Adult Onset Still’s Disease (AOSD) is a rare systemic autoinflammatory disorder involving widespread inflammation. Its exact cause is unknown, but it involves the immune system mistakenly attacking the body’s tissues. The condition is not inherited and can appear unexpectedly.
AOSD typically affects young adults, with peak occurrences in individuals aged 16 to 35. Although less common, a second peak can occur between the ages of 36 and 46. The name originates from the British physician Sir George Frederic Still, who first described a similar condition in children in 1896, now known as systemic juvenile idiopathic arthritis.
Key Symptoms of AOSD
The presentation of Adult Onset Still’s Disease is marked by a classic triad of symptoms. One of the most prominent signs is a high, spiking fever, often exceeding 102.2°F (39°C), that occurs once or twice daily. These fevers frequently peak in the late afternoon or evening and then return to a normal or near-normal level. This recurring pattern is a distinctive feature.
Accompanying the fever is a characteristic rash. This rash is typically a salmon-pink color and presents as flat or slightly raised spots (macular or maculopapular). It is often described as evanescent, meaning it appears and disappears quickly, usually in conjunction with the fever spikes. The rash most commonly emerges on the trunk and the upper parts of the arms and legs.
Joint pain, or arthralgia, is the third component of the classic triad. Initially, the pain may migrate from one joint to another, but it often evolves into persistent arthritis with joint swelling and stiffness. The knees and wrists are the most commonly affected joints, though the ankles, shoulders, elbows, and fingers can also be involved. Morning stiffness lasting for at least an hour is a common experience.
Beyond the main three symptoms, a severe sore throat is often one of the first complaints, frequently leading individuals to seek medical care. This is due to inflammation rather than an infection. Other common symptoms include muscle pain (myalgia) that can limit daily activities, swollen lymph nodes, especially in the neck, and significant fatigue.
The Diagnostic Process
There is no single definitive test for Adult Onset Still’s Disease. The condition is a “diagnosis of exclusion,” meaning physicians must systematically rule out other diseases that present with similar symptoms before confirming AOSD. This process can sometimes lead to a diagnostic delay.
The initial steps involve excluding conditions such as infections, cancer like lymphoma, and other autoimmune or rheumatic diseases. This requires a medical history, a physical examination, and laboratory tests. Blood tests are performed to rule out other conditions like rheumatoid arthritis and lupus, for which tests like rheumatoid factor (RF) and antinuclear antibody (ANA) are usually negative in AOSD.
Blood tests also reveal indicators that point toward an AOSD diagnosis. A complete blood count often shows a high white blood cell count, particularly neutrophils. Inflammatory markers, such as C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR), are typically elevated. A markedly high level of serum ferritin, a protein that stores iron, is a strong indicator, as extremely high levels are less common in other inflammatory conditions.
To formalize the diagnosis, clinicians often use established criteria, with the Yamaguchi criteria being the most widely used. Major criteria include the characteristic high fever, joint pain lasting two weeks or more, the typical salmon-pink rash, and a high white blood cell count. Minor criteria include a sore throat, swollen lymph nodes or an enlarged spleen, liver dysfunction, and negative RF and ANA tests. A diagnosis generally requires five or more total criteria, with at least two being from the major category.
Treatment Approaches
The management of Adult Onset Still’s Disease focuses on controlling inflammation and managing symptoms, with treatment tailored to the individual’s condition. For those with milder symptoms, the first line of therapy is often nonsteroidal anti-inflammatory drugs (NSAIDs).
When symptoms are more severe, corticosteroids like prednisone are used. These powerful anti-inflammatory drugs are effective at quickly controlling the high fevers, rash, and severe joint inflammation. The goal is to bring the disease under control, then gradually reduce the dose to minimize long-term side effects like weight gain and bone density loss.
For individuals who do not respond adequately to steroids or who require long-term management, disease-modifying antirheumatic drugs (DMARDs) are introduced. Methotrexate is one of the most commonly used DMARDs and acts as a steroid-sparing agent, helping to reduce reliance on corticosteroids. These medications work more slowly than steroids but are important for sustained control.
In cases resistant to traditional therapies, biologic drugs offer targeted treatment. These medications block specific proteins involved in the inflammatory process. One class of biologics targets interleukin-1 (IL-1), a cytokine implicated in AOSD, with drugs like anakinra and canakinumab. Another class targets interleukin-6 (IL-6) with drugs such as tocilizumab. These agents can be highly effective in managing symptoms in severe or persistent cases.
Disease Progression and Potential Complications
The long-term course of Adult Onset Still’s Disease varies significantly among individuals and generally follows one of three patterns. Some people experience a monophasic or self-limited pattern, where they have a single episode of the disease that lasts for less than a year and then resolves without returning. Others may have a polycyclic or intermittent pattern, characterized by recurrent disease flares with periods of remission in between. A third group develops a chronic articular pattern, where joint pain and arthritis become persistent and can lead to joint damage over time.
While many people with AOSD can manage their condition effectively, there is a risk of serious complications. The most significant is Macrophage Activation Syndrome (MAS). MAS is a rare but life-threatening complication from a severe overreaction of the immune system, leading to hyperactivation of immune cells called macrophages. This can cause a rapid decline with persistent high fever, a sudden drop in blood cell counts, liver dysfunction, and coagulation abnormalities.
The development of MAS is a medical emergency requiring immediate treatment. It is characterized by a dramatic spike in ferritin levels, often much higher than those seen during a typical AOSD flare. Early recognition and intervention, typically with high-dose intravenous steroids and biologic therapies like anakinra, are necessary to control the hyperinflammation and prevent multi-organ failure.