How to Diagnose Antisynthetase Syndrome

The high prevalence of ILD in patients carrying ARS antibodies and the need for specific immunosuppressive treatment emphasize the need for timely detection of this clinical syndrome. This is, however, often severely hampered by the variable time relationship between the onset of ILD and the onset of myositis or other ASS-specific features. ILD can precede (10–30%), occur concurrently (53–70%) or follow (6–20%) the onset of myositis.^5,6

Organized multidisciplinary follow-up by both pulmonologists and rheumatologists increases the alertness for subtle clinical signs suggesting an underlying AS.

When faced with a patient with AS, the identification of the underlying ARS antibody specificity is relevant. Increasing recent evidence supports clinical heterogeneity between anti-Jo-1- and non-Jo-1-positive patients with differences in presenting symptoms and prognosis. On the one hand, patients positive for anti-Jo-1 frequently present with muscle and joint involvement and severe and treatment-resistant myositis. On the other hand, non-Jo-1-positive patients often present with nonmyositis connective tissue disease symptoms (Raynaud’s, cutaneous changes, and constitutional symptoms) and pulmonary manifestations.^6-8

Anti-PL-7- and anti-PL-12-positive patients cluster together with a 98% prevalence of ILD and isolated ILD in 62%. The behavior of anti-PL-7- and anti-PL-12-positive patients is substantially different from anti-Jo-1-positive patients (ILD in 78%).⁹

Identification of the ARS antibody allows for prognostic stratification. Recent reports indicate that non-Jo-1-positive patients have decreased survival compared with anti-Jo-1-positive patients (five- and 10-year unadjusted survival of 90% and 70% in anti-Jo-1-positive patients, and 75% and 47% in non-Jo-1-positive patients).⁸

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Table 1: Myositis-Specific Autoantibodies

In one study that compared the characteristics between AS patients with anti-Jo-1 and those with anti-PL-7/PL-12 antibodies, the anti-Jo-1-positive patients more often developed severe myositis and joint manifestations, including erosive arthritis and often exhibited cancer, whereas anti-PL-7/PL-12-positive patients more commonly experienced early and severe ILD.¹⁰

Anti-PL-7/PL-12-positive patients more frequently had gastrointestinal complications, especially intestinal pseudo-obstruction. A retrospective study of 17 cases to examine the clinical manifestations of AS positive for anti-PL-12 antibodies showed that all patients presented with ILD, and mild myositis was seen in 41% of the patients.¹¹ Raynaud’s phenomenon and general impairment were common, whereas rheumatic and dermatological symptoms were uncommon. A high prevalence of esophageal involvement (23.5%) was seen. AS appeared as an isolated diffuse interstitial pneumonia in 29.4% of patients.

The presence of anti-PL-12 antibodies in patients with presumed ILD may constitute a subset of patients who may have a favorable response to treatment with improved prognosis of their lung disease.¹² However, we do not have any longitudinal data to characterize disease behavior in these patients. There is a need for prospective studies to provide further insight into the clinical consequences of anti-PL-12 antibodies and idiopathic ILD.