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A rare idiopathic inflammatory myopathy (IIM) characterized principally by myositis, generally symmetrical arthritis and interstitial lung disease (ILD) in association with serum autoantibodies to aminoacyl-transfer RNA synthetases (anti-ARS). More variable features include arthralgia, Raynaud phenomenon, heliotrophic rash, distal esophageal dysmotility and mechanic's hands.
ORPHA:81Classification level: Disorder
- AS syndrome
- Anti-Jo1 syndrome
- Prevalence: 1-9 / 100 000
- Inheritance: Not applicable
- Age of onset: Adult, Elderly
- ICD-10: M35.8
- OMIM: -
- UMLS: C2609059
- MeSH: C537778
- GARD: 735
- MedDRA: 10068801
About a quarter of all IIM patients may have antisynthetase syndrome (ASyS), providing a prevalence estimate of 1/25,000-33,000 worldwide. The disorder affects females twice as often as males.
The age of onset is highly variable with a mean of 50 years (range 19 to 82). Myositis, arthritis, ILD are key features of the disease. ILD is one of the clinical hallmarks. Respiratory symptoms (shortness of breath, coughing, dysphagia) are found in 40-60% of patients at disease onset. Respiratory insufficiency may be acute or develop gradually. Some patients develop clinically overt myositis while others have hypomyopathic or even amyopathic forms of the disorder. At onset, 20-70% of patients have muscle weakness of the proximal and axial muscles, and many have myalgia and muscle stiffness, similar to the milder presentations of other idiopathic inflammatory myopathies. Non-specific symptoms of fever, loss of appetite, or weight loss may occur. Rarely reported manifestations include Shawl and V signs (erythema over the back and shoulders or over the anterior neck and chest in a V), and periungual erythema. Pulmonary arterial hypertension is possible but rare. The incidence of malignancies appears to be fairly low.
The exact pathophysiology is not known. It is currently thought that the disease starts in the lungs triggered by environmental factors (tobacco exposure, airborne contaminants) and infections, and favored by a genetic predisposition. The non-specific tissue damage activates the innate immune system, leading to release of immunogenic neo-antigens. This, in turn, induces the activation of the adaptive immune system with the production of anti-ARS antibodies, and the spreading of the immune response to targeted tissues (muscle, joint, skin).
The diagnosis is based on the clinical features and is confirmed in the presence of positive serologic testing for anti-ARS antibodies (anti-Jo-1, anti-PL-12, anti-PL-7, anti-OJ, anti-KS, anti- YRS, anti-Zo). ILD is diagnosed by high resolution computed tomography (HRCT) of the lungs. The most frequent patterns are non-specific interstitial pneumonia (70% of the patients) and organizing pneumonia (20% of the patients). Creatine kinase (CK) levels are often significantly elevated. Absence of myositis or ILD does not exclude the diagnosis of ASyS. Diagnosis is considered probable in patients with ILD and/or inflammatory myopathy in the presence of anti-ARS. The features on the muscle biopsy include necrosis and regenerative myofibers, C5b-9 depositions on sarcolemma of non-necrotic myofibers, and sarcolemmal MHC class I overexpression with inflammatory cells infiltrates. These features occur mainly in the perifascicular area.
Differential diagnoses include other inflammatory myopathies and idiopathic isolated ILD such as usual interstitial pneumonia. Joint involvement may also mimic or even overlap with rheumatoid arthritis.
Management and treatment
Whilst there is no consensus on treatment regimens, oral corticosteroids (prednisone) and immunosuppressive agents are the mainstay of treatment. The presence and the severity of ILD is a key point to consider. Depending on the presentation and severity, drug therapy regimens may include azathioprine, methotrexate, cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, polyvalent immunoglobulins or rituximab. Dermatological symptoms have been treated effectively with hydroxychloroquine. ILD generally responds well to immunosuppressive treatment. Exercise is recommended to improve muscle strength. Response to therapy should be assessed clinically on muscle strength and CK levels. Pulmonary function tests and HRCT imaging are important for ILD follow-up.
The disease is chronic, requiring long-term treatment. Prognosis is guarded in severe cases but may stabilize or improve in other cases. Progression of ILD is the main prognostic factor (with aggravation in 20% of cases despite treatment) and is more likely in patients with non-anti-JO-1 antibodies.
Article for general public
- Summary information
- Suomi (2014, pdf)