Antisynthetase syndrome

The signs and symptoms of antisynthetase syndrome vary but may include:^[5][1][2]

• Fever
• Loss of appetite
• Weight loss
• Muscle inflammation (myositis)
• Inflammation of multiple joints (polyarthritis)
• Interstitial lung disease (ILD) causing shortness of breath, coughing, and/or dysphagia
• Mechanic's hands (thickened skin of tips and margins of the fingers)
• Raynaud phenomenon

Some studies suggest that affected people may be at an increased risk for various types of cancer, as well.^[1] Some symptoms of the disease seem to vary according to the autoantibody involved in the disease. Myopathy occurs more often in patients with anti-Jo-1 or anti-PL-7; anti-Jo-1 is related to severe arthritis and "mechanic's hand", while anti-PL-12 with higher rates of Raynaud phenomenon; and anti-PL-7, anti-PL-12, anti-KS, and anti-OJ with cases of ILD.^[6] 

The underlying cause of antisynthetase syndrome is currently unknown. However, it is considered an autoimmune disease. Autoimmune disorders occur when the body's immune system attacks and destroys healthy body tissue by mistake. In antisynthetase syndrome, specifically, the production of autoantibodies (antibodies that attack normal cells instead of disease-causing agents) that recognize and attack certain enzymes in the body called 'aminoacyl-tRNA synthetases' appears to be linked to the cause of the syndrome. Aminoacyl-tRNA synthetases are involved in protein production within the body. These autoantibodies seem to appear after certain viral infections, drug exposure or in some people who already have a genetic predisposition. The exact role of autoantibodies in causing antisynthetase syndrome is not yet understood.^[1][2]

Aminoacyl-tRNA synthase (ARS) autoantibodies  associated with ASS include anti-Jo1 (anti-histidyl),  anti-EJ (anti-glycyl), anti-OJ (anti-isoleucyl), anti-PL7 (anti-threonyl), anti-PL12 (anti-alanyl), anti-SC (anti-lysil), anti-KS (anti-asparaginyl), anti-JS (anti-glutaminyl), anti-Ha or anti-YRS (anti-threonyl), anti-tryptophanyl, and anti-Zo (anti-phenylalanyl) autoantibodies, with anti-Jo1 being the most common.^[7]

A diagnosis of antisynthetase syndrome is often suspected based on the presence of characteristic signs and symptoms once other conditions that cause similar features have been ruled out. Additional testing can then be ordered to confirm the diagnosis, determine the severity of the condition, and assist with determining treatment. This testing varies based on the signs and symptoms present in each person, but may include:^[1][3]

• Blood tests to evaluate levels of muscle enzymes such as creatine kinase and aldolase
• Laboratory tests to look for the presence of autoantibodies associated with antisynthetase syndrome
• High resolution computed tomography (HRCT) of the lungs
• Electromyography (EMG)
• Muscle biopsy
• Pulmonary function testing
• Magnetic resonance imaging (MRI) of affected muscles
• Evaluation of swallowing difficulties and aspiration risk
• Lung biopsy

Not all patients with antisynthetase antibodies or even those classified as having the antisynthetase syndrome have all manifestations of this syndrome. Diagnosis is considered in patients with an antisynthetase antibody plus two major criteria or one major criterion and two minor criteria:^[2][6]

Major criteria:

1. Interstitial lung disease (not explained by environmental, occupational, medication exposure, and not related to any other base disease)

2. Polymyositis or dermatomyositis

Minor criteria:

1. Arthritis

2. Raynaud phenomenon

3. Mechanic's hand

Corticosteroids are typically the first-line of treatment and may be required for several months or years. These medications are often given orally; however, in severe cases, intravenous methylprednisolone may be prescribe initially. Immunosuppressive medications may also be recommended, especially in people with severe muscle weakness or symptomatic interstitial lung disease.^[1][3] According to recent studies, Rituximab is the medication option when patients with lung disease do not respond well to other treatments.^[8]  Physical therapy is often necessary to improve weakness, reduce further muscle wasting from disuse, and prevent muscle contractures.^[1][3]

The long-term outlook (prognosis) for people with antisynthetase syndrome varies based on the severity of the condition and the signs and symptoms present. Although the condition is considered chronic and often requires long-term treatment, those with muscle involvement as the only symptom are generally very responsive to treatment with corticosteroids and/or immunosuppressive medications. When the lungs are affected, the severity and type of lung condition generally determines the prognosis.^[1][2][3] For example, patients with a progressive course of interstitial lung disease generally have a worse prognosis than those with a nonprogressive course, because respiratory failure is the main cause of death. However, in most cases the interstitial lung disease is nonprogressive.^[9]

Several studies have shown that the following factors may be associated with a worse prognosis:^[1][3][7]

• Older age at onset (greater than 60 years)
• Severity and extension of lung disease: The more severe and extensive lung involvement the worse the prognosis
• Presence of malignancy (cancer)
• Delay in diagnosis and treatment: Prognosis is better when the patients are treated early
• Having a negative Jo1 antibody test: Several studies have shown that Jo1 status seems to be associated with prognosis, suggesting that non-Jo1 patients (patients who have other anti-ARS antibodies, that are non-Jo1) have worse survival rates than Jo1 patients.