Antisynthetase syndrome
Synonyms and keywords:

# Overview
Antisynthetase syndrome, an uncommon autoimmune disorder, is characterized by antibodies against aminoacyl-transfer ribonucleic acid synthetases, with various combinations of three cardinal manifestations of interstitial lung disease (ILD), polymyositis, and arthritis.  Other features of antisynthetase syndrome may include pyrexia of unknown origin, mechanic's hand (hyperkeratotic skin changes along the lateral surfaces of the digits) and Raynaud's phenomenon.
So far, nine different anti-aminoacyl t-RNA synthetase (ARS) antibodies have been identified to play a role in the development of antisynthetase syndrome.

# Historical Perspective
In 1990, Marguerie et al and coworkers first described antisynthetase syndrome as a triad of polymyositis, interstitial lung disease (ILD), and the presence of myositis-specific autoantibodies to aminoacyl-transfer ribonucleic acid synthetases.

# Classification
Antisynthetase syndrome may be classified in accordance with the type of antibodies that are present.  Some of the identified antibodies include Anti-Jo-1, Anti PL-12, Anti-Pl-7, Anti-OJ, Anti-KS, Anti-EJ, Anti-Ha, and Anti-Zo.

# Pathophysiology
Antisynthetase syndrome is characterized by the presence of myositis-specific anti-synthetase antibodies.

# Causes
The exact cause of antisynthetase syndrome is not fully understood.

# Differentiating Antisynthetase syndrome from other Diseases
Antisynthetase syndrome may be misdiagnosed as idiopathic interstitial lung disease (ILD) or inflammatory myopathy, as a result of rarity, lack of awareness of the disease, as well as due to the lack of available testing for anti-ARS antibodies.

# Epidemiology and Demographics

## Age
The mean age at onset of antisynthetase syndrome in adults varies from 43 to 60 years.

## Gender
Antisynthetase syndrome is 23 times more common in women than in men.

## Race
Antisynthetase syndrome usually affects individuals of the black American ethnicity race.

# Risk Factors
There are several environmental exposures associated with antisynthetase syndrome.  These include ultraviolet radiation, stress, muscle overexertion, collage implants, infections such as retroviruses and streptococci bacteria, and certain drugs and chemicals.

# Natural History, Complications and Prognosis
Main causes of death in antisynthetase syndrome is anti-Jo-1-positive patients included interstitial lung disease, neoplasm, infectious diseases including pneumonia, severe myositis and cardiovascular disorders.
The cumulative ten-year survival rate in patients with antisynthetase syndrome was estimated as 76.8%.

# Diagnosis

## Diagnostic Criteria
In 2010, Connors et al proposed a formal criteria for the diagnosis of antisynthetase syndrome.  This criteria proposed that all patients must have a presence of an anti-aminoacyl tRNA synthetase antibody in addition to one or more of the following clinical features: mechanics hands, Raynauds phenomenon, myositis, interstitial lung disease (ILD), arthritis, and/or unexplained fever.
In 2011, Solomon et al proposed alternative criteria, which is more strict.  This criteria requires the presence of anti-aminoacyl tRNA synthetase antibody plus two major or one major and two minor criteria.
Major criteria includes: Interstitial Lung Disease (not attributable to another cause), and Polymyositis or dermatomyositis.
Minor criteria includes: arthritis, Raynauds phenomenon, and mechanics hands.

## Symptoms
Symptoms seen at the diagnosis of antisynthetase syndrome include the following:

## Physical Examination
Physical exam findings play an important role in diagnosis of antisynthetase syndrome as the findings may be classified into major and minor criteria.  Clinical findings on examination includes:

## Laboratory Findings
Suggested lab findings based on the systems are as follows:

## Imaging Findings
As antisynthetase syndrome is associated with interstitial lung disease, and therefore, high resolution computed tomography (HRCT) plays an important role in its work up, as well as to monitor the disease activity.  Radiographic features seen on HRCT at the initial diagnosis include traction bronchiectasis, ground glass opacities and reticulation.

## Other Diagnostic Studies
Pertinent diagnostic studies can be found under the laboratory findings.

# Treatment

## Medical Therapy
Various immunosuppressive agents, such as azathioprine, mycophenolate mofetil, and/or tacrolimus, are used in the treatment of antisynthetase syndrome.  Additionally, corticosteroids may be added for management of the myositis and pulmonary manifestations of anti-synthetase syndrome.  The choice of immunosuppressive agent is dependent on the practitioner and is based on the potential risks of therapy as no agent is superior to the other.
Prednisone and azathioprine or mycophenolate mofetil may be used in patients with anti-synthetase syndrome related interstitial lung disease (ILD).  In addition to that, tacrolimus may be added for rapid disease control in more severe cases of ILD.
In patients with severe progressive or refractory ILD, rituximab may be added; while cyclophosphamide is reserved for those with acute respiratory distress syndrome.
The physician must also been on the lookout for other co-morbid conditions associated with antisynthetase syndrome i.e. pulmonary hypertension and screening for malignancies.

## Surgery
Surgical intervention is not recommended for the management of antisynthetase syndrome.

## Prevention
There are no primary preventive measures available for antisynthetase syndrome.