Antisynthetase syndrome (ASyS) is a rare, chronic condition that typically occurs in those with myositis together with one of several autoantibodies known as antisynthetase antibodies. ASyS is two to three times more common in women than men. Estimates show that 20-25% of individuals diagnosed with dermatomyositis or polymyositis have antysynthetase autoantibodies in their blood.

Antisynthetase autoantibodies are immune system components that mistakenly target and attack an enzyme important in the process of building new proteins in the body. You can find out if you have one of these autoantibodies through a blood test that screens for a number of myositis-specific autoantibodies.

By far the most common of these is anti-Jo-1. Others include PL-7 and PL-12. Five additional antisynthetase antibodies have been identified so far, but these are much more rare, and their implications are not well understood yet.

Anti-Jo-1 antibody is most common antisynthetase antibody. Others include PL-7 and PL-12. Five additional antisynthetase antibodies have been identified so far, but there are much more rare and their implications are not well understood yet. Researchers are still identifying new autoantibodies of significance to myositis diseases.

See autoantibodies for more details about antisynthetase and other autoantibodies.

Symptoms associated with antisynthetase syndrome include the following:

Interstitial lung disease (ILD) – As many as 75% of those with antisynthetase syndrome have interstitial lung disease.

Muscle inflammation – Antisynthetase syndrome typically affects those with dermatomyositis, polymyositis, or necrotizing myopathy.

Inflammatory arthritis – Patients may experience pain, stiffness, swelling, redness, or warmth in and around joints. It is unusual, however, to experience the sort of joint deformity seen in rheumatoid arthritis.

Fever – About 30% of patients with antisynthetase syndrome will experience fever that is unrelated to infection or other causes.

Raynaud’s phenomenon (or syndrome) – This is a condition in which spasms of the arteries cause episodes of reduced blood flow, typically involving the fingers and toes. Nose and ears can also be affected. These episodes are usually triggered by cold or stress.  They can last several minutes to several hours and can cause the affected part to feel numb and cold and to turn white or blue.

Mechanic’s hands – This is a condition that involves thickened, dry, cracked skin on the sides of the fingers and palms, which can be painful. The term “mechanic’s hands” is used, because the condition makes the hands look rough and dirty, resembling those of a manual laborer.

Risk factors

  • Antisynthetase syndrome typically occurs in patients whose average age at the onset of disease is 50.
  • Antisynthetase syndrome is seen twice as often in women than men.
  • Patients with antisynthetase syndrome are less likely to experience cancer-associated myositis.
  • Interstitial lung disease may be the first or only symptom of antisynthetase syndrome.
  • Mortality risk is not increased because of antisynthetase syndrome, but the presence of severe interstitial lung disease is most frequently associated with early death.

Treatment of antisynthetase syndrome is similar to treatments recommended for other inflammatory myositis diseases. Early and aggressive treatment with corticosteroids (prednisone) is especially important with this condition. Physicians also often start second-line therapy together with steroids right from the beginning.

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. Flares tend to occur when medications are tapered too rapidly.

Some of these second- or third-line medications have special considerations with antisynthetase syndrome.

Anti-TNF inhibitors, such as etanercept (Enbrel) and adalimumab (Humira), are medications typically used for rheumatoid arthritis. If arthritis symptoms are predominant in a patient with antisynthetase syndrome, these medications may be preferred. They should be used with caution, however, as these biologic drugs are sometimes associated with the development of myositis.

Azathioprine (Imuran) is a good choice for muscle and lung disease.

Cyclophosphamide (Cytoxan) is used especially with interstitial lung disease.

Methotrexate (MTX) may make lung disease worse, so some physicians choose not to use this to treat antisynthetase syndrome.

Mycophenolate mofetil (CellCept) is a good choice for skin and lung disease.

Rituximab (Rituxan) has been shown to be effective for antisynthetase symptoms, especially for patients with anti-Jo-1 antibodies.

Tacrolimus seems to work well for lung disease.

Additional information about antisynthetase syndrome can be found in the Myositis Library section of this website.

Antisynthetase syndrome – Some stories – from the TMA newsletter The OutLook

Antisynthetase syndrome – video presentation by former TMA medical advisor Dr. Lisa Christopher-Stine at the 2016 TMA Annual Patient Conference.

Antisynthetase syndrome: Ask the Experts Podcast Series – 11/20/2017 from Rare Genomics Institute
This podcast features Dr. Sonye Danoff (Johns Hopkins Interstitial Lung Disease Clinic) and former TMA medical advisor Dr. Frederick Miller (National Institute of Environmental Health Sciences at the NIH) answering questions about antisynthetase syndrome.