Antisynthetase syndrome

Antisynthetase syndrome is a rare condition where your immune system mistakenly attacks your own body, causing inflammation in muscles, joints, lungs, skin, and blood vessels.

Table of contents

• What is antisynthetase syndrome?
• How common is this condition?
• Symptoms and complications
• What causes antisynthetase syndrome?
• How is it diagnosed?
• Treatment approaches
• Outlook and survival

What is antisynthetase syndrome?

Antisynthetase syndrome is a rare autoimmune disease, which means it occurs when your immune system mistakenly attacks healthy parts of your body instead of protecting it^[1]. Your immune system is made up of organs and cells designed to protect your body from harmful invaders like bacteria and viruses. In autoimmune diseases, something goes wrong and your immune system starts attacking your own tissues^[1].

This condition is characterized by the presence of specific autoantibodies (immune proteins that attack your own body) directed against enzymes called aminoacyl-tRNA synthetases, which your body needs to build proteins^[3]. These autoantibodies are found alongside various symptoms that can affect multiple parts of your body.

• Muscles
• Joints
• Lungs
• Skin
• Blood vessels

How common is this condition?

Antisynthetase syndrome is considered a rare disease. Experts estimate that fewer than 50,000 people in the United States have it^[1]. Worldwide estimates suggest it affects between 1 and 3 people per 100,000^[2]. Some sources estimate the frequency at approximately 1 in 25,000 to 33,000 people globally^[2].

The exact number is difficult to determine because so few cases are reported each year, and many people may not be diagnosed correctly if their symptoms are mistaken for other conditions with similar features^[1]. The condition affects women two to three times more often than men^[4][7]. The average age when symptoms begin is around 50 years old^[6].

Symptoms and complications

Which symptoms you experience depends on where and how severely your immune system damages tissue inside your body^[1]. Not all symptoms will appear in every person, and each patient’s experience is unique^[4]. According to diagnostic criteria, the presence of an antisynthetase antibody plus certain combinations of symptoms is required for diagnosis^[3].

Muscle problems (Myositis)

Between 67% and 100% of people with antisynthetase syndrome experience muscle inflammation called myositis^[2]. This causes chronic muscle pain and weakness, particularly in muscles closest to the center of your body (proximal muscles)^[1]. About 91% of patients display weakness in their muscles^[2].

The muscle weakness can range from mild to severe. Some people have difficulty climbing stairs, reaching overhead cupboards, or getting up from a seated position^[2]. Between 30% and 89% of people report persistent muscle tenderness and pain^[2]. Myositis can also weaken the muscles in your throat that help you swallow, causing difficulty swallowing (dysphagia)^[1].

Lung disease

Interstitial lung disease (ILD) is a serious complication that affects between 67% and 100% of people with antisynthetase syndrome^[2][4]. This condition damages the tissues between the small air sacs in your lungs and the blood vessels around them^[1].

The most common symptoms are shortness of breath (especially during physical activity) and a dry cough^[2]. You may also experience fatigue and chest discomfort^[1]. Lung symptoms may appear early alongside other symptoms, or they may develop later as the condition progresses^[2]. For some people, interstitial lung disease may be the first or only symptom^[4][6].

The lung disease in antisynthetase syndrome is often severe and can progress rapidly, which is why it causes much of the increased health risks associated with this condition^[3]. A recent study found that about 42% of patients also had fluid around their lungs (pleural effusions)^[2].

Joint problems (Arthritis)

Arthritis occurs in about 18% to 55% of people with inflammatory muscle diseases like antisynthetase syndrome^[2]. The arthritis is typically described as symmetrical (affecting the same joints on both sides of your body) and non-erosive (not causing permanent joint damage), most commonly affecting the small joints of your hands and feet^[2].

You may feel joint pain, stiffness, and swelling in your affected joints^[1]. Arthritis is the first symptom in about 24% to 66% of patients, which can sometimes lead to delays in getting the correct diagnosis^[2]. About 50% of patients show abnormalities on hand X-rays, such as erosions, calcium deposits around joints, or joint misalignments^[2].

Skin changes

About 30% of people with antisynthetase syndrome develop a condition called “mechanic’s hands”^[7]. This involves thickened, dry, cracked skin on your palms and the sides of your fingers^[1][4]. The condition gets its name because the hands look rough and dirty, resembling those of someone who does manual labor^[4].

Raynaud’s phenomenon

About 40% of people with antisynthetase syndrome experience Raynaud’s phenomenon^[7]. This condition causes episodes of reduced blood flow to your fingers and toes, usually triggered by cold temperatures or stress^[4]. During an episode, the affected areas may feel numb and cold and turn white, blue, or red^[1][4]. These episodes can last several minutes to several hours^[4].

Fever

Some people develop fevers that are not related to infection or other causes^[1]. About 20% to 30% of patients experience unexplained fever^[4][7]. The fever may occur when the disease first begins and may persist or return during relapses^[7].

Other symptoms

Some patients may also experience loss of appetite, weight loss, and extreme fatigue that can significantly affect daily life^[6].

What causes antisynthetase syndrome?

Experts are not sure what causes antisynthetase syndrome^[1][6]. It is classified as a chronic autoimmune disease, but the exact reason why the immune system begins attacking the body is unknown^[7].

Most people with antisynthetase syndrome have specific autoantibodies in their blood that show their immune system has been attacking their body^[1]. Antibodies are normally proteins that protect you when unwanted substances like bacteria or viruses enter your body. They act like chemical signals your immune system uses to flag harmful invaders^[1].

In autoimmune diseases, your immune system mistakenly makes and sends out antibodies that attack healthy tissue. People with antisynthetase syndrome usually have autoantibodies that attack enzymes called tRNA synthetases^[1]. These are helpful enzymes your body needs to build proteins and function correctly.

The most commonly detected antibody is anti-Jo-1^[2][4]. Other antisynthetase antibodies include PL-7, PL-12, OJ, EJ, KS, Wa, YRS, and Zo^[4][7]. While experts don’t know why your immune system starts making these autoantibodies, finding evidence of them in your blood strongly suggests you have antisynthetase syndrome^[1].

How is it diagnosed?

Diagnosing antisynthetase syndrome can be challenging and requires cooperation between different medical specialists^[10]. The diagnosis is made by combining information from your symptoms, medical history, and various tests^[2][3]. Prompt communication and care coordination between your primary care doctor and specialists (such as rheumatologists and lung doctors) are essential to speed up diagnosis and begin treatment early^[10].

Blood tests

You can find out if you have antisynthetase autoantibodies through a blood test that screens for myositis-specific autoantibodies^[4]. Blood tests may also check for elevated muscle enzymes such as creatine kinase and aldolase, which are often increased when muscles are inflamed^[7].

Imaging tests

High-resolution computed tomography (CT) scans of your chest can show lung abnormalities^[6][10]. Magnetic resonance imaging (MRI) of affected muscles may be performed to visualize muscle inflammation^[7].

Lung and muscle function tests

Pulmonary function tests measure how well your lungs work^[6][10]. These tests can show a restrictive pattern with reduced lung volumes if you have interstitial lung disease^[10]. Electromyography (EMG) can assess muscle electrical activity^[7].

Biopsies

A muscle biopsy may be taken to examine muscle tissue under a microscope and confirm inflammatory myopathy^[7][10]. In some cases, a lung biopsy may be necessary to evaluate lung tissue^[3][10].

Other tests

Nailfold capillaroscopy can examine tiny blood vessels at the base of your fingernails, where abnormalities are sometimes found in people with antisynthetase syndrome^[7]. Your doctor may also evaluate your ability to swallow and assess your risk for aspiration^[7].

Treatment approaches

While there is no cure for antisynthetase syndrome, you should be able to manage your symptoms with a combination of medications and physical or pulmonary therapies^[1]. Treatment aims to reduce inflammation and manage symptoms^[6]. Your treatment plan will target your particular symptoms, depending on which parts of your body are affected^[6].

Corticosteroids

Corticosteroids (steroid medications) are the main treatment for antisynthetase syndrome^[7]. Prednisone is typically given at high doses initially (about 1 milligram per kilogram of body weight per day) for 4 to 6 weeks to control the disease^[7]. The dose is then slowly reduced over 9 to 12 months to the lowest amount needed to keep symptoms under control.

In more severe cases, you may need intravenous (IV) methylprednisolone for 3 to 5 days^[7]. Early and aggressive treatment with corticosteroids is especially important with this condition^[4]. Improvement in muscle strength can take several weeks or months, so how you feel is a more reliable sign of response to treatment than test results alone^[7].

Immunosuppressive medications

Immunosuppressive therapy (medications that calm down your immune system) is needed to control the muscle and lung problems of the disease^[2][6]. Doctors often start these medications together with steroids right from the beginning^[4].

Commonly used immunosuppressive medications include azathioprine, mycophenolate mofetil, and tacrolimus^[2][6]. In refractory cases (when other treatments don’t work), rituximab may be used^[12]. Cyclophosphamide may be used for severe cases^[10].

It can take two or three months for some medications to have their full effect^[6]. Some patients may need to remain on medication for their entire lives, but blood work will be checked periodically to assess changes and adjust your treatment plan^[6].

Additional treatments

Other treatment options may include intravenous immunoglobulins and plasma exchange^[10]. For lung problems, anti-fibrotic therapies and oxygen therapy may be needed^[10]. If you have severe arthritis symptoms, your doctor may consider medications typically used for rheumatoid arthritis, such as etanercept or adalimumab^[4].

Physical and supportive therapies

It is very important to maintain an active and healthy lifestyle^[15]. Depending on your symptoms, it may be difficult to exercise without pain, so physical or occupational therapy can be very helpful in strengthening your muscles^[15].

Participating in pulmonary rehabilitation programs can help if you have lung involvement^[20]. Maintaining a healthy diet and exercise routine and keeping up to date with vaccinations are also important parts of managing the condition^[20].

Remission and flares

Antisynthetase syndrome can go into remission, especially for those with milder lung disease, but patients are more likely to remain symptom-free while continuing treatment^[4]. Flares (when symptoms return or worsen) tend to occur when medications are reduced too rapidly^[4].

Outlook and survival

The outlook for people with antisynthetase syndrome varies depending on the severity of symptoms and how quickly treatment begins. The long-term care requires careful attention to both the side effects of chronic immunosuppressive therapy and disease-related complications^[3].

It is believed that the mortality rate for antisynthetase syndrome is significantly higher than that of the general population^[2]. The estimated ten-year survival rate for patients with different antisynthetase antibodies is about 77%^[2].

Mortality risk is not increased solely because of antisynthetase syndrome itself, but the presence of severe interstitial lung disease is most frequently associated with early death^[4]. Disease-related complications can include progressive interstitial lung disease that may require lung transplantation, pulmonary hypertension (high blood pressure in the lungs), malignancy, and decreased survival^[3].

Greater awareness of the clinical features of this syndrome allows for earlier diagnosis and appropriate treatment, which can improve outcomes^[3]. Early recognition and successful treatment are crucial to prevent complications and improve quality of life^[10].

If you are noticing new symptoms like joint pain, changes to your skin, or trouble breathing, visit a healthcare provider^[1]. Getting help early can make a significant difference in managing this condition.