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Adult-onset Still's Disease

Disease Details

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Description: Adult-onset Still's disease (AOSD) is a rare inflammatory disorder characterized by high fevers, rash, and arthritis.
Type: Adult-onset Still's disease (AOSD) is an inflammatory condition classified as a type of autoinflammatory disease. Regarding genetic transmission, it typically does not follow a clear pattern of inheritance and is generally considered sporadic rather than hereditary.
Signs And Symptoms: The disease typically presents with joint pain, high fevers, a salmon-pink macular or maculopapular rash, enlargement of the liver and spleen, swollen lymph nodes, and a neutrophil-predominant increased white blood cell count in the blood. Tests for rheumatoid factor and anti-nuclear antibodies are usually negative and serum ferritin is markedly elevated. Patients experiencing a flare-up from adult-onset Still's disease usually report extreme fatigue, swelling of the lymph nodes and, less commonly, fluid accumulation in the lungs and heart. In rare cases, AOSD can cause life-threatening complications, including hemophagocytic lymphohistiocytosis, IVDC, fulminant hepatitis, or disabling conditions such as aseptic meningitis and sensorineural hearing loss.
Prognosis: Adult-onset Still's disease (AOSD) prognosis can vary. Many people experience a single episode or intermittent flare-ups, while others may develop chronic symptoms. Long-term outcomes depend on the severity and frequency of flares, response to treatment, and potential complications like joint damage or organ involvement. Early and effective management typically improves the overall prognosis.
Onset: Adult-onset Still's disease (AOSD) typically presents with systemic symptoms such as high spiking fevers that usually occur in the late afternoon or evening, a characteristic salmon-pink rash that comes and goes, and arthritis or arthralgia affecting multiple joints. The onset can be abrupt or gradual. Causes are unknown, and triggers might include infections or other environmental factors.
Prevalence: The prevalence of Adult-Onset Still's Disease (AOSD) is rare, estimated to be about 1-34 cases per million people per year.
Epidemiology: Adult-onset Still's disease is rare and has been described all over the world. The number of new cases per year is estimated to be 1.6 per 1,000,000 population. The number of people currently affected is estimated at 1.5 cases per 100,000–1,000,000 population. Onset is most common in two age ranges, between ages 16–25 and between ages of 36–46 years.
Intractability: Adult-onset Still's disease (AOSD) can be challenging to manage, but it is not considered intractable. Treatment typically involves anti-inflammatory medications, corticosteroids, and immunosuppressive drugs. Many patients respond well to these treatments, though some may experience chronic symptoms or flares that require ongoing management.
Disease Severity: Adult-onset Still's disease (AOSD) severity can range from mild to severe. Mild cases might present with symptoms like fever, rash, and joint pain. More severe cases can involve chronic arthritis leading to joint destruction, and systemic complications such as pleuritis, pericarditis, or hepatic dysfunction. Elevated inflammatory markers, liver enzymes, and ferritin levels are typical in more severe instances.
Healthcare Professionals: Disease Ontology ID - DOID:14256
Pathophysiology: The cause of adult-onset Still's disease is unknown and it is not heritable, but it presumably involves interleukin-1 (IL-1), since medications that block the action of IL-1β are effective treatments. Interleukin-18 is expressed at high levels.
Carrier Status: Adult-onset Still's disease (AOSD) is not a hereditary condition, so there is no carrier status associated with it. The exact cause of AOSD is unknown, but it is believed to involve a combination of genetic predisposition, environmental factors, and possibly infections.
Mechanism: Adult-onset Still's disease (AOSD) is a rare inflammatory condition characterized by high fevers, arthritis, and a salmon-colored bumpy rash. Although the precise mechanism of AOSD is not entirely understood, several molecular mechanisms have been implicated in its pathogenesis:

1. **Cytokine Dysregulation:** AOSD is associated with an overproduction of pro-inflammatory cytokines, particularly interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-18 (IL-18). These cytokines play a pivotal role in driving the inflammatory processes seen in AOSD.

2. **Inflammasome Activation:** The NLRP3 inflammasome, part of the innate immune system, is often activated in AOSD. This leads to the production of IL-1β, a crucial mediator of inflammation, which contributes to fever and systemic inflammation.

3. **Toll-Like Receptors (TLRs):** There is evidence that TLRs, which recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), are involved in AOSD. Their activation can lead to the production of pro-inflammatory cytokines.

4. **Genetic Susceptibility:** Certain genetic factors may predispose individuals to AOSD. Variants of genes encoding proteins involved in the immune response, such as the HLA-DRB1 gene, have been associated with the disease.

These mechanisms collectively result in the characteristic systemic inflammation observed in AOSD, affecting multiple organs and systems.
Treatment: Adult-onset Still's disease is treated with anti-inflammatory medications. Steroids such as prednisone are used to treat severe symptoms of Still's. Other commonly used medications include hydroxychloroquine, penicillamine, azathioprine, methotrexate, etanercept, anakinra, tocilizumab, cyclophosphamide, adalimumab, rituximab, and infliximab.Newer medications target interleukin-1 (IL-1), particularly IL-1β. A randomized, multicenter trial reported better outcomes in a group of 12 patients treated with anakinra than in a group of 10 patients taking other disease-modifying antirheumatic drugs. In June 2020 FDA approved Ilaris (canakinumab) for the treatment of AOSD, this is the first FDA approved treatment for AOSD. Canakinumab is another anti-IL1 drug which selectively binds IL-1β and rilonacept which blocks both IL-1A and IL-1β. The monoclonal anti-IL6 antibody tocilizumab is another treatment option as effective as anakinra.The condition "juvenile-onset Still's disease" is now usually grouped under juvenile rheumatoid arthritis. However, there are obvious similarities between the two conditions, and there is some evidence that they may be closely related.
Compassionate Use Treatment: Adult-onset Still's disease (AOSD) is a rare inflammatory condition characterized by high fevers, joint pain, and a distinctive salmon-colored bumpy rash. For patients who do not respond to standard treatments, there are some off-label and experimental therapies that clinicians may consider:

1. **Biologic Agents:**
- **Anakinra:** An interleukin-1 receptor antagonist, has shown effectiveness and is often used off-label for AOSD.
- **Canakinumab:** Another IL-1 inhibitor, can be considered for patients who do not respond to other treatments.
- **Tocilizumab:** An IL-6 receptor inhibitor, has also been used off-label with some success.
- **Rituximab:** A monoclonal antibody against CD20, used in refractory cases.

2. **Janus Kinase (JAK) Inhibitors:**
- **Tofacitinib or Baricitinib:** These JAK inhibitors are being explored in clinical trials for their potential efficacy in treating refractory AOSD.

3. **Compassionate Use:**
- For patients with severe, refractory AOSD who have not responded to approved treatments, compassionate use of experimental therapies (those not yet approved but showing promise in clinical trials) may be considered. This typically requires regulatory approval and is evaluated on a case-by-case basis.

4. **Immunosuppressants:**
- **Methotrexate:** Typically used as a disease-modifying antirheumatic drug (DMARD), it can be used off-label to manage symptoms.
- **Cyclosporine or Azathioprine:** These immunosuppressive drugs are another alternative for refractory cases.

It's important for patients to discuss these options with their healthcare provider to carefully weigh the benefits and potential risks associated with off-label or experimental treatments.
Lifestyle Recommendations: Lifestyle recommendations for managing Adult-Onset Still's Disease (AOSD) include:

1. **Regular Exercise**: Engage in low-impact exercises such as walking, swimming, and yoga to maintain joint flexibility and reduce stiffness.
2. **Balanced Diet**: Consume a diet rich in fruits, vegetables, lean proteins, and whole grains to support overall health and reduce inflammation.
3. **Adequate Rest**: Ensure adequate sleep and take breaks as needed to manage fatigue and support recovery.
4. **Stress Management**: Practice stress-reducing techniques such as meditation, deep breathing exercises, and mindfulness to help manage symptoms.
5. **Avoid Smoking and Limit Alcohol**: Smoking and excessive alcohol can exacerbate inflammation and hinder immune function.
6. **Stay Hydrated**: Drink plenty of water to help flush out toxins and support overall bodily functions.
7. **Monitor Symptoms**: Regularly monitor and keep track of symptoms to report any changes to your healthcare provider promptly.
8. **Medication Adherence**: Follow your prescribed medication regimen and attend follow-up appointments to manage the disease effectively.

These lifestyle adjustments, in conjunction with medical treatment, can help manage symptoms and improve quality of life for individuals with AOSD.
Medication: Adult-onset Still's disease (AOSD) is treated with various medications to manage symptoms and inflammation. Common treatments include:

1. Nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce pain and inflammation.
2. Corticosteroids like prednisone for controlling severe inflammation.
3. Disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, to control the immune system.
4. Biologic agents like anakinra or tocilizumab that target specific pathways in the immune response.

The choice of medication depends on the severity of the disease and the patient's response to initial treatments. Regular monitoring and adjustment of therapy may be necessary.
Repurposable Drugs: For adult-onset Still's disease, several repurposable drugs have been utilized to manage symptoms and inflammation. Notably, these include:

1. **Methotrexate**: Commonly used in rheumatoid arthritis, it helps reduce inflammation and suppress the immune system.
2. **Anakinra**: An interleukin-1 receptor antagonist initially used for rheumatoid arthritis, effective in reducing inflammation in Still's disease.
3. **Tocilizumab**: An interleukin-6 receptor inhibitor, also used in rheumatoid arthritis and has shown benefits for Still's disease.
4. **Corticosteroids**: Such as prednisone, which are broadly used for their potent anti-inflammatory effects.
5. **Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)**: Like ibuprofen, used to manage pain and fever.

These drugs, though initially for other conditions, have been found beneficial in managing the symptoms of adult-onset Still's disease.
Metabolites: Adult-onset Still's disease (AOSD) is an inflammatory condition characterized by high fevers, joint pain, rash, and elevated white blood cell count. Specific metabolites associated with AOSD are not well-defined. However, elevated levels of ferritin, liver enzymes, and acute phase reactants like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are commonly observed.
Nutraceuticals: Nutraceutical interventions for Adult-Onset Still's Disease (AOSD) are not well-established due to limited research. There is no specific nutraceutical treatment proven to manage or mitigate the symptoms of AOSD effectively. Management typically focuses on pharmaceutical interventions such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressive agents. Nutraceuticals have not shown significant evidence to replace or complement these conventional treatments. Always consult healthcare professionals before adding supplements to your regimen.
Peptides: Adult-onset Still's disease (AOSD) doesn't have a treatment specifically based on peptides or nanotechnology as of now. Standard treatments typically include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs). Biologic agents that target specific parts of the immune system, such as interleukin-1 and interleukin-6 inhibitors, may also be used. Advances in peptides and nanotechnology might hold future potential, but current therapies focus mainly on controlling inflammation and managing symptoms.