disease (AOSD) is a rare inflammatory disorder that affects the entire body (systemic disease). The cause of the disorder is unknown (idiopathic). Affected individuals may develop episodes of high, spiking fevers, a pink or salmon colored rash, joint pain, muscle pain, a sore throat and other symptoms associated with systemic inflammatory disease. The specific symptoms and frequency of episodes vary from one person to another and the progression of the disorder is difficult to predict. In some individuals, the disorder appears suddenly, disappears almost as quickly and may not return. In other people, adult onset Still's disease is a chronic, potentially disabling, condition. Various medications are used to treat individuals with adult onset Still's disease, affected individuals may respond to therapy differently. Adult onset Still's disease does not appear to run in families. Adult onset Still's disease is the adult form of systemic juvenile rheumatoid arthritis (juvenile Still's disease). The disorders are name after a British physician who first described systemic juvenile rheumatoid arthritis in the medical literature in 1896. The term "adult Still's disease" was first used in the medial literature in 1971, but cases that fit the description of the disorder appear in the medical literature as early as the late 1800s. Signs & Symptoms The symptoms, progression and severity of adult onset Still’s disease are highly variable from one person to another. Some individuals may only develop one random episode that responds to treatment and resolves within one year. In some cases, a new episode does not occur or does not occur until many years later. Other individuals may develop chronic disease, in which episodes come and go, often years apart and with no symptoms in-between episodes. Still other individuals may experience frequent episodes that occur every several weeks or months. Individuals with chronic adult onset Still’s disease may have a form predominantly characterized by fever or a form predominantly characterized by joint disease (chronic arthritis). Chronic adult onset Still’s disease can potentially cause long-term, severe and disabling complications.

What are the Symptoms of Adult-onset Still's disease

Most individuals with adult onset Still’s disease develop some combination of the symptoms normally associated with systemic inflammatory disease. Such symptoms include a spiking fever greater than 102.2 degrees Fahrenheit (39 degrees Celsius), joint pain (arthralgia) and inflammation (arthritis), muscle pain (myalgia), and a skin rash.

In some cases, fevers are a daily occurrence and usually peak or spike in the late afternoon or early evening. In rare cases, some individuals develop two spiking fevers in one day. The rash is pink or salmon colored, and usually develops during a fever episode. The chest and thighs are most often affected by the rash. The arms, legs and face are affected less often. The rash may or may not be itchy and tends to disappear quickly (evanescent).

Affected joints may become swollen, stiff and inflamed and may persist for a couple of weeks. The knees, wrists and ankles are most commonly affected. Muscle and joint pain can be intense and is often worse during a fever episode. If adult onset Still’s disease goes untreated, chronic inflammation of the joints can potentially result in deterioration and destruction of the affected joints.

Additional findings may occur in some cases including a sore throat, enlargement of the spleen (splenomegaly), enlargement of the liver (hepatomegaly), and enlargement of the lymph nodes (lymphadenopathy).

In some cases, the thin, sac-like membrane that surrounds the heart (pericardium) or the heart muscle (myocardium) may become inflamed (pericarditis or myocarditis). The membrane lining the chest cavity may also become inflamed and may cause fluid to accumulate in the lungs (pleural effusion). Heart and lung involvement can cause difficulty breathing and chest pain, but in most cases it is usually not severe enough to be readily apparent and is often only detected during a physical examination by a physician.

What are the Causes of Adult-onset Still's disease

The cause of adult onset Still’s disease is unknown (idiopathic). Researchers believe an abnormal or exaggerated response to an infection or toxic substance may cause the disorder.

Some researchers believe that adult onset Still’s disease is an autoinflammatory syndrome. Auto-inflammatory syndromes are a group of disorders characterized by recurrent episodes of inflammation due to an abnormality of the innate immune system. They are not the same as autoimmune disorders, in which the adaptive immune system malfunctions and mistakenly attacks healthy tissue.

Researchers also believe that cytokines (specialized proteins secreted from certain immune system cells that either stimulate or inhibit the function of other immune system cells) may also play a role in the development of adult onset Still’s disease. Interleukin-1 (IL-1) a cytokine that is known to mediate cell response to inflammation may play a role the development of adult onset Still’s disease. Abnormal clinical findings involving interleukin-1 have been found in some individuals with adult onset Still’s disease and therapy with a drug to block the activity of interleukin-1 is being explored (see Investigational Therapies below). Additional cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are also believed to play a role in the development of adult onset Still’s disease.

Who gets Affected by Adult-onset Still's disease

Adult onset Still’s disease affects men and women in equal numbers. Some reports state that the disorder affects women slightly more often than men. It primarily affects young adults between the ages of 16-35. The incidence of adult onset Still’s disease is unknown. Because of the highly variable symptoms and rarity of the disorder, it often goes undiagnosed or misdiagnosed making it difficult to determine its true frequency in the general population.

Related Disorders Symptoms of the following disorders can be similar to those of adult onset Still’s disease. Comparisons may be useful for a differential diagnosis.

Auto-inflammatory syndromes are a group of disorder characterized by recurrent episodes of inflammation due to an abnormality of the innate immune system. Symptoms of the syndromes often include periodic fevers, rash, abdominal pain, joint pain, bone pain and other characteristic findings associated with chronic inflammation. These disorders include the cryoprin-associated periodic syndromes (familial cold auto-inflammatory syndrome, CINCA, and Muckle-Wells syndrome), hyperimmunoglobulin D syndrome (HIDS), familial Mediterranean fever (FMF), TRAPS, Schnitzler syndrome and mevalonate kinase deficiency. (For more information on this disorder, choose the specific disorder name as your search term in the Rare Disease Database.)

Autoimmune disorders are a group of disorders in which the abnormalities affecting the adaptive immune system, which consists of cells and proteins (antibodies) that are supposed to protect the body from infection. These antibodies mistakenly attack healthy tissue and may be referred to as autoantibodies. Symptoms common to many autoimmune disorders include repeated episodes of fever, rash, abdominal pain, joint pain and other symptoms associated with chronic inflammation. Autoimmune disorders that may resemble adult-onset Still’s disease include systemic lupus erythematosus, dermatomyositis, and rheumatoid arthritis. (For more information on this disorder, choose the specific disorder name as your search term in the Rare Disease Database.)

A wide variety of additional disorders can resemble adult onset Still’s disease including Reiter’s syndrome, inflammatory bowel disease, Sweet syndrome, certain cancers such as lymphoma and leukemia and certain infections such as tuberculosis, mononucleosis and toxoplasmosis. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

How is Adult-onset Still's disease Diagnosed

The diagnosis of adult onset Still’s disease is difficult because there are no specific tests or distinguishing laboratory (histopathologic) findings that clearly differentiate the disorder from similar disorders. A diagnosis of adult onset Still’s disease is usually made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings, and the exclusion of other possible disorders (diagnosis of exclusion). A variety of tests may be performed to aid in a diagnosis including blood tests and x-ray studies that reveal changes in the bones or joints or enlargement of the spleen or liver. An echocardiogram, which uses sound waves to create a picture of the heart, may reveal inflammation of the pericardium or myocardium.

Blood tests may reveal characteristic changes to blood cell levels normally associated with adult onset Still’s disease. Affected individuals often have elevated levels of white blood cells and/or platelets or low levels of red blood cells. A common blood test for individuals suspected of having an inflammatory disorder is an erythrocyte sedimentation rate. Sedimentation rate measures how long it takes red blood cells (erythrocytes) to settle in a test tube over a given period. Many individuals with adult’s onset Still’s disease have an elevated sedimentation rate, which is an indication of inflammation. Another blood test commonly used is serum ferritin that is frequently disproportionally elevated in AOSD.

How is Adult-onset Still's disease Treated

Many different therapies have been tried for individuals with adult onset Still’s disease. No one treatment has proven consistently effective in all cases. A variety of different drugs taken alone or in combination may be used to treat affected individuals.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to treat symptoms of inflammation. Fever, joint pain and bone pain have responded to treatment with these drugs. Other painkillers (analgesics) such as acetaminophen and paracetamol may also be used. Corticosteroid drugs such as prednisone may be used to treat systemic symptoms. Affected individuals may receive high-doses of corticosteroids initially, with the dosage progressively reduced over time. Long-term use of corticosteroids are associated with a variety of side-effects and researchers are exploring medications that can replace corticosteroids or permit lower doses of corticosteroids to be used (see Investigational Therapies below).

One drug commonly used in conjunction with corticosteroids to treat individuals with adult onset Still’s disease is the immunosuppressive drug methotrexate. Methotrexate is commonly used to treat arthritis and other rheumatic conditions. When used for individuals with adult onset Still’s disease, methotrexate may be known as a “steroid-sparing agent” because it permits lower doses of corticosteroids to be used, thereby lowering the associated risk of side effects.

Additional treatment is symptomatic and supportive.

Investigational Therapies

In recent years, some promising therapies have been studied for adult onset Still’s disease including drugs known as biological response modifiers. These drugs block the activity of substances (cytokines) that are believe to play a role in the development of the disorder.

Anakinra, an interleukin-1 receptor antagonist, is a drug that blocks the activity of interleukin-1, which some researchers believe plays a key role in the development of adult onset Still’s disease. Although anakinra has only been used in a small amount of individuals with adult onset Still’s disease, many of those who have received the therapy have rapidly and markedly improved. More research is necessary to determine the long-term safety and effectiveness of this promising therapy for individuals with adult onset Still’s disease.

Individuals with adult onset Still’s disease have also been treated with TNF-alpha antagonists, drugs that block the activity tumor necrosis factor-alpha. TNF-alpha antagonists are often used to treat individuals with rheumatoid arthritis. These drugs include infliximab and etanercept and have shown promise in small studies involving individuals with adult onset Still’s disease. However, more research is necessary to their long-term safety and effectiveness.

Actemra, also known as tocilizumab, by Genentech, Inc. was approved for patients two years of age and older by the FDA in 2011 as a treatment for systemic onset juvenile idiopathic arthritis (soJIA), formerly called Pediatric Still’s disease. Systemic Juvenile Idiopathic Arthritis is a disease that is very closely related to AOSD and many experts consider it the same disease in different age groups. Actemra was approved by the FDA in 2010 for the treatment of adult patients with moderately to severely active Rheumatoid Arthritis who have had an inadequate response to one or more TNF inhibitors. Actemra is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody.

Data regarding the efficacy of the newer, long acting IL-1 inhibitors rilonacept and canakinumab in refractory AOSD cases was presented at conferences held in 2011 by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).

Additional drugs that have been studied or used to treat individuals with adult onset Still’s disease include intravenous immunoglobulin, cyclosporin A, gold, azathioprine, leflunomide, cyclophosphamide, and thalidomide.