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In short
- Call 000 for severe breathlessness at rest, blue or grey lips, chest pain, new confusion, or coughing up more than a streak of blood.
- Go to the emergency department today if your breathing is getting worse over days, you have a fever on immune-suppressing treatment, or you choke every time you eat or drink.
- Tell your specialist team about new muscle weakness or breathing that is clearly worse than usual.
- Supervised exercise builds fitness and strength. It starts gently during a flare and builds as the disease settles.
- Strength work helps counter the muscle loss that long courses of prednisolone can cause.
Antisynthetase syndrome is a rare condition where the immune system makes antibodies against proteins inside your own cells. It can inflame the lungs, the muscles and the joints, and it often causes cracked, thickened skin on the fingers. The lungs matter most. Inflammation in the lung tissue makes you breathless when you are active and can cause a dry cough. If it is left untreated it can leave scarring. Treatment that calms the immune system usually slows it down, and it often improves it. Tell your doctor promptly if your breathing gets worse, even if your muscles and joints feel settled. Exercise is safe and helps, as long as it is matched to how active the disease is at the time.
Definition
Antisynthetase syndrome is an autoimmune disease defined by an antibody against one of the aminoacyl-tRNA synthetases. These are enzymes that every cell uses to build proteins. It is usually grouped with the idiopathic inflammatory myopathies (myositis), but many people have little or no muscle disease and present first with lung or joint problems.1,2 The lung disease is a form of interstitial lung disease. It sits within connective tissue disease-associated ILD.
The antibodies
| Antibody | How common | What it tends to look like |
|---|---|---|
| Anti-Jo-1 | The most common, found in over half of people with the syndrome | Muscle, lung and joint involvement more often occur together |
| Anti-PL-7 and anti-PL-12 | The next most common | Lung disease is often the main or only feature, with milder muscle involvement |
| Anti-EJ, anti-OJ and rarer types | Uncommon | Variable; anti-OJ is often lung-predominant |
A second antibody, anti-Ro52, is often found alongside. It is linked with more extensive lung disease.3,4
Pathophysiology
Immune injury in the lung
The immune system targets tissue in the lungs, muscles and joints. In the lung, inflammation settles in the thin walls between the air sacs. That makes the lung stiffer and slows the movement of oxygen into the blood. Early on, this inflammation can be reversed. Over time, some of it can turn into fixed scarring. That is why early treatment matters.1,3
Why breathing is affected in more than one way
Breathlessness can come from the lung tissue itself, from weak breathing muscles when myositis affects the diaphragm, from weak throat muscles that let food or drink go down the wrong way, and from strain on the right side of the heart if pressure in the lung arteries rises. Each of these is treated differently, so it helps to know which ones are present.
Co-morbidities
- Pulmonary hypertension: raised pressure in the lung arteries, usually linked to more extensive lung disease.
- Swallowing difficulty: weakness in the throat muscles raises the risk of aspiration pneumonia.
- Heart muscle involvement: inflammation of the heart muscle is uncommon but important.
- Effects of treatment: long courses of prednisolone can cause muscle weakness, bone thinning, raised blood sugar and weight gain. Immune-suppressing medicines raise the risk of infection.
- Raynaud's phenomenon: fingers that turn white or blue in the cold.
Prevalence
Antisynthetase syndrome is rare. Estimates suggest a few people in every 100,000. It is diagnosed about twice as often in women, most often between the ages of 40 and 60. Lung involvement is found in most people with the syndrome at some point, and in some it is the first sign.1,2,3
Causes and risk
The cause is not known. As with other autoimmune diseases, it is thought to arise from a combination of genetic make-up and an environmental trigger, such as an infection or an inhaled exposure. It is not passed from person to person, and it is not caused by anything you did. Compared with some other forms of myositis, antisynthetase syndrome is less strongly linked with cancer. Your specialist will still decide whether screening is needed.
Symptoms
What you might notice
- Breathlessness when walking, climbing stairs or carrying things, often building up over weeks or months.
- A dry cough.
- Muscle weakness around the hips and shoulders: trouble getting out of a low chair, climbing stairs or lifting your arms to wash your hair.
- Painful or swollen joints, usually in the hands and wrists.
- Rough, cracked, thickened skin on the sides of the fingers ("mechanic's hands").
- Fevers, tiredness and weight loss, especially when the disease is active.
- Fingers that change colour in the cold.
Not everyone has all of these. Some people have only the lung features. Others first notice their hands or joints.
Warning signs
Diagnosis
How it is diagnosed
Diagnosis brings together the symptoms, the blood test for the antibody, and evidence of lung, muscle or joint involvement. A specialist in rheumatology or respiratory medicine usually leads this.2,5
- Blood tests: the myositis antibody panel, and muscle enzymes such as creatine kinase (CK).
- Breathing tests: spirometry and a gas transfer test show how stiff the lungs are and how well oxygen passes into the blood.
- High-resolution CT scan of the chest to show the pattern and extent of lung involvement.
- A walking test such as the six-minute walk test, which shows whether oxygen levels drop with activity.
- Muscle tests: strength testing, and sometimes an MRI scan, nerve and muscle studies or a muscle biopsy.
- Heart tests: an echocardiogram if pulmonary hypertension or heart involvement is suspected.
Screening
Because lung disease is so common in this syndrome, anyone diagnosed should have breathing tests and a CT scan, even without breathing symptoms. Breathing tests are then repeated regularly, usually every 3 to 6 months in the first year.5
Management
Treatment is led by your specialist team and is aimed at calming the immune system, protecting the lungs, and keeping you strong and active.
Living with antisynthetase syndrome
Flares and quieter periods
The disease often settles with treatment and can flare again, particularly as medicines are reduced. Learning what your early signs of a flare look like helps you and your team act early. For many people those signs are more breathlessness, new weakness or sore joints.
Infection
Immune-suppressing treatment makes infections more likely and can make them more serious. Keep up to date with influenza, COVID-19 and pneumococcal vaccines, as advised by your doctor. Treat a fever as a reason to seek advice the same day.
Energy and pacing
Tiredness comes from the disease, the medicines, breathlessness and loss of fitness together. Pacing means spreading activity across the day and week, and not doing everything on a good day. It keeps you active without triggering a crash.
Staying active
Exercise does not make myositis worse. Regular exercise improves strength, fitness and everyday function.6 The type and amount should match how active the disease is. Lighter work suits a flare; building strength suits a settled phase. It should also fit around your breathing and your joints.
Hands and skin
Cracked skin on the fingers can be painful. A regular moisturiser, gloves in the cold and care with detergents all help.
Prognosis
Outcomes vary widely. Many people do well on treatment, with stable lung function over years. The extent of lung disease at diagnosis, how quickly it changes in the first year, and the type of antibody all influence the outlook. Lung-predominant disease with anti-PL-7 or anti-PL-12 has tended to do less well, partly because it is often recognised later.4 Regular breathing tests are the best way to track how things are going.
Role of the physiotherapist
Assessment
We measure your breathlessness, your walking distance and whether your oxygen level drops with activity, and the strength of your breathing and leg and arm muscles. We also check how you manage everyday tasks such as stairs and getting up from a chair. We look at which of these actually limits you most, because it is often not the lungs alone.
Exercise training
A supervised programme builds fitness and strength. Where oxygen drops or tiredness limits continuous exercise, we use shorter intervals with rest. We use oxygen during exercise where it has been prescribed. We start gently during a flare, build steadily as the disease settles, and include strength work to counter the effects of prednisolone on muscle.6
Breathing and breathlessness
Breathing control, positions that ease breathlessness, a handheld fan and pacing help you manage the symptom day to day. See managing breathlessness.
Working with your team
We keep your specialist and GP informed. If your breathlessness, oxygen levels or exercise tolerance change noticeably, we refer you back to the team rather than adjusting the programme around it.
Part 1 · References
- Connors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest 2010;138(6):1464–1474.
- Solomon J, Swigris JJ, Brown KK. Myositis-related interstitial lung disease and antisynthetase syndrome. J Bras Pneumol 2011;37(1):100–109.
- Marco JL, Collins BF. Clinical manifestations and treatment of antisynthetase syndrome. Best Pract Res Clin Rheumatol 2020;34(4):101503.
- Aggarwal R, Cassidy E, Fertig N, et al. Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients. Ann Rheum Dis 2014;73(1):227–232.
- Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Rheumatol 2024;76(8):1182–1200.
- Alexanderson H. Physical exercise as a treatment for adult and juvenile myositis. J Intern Med 2016;280(1):75–96.
References are numbered in citation order (Vancouver/BMJ style) and were current at the time of writing. Guidelines are living documents — verify against the latest version before clinical use.
We assess your breathing, exercise capacity and oxygen levels, then build a supervised exercise and breathing programme that changes with the disease: gentle during a flare, building as it settles. We work alongside your rheumatology and respiratory teams.
Clinical evidence
Part 1 covers the same condition without the technical detail. What follows is the evidence base behind it, written for clinicians — the literature, the reasoning and the gaps.
For clinicians: this summary supports clinical reasoning and is not a protocol. Check current guidelines and local policy before applying it, and read it alongside the key references and guidelines directory.
Framing. Antisynthetase syndrome is defined serologically, not by the muscle. Classification has moved from the Connors (2010) and Solomon (2011) clinical criteria, which required an anti-synthetase antibody plus one or two of myositis, ILD, arthritis, fever, Raynaud's and mechanic's hands, towards data-driven criteria being developed by the international CLASS project. The 2017 EULAR/ACR myositis criteria do not capture amyopathic, lung-predominant disease well.1,2,3 For the physiotherapist, the practical consequence is that a normal CK does not exclude the diagnosis, and ILD may be the only active organ.
Antibody specificity and phenotype
- In the international AENEAS cohort, the classic triad was present at onset in a minority. Jo-1-positive patients more often developed the full triad over time. Non-Jo-1 patients (PL-7, PL-12) more often presented with isolated ILD and accumulated fewer additional features.4
- Non-Jo-1 antibodies were associated with worse survival in a large single-centre cohort. Much of this was attributed to delayed diagnosis and ILD-driven mortality rather than to a more aggressive disease biology.5
- Anti-Ro52 co-positivity is associated with more extensive and more progressive ILD, and it is a reasonable marker for closer surveillance.3
ILD pattern
The commonest HRCT patterns are NSIP and organising pneumonia, often overlapping. A UIP pattern is less frequent. A minority present with acute or subacute disease that resembles diffuse alveolar damage and needs urgent escalation.3 The screening and monitoring guideline recommends PFTs with DLCO, plus HRCT, at diagnosis for all patients with myositis-spectrum disease. It also recommends ambulatory desaturation testing and PFTs repeated every 3 to 6 months in the first year.6
Treatment evidence
- There are no disease-specific randomised trials. Glucocorticoids combined early with a steroid-sparing agent (mycophenolate, azathioprine or a calcineurin inhibitor) are standard, on the basis of observational series that show higher relapse rates with steroid monotherapy.3
- RIM randomised rituximab timing in refractory myositis. It did not meet its primary endpoint, but 83% of participants met the definition of improvement, and anti-synthetase positivity predicted response in secondary analyses.7
- RECITAL compared rituximab with intravenous cyclophosphamide in severe or progressive CTD-ILD, including idiopathic inflammatory myopathy. Improvement in FVC at 24 weeks was similar in both arms, and rituximab had fewer adverse events.8
- INBUILD included autoimmune ILDs within progressive fibrosing ILD and showed a consistent reduction in FVC decline with nintedanib. This supports adding an antifibrotic when fibrosis progresses despite immunosuppression.9
Exercise and rehabilitation
- A systematic review in the idiopathic inflammatory myopathies found that exercise training is safe: CK and inflammatory markers did not rise. It also improves aerobic capacity, strength and function in both established and recent-onset disease.10,11
- Pulmonary rehabilitation in ILD improves 6MWD, symptoms and quality of life. The effect is larger in non-IPF ILD, although myositis-ILD is poorly represented in the trials.12
- Walk tests should follow the ERS/ATS technical standard. Record nadir SpO₂ and recovery time, because exertional desaturation is a common and prognostically relevant finding in this group.13
Clinical reasoning
Establish which limitation dominates: parenchymal (desaturation, DLCO), respiratory muscle (low maximal inspiratory pressure and sniff pressure, orthopnoea, a vital capacity that falls when supine), peripheral muscle (proximal weakness, steroid myopathy), or pulmonary vascular (desaturation out of proportion to CT extent, falling DLCO with stable FVC). Screen for dysphagia before recommending any airway clearance or respiratory muscle loading. Match load to disease activity: low-load, higher-repetition work in active myositis, and progressive resistance once enzymes and strength have stabilised. A step change in breathlessness, a new oxygen requirement or a fall in walk distance is a clinical event for the treating team, not a reason to regress the programme quietly.
Evidence gaps
- No randomised treatment trials are specific to antisynthetase syndrome; practice extrapolates from myositis and CTD-ILD cohorts.
- The optimal first-line steroid-sparing agent, and when to start rituximab or an antifibrotic, have not been compared head to head.
- Rehabilitation trials rarely separate myositis-ILD from other ILDs, and none addresses combined respiratory and peripheral muscle weakness.
References for the clinical evidence summary
- Connors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest 2010;138(6):1464–1474.
- Solomon J, Swigris JJ, Brown KK. Myositis-related interstitial lung disease and antisynthetase syndrome. J Bras Pneumol 2011;37(1):100–109.
- Marco JL, Collins BF. Clinical manifestations and treatment of antisynthetase syndrome. Best Pract Res Clin Rheumatol 2020;34(4):101503.
- Cavagna L, Trallero-Araguás E, Meloni F, et al. Influence of antisynthetase antibodies specificities on antisynthetase syndrome clinical spectrum time course. J Clin Med 2019;8(11):2013.
- Aggarwal R, Cassidy E, Fertig N, et al. Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients. Ann Rheum Dis 2014;73(1):227–232.
- Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Rheumatol 2024;76(8):1182–1200.
- Oddis CV, Reed AM, Aggarwal R, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum 2013;65(2):314–324.
- Maher TM, Tudor VA, Saunders P, et al. Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease (RECITAL). Lancet Respir Med 2023;11(1):45–54.
- Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases (INBUILD). N Engl J Med 2019;381(18):1718–1727.
- Habers GE, Takken T. Safety and efficacy of exercise training in patients with an idiopathic inflammatory myopathy — a systematic review. Rheumatology (Oxford) 2011;50(11):2113–2124.
- Alexanderson H. Physical exercise as a treatment for adult and juvenile myositis. J Intern Med 2016;280(1):75–96.
- Dowman L, Hill CJ, May A, Holland AE. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev 2021;(2):CD006322.
- Holland AE, Spruit MA, Troosters T, et al. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J 2014;44(6):1428–1446.
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