Still’s Disease: A Rare Inflammatory Disorder Marked by Elevated Ferritin

By SWA

Still’s disease is a rare, systemic autoinflammatory condition that causes recurrent fevers, joint inflammation, and a distinctive salmon-colored rash. Though its exact cause is unknown, Still’s disease involves excessive activation of the immune system, leading to widespread inflammation. One of the key laboratory hallmarks of this disease is elevated ferritin levels, often far above the normal range.

This article explores the symptoms, diagnosis, and treatment of Still’s disease—with a focus on the role of ferritin as both a diagnostic marker and an indicator of disease severity.

What Is Still’s Disease?

Still’s disease exists in two main forms:

  • Systemic juvenile idiopathic arthritis (sJIA): Occurs in children and adolescents

  • Adult-onset Still’s disease (AOSD): Develops in adults, typically between the ages of 16 and 35

Both forms share similar clinical features and are classified as autoinflammatory disorders, driven by innate immune system dysregulation rather than autoantibodies (as seen in classic autoimmune diseases).

Clinical Features

Still’s disease is characterized by the following classic triad:

  1. Daily high-spiking fevers (often in the evening or late afternoon)

  2. Evanescent salmon-pink rash, usually appearing during fever spikes

  3. Arthritis or joint pain, affecting both small and large joints

Additional symptoms may include:

  • Sore throat (often an early symptom)

  • Swollen lymph nodes

  • Fatigue and malaise

  • Enlarged liver or spleen (hepatosplenomegaly)

  • Chest pain due to inflammation of the lining of the heart or lungs (pericarditis or pleuritis)

The Role of Ferritin in Still’s Disease

One of the most notable lab abnormalities in Still’s disease is markedly elevated serum ferritin—often thousands of nanograms per milliliter.

Why does ferritin rise in Still’s disease?

  • Ferritin is an acute-phase reactant, meaning it increases during inflammation.

  • In Still’s disease, excessive production of pro-inflammatory cytokines like interleukin-1 (IL-1), IL-6, and IL-18 stimulates ferritin production.

  • Ferritin levels can exceed 1,000–3,000 ng/mL, and in severe cases (such as macrophage activation syndrome), levels can exceed 10,000 ng/mL.

Clinical significance:

  • Diagnostic clue: Very high ferritin levels support the diagnosis, especially when other causes of hyperferritinemia (e.g., infections, liver disease, malignancies) are ruled out.

  • Disease activity marker: Ferritin levels often correlate with disease severity and inflammation.

  • Monitoring tool: Levels typically decrease with successful treatment, making ferritin useful for tracking response to therapy.

Diagnosis

There is no single test to diagnose Still’s disease. Diagnosis is clinical and based on:

  • Pattern of symptoms (fever, rash, joint pain)

  • Exclusion of other conditions (e.g., infections, autoimmune diseases, malignancies)

  • Laboratory findings, which may include:

    • Elevated ferritin (often extreme)

    • Elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)

    • Leukocytosis (high white blood cell count)

    • Mild anemia

    • Negative ANA and rheumatoid factor (distinguishing it from lupus or rheumatoid arthritis)

Complications

A dangerous complication of Still’s disease is macrophage activation syndrome (MAS), a form of secondary hemophagocytic lymphohistiocytosis (HLH). This is a life-threatening cytokine storm with:

  • Very high ferritin (>10,000 ng/mL)

  • Pancytopenia (low blood counts)

  • Liver dysfunction

  • Coagulopathy (bleeding problems)

  • Multi-organ failure if not treated rapidly

Treatment

Treatment focuses on reducing inflammation and preventing joint damage:

First-line:

  • Non-steroidal anti-inflammatory drugs (NSAIDs) for mild symptoms

  • Corticosteroids (e.g., prednisone) for moderate to severe inflammation

Second-line (especially in chronic or steroid-dependent cases):

  • Biologic therapies, particularly those targeting cytokines:

    • IL-1 inhibitors (e.g., anakinra, canakinumab)

    • IL-6 inhibitors (e.g., tocilizumab)

    • TNF inhibitors (less commonly used)

For MAS:

  • High-dose corticosteroids

  • Immunosuppressive agents (e.g., cyclosporine)

  • IL-1 blockade (anakinra)

Summary

Still’s disease is a rare but serious systemic inflammatory condition, presenting with high fevers, rash, and joint pain. A key laboratory finding—markedly elevated ferritin—can help differentiate Still’s disease from other causes of inflammation or infection.

Key takeaways:

  • Ferritin is both a diagnostic marker and a monitor of disease activity in Still’s disease.

  • Extremely high ferritin levels (>3,000–10,000 ng/mL) should prompt consideration of Still’s disease or MAS.

  • Early recognition and targeted immunotherapy can significantly improve outcomes.

     

References:  

Ferritin in Adult-Onset Still's Disease: Just a Useful Innocent Bystander?
https://pmc.ncbi.nlm.nih.gov/articles/PMC3321299/

Adult-Onset Still's Disease: Causes, Symptoms, And Treatment.
https://www.youtube.com/watch?v=WPz5q8LCPG4

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

Comments

Post a Comment

Popular posts from this blog

Schnitzler Syndrome: A Rare Autoinflammatory Disorder

By SWA
Schnitzler syndrome is a rare, chronic autoinflammatory disease characterized by chronic urticaria (hives), recurrent fever, joint pain, and monoclonal gammopathy (abnormal proteins in the blood). First described by Dr. Liliane Schnitzler in 1972 , this condition is often misdiagnosed, leading to years of untreated symptoms before a correct diagnosis is made. The case report, " A 58-Year-Old Woman With Urticaria, Fever, and Joint Pain " , describes a case that closely aligns with my own experience with this challenging disorder. Key Features of Schnitzler Syndrome Schnitzler syndrome presents with a characteristic set of symptoms, though not all patients experience them in the same way: Chronic Urticaria (Hives) – Persistent, non-itchy or mildly itchy red patches that do not respond to antihistamines. Monoclonal Gammopathy (IgM or IgG type) – Abnormal monoclonal immunoglobulin detected in the blood (most commonly IgM ). Recurrent Fever – Unexplained fever episodes, often...
Read more

Dysferlin Protein: Key Roles, Genetic Locations

By SWA
Image
The purpose of this article is to share and discuss the details of a new discovery, which is highlighted within: CRISPR-Cas9: A Breakthrough Tool to Repair the DYSF Gene The dysferlin protein plays an essential role in maintaining the integrity of muscle cell membranes, particularly in tissues that endure significant mechanical stress, such as skeletal and cardiac muscles . Encoded by the DYSF gene , dysferlin is indispensable for repairing damaged cell membranes after injury caused by muscle contraction or external forces. This article explores the main locations where dysferlin is produced, its role in muscle repair, and supportive nutritional and therapeutic strategies for individuals with dysferlin deficiency, such as those affected by dysferlinopathies (e.g., Limb-Girdle Muscular Dystrophy Type 2B or Miyoshi Myopathy). Currently, there is no definitive answer as to why the severity of dysferlin protein expression or depletion varies. Do pathogens play a role in the methylation o...
Read more

Very Long-Chain Fatty Acids (VLCFAs) X-ALD and Spinal Muscular Atrophy (SMA): Exploring the Connection

By SWA
Image
Update Oct 28th 2024:  A Novel Mouse Model for Cerebral Inflammatory Demyelination in X-Linked Adrenoleukodystrophy: Insights into Pathogenesis and Potential Therapeutic Targets https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.27117 Progressive loss of cognitive abilities ""childhood dementia" and are among the rare diseases: Depending on the form of the disease, childhood neurodegeneration affects between 1 in 2,000 and 1 in 500,000 newborns. Examples include the cerebral form of X-linked adrenoleukodystrophy (X-ALD)" Very Long-Chain Fatty Acids (VLCFAs) are a specific type of fatty acid that are broken down in the body by specialized cellular structures called peroxisomes. These organelles play a critical role in maintaining metabolic balance by degrading VLCFAs. When this process is disrupted, VLCFAs accumulate in various tissues, which can lead to serious metabolic and neurological complications. Elevated VLCFA levels are characteristic of several p...
Read more