Antisynthetase syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M. Hassan, M.B.B.S

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.

Till date, 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.

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.

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: mechanic’s hands, Raynaud’s phenomenon, myositis, 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, Raynaud’s phenomenon, and mechanic’s hands.

Connors et al (2010) criteria
Required: Presence of an anti-aminoacyl tRNA synthetase antibody
PLUS one or more of the following clinical features: 1) Raynaud’s phenomenon 2) Arthritis 3) Interstitial lung disease 4) Fever (not attributable to another cause) 5) Mechanic’s hands (thickened and cracked skin on hands, particularly at fingertips)

Solomon et al (2011) criteria
Required: Presence of anti-aminoacyl tRNA synthetase antibody
PLUS two major or one major and two minor criteria: Major: 1) Interstitial Lung Disease (not attributable to another cause) 2) Polymyositis or dermatomyositis Minor: 1) Arthritis 2) Raynaud’s phenomenon 3) Mechanic’s hands

Symptoms

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

Symptoms of antisynthetase syndrome
1) Fever
2) Weight loss
3) Anorexia
4) Dyspnea
5) Dry cough
6) Arthralgia
7) Joint swelling
8) Proximal muscle weakness
9) Myalgia
10) Raynaud's phenomenon

Physical Examination

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

Clinical findings
1) Polyarthritis
2) Mechanics hands (hyperkeratotic lesions on the radial and palmar aspects of the hands and fingers with fissuring and scaling of the skin)
3) Calcinosis cutis
4) Malar rash
5) Cutaneous ulcers
6) Crackles on chest auscultation

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.

Case courtesy of Dr David Cuete

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 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.