Antisynthetase Syndrome

What is Antisynthetase Syndrome?

The chronic autoimmune condition, which affects muscles and other body parts is termed as Antisynthetase syndrome. Antisynthetase syndrome has multiple inflammatory manifestations affects muscles (myositis) and many joints (polyarthritis), hands skin become thicker and cracked and Raynaud phenomenon.

In Antisynthetase syndrome, abnormal production of antibodies attacks normal cells. However, the detail etiology and pathophysiology is unclear. But it has been found that ‘aminoacyl-tRNA synthetases’ enzymes are attacked by autoimmune syndrome and the condition is termed as ‘aminoacyl-tRNA synthetases’.

It has been hypothesized that this enzymatic effect may cause the Antisynthetase syndrome. The auto-antibodies production may have linked with certain viral infection attacks or genetic predisposition. The therapeutic goal for treating the Antisynthetase syndrome is to symptomatic relief and controlling the production of auto-antibodies^1,2.

Symptoms

The signs and symptoms of Antisynthetase syndrome is not uniform in all the affected cases, the following are Antisynthetase syndrome related sign and symptoms

• Fever
• Anorexia or loss of appetite
• Unexplained weight loss
• Myositis or muscle inflammation
• Multiple joint inflammatory conditions (polyarthritis)
• Respiratory symptoms include coughing, breathing shortness, dysphagia due to interstitial lung disorder
• Fingertips, marginal skin and tips of the finger become thickened, and clinically this condition is termed as Mechanic’s hands.
• Raynaud phenomenon (certain body parts such as fingers, toes become numb and cool in exposure to cold weather and in enhancement of stress level)
• Antisynthetase syndrome affected individuals are usually has increased the risk of cancer^1,2,3.

Causes

The exact cause of Antisynthetase syndrome is not clear. But it has been considered that autoimmune disease is closely associated with Antisynthetase syndrome. In an autoimmune disorder, healthy body tissues are destroyed by the faulty production of antibodies.

In Antisynthetase syndrome, ‘aminoacyl-tRNA synthetases’ enzymes get affected due to the synthesis of auto-antibodies. In normal health condition, aminoacyl-tRNA synthetases’ enzyme is taking part into protein synthesis within the body.

Usually, certain viral infection, drug exposure or genetic predisposition are linked with autoimmunity and that leads to the onset of Antisynthetase syndrome^1,2.

Diagnosis

The physical examination and symptomatic analysis are the initial diagnostic criteria require detecting the Antisynthetase syndrome. Antisynthetase syndrome specific tests are not available, but following tests assist in diagnosing the condition. However, all the test may not be conducted for every case. The diagnosis test conduction depends upon symptomatic analysis and physical examination findings:

• Elevated level of certain muscular enzymes like creatinine kinase (CK) and aldolase
• Finding of muscular antibodies
• Electromyography (EMG)
• MRI (Magnetic resonance imaging) test conducted in considering of affected muscles
• Biopsy test conducted by taking sample from affected muscle
• Lung function tests
• High-resolution CT (computed tomography) scan of the chest
• Assessing swallowing difficulties and aspiration risk
• Biopsy test is conducted by taking sample from lungs ^1,3

Treatment

The following treatment options available for Antisynthetase Syndrome:

Steroidal Drugs

In Antisynthetase Syndrome, the first line treatment is Corticosteroids; however, the required time for treatment may vary from several months to years.

Generally, the medication administration route is oral; however, in severe cases, methylprednisolone may inject through intravenous route to control the severity of the condition. Glucocorticosteroids also prescribed for treating Antisynthetase Syndrome.

Usually, to control the symptoms of Antisynthetase Syndrome, Prednisone is initially prescribed with high doses for 4–6 weeks. After controlling the condition, slowly tapered down the Prednisone over 9–12 months and continue the therapy with the lowest effective dose to maintain the remission.

Prophylactic therapy often needs to start prior to the steroidal therapy commencement, as steroidal drugs often lead to osteoporosis and provoke certain fungal infections like Pneumocystis jirovecii. The doctor usually provides immunization to control the adverse effects of steroidal therapy.

Immunosuppressive medications

Immunosuppressive medications are prescribed for the patients suffering from severe muscle weakness or symptomatic interstitial lung disease.

In the case of patients with severe lung symptoms do not respond well with other treatment options, then  Rituximab is prescribed for them. Other included immunosuppressive medications are Azathioprine, Methotrexate, Cyclophosphamide, Tacrolimus, Ciclosporin, Mycophenolate.

Physical therapy

Often doctors advise for physical therapy for improvement of the muscle weakness, prevention of muscle contractures and reduction of muscle wasting from disuse. Physical therapy required to start at the initial stage of the disease to get the optimal result.

The symptomatic improvement and muscle strength enhancement considered as a reliable indicator for effective treatment measurement^1,2,4.

Prognosis

Steroidal therapy and/ or immunosuppressive agents provide good prognosis in case of only muscle involvement in Antisynthetase Syndrome. In the case of lung association with Antisynthetase Syndrome, the severity of the condition influence the prognosis. Elderly patients (more than 60 years of age) in association with malignancy and negative ANA antibody test present a poorer prognosis^2,3.

Life Expectancy

The usually Antisynthetase Syndrome is detected in age between 15–68 years (mean average age is 40 years). In the case of milder manifestations and only associated with muscle provides good life expectancy, but in association with lung cancer or other malignancy leads to early death of the patient⁵.

References

1. Antisynthetase Syndrome, Genetic and Rare Diseases Information Center; Retrieved from https://rarediseases.info.nih.gov/diseases/735/antisynthetase-syndrome/cases/21612
2. Dr. Athanaslos. G. Tzloufas. Antisynthetase Syndrome. Orphanet. Retrieved from https://www.orpha.net/data/patho/GB/uk-antisynthetase.pdf
3. Dr. Priyam Sobarun. Antisynthetase syndrome. DermaNet New Zealand. Retrieved from http://www.dermnetnz.org/topics/antisynthetase-syndrome/
4. Lívia Regina Theilacker, Fabíola Sampaio Brandão, Fernanda Velloso Goulart, João Luiz Pereira Vaz, Luiz Octávio Dias D’Almeida, Maria Cecília da Fonseca Salgado. Antisynthetase Syndrome: two case reports and literature review. Revista Brasileira de Reumatologia, Volume 55, Issue 2, March–April 2015, Pages 177-180
5. Volume 55, Issue 2, March–April 2015, Pages 177–180. Retrieved from http://www.sciencedirect.com/science/article/pii/S2255502114001680
6. Joshua Solomon, Jeffrey J. Swigris, Kevin K. Brown. Myositis-related interstitial lung disease and antisynthetase syndrome. J Bras Pneumol. Author manuscript; available in PMC 2013 Jun 9. Published in final edited form as: J Bras Pneumol. 2011 Feb; 37(1): 100–109. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676869/