Adult Still Disease: Symptoms, Types, Causes and Treatment

Adult Still Disease (ASD), also known as adult-onset Still’s disease (AOSD), is an uncommon but impactful systemic inflammatory disorder. It can be challenging to diagnose and manage due to its diverse symptoms, fluctuating disease patterns, and unclear origins. Understanding ASD is important for early recognition, precise diagnosis, and effective treatment. In this article, we will explore the main features of ASD, including its symptoms, types, causes, and available treatments, synthesizing the latest evidence to provide a comprehensive and patient-centered overview.

Symptoms of Adult Still Disease

Adult Still Disease often begins suddenly, but its symptoms can be puzzling and may mimic many other conditions. Recognizing the characteristic signs and laboratory findings is vital for both patients and healthcare professionals.

Symptom	Description	Frequency/Indicator	Source(s)
Fever	High, spiking, often >39°C	Nearly all patients	1 2 3 5 6
Rash	Evanescent, salmon-pink, often with fever	Very common	2 3 4 5 6
Arthralgia	Joint pain; may progress to arthritis	Common	1 2 3 4 5 6
Sore Throat	Early sign, sometimes overlooked	Frequently observed	2 3 4 6
Leukocytosis	High white blood cell count, neutrophilia	Laboratory hallmark	1 2 3 5 6
Hyperferritinemia	Very high ferritin levels	Key diagnostic clue	1 2 3 4 5

Table 1: Key Symptoms and Findings in Adult Still Disease

Understanding the Symptoms

Fever

Fever in ASD is typically high (≥39°C), with spikes often occurring once or twice daily, sometimes accompanied by chills. This pattern, especially when paired with other symptoms, is a major diagnostic clue 1 2 3 5 6.

Rash

AOSD’s rash is described as "evanescent"—it appears and disappears quickly, often at the peak of fever. The rash is usually salmon-pink and non-itchy, found mostly on the trunk and limbs 2 3 4 5 6. Many patients may not notice it, as it can be fleeting.

Joint Pain and Arthritis

Joint involvement is universal. Early in the disease, patients may feel pain in multiple joints (polyarthralgia), which can evolve into frank arthritis with swelling and reduced mobility. Chronic cases may develop joint erosions 1 2 3 4 5.

Sore Throat

A sore throat is a common early symptom and can sometimes precede other findings. It may be mistaken for an upper respiratory infection but tends to persist or recur 2 3 4 6.

Laboratory Findings

• Leukocytosis: A high white blood cell count, especially neutrophils, is a laboratory hallmark.
• Hyperferritinemia: Ferritin levels are often dramatically elevated, sometimes more than ten times the upper limit of normal, and the glycosylated fraction is low. This combination is rarely seen in other conditions 1 2 3 4 5.
• Elevated inflammatory markers: ESR and CRP are consistently raised.
• Negative autoantibodies: Unlike other rheumatic diseases, rheumatoid factor and antinuclear antibodies are almost always negative 1 2 3 6.

Other Features

• Sore muscles (myalgias)
• Lymphadenopathy (swollen lymph nodes)
• Hepatosplenomegaly (enlarged liver/spleen)
• Liver dysfunction (abnormal liver tests)
• Serositis (inflammation of membranes around organs) 1 2 4 6

Complications

Life-threatening complications can occur, such as macrophage activation syndrome (MAS), a severe inflammatory state with high mortality 4 7.

Types of Adult Still Disease

ASD does not follow a single course. Recognizing the different patterns helps guide management and gives insight into prognosis.

Type	Description of Course	Prognosis/Clinical Features	Source(s)
Monocyclic	Single episode, resolves in <1 year	Best prognosis	2 4 5 7
Polycyclic	Multiple flares with remission in between	Intermediate prognosis	2 4 5 7
Chronic	Ongoing disease, usually with persistent arthritis	Higher risk of joint damage	2 3 4 5 7

Table 2: Types of Disease Course in Adult Still Disease

Disease Course Explained

Monocyclic (Self-Limited) Pattern

• One episode that resolves within a year.
• Symptoms subside, and the patient remains in remission.
• Most favorable outcome; less risk of chronic complications 2 4 5 7.

Polycyclic (Intermittent) Pattern

• Characterized by multiple disease flares (relapses) alternating with symptom-free periods.
• Each episode typically lasts less than a year.
• Requires close monitoring to manage recurrences 2 4 5 7.

Chronic (Articular) Pattern

• Symptoms persist, particularly joint pain and arthritis.
• Chronic joint inflammation may lead to erosions, deformities, and long-term disability.
• Systemic symptoms (fever, rash) may become less prominent.
• More likely to need aggressive long-term therapy 2 3 4 5 7.

Factors Affecting Disease Course

• Initial presentation: Highly symptomatic, feverish onset often leads to systemic (monocyclic or polycyclic) forms, while gradual, joint-dominant onset predicts chronic articular disease 3 7.
• Age: Younger patients may be more resistant to first-line treatments 7.
• Complications: Severe complications like MAS are more common in systemic, highly active disease 4.

Causes of Adult Still Disease

The root cause of ASD remains elusive, but recent research has shed light on the processes driving the disease.

Cause/Theory	Key Points	Evidence Type	Source(s)
Genetic Factors	Genetic predisposition suspected	Family clusters, HLA studies	3 8
Infectious Triggers	Viral or bacterial triggers proposed	No single agent confirmed	2 3 9
Immune Dysregulation	Innate immunity overactivation, cytokine storm	Elevated cytokines, autoinflammatory features	3 8 9

Table 3: Proposed Causes of Adult Still Disease

Pathogenesis in Detail

Genetic Susceptibility

While no single gene mutation causes ASD, some people may inherit genetic variants that predispose them to exaggerated inflammatory responses. Associations with certain HLA subtypes have been reported 3 8.

Infectious Triggers

Many patients recall a preceding infection—such as a sore throat or flu-like illness—before ASD onset. Various viruses and bacteria have been proposed as triggers, but no consistent infectious cause has been identified 2 3 9.

Aberrant Immune Response

ASD is now considered an autoinflammatory disease, meaning it results from abnormal activation of the innate (non-specific) immune system, rather than the adaptive (antibody-mediated) system seen in classic autoimmune diseases 3 8. Key points:

• Cytokine storm: Overproduction of pro-inflammatory cytokines, especially IL-1, IL-6, and IL-18, leads to systemic inflammation and tissue damage 3 8 9.
• Macrophage and neutrophil activation: These immune cells drive the inflammatory process, sometimes resulting in severe complications like MAS 3 4 9.
• Low natural killer cell function: Impaired regulation of inflammation may contribute to uncontrolled immune activity 3.

Environmental Factors

Environmental triggers, including stress and possibly other unknown agents, may play a role, especially in genetically predisposed individuals 3 8.

Treatment of Adult Still Disease

Treatment aims to control inflammation, prevent complications, and maintain quality of life. Because ASD is rare, management is often based on clinical experience and emerging evidence.

Therapy Type	Examples/Agents	Indications/Effectiveness	Source(s)
NSAIDs	Ibuprofen, naproxen	Mild cases, initial therapy	2 4 5 9
Corticosteroids	Prednisone	First-line, systemic symptoms	2 4 5 9
DMARDs	Methotrexate, cyclosporine, leflunomide	Steroid-sparing, chronic cases	4 5 9
Biologics	Anakinra, tocilizumab, canakinumab, TNF inhibitors	Refractory or severe cases	3 5 9 10 11

Table 4: Main Treatment Options for Adult Still Disease

First-Line Treatments

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• Used in mild or early cases to reduce fever and pain.
• Most patients require stronger therapy for sustained control 2 4 5 9.

Corticosteroids

• Prednisone and similar agents are the backbone of treatment, especially for systemic symptoms.
• High doses are often needed initially.
• Tapering is attempted as soon as possible to minimize side effects 2 4 5 9.

Disease-Modifying Antirheumatic Drugs (DMARDs)

Methotrexate

• Added when arthritis is prominent or when the disease is steroid-dependent.
• Helps reduce steroid dosage and controls chronic joint inflammation 4 5 9.

Other DMARDs

• Cyclosporine, leflunomide, and azathioprine may be used in select cases, especially if methotrexate is not tolerated 4 9.

Biologic Therapies

Biologics target specific cytokines or immune pathways implicated in ASD’s pathogenesis.

IL-1 Inhibitors (Anakinra, Canakinumab, Rilonacept)

• Particularly effective in systemic and refractory cases.
• Canakinumab has shown improvement in joint disease 3 5 10 11.
• Anakinra is often a steroid-sparing agent 3 11.

IL-6 Inhibitor (Tocilizumab)

• Effective for both systemic and articular symptoms.
• Shown to induce remission in a high proportion of patients 3 5 11.

TNF Inhibitors (Infliximab, Etanercept, Adalimumab)

• Used in chronic, polyarticular disease, especially when other treatments fail.
• Less effective for systemic symptoms compared to IL-1/IL-6 inhibitors 3 5 11.

Others

• Agents like rituximab and abatacept are used rarely in resistant cases 11.

Special Considerations

Macrophage Activation Syndrome (MAS)

• Life-threatening; requires aggressive immunosuppression (high-dose steroids, cyclosporine, biologics) 4 9.
• Early recognition is critical.

Monitoring and Support

• Regular monitoring for treatment side effects and disease complications.
• Physical therapy and supportive care to maintain function and quality of life.

Future Directions

• Research into small-molecule inhibitors and personalized therapies is ongoing 4 8.

Conclusion

Adult Still Disease is a rare, complex, and often misunderstood condition. Awareness of its distinct clinical features, understanding its varied courses, and staying up-to-date with evolving treatments can make a significant difference in patient outcomes.

Key Takeaways:

• ASD is characterized by high fevers, fleeting rash, joint pain, and striking laboratory findings (especially high ferritin and leukocytosis) 1 2 3 5 6.
• Disease course can be monocyclic, polycyclic, or chronic, with significant implications for prognosis and management 2 4 5 7.
• The cause remains unclear, but genetic predisposition, infectious triggers, and immune dysregulation play key roles 3 8 9.
• Treatment is multifaceted, including NSAIDs, corticosteroids, DMARDs, and biologics, tailored to disease severity and patterns 2 3 4 5 9 10 11.
• Early recognition and aggressive management of severe complications, such as MAS, are essential 4 7 9.
• Ongoing research promises better diagnostics and more targeted therapies in the future 4 8 10 11.

A patient-centered approach, informed by the latest evidence, remains vital in managing this challenging disease.