Adult Still Disease

Overview

Adult-onset Still's disease is a rare inflammatory disease characterized by high fever, joint pain, and rash. The immune system mistakenly targets the body's own tissues. It can affect many organ systems. Joints, skin, liver, spleen, lymph nodes, heart, and lungs can be involved. Only one organ or many organs can be affected at the same time.

It is the adult version of childhood Still's disease but can show differences. Adult-onset Still's disease is rarely seen. It can occur in 1-2 people per million each year. It can start at any age but there are two peaks. It can be seen more frequently between ages 15-25 and 36-46.

Adult-onset Still's disease can follow three different courses:

• Single-attack type: The disease appears in a single period, lasts several weeks or months, and recovers completely.
• Intermittent type: The disease comes in attacks, with symptom-free periods lasting weeks or years between attacks.
• Chronic type: Disease symptoms continue constantly, with joint involvement particularly prominent.

Diagnosis is difficult because symptoms can resemble many diseases. Infection, cancer, and other rheumatological diseases must be excluded. When correctly diagnosed, it is a treatable condition. Steroids and immunosuppressive medications are effective. Some patients can recover completely. In others, it can become chronic.

The disease rarely threatens life, but if left untreated can lead to chronic joint damage. With current treatments, symptoms can usually be brought under control.

Symptoms

The three most common main symptoms of adult-onset Still's disease are fever, rash, and joint pain. This triad is seen in approximately 75-95% of patients.

• Fever. This is the most typical symptom and is seen in almost every patient. Fever generally rises above 39°C and follows a characteristic course. It shows a sudden rise once or twice a day, often in the afternoon or evening hours. After the fever rises, it returns to normal on its own. For this reason, noting the course of fever during the day is very valuable for diagnosis.
• Rash. A typical rash appears together with fever. The rash is generally salmon-colored, flat or slightly raised, and spotted in appearance. It is most commonly seen on the trunk, arms, and legs. The most important feature of the rash is that it is "transient"; it appears with fever, disappears when fever drops, and generally does not itch.
• Joint pain and swelling. Joint pain or joint inflammation is seen in the great majority of patients. The most commonly affected joints are the knee, wrist, and ankle. Joint pain generally intensifies with fever. When the disease becomes chronic, permanent damage can develop in the joints.

Other symptoms:

• Sore throat (seen in approximately 70% of patients, does not respond to antibiotics)
• Muscle pain
• Enlargement of lymph nodes
• Liver or spleen enlargement
• Weakness, fatigue, loss of appetite, and weight loss

When to See a Doctor

You should consult a rheumatology specialist in the following situations:

• If you have an unexplained fever reaching 39°C, especially one that rises and falls once or twice a day
• If you have a salmon-colored rash that appears with fever
• If you have unexplained pain or swelling in your joints, especially in the wrist, knee, or ankle
• If you have a severe sore throat that does not go away and does not respond to antibiotics
• If all these symptoms are accompanied by weakness, fatigue, and weight loss
• If suddenly starting severe chest pain, shortness of breath, or confusion develops, call emergency services immediately

Causes and Risk Factors

The exact cause of adult-onset Still's disease is not known. Research suggests that in people with genetic predisposition, some environmental triggers (especially infections) initiate the disease.

Genetic predisposition. Some people's genetic makeup can cause the immune system to overreact to triggers such as infections. However, this does not mean the disease is directly hereditary; the risk of seeing the disease in family members is very low.

Infections. This is the most commonly blamed trigger factor in the emergence of the disease. In many patients, symptoms begin after an infection such as an upper respiratory tract infection. Viral infections (EBV, CMV, parvovirus) or some bacterial infections can be triggers.

Immune system disorder. In the disease, some proteins of the immune system (such as IL-1, IL-6, TNF-alpha) are produced in excessive amounts. This "cytokine storm" leads to symptoms such as fever, rash, and joint inflammation.

Who is at risk?

• Age: Most commonly seen in young adults between 16-35 years old.
• Gender: Slightly more common in women than men.
• Geography: Can be seen everywhere in the world.

Complications

Adult-onset Still's disease can lead to some complications, especially if left untreated:

• Chronic joint damage. In cases where the disease follows a chronic course, permanent damage can develop in joints, especially in the wrists. As a result of repeated inflammations, joint cartilage can wear away, joint space can narrow, and in advanced cases, fusion between bones can occur.
• Macrophage activation syndrome (MAS). This is the most serious and life-threatening complication of the disease. It is rarely seen, but if not recognized can be fatal. In MAS, the immune system becomes overactivated in an uncontrolled manner and attacks the body's own cells. High fever, liver and spleen enlargement, bleeding disorders, and organ failures can develop.
• Heart and lung involvement. Inflammation of the membrane surrounding the heart (pericarditis) can lead to chest pain, while inflammation of the lung membrane (pleurisy) can lead to shortness of breath.
• Liver damage. Elevation of liver enzymes during active disease periods is common. This is usually temporary and returns to normal when the disease is brought under control.
• Decline in quality of life. Recurrent fever attacks, chronic joint pain, and fatigue can negatively affect daily life, work performance, and social life.

Diagnosis

The diagnosis of adult-onset Still's disease is difficult because there is no specific test. Diagnosis is made with typical symptoms, laboratory findings, and exclusion of other diseases that create a similar picture (infections, cancers, other rheumatic diseases).

The main methods used in the diagnostic process:

Detailed history and physical examination. Your doctor questions the course of fever, rash, your joint pain, and other symptoms in detail. Noting the course of fever during the day is very valuable for diagnosis.

Blood tests:

• Complete blood count: In active disease, white blood cell count is usually elevated (leukocytosis).
• Inflammation markers: CRP and sedimentation (ESR) are high in almost all patients.
• Ferritin: This is one of the most characteristic findings of adult-onset Still's disease. Ferritin level usually rises above 5 times normal. A low glycosylated ferritin ratio (below 20%) is quite specific for the disease.
• Autoantibody tests: ANA and rheumatoid factor (RF) are usually negative. This negativity helps exclude other rheumatic diseases.
• Infection tests: Infections are excluded with blood cultures and viral tests.

Imaging methods:

• Joint X-rays: Used to evaluate joint damage in advanced cases.
• Chest X-ray and CT: Done in case of suspected lung involvement.
• Echocardiography: Used in case of suspected heart involvement.

Tissue biopsy. Rarely, especially to exclude cancers like lymphoma, bone marrow or lymph node biopsy may be needed.

Treatment

The goal in treatment of adult-onset Still's disease is to bring inflammation under control, relieve symptoms, prevent organ damage, and prevent disease recurrence. Treatment is personalized according to the severity of the disease and affected organs.

Nonsteroidal anti-inflammatory drugs (NSAIDs). Can be used as first-line treatment in mild cases. Medications like ibuprofen and naproxen can be effective in relieving fever and joint pain. However, most patients need more powerful treatments.

Corticosteroids. These are the first choice medications in moderate and severe cases. Corticosteroids like prednisolone bring fever, rash, and joint pain under control by rapidly suppressing inflammation. They are usually started at high doses, and after symptoms are brought under control, the dose is slowly reduced. With long-term use, side effects such as weight gain, bone loss, and diabetes can be seen.

Disease-modifying antirheumatic drugs. Used to reduce or stop the dose of corticosteroids. The most commonly used is methotrexate. Its effect may take weeks or months to begin. Requires regular blood monitoring.

Biological agents. These are currently the most effective medications in adult-onset Still's disease treatment. They target proteins (cytokines) that the immune system produces excessively:

• IL-1 inhibitors: Anakinra, canakinumab. Rapidly bring systemic symptoms (fever, rash) under control especially.
• IL-6 inhibitors: Tocilizumab. Effective in both systemic symptoms and joint involvement.

Biological agents are usually administered as injections or infusions. They can be very effective in patients who do not respond to other treatments.

Living with Adult-Onset Still's Disease

Adult-onset Still's disease is a chronic condition, but with proper treatment and regular follow-up, most patients can live a normal life.

• Use your medications regularly. Taking your medications as your doctor recommends is very important for disease control. Never stop your medications without consulting your doctor.
• Do not miss your regular doctor checkups. Regular visits with your rheumatology specialist are necessary to monitor the course of the disease and adjust treatment when needed. Have your blood tests done regularly.
• Protect yourself from infections. Medications used can increase infection risk. Wash your hands frequently, avoid crowded environments, get your flu and pneumonia vaccines. Consult your doctor if you have infection symptoms such as fever or cough.
• Update your vaccines. Get recommended vaccines such as flu vaccine, pneumonia vaccine, and COVID-19 vaccine after consulting your doctor. Live virus vaccines (measles, mumps, chickenpox) should not be used with some medications.
• Eat healthily. Balanced and healthy eating supports your general health. If you are using corticosteroids, pay attention to salt and sugar consumption, consume calcium-rich foods (milk, yogurt, cheese).
• Exercise regularly. Exercise preserves joint mobility, strengthens muscles, and reduces fatigue. Low-impact exercises such as swimming, walking, and cycling are ideal. Consult your doctor before starting an exercise program.
• Rest adequately. During disease periods, your body needs rest. Rest when you feel tired, take care of your sleep routine.
• Stress management. Stress can trigger the disease or worsen symptoms. Learn stress management techniques (meditation, yoga, deep breathing exercises), engage in activities that make you feel good.
• Pregnancy planning. Women with adult-onset Still's disease should definitely consult with rheumatology and obstetrics doctors before planning pregnancy. It is important that the disease is under control before pregnancy. Medications used may not be safe during pregnancy and may need to be changed.
• Inform your relatives. Give information about your disease to your family and close friends. Do not hesitate to ask for help during attack periods.

Preparing for Your Appointment

Preparing before going to your doctor's appointment makes the visit more productive.

What you can do:

• Note your symptoms: Note when the fever started, at what hours of the day it rose, to what degree it reached. Record whether there was a rash with fever, where the rash appeared, and how long it lasted. Specify which joints have pain or swelling, when pain increases.
• Track fever: Keeping a fever tracking chart showing the course of fever during the day will give very valuable information to the doctor.
• List medications you use: Write down all your prescription and over-the-counter medications, vitamins, and supplements.
• Collect your past medical records: If available, previously done blood tests, imaging reports, hospital admission histories.
• Write down your questions in advance: List what you want to ask so you don't forget.

Questions you can ask your doctor:

• Is the diagnosis of adult-onset Still's disease certain in my case?
• What type is my disease following?
• Which treatment is most suitable for me?
• What are the side effects of my medications? What should I pay attention to?
• How often should I have checkups?
• Can I exercise? Which exercises are appropriate?
• I am planning pregnancy, what should I pay attention to?
• Should I get my vaccines?
• What should I do during an attack period?

Your doctor may ask you:

• When did your fever start? How many times a day does it rise?
• Do you get a rash with fever? Where does the rash appear?
• Which joints have pain or swelling?
• Do you have a sore throat?
• Have you had an infection recently?
• Have you had such a disease before?
• Are there medications you are using?