Search for a rare disease
Other search option(s)
A clinically heterogeneous form of idiopathic inflammatory myopathy characterized by myositis, arthralgia, Raynaud phenomenon, mechanic hands, interstitial lung disease (ILD), and serum autoantibodies to aminoacyl transfer RNA synthetases (anti-ARS).
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
Prevalence and annual incidence are not known. AS syndrome represents a subset of polymyositis and dermatomyositis (PM, DM, see these terms), disorders which have estimated prevalence of about 1/4,650. About a quarter of these patients may have AS syndrome, providing a prevalence estimate of 1/25,000 - 1/33,000 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). 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 PM/DM. The other main clinical features are fever, loss of appetite, weight loss, generally symmetrical arthritis, arthralgia, tenosynovitis, Raynaud phenomenon, heliotrophic rash, distal esophageal dysmotility, and mechanic's hands (fissuring and scaling of the lateral and distal aspects of the hands). 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 (PAH, see this term) has been reported as a severe complication in some patients. The incidence of malignancies appears to be fairly low.
The exact mechanisms leading to the disorder are not known. Viral infections are thought to promote formation of antisynthetase antibodies. HLA-DRB1*0301, DQA1*0501 and DQB1*0201genes are risk factors for the development of anti-Jo-1+ AS syndrome.
Patients are mostly positive for one of the seven antisynthetase autoantibodies that have been identified; anti-Jo-1 is the most common (70% of the cases). 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). ILD is diagnosed by high resolution computed tomography (HRCT) of the lungs. Creatin kinase (CK) levels are often significantly elevated. Absence of myositis or ILD does not exclude the diagnosis of AS syndrome. Diagnosis is considered probable in patients with ILD and/or inflammatory myopathy in the presence of anti-ARS.
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 (see this term).
Management and treatment
Oral corticosteroids (prednisone) and immunosuppressive agents are the mainstay of treatment. There is no consensus on treatment regimens in AS syndrome. Depending on the presentation and severity, drug therapy regimens may include azathioprine, methotrexate, cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, or rituximab. Dermatological symptoms have been treated effectively with hydroxychloroquine. In patients with associated ILD, the response to immunosuppressive treatment is generally good.
Prognosis is guarded in severe cases, sometimes with fatal outcomes. In other cases, stabilization or improvement may be achieved. Progression of ILD is the main prognostic factor. The disease course is chronic, requiring long-term treatment.
Article for general public
- Summary information
- Suomi (2014, pdf)