Last updated:
9/24/25
Years published: 2018, 2023, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Frederick W. Miller, MD, PhD, Scientist Emeritus, National Institutes of Health, former Chief, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, for assistance in the preparation of this report.
Antisynthetase syndrome is a rare, chronic disorder that can affect multiple systems of the body. The disorder is immune-mediated, which means there is inflammation resulting from abnormal functioning of the immune system and the presence of specific autoantibodies that target specific proteins in the body. The symptoms and severity of the disorder can vary greatly among affected individuals. Common symptoms include inflammation of the muscles (myositis), inflammation of several joints (polyarthritis), interstitial lung disease and thickening and cracking (fissuring) and discoloration of the skin of the fingers, called mechanic’s hands. Some individuals develop pain and numbness or a prickly feeling in the fingers and toes in response to cold (Raynaud phenomenon). During a Raynaud episode, the fingers or toes may turn white or blue.
Affected individuals can also have nonspecific symptoms like fatigue, unexplained fevers and unintended weight loss. The exact, underlying cause is not fully understood, but some genetic and environmental risk factors have been identified. Antisynthetase syndrome sometimes occurs along with other conditions such as uncommon inflammatory muscle diseases like dermatomyositis or polymyositis.
There is no cure or specific treatment guidelines. Treatment depends on the specific symptoms and may include medication and supporting therapy such as physical therapy.
The signs and symptoms of antisynthetase syndrome vary widely from one person to another. Some people may develop symptoms suddenly, while in others the condition progresses more gradually. Not every person will have all the symptoms listed below. For example, some people may have little muscle involvement but significant lung disease. The three main features, muscle inflammation, lung disease and joint inflammation, are often called the “classic triad”, though they may not appear at the same time.
Common symptoms include:
Other possible symptoms include:
The exact cause of antisynthetase syndrome is not fully understood. Affected individuals have autoantibodies. Antibodies are part of the immune system; they are specialized proteins that target foreign or invading organisms. Autoantibodies are antibodies that mistakenly attack healthy tissue. In antisynthetase syndrome, affected individuals have autoantibodies that target certain enzymes in the body called aminoacyl-tRNA synthetases. Enzymes are specialized proteins that help to bring about specific biochemical reactions in the body and aminoacyl-tRNA synthetases help to regulate the production of other proteins and are important for the overall health and function of the body. Researchers do not know why these autoantibodies target aminoacyl-tRNA synthetases. Not every person who develops these autoantibodies will go on to develop symptoms of antisynthetase syndrome.
The exact role these autoantibodies play in the development of antisynthetase syndrome is not fully understood. The autoantibodies that have identified in this disorder include anti-Jo1, anti-EJ, anti-OJ, anti-PL7, anti-PL12, anti-SC, anti-KS, anti-JS, anti-HA, anti-YRS, anti-tryptophanyl and anti-Zo, and each of these target a different aminoacyl-tRNA synthetase. Anti-Jo1 is the most common autoantibody in individuals with antisynthetase syndrome.
Some autoantibodies are more likely to be associated with specific symptoms. Muscle disease occurs more often with anti-Jo1 or anti-PL7. Interstitial lung disease occurs more often with anti-PL7, anti-PL12, anti-KS and anti-OJ autoantibodies. Some individuals with anti-OJ autoantibodies have developed severe muscle weakness.
These autoantibodies are thought to be produced after a ‘triggering’ event such as a viral infection or exposure to certain drugs. When the immune system responds to these triggering events, something goes wrong, and these autoantibodies are created that could then damage healthy tissue.
Some affected individuals may have a genetic predisposition to developing antisynthetase syndrome. A genetic predisposition means that a person may carry one or more gene changes (variants) associated with the condition, but the condition will not develop unless other factors help to trigger it. Most likely, antisynthetase syndrome is a multifactorial disease, in which immune, genetic and environmental factors are necessary for the development of the disorder.
Antisynthetase syndrome is rare. The exact incidence or prevalence of the disorder is unknown, but it is estimated to have an incidence of 0.56 per 100,000 population and prevalence of 9.21 per 100,000. Antisynthetase syndrome affects females twice as often as males. Age of onset can range from the late teens to the elderly, with a mean average of the 50s. Because rare disorders often go undiagnosed or misdiagnosed, determining the true frequency of antisynthetase syndrome in the general population is difficult.
A diagnosis of antisynthetase syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and tests that confirm the presence of autoantibodies against the one of the aminoacyl-tRNA synthetase enzymes.
Clinical Testing and Workup
Blood tests can show the presence of autoantibodies against one of the aminoacyl-tRNA synthetase enzymes. Every person who has one of these autoantibodies does not necessarily, develop antisynthetase syndrome. There are published criteria that have been proposed to help with diagnosis. However, these criteria are not universally accepted, and some doctors think some people may have antisynthetase syndrome even if they do not meet the requirements for diagnosis under these guidelines. Based on some of the guidelines, affected individuals must also have two major criteria or one major criterion and two minor criteria of the disorder. The two major criteria are interstitial lung disease and muscle disease. Minor criteria are arthritis, Raynaud phenomenon or thickening and cracking of the skin of the hands (mechanic’s hands).
Blood tests can also show elevated levels of creatine kinase or aldolase, which are muscle enzymes. When these muscle enzymes are elevated, it is a sign of muscle damage. This is not specific to antisynthetase syndrome and is a sign of many different types of muscle disease.
A specialized imaging technique called high resolution computerized tomography (CT) scanning may be used to detect and evaluate lung disease. During CT scanning, a computer and X-rays are used to create cross-sectional images of certain tissue structures. High resolution CT scanning involves specific techniques that enhance or improve the resolution of the images. Pulmonary function tests may be administered to determine how well or poorly the lungs are working.
Specialized testing that records electrical activity in skeletal muscle at rest and during muscle contraction (electromyography) may be performed to determine the health of the muscles.
Treatment
The treatment of antisynthetase syndrome is personalized because the condition can affect people in very different ways. Treatment is best done by a team of specialists, which may include lung doctors (pulmonologists), joint and muscle doctors (rheumatologists and neurologists) and immune system specialists (immunologists). Emotional and social support for both the affected person and their family is also an important part of treatment, since the condition can be long-lasting and affect daily life.
Medicines that reduce inflammation are the foundation of treatment. Most people are started on corticosteroids (often called “steroids”), which work quickly to control swelling and inflammation. However, steroids can cause serious side effects if used at high doses for too long, so doctors try to reduce the dose as soon as possible. To do this, they add other medicines that calm the immune system, called immunosuppressants. These include mycophenolate mofetil (MMF), methotrexate (MTX) and azathioprine (AZA). Unfortunately, these medicines do not always work well for antisynthetase syndrome. Other medicines, such as tacrolimus and ciclosporin (called calcineurin inhibitors) can help in difficult-to-treat cases. Intravenous immunoglobulin (IVIG), a treatment made from donated antibodies, can be effective for severe skin or muscle involvement. Hydroxychloroquine may help with rashes but does not treat the lung, muscle, or joint problems.
One medicine, rituximab, has shown to be beneficial in some people. Rituximab is a type of biologic drug that targets specific immune cells (B cells) that are thought to drive the disease. Studies show that rituximab can stabilize lung disease, improve muscle and joint symptoms and allow patients to safely reduce their steroid use. This is especially important because lowering steroid doses reduces the risk of infections and other complications. In people with more aggressive forms of arthritis, especially those with antibodies also seen in rheumatoid arthritis (rheumatoid factor or anti-CCP), rituximab often works better than standard medicines. Because of these results, rituximab is now considered by many specialists to be a good treatment option for antisynthetase syndrome.
For people whose lung disease becomes more fibrotic (meaning scarred and less able to heal), antifibrotic medicines such as nintedanib may be used. These do not treat inflammation directly but can slow down further scarring and loss of lung function. While not the first choice, they can be an important addition for people whose disease progresses despite immune treatments.
Physical therapy is recommended to help patients maintain or rebuild muscle strength and reduce muscle wasting. People with severe lung disease may need oxygen therapy. Because patients often take medicines that weaken the immune system, they are at higher risk of infections such as Pneumocystis jirovecii pneumonia (PJP), a serious lung infection. In these cases, doctors may prescribe preventive antibiotics, such as co-trimoxazole, to lower that risk. Regular check-ups with breathing tests, chest scans and blood work are essential so doctors can see how the disease and treatments are affecting the body.
The overall goal of treatment is to control inflammation early, protect the lungs and muscles from long-term damage, minimize the use of steroids and reduce the risk of complications.
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JOURNAL ARTICLES
Coffey CM, Hulshizer CA, Crowson CS, Ryu JH, Ernste FC. Epidemiology of Antisynthetase Syndrome and Risk of Malignancy in a Population-Based Cohort (1998-2019). J Rheumatol. 2025;52(3):280-284. Published 2025 Mar 1. doi:10.3899/jrheum.2024-0945
Kouranloo K, Dey M, Elwell H, Yioe V, Spencer LG, Cotton CV. Management and outcomes of interstitial lung disease associated with anti-synthetase syndrome: a systematic literature review. Rheumatology (Oxford). 2025;64(1):45-55. doi:10.1093/rheumatology/keae403
Liu J, Nie N, Zhang R, Wang D, Lin Y, Chang H. Anti-synthetase syndrome with anti-PL-7 antibody positive in a child: a case report and literature review. Front Immunol. 2025;16:1525432. Published 2025 Mar 3. doi:10.3389/fimmu.2025.1525432
Conticini E, Cameli P, Grazzini S, et al. Efficacy and safety of a step-down regimen of low dosage of glucocorticoids combined with early administration of synthetic or biologic immunosuppressants in anti-synthetase syndrome: A pilot study. Semin Arthritis Rheum. 2024;69:152560. doi:10.1016/j.semarthrit.2024.152560
Patel P, Marinock JM, Ajmeri A, Brent LH. A Review of Antisynthetase Syndrome-Associated Interstitial Lung Disease. Int J Mol Sci. 2024;25(8):4453. Published 2024 Apr 18. doi:10.3390/ijms25084453
Zanframundo G, Faghihi-Kashani S, Scire CA, et al. Defining anti-synthetase syndrome: a systematic literature review. Clin Exp Rheumatol. 2022 Feb;40(2):309-319. https://pubmed.ncbi.nlm.nih.gov/35225224/
Meyer A, Lannes B, Goetz J, et al. Inflammatory myopathies: a new landscape. Joint Bone Spine. 2018;85:23-33. https://www.ncbi.nlm.nih.gov/pubmed/28343013
Gonzalez-Gay MA, Montecucco C, Selva-O’Callaghan A, et al. Timing of onset affects arthritis presentation pattern in antisynthetase syndrome. Clin Exp Rheumatol. 2018;36:44-49. https://www.ncbi.nlm.nih.gov/pubmed/28770709
Castaneda S, Cavagna L, Gonzalez-Gay MA, AENEAS (American-European Network of Antisynthetase Syndrome) collaborative groups members. Comments on the “2017 Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups.” Points of Concern. Arthritis Rheumatol. 2018. https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.40478
Noguchi E, Uruha A, Suzuki S, et al. Skeletal muscle involvement in antisynthetase syndrome. JAMA Neurol. 2017;74:992-999. https://www.ncbi.nlm.nih.gov/pubmed/28586844
Bartoloni E, Gonzazlez-Gay MA, Scire C, et al. Clinical follow-up predictors of disease pattern change in anti-Jo1 positive anti-synthetase syndrome: results from a multicenter, international and retrospective study. Autoimmune Rev. 2017;16:253-257. https://www.ncbi.nlm.nih.gov/pubmed/28147261
Witt LJ, Curran JJ, Strek ME. The diagnosis and treatment of antisynthetase syndrome. Clin Pulm Med. 2016;23:218-226. https://www.ncbi.nlm.nih.gov/pubmed/27594777
Zamora AC, Hoskote SS, Abascal-Bolado B, et al. Clinical features and outcomes of interstitial lung disease in anti-Jo-1 positive antisynthetase syndrome. Respir Med. 2016;118:39-45. https://pubmed.ncbi.nlm.nih.gov/27578469/
Mahler M, Miller FW, Fritzler MJ. Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev. 2014;13:367-371. https://www.ncbi.nlm.nih.gov/pubmed/24424190
Sem M, Molberg O, Lund MB, Gran JT. Rituximab treatment of the anti-synthetase syndrome: a retrospective case series. Rheumatology (Oxford). 2009;48:968-971. https://www.ncbi.nlm.nih.gov/pubmed/19531628
INTERNET
Christopher-Stine L Vleugels RA and Amato AA. Clinical manifestations of dermatomyositis and polymyositis in adults. UpToDate, Inc. Apr 19, 2024. Available at: https://www.uptodate.com/contents/clinical-manifestations-of-dermatomyositis-and-polymyositis-in-adults Accessed Sept 9, 2025.
Benveniste O. Antisynthetase Syndrome. Orphanet. Feb 2021.Available at: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=81 Accessed Sept 9, 2025.
The Myositis Association. What is Antisynthetase syndrome? Available at: https://www.myositis.org/learn-about-myositis/faqs/539-what-is-antisynthetase-syndrome Accessed Sept 9, 2025.
American Thoracic Society. Interstitial Lung Disease. Available at: https://www.thoracic.org/statements/insterstitial-lung-disease.php Accessed Sept 9, 2025.
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