Adult-Onset Still’s Disease is a rare type of inflammatory arthritis. It is considered the adult counterpart to a childhood condition known as Systemic Juvenile Idiopathic Arthritis (SJIA). AOSD is a systemic disease, meaning it can affect the entire body, and it is autoinflammatory in nature.

To understand what this means, it is helpful to distinguish it from a classic autoimmune disease.

• In autoimmune diseases like lupus, the body’s adaptive immune system makes a mistake and creates highly specific antibodies that attack the body’s own tissues.
• In autoinflammatory diseases like AOSD, the problem lies with the innate immune system, the body’s non-specific, first line of defense. This system becomes overactive and, for no apparent reason, launches a massive, widespread inflammatory response.

A helpful analogy is to think of your immune system as a nation’s emergency alert system.

• In a normal situation, an alert is only sent out in response to a real, specific threat, like an invading army (an infection).
• In Adult-Onset Still’s Disease, the alert system itself is faulty. It is stuck in a state of high alert and begins to blare every emergency siren in the country at full volume, every single day.
• This “siren” is a massive flood of powerful inflammatory signaling molecules called cytokines, particularly Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Interleukin-18 (IL-18).
• This “cytokine storm” is what causes the widespread chaos seen in the disease: a daily high “fever alert,” “joint pain” roadblocks that appear and disappear, and a “skin rash” broadcast on every screen. The problem is not an external invasion; it is a malfunction in the emergency alert system itself.

In my experience, Adult-onset Still’s Disease often presents like an infection, with high fevers and joint pain, leading to misdiagnosis until other autoimmune causes are ruled out.

The exact cause of Adult-Onset Still’s Disease is unknown. It is not considered a classic hereditary disease, but it is believed that individuals who develop it have a certain genetic predisposition that makes their innate immune system susceptible to over-reacting.

The leading theory is that in a genetically susceptible person, an environmental trigger “switches on” this dysregulated inflammatory response. The most suspected triggers are infections. It is thought that a viral or bacterial infection may activate the immune system, but instead of shutting down properly after the infection is cleared, the system gets stuck in a state of continuous, uncontrolled inflammation.

Clinically, the exact cause remains unclear, but I’ve seen evidence suggesting an abnormal immune response possibly triggered by infections or environmental factors in genetically predisposed individuals.

A person develops AOSD as a result of the complex interplay between their genetic background and a likely environmental trigger. It is not contagious, and you cannot catch it from another person. There are no well-established lifestyle or environmental risk factors that can be avoided to prevent the disease. It appears to affect men and women relatively equally and, while it can occur at any age, it has two common peaks of onset: one in young adulthood (ages 16-25) and another later in life (ages 36-46).

In my experience, it seems to strike unpredictably usually in young to middle-aged adults without clear familial patterns or identifiable risk factors.

The presentation of AOSD is defined by a classic triad of symptoms, accompanied by other systemic signs of inflammation.

The Classic Triad

1. High-Spiking Fevers: This is a hallmark of the disease. The fever pattern is very characteristic. It typically spikes once or twice a day, often to a high level of 102°F (39°C) or more, usually in the late afternoon or evening. Crucially, between the spikes, the patient’s temperature returns to normal or near-normal.
2. Arthritis or Arthralgia: Joint involvement is present in almost all patients. It may start as arthralgia (joint pain without swelling) and progress to a true, inflammatory arthritis with pain, stiffness, and swelling. The knees and wrists are the most commonly affected joints.
3. The Evanescent Rash: This is another classic sign. It is a distinctive, non-itchy, salmon-pink colored rash. The term “evanescent” means it is fleeting. It characteristically appears on the trunk and limbs during the fever spikes and then disappears as the fever subsides.

Other Common Signs and Symptoms

• A very sore throat (pharyngitis) is often one of the very first symptoms and can be severe, leading to an initial misdiagnosis of strep throat.
• Swollen lymph nodes in the neck (lymphadenopathy).
• Enlargement of the liver and spleen (hepatosplenomegaly).
• Muscle pain (myalgia) that is often severe during fevers.
• Inflammation of the lining of the heart (pericarditis) or lungs (pleuritis).

A Serious Complication: Macrophage Activation Syndrome (MAS)

In a small number of patients, the systemic inflammation of AOSD can go into extreme overdrive, leading to a life-threatening complication called Macrophage Activation Syndrome (MAS), also known as a secondary hemophagocytic lymphohistiocytosis (HLH). This requires urgent, intensive hospital care.

Clinically, I consider AOSD when patients present with fever of unknown origin, sore throat, elevated liver enzymes, and high ferritin levels without evidence of infection or malignancy.

Diagnosing AOSD is notoriously difficult and is a classic diagnosis of exclusion. There is no single test that can confirm the disease. The entire diagnostic process is focused on methodically ruling out the many other conditions that can cause a high fever and widespread inflammation.

The workup is usually performed by a rheumatologist, often in a hospital setting for a patient with a “fever of unknown origin.”

1. Excluding Infections: This is the first and most critical step. The doctor will perform extensive tests to rule out any underlying bacterial or viral infection. This includes multiple blood cultures, urine cultures, and imaging like chest X-rays and CT scans to look for a hidden abscess or infection.
2. Excluding Malignancy: Cancers, particularly lymphoma and leukemia, can cause fever, night sweats, and swollen lymph nodes, mimicking AOSD. A thorough evaluation is needed to rule these out.
3. Excluding Other Autoimmune Diseases: The doctor will perform blood tests to look for the specific antibodies associated with other conditions like lupus and rheumatoid arthritis. In AOSD, these tests are characteristically negative.

Supportive Laboratory Findings

While ruling other diseases out, doctors look for a characteristic pattern of laboratory results that point toward a diagnosis of AOSD.

• Very high levels of inflammatory markers, such as the Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP).
• A very high white blood cell count, composed mostly of neutrophils.
• High levels of liver enzymes.
• An extremely high serum ferritin level is a classic hallmark of AOSD and a major diagnostic clue. Ferritin is an iron-storage protein, but it is also an acute phase reactant that skyrockets during the intense inflammation of Still’s disease.

Once infections, cancer, and other rheumatic diseases have been excluded, a doctor will use a formal set of diagnostic criteria, such as the Yamaguchi criteria, to make a clinical diagnosis of Adult-Onset Still’s Disease based on the combination of major and minor symptoms and lab findings.

Clinically, I rely on exclusion ruling out infections, malignancies, and other autoimmune diseases while looking for supporting features like high serum ferritin and leukocytosis.

There is no cure for AOSD, but it is a treatable condition. The goal of treatment is to control the systemic inflammation, relieve symptoms like fever and joint pain, and prevent long-term joint damage. Treatment is managed by a rheumatologist and typically follows a step-up approach.

1. First-Line Therapies

• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): For patients with very mild disease dominated by joint pain, high-dose NSAIDs may be tried first.
• Corticosteroids: For almost all patients with moderate to severe systemic disease (i.e., high fevers), corticosteroids like prednisone are the cornerstone of treatment. A high dose is used initially to quickly bring the severe inflammation under control. The response is often dramatic, with the fevers and pain resolving within days.

2. Steroid-Sparing Agents

Because long-term use of high-dose steroids has significant side effects, a doctor will always try to taper the prednisone dose down. If symptoms recur as the dose is lowered, a “steroid-sparing” medication is added.

• Conventional DMARDs: The most commonly used medication in this class is methotrexate. It can help to control the underlying inflammation and allow for a lower maintenance dose of steroids.

3. Biologic Therapies

These modern, targeted medications have revolutionized the treatment of severe or refractory AOSD. They work by blocking the specific cytokines that are driving the disease.

• IL-1 Inhibitors: Drugs like anakinra or canakinumab directly block Interleukin-1. They can be extremely effective at controlling the fevers and systemic inflammation of AOSD.
• IL-6 Inhibitors: Drugs like tocilizumab work by blocking Interleukin-6 and are also highly effective, particularly for the chronic arthritis component of the disease.

Clinically, I’ve found that early introduction of disease-modifying agents can prevent joint damage and improve long-term outcomes, especially in polycyclic or chronic forms.

Adult-Onset Still’s Disease is a rare, complex, and serious autoinflammatory disorder that can be a true diagnostic puzzle, often imitating severe infections or cancer. The journey to a diagnosis is frequently a long and frustrating process of exclusion, marked by high-spiking fevers, a fleeting rash, and debilitating joint pain. However, receiving a correct diagnosis is a crucial turning point that transforms uncertainty into a clear path for treatment. While the disease can be severe, it is highly responsive to anti-inflammatory therapies. With corticosteroids to control the initial inflammation and modern biologic therapies that precisely target the key drivers of the disease, the systemic inflammation can be effectively managed. In my experience, patients with AOSD often experience significant diagnostic delays due to its rarity and overlap with more common conditions but once identified, targeted therapy can be life-changing.

The American College of Rheumatology. (2023). Adult-Onset Still’s Disease. Retrieved from https://rheumatology.org/patients/adult-onset-stills-disease

The Arthritis Foundation. (n.d.). Still’s Disease. Retrieved from https://www.arthritis.org/diseases/stills-disease

National Organization for Rare Disorders (NORD). (2023). Adult Onset Still’s Disease. Retrieved from https://rarediseases.org/rare-diseases/adult-onset-stills-disease/