Adult Still’s disease is an immune-mediated rare type of inflammatory arthritis that features fevers, rash, joint pain, morning stiffness and, multiple joints pain. Some people may have just one episode of adult Still’s disease and other people, the condition persists or recurs. This inflammation can destroy affected joints, particularly the wrists joints. Treatment involves medications, such as prednisone, immunosuppressant drugs that help control inflammation. (source)
Adult-onset Still’s disease (AOSD) is an inflammatory condition that affects multiple organs and joint. The most common symptoms are high fevers, skin rash, arthritis, and high levels of serum ferritin, a protein that stores iron in the blood. Other symptoms include an enlarged spleen, liver and lymph nodes, joint pain, and sore throat. In some cases, symptoms may be severe and lead to organ and joint damage partially or totally. The cause of AOSD is unknown but genetic and other unknown factors may be involved in genetics. [rx][rx][rx][rx]
Causes
It’s not known certain what causes adult Still’s the disease. Some researchers suspect the condition might be triggered by a viral or bacterial infection and malformation of immune cells in our body.
The cause of AOSD is unknown (idiopathic). Researchers believe that the disorder might be caused by a combination of genetic factors and an abnormal or exaggerated response to infections or other environmental exposures and low blood cell and weak immunity. AOSD is not a hereditary disease and does not run in families.
Some researchers believe that AOSD is an autoinflammatory syndrome with cortisol hormone abnormality. They are not the same as autoimmune disorders, in which the adaptive immune system (the second line of defense of the immune system) malfunctions and mistakenly attacks healthy tissue.
Researchers also believe that a specialized group of proteins that modulate the immune system (cytokines) may also play a role in the development of AOSD. Interleukin-1 (IL-1), a cytokine that is known to mediate cell response to inflammation, may play a role in the development of the disease, as abnormal clinical findings involving IL-1 have been found in some individuals with AOSD. For this reason, therapy with a drug to block the activity of IL-1 is being explored (see Investigational Therapies below). Additional cytokines including interleukin-6 (IL-6), IL-18, and tumor necrosis factor-alpha (TNF-alpha) are also believed to play a role in the development of AOSD and could therefore potentially be targeted for treatment.
Symptoms
Most people with adult Still’s disease have a combination of the following signs and symptoms:
- Fever. You might have a daily fever of at least 102 F (38.9 C) for a week or longer. The fever usually peaks in the late afternoon or early evening. You might have two fever spikes daily, with your temperature returning to normal in between.
- Rash. A salmon-pink rash might come and go with the fever. The rash usually appears on your trunk, arms or legs.
- Sore throat. This is one of the first symptoms of adult Still’s disease. The lymph nodes in your neck might be swollen and tender.
- Achy and swollen joints. Your joints — especially your knees and wrists — might be stiff, painful and inflamed. Ankles, elbows, hands and shoulders might also ache. The joint discomfort usually lasts at least two weeks.
- Muscle pain. Muscular pain usually ebbs and flows with the fever, but the pain can be severe enough to disrupt your daily activities.
The signs and symptoms of this disorder can mimic those of other conditions, including lupus and a type of cancer called lymphoma.
When to see a doctor
If you have a high fever, rash and achy joints, see your doctor. Also, if you have adult Still’s disease and develop a cough, difficulty breathing, chest pain or any other unusual symptoms, call your doctor.
Diagnosis
The diagnosis of AOSD is difficult to make because there is no specific test or distinguishing laboratory finding that clearly differentiates the disorder from similar disorders. A diagnosis of AOSD 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 as well as imaging studies that might 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 AOSD. Affected individuals often have elevated levels of white blood cells (leukocytosis) and/or platelets (thrombocytosis) or low levels of red blood cells (anemia). However, this pattern of laboratory abnormalities is seen in many inflammatory disorders. Another common laboratory finding for individuals suspected of having an inflammatory disorder, including AOSD, is elevated inflammatory markers, namely the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Another blood test commonly used is serum ferritin, which is frequently disproportionally elevated in AOSD. Additionally, some patients have high blood levels of enzymes that are released by the liver, namely alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). To exclude other disorders, levels of certain antibodies such as antinuclear antibodies (ANA) and rheumatoid factor (RF) are usually measured. However, these antibodies are typically absent in patients with AOSD.
Although they are not perfect, certain sets of criteria can also help with the diagnosis of AOSD. The most commonly used set of criteria are the Yamaguchi criteria. To be considered for a diagnosis of AOSD, affected individuals need to fulfill at least 5 criteria, including at least 2 major criteria. Conditions that can mimic AOSD also need to be excluded to make a diagnosis. The Yamaguchi criteria are the following:
Major criteria
- Fever of at least 102.2oF (39oC) that lasts at least one week
- Arthralgia or arthritis lasting at least 2 weeks
- Appearance of a pink or salmon-colored rash during fever spikes
- Elevated white blood cell count (leukocytosis)
Minor criteria
- Sore throat
- Lymphadenopathy
- Hepatomegaly or splenomegaly
- Elevated liver enzymes
- Negative tests for antinuclear antibodies and rheumatoid factor
Treatment
Many different therapies have been tried for individuals with AOSD. No one treatment has proven consistently effective in all patients. In addition to symptomatic and supportive treatment, 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. Examples of NSAIDs include ibuprofen, naproxen, indomethacin and diclofenac. Other painkillers (analgesics) such as acetaminophen (Tylenol) may also be used. Corticosteroid drugs such as prednisone may be used to treat systemic symptoms. Corticosteroids have powerful anti-inflammatory properties. However, long-term use of corticosteroids is associated with many side effects. Affected individuals may therefore receive high doses of corticosteroids that will be progressively reduced over time. Researchers are also exploring medications that can replace corticosteroids or permit lower doses to be used (see Investigational Therapies below). One approved drug sometimes used in conjunction with corticosteroids to treat individuals with AOSD is the immunosuppressive drug methotrexate. Methotrexate is commonly used to treat arthritis and other conditions that affect joints (rheumatic diseases). When used for individuals with AOSD, 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.
In 2020, the U.S. Food and Drug Administration (FDA) approved canakinumab (Ilaris) to treat patients with active Still’s disease, including AOSD. Canakinumab blocks the cytokine IL-1. This medication is typically used if corticosteroids and methotrexate have not been successful.
Complications
Most complications from adult Still’s disease arise from chronic inflammation of organs and joints.
- Joint destruction. Chronic inflammation can damage your joints. The most commonly involved joints are your knees and wrists. Your neck, foot, finger and hip joints also may be affected, but much less frequently.
- Inflammation of your heart. Adult Still’s disease can lead to an inflammation of the saclike covering of your heart (pericarditis) or of the muscular portion of your heart (myocarditis).
- Excess fluid around your lungs. Inflammation may cause fluid to build up around your lungs, which can make it hard to breathe deeply.
- Macrophage activation syndrome. This rare, but potentially fatal complication of adult Still’s disease, can cause low blood cell counts, very high triglyceride levels and abnormal liver function.
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