What is Still Disease?
Adult-onset Still disease (AOSD) is a uncommon disease that affects the entire body, causing daily fevers, inflammation in multiple joints, and a temporary salmon-pink spotted rash. This disease was first reported in children by George Still in 1896, and is known as ‘Still disease’ or systematic juvenile idiopathic arthritis. ‘Adult-onset Still disease’ refers to the same condition when it shows up after the age of 16.
What Causes Still Disease?
The exact cause of AOSD, or Adult Onset Still’s Disease, isn’t quite clear. However, some believe that AOSD may be a reaction to certain triggers, like viruses and bacteria, in people who are genetically susceptible. There’s evidence that infections, and certain bacteria like Yersinia enterocolitica and Mycoplasma pneumoniae, may play a big role in causing AOSD.
It’s also uncertain whether all people with AOSD share the same cause. A French study that looked at 62 patients found that AOSD was linked to specific versions of a gene called the human leukocyte antigen (HLA). Additionally, there have been cases reported where twins both developed the disease.
Risk Factors and Frequency for Still Disease
AOSD, or Adult Onset Still’s Disease, is a very rare condition. It’s most commonly found in Europe, with only about 0.1 to 0.4 cases for every 100,000 people each year. The disease seems to affect more females than males. There are two age groups where the disease is most commonly diagnosed: between 15 and 25 years old, and then again between 36 and 46 years old. However, most patients (about three-quarters of them) first experience symptoms of the condition between the ages of 16 and 35. In rare cases, people over the age of 70 have been known to develop the disease.
- AOSD is a rare disease, with around 0.1 to 0.4 cases per 100,000 people each year in Europe.
- The condition tends to affect more females than males.
- The disease commonly appears in two age groups: 15-25 years and 36-46 years.
- About three-quarters of patients first see symptoms between the ages of 16 and 35.
- In rare cases, people over 70 can also develop AOSD.
Signs and Symptoms of Still Disease
Adult-Onset Still’s Disease (AOSD) often has three types of patterns: monophasic, intermittent, and chronic. While each type is seen about equally in patients, some studies indicate that the chronic articular pattern may be more prevalent. It’s also common for the initial monophasic or intermittent patterns to morph into a chronic version over time.
The main symptoms of AOSD include fever, a distinctive rash, and joint pain or arthritis, occurring in around 75% to 95% of patients. Other common symptoms include muscle pain, sore throat, enlarged lymph nodes, and an enlarged spleen. Less frequently seen symptoms include an enlarged liver, pleuritis (inflammation of the tissues that line the lungs and chest cavity), pericarditis (swelling and irritation of the thin sac-like membrane surrounding the heart), and abdominal pain.
The fever in AOSD often follows a quotidian pattern, meaning it recurs daily with temperature returning to normal between fever spikes. This often happens late in the day and usually precedes other symptoms. In about 20% of cases, the fever persists between spikes, or an additional spike occurs in the morning. Sometimes, AOSD may present as a fever of unknown origin, with a temperature of more than 39.5 °C suggesting a monophasic pattern.
The rash in AOSD is typically fleeting, with a salmon-colored, flat, or slightly raised appearance. It is usually not itchy and tends to appear with the onset of fever, most likely observed on the torso and limbs. However, it can also appear on the palms, soles, and face. The rash can sometimes be triggered by heat or skin friction, known as the Koebner phenomenon.
The joint pain or arthritis in AOSD can initially be mild and short-lived, affecting only a few joints, but it can become severe, causing damage and affecting many joints symmetrically. Commonly affected joints are the knees, wrists, and ankles, but other joints such as the elbows, fingers, shoulders, and jaw can also be involved. Joining of the wrist joint is a characteristic of AOSD but is only seen in a few patients.
Other symptoms such as muscle pain, sore throat, enlarged lymph nodes, and an enlarged spleen are also common in AOSD. Muscle pain often worsens during fever spikes and can be severe and disabling. A sore throat often recurs during disease outbreaks, and examination of such cases typically reveals severe, nonsuppurative (no pus formation) pharyngitis. Enlarged lymph nodes and an enlarged spleen have been reported in many patients with AOSD.
Less common symptoms include an enlarged liver, pleuritis, pericarditis, and abdominal pain. In fact, abdominal pain is reported in 1% to 48% of the patients, and additional symptoms such as nausea, loss of appetite, lymphadenitis, pancreatitis, and weight loss can also occur.
Testing for Still Disease
The laboratory results discussed here are common in people with Adult-Onset Still’s Disease (AOSD), but they are not definitive proof of it. Therefore, these signs combined with the symptoms the patient is experiencing can assist doctors in confirming the diagnosis after they’ve ruled out other causes.
Ferritin levels, which are a measure of the amount of iron stored in your body, are usually more than five times higher than normal in patients with AOSD. If this level is elevated, it indicates the disease is likely with an 80% probability and 46% certainty. However, when this is combined with a drop in the proportion of glycosylated ferritin (below 20%), the certainty rises to 93%. Doctors also monitor ferritin levels during treatment.
Almost all patients with AOSD have increased levels of inflammatory markers like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Blood test results may show more white blood cells than normal, specifically over 15,000 cells per microliter with a main count of neutrophil cells above 80%, anemia with normal-looking red blood cells, and an increased platelet count. In some severe cases, these blood changes can resemble a blood disorder, and some patients may show signs of red blood cell aplasia, a condition where the bone marrow does not create enough red blood cells to replace the naturally dying ones.
The study of the bone marrow shows induced growth of granulocytic precursors – cells that will become a type of white blood cell. Some patients may also have overactive and hungry (‘hemophagocytic’) cells. Up to 75% of patients have increased levels of liver enzymes, which could be due to liver inflammation. In addition, raised aldolase levels, another marker of tissue damage, may also be detected.
Less than 10% of patients have detectable antinuclear antibodies (ANA) and rheumatoid factor (RF), but usually only in low amounts. The absence of these antibodies underlines the importance of considering other diagnostic factors and symptoms when evaluating a possible diagnosis of AOSD.
The fluid in the joints usually shows signs of inflammation, with a varied number of white cells. This, together with inflammatory markers in this fluid, confirms that AOSD affects the whole body and helps doctors to select the best therapeutic approach.
In the early stages of the disease, X-rays are either normal or may show a slight narrowing of the space between the joints or thinning of the bone near the joints. A typical X-ray sign of AOSD is a narrowing of the spaces in the wrist joint, which may eventually lead to the bones fusing together.
Computed tomography (CT) scans and F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans can show abnormalities like enlarged lymph nodes, an enlarged spleen, abnormalities in the lungs, and an enlarged liver. These imaging techniques play a crucial role in showing how much the disease is affecting the body and contribute to a comprehensive evaluation of the diagnosis.
Doctors can also use the following additional tests to help confirm the diagnosis: a Complete Blood Count (CBC), testing for ANA, RF, and anti-citrullinated peptide (anti-CCP) antibodies, blood cultures, liver enzyme tests, blood tests for hepatitis B and C, Epstein Barr virus, human parvovirus B19, and HIV, X-rays of the chest, blood tests for Blood Urea Nitrogen (BUN), creatinine, and testing of the urine.
Treatment Options for Still Disease
The goal of treating Adult Onset Still’s Disease (AOSD – a rare type of inflammatory arthritis) is to manage symptoms, reduce inflammation, prevent damage to organs, and minimize the long-term effects of treatment.
The effectiveness of treatments for AOSD is based on observation studies and clinical experience. The initial treatment decisions are made based on how severe the disease is, and later decisions are based on the patient’s response to treatment.
When AOSD presents as a mild disease, it may show symptoms like fevers, rashes, joint pain, or mild arthritis. While some patients may find relief from nonsteroidal anti-inflammatory drugs (NSAIDs – drugs that reduce pain, decrease fever, prevent blood clots, and decrease inflammation), most patients benefit from a low dose of glucocorticoids (a type of steroid hormone that reduces inflammation).
A moderate presentation of AOSD can show severe joint symptoms, high fever, or non-life-threatening involvement of internal organs. Severe AOSD, on the other hand, can involve potentially life-threatening complications like issues with the heart, blood vessels, or liver. For moderate to severe cases, Anakinra (a medication that blocks the actions of chemicals in the body that are involved in inflammatory and immune responses) is often the initial treatment of choice in patients without joint erosion, while Methotrexate (a drug used to reduce the effects of the immune system) is preferred in patients with prevalent joint disease. Glucocorticoids are considered as a second-line treatment after anakinra.
Patients need to be regularly monitored, with periodic checks on their blood count, kidney function, electrolyte levels, protein responsible for blood clotting, liver enzymes, etc.
Most patients with AOSD can eventually stop therapy. Some will only experience one episode of AOSD. There are no established protocols for slowly reducing and stopping disease-modifying antirheumatic drugs (DMARDs – used to decrease joint damage and disability caused by diseases like rheumatoid arthritis). For patients who have been in complete remission for at least 3 months, medications should be tapered gradually to eventually stop all drugs. Regular monitoring during the tapering down of medication helps tailor management for each patient with AOSD.
What else can Still Disease be?
Diagnosing Adult-Onset Still’s Disease (AOSD) involves a thorough examination of clinical signs, lab results, and imaging studies. This is necessary to distinguish it from other conditions that can cause similar symptoms. These other conditions could include infections, cancer, rheumatic diseases, and adverse reactions to certain drugs.
Different infections like acute viral infections, such as parvovirus B19 and hepatitis, and blood stream bacterial infections, can produce symptoms similar to AOSD. These symptoms might include fever, increased white blood cell count, and elevated inflammation markers.
Rheumatic diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and reactive arthritis can also result in elevated inflammation markers. Additionally, vasculitic disorders, which involve inflammation of the blood vessels, such as polyarteritis nodosa (PAN) can mimic AOSD with their accompanying symptoms like fever, joint pain, skin lesions, and abdominal pain.
Lastly, cancer, particularly lymphomas, might resemble AOSD because they might both lead to symptoms like enlarged lymph nodes, fever, and increased white blood cell count.
What to expect with Still Disease
Adult-Onset Still’s Disease (AOSD) usually follows one of three patterns: it can be a one-time illness, it can come and go in flares, or it can become a long-term condition known as chronic Still’s disease. Some factors can indicate a higher chance of AOSD becoming a long-term problem, such as the presence of erosive polyarthritis (a type of severe joint inflammation that can cause bone erosion) at the beginning of the disease and if it affects the shoulders or hips.
Moreover, if a patient has been on systemic glucocorticoids for more than 2 years before the routine use of biologics (a type of medication made from living organisms), it is considered a sign of poor prognosis. To simplify, this means that the condition might not improve significantly or may even worsen over time.
Possible Complications When Diagnosed with Still Disease
Complications stemming from AOSD (also known as Adult-onset Still’s Disease), include numerous potentially serious conditions. Some of these conditions include MAS, which is a severe, potentially life-threatening condition, amyloidosis, which is a rare disease that occurs when a substance called amyloid builds up in your organs, and disseminated intravascular coagulopathy, a complicated condition causing the blood to clot improperly. Other complications are PAH (Pulmonary Arterial Hypertension), a type of high blood pressure that affects the arteries in the lungs and the right side of the heart, TTP (Thrombotic Thrombocytopenic Purpura), a rare blood condition characterized by blood clots, and diffuse alveolar hemorrhage, a serious lung condition involving bleeding into the lungs. It is very important to quickly recognize and manage these complications to improve patient outcomes and to minimize potential long-term negative effects.
Common Complications:
- MAS (a severe, potentially life-threatening condition)
- Amyloidosis (disease due to buildup of amyloid in your organs)
- Disseminated intravascular coagulopathy (complicated condition causing blood to clot improperly)
- PAH (Pulmonary Arterial Hypertension – high blood pressure affecting the arteries in the lungs and the right side of the heart)
- TTP (Thrombotic Thrombocytopenic Purpura – rare blood condition characterized by blood clots)
- Diffuse alveolar hemorrhage (serious lung condition involving bleeding into the lungs)
Preventing Still Disease
When it comes to managing Adult-Onset Still’s Disease, or AOSD, it’s important that doctors and patients work together. This will help in both preventing the disease and taking care of it. Recognizing AOSD early is key. So, you need to know what to look out for. Symptoms often include ongoing fevers, a rash, and pain in the joints. If you notice any of these, don’t hesitate to get medical help right away.
Regular doctor’s visits and diagnostic tests, like blood tests or imaging scans, are crucial so that doctors can keep an eye on the disease and change your treatment if needed. It’s also vital that you take your medication just like the doctor tells you. Following your treatment plan closely can help you get better quicker.
Maintaining a healthy lifestyle, like eating right and staying physically active, can also help your overall health. Education is key to helping you understand AOSD. Knowing about your disease, your treatment options, and what complications might come up can empower you as a patient. It can also be helpful to connect with organizations and support groups for people with AOSD.
In addition to physical health, don’t forget about your mental health. It’s equally important. Seeking the right support can greatly help in coping with your condition. At the end of the day, it’s the teamwork between doctors and patients that can effectively navigate the challenges that come with managing AOSD.
