Background Anti-synthetase syndrome (ASS) is characterised by interstitial lung disease (ILD), myositis, arthropathy, fever, Raynaud’s, and mechanics hands associated with antisynthetase antibodies (including Jo-1, PL-7 and PL-12). ILD is the major determinant of mortality in ASS.
ANA is commonly used to screen for autoimmune diseases. If negative, in many centres extractable nuclear antigens (ENAs) are not tested. This study aims to highlight the inadequacy of this approach.
Method We retrospectively examined consecutive patients in the Oxford ILD and Rheumatology services with ASS-ILD between 2009–2014. CT scans were reviewed to identify the pattern of ILD. Immunology, lung function and medication were identified from patient records.
Results 24 patients were identified with ASS-ILD: age 33–78 years (mean 54); 9 male, 15 female. Disease severity was assessed by lung function at presentation: FVC 42–118% (mean 77.9%) predicted, TLco 10–99% (mean 56%) predicted.
Only 1 of 24 (4.2%) were ANA positive (titre 1:80). 18 of 24 (75%) had a positive ENA screen (ELISA): 13 Jo-1; 4 Jo-1 and Ro-52; and 1 Ro. 6 (25%) patients had a negative ENA screen. 5 of these had a positive myositis blot (1 Jo-1, 3 PL-7, 1 PL-12) and 1 was negative for all 3 autoantibodies. Of 7 patients who were Jo-1 positive on ENA screen, 4 had a negative Jo-1 myositis blot.
CT patterns of disease: organising pneumonia (OP; n = 7), non-specific interstitial pneumonia (NSIP; n = 7), OP/NSIP overlap (n = 9), acute interstitial pneumonia (AIP; n = 1). There was no relationship between anti-synthetase antibody and CT pattern.
The identification of an ASS antibody significantly changed management in most patients; 17 were treated with (iv) cyclophosphamide and rituximab was added to 8 cases.
Conclusion The identification of an anti-synthetase antibody is central to diagnosis and significantly impacts on patient management. This data demonstrates that ANA is an inadequate screening test. If ASS is clinically suspected, ENA testing should be performed despite a negative ANA result. The data also demonstrate that either an ENA screen or a myositis blot used in isolation lack the required sensitivity. These tests need to be used in combination to avoid false negative results.