Defining anti-synthetase syndrome: a systematic literature review

Abstract

Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance. PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018. Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate. Methods We searched ResultsWe retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly. ConclusionThe current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.

A Case of Antisynthetase Syndrome in the Setting of SARS-Cov-2 Infection

“…Antisynthetase syndrome is a heterogeneous disorder that involves different organs and systems. Several diagnostic criteria have been proposed to guide the diagnosis, as it can be challenging [ 6 ]. Connors and Solomon have proposed criteria to facilitate the diagnosis of this rare entity (Table 2 ) [ 7 , 8 ].…”

Review of Pulmonary Manifestations in Antisynthetase Syndrome

“…A recent systematic review revealed numerous variabilities in defining ASyS across the literature, coupled with a lack of sensitivity and specificity of its clinical variables including muscle biopsy findings. 130 In our practice, we have a high index of suspicion for ASyS even in the absence of extrapulmonary symptoms, especially in patients with an NSIP, OP, or NSIP-OP overlap pattern of ILD; and routinely screen for ASA. Despite the above-mentioned limitations, we rely on Connor's criteria because of our long-standing experience with it and its relative simplicity.…”

A multidisciplinary approach to the diagnosis of antisynthetase syndrome

“…Presently, no data driven or validated classification criteria exist for ASyS and definitions vary widely across the literature and are poorly evidenced ( 11 ). Project CLASS is an ongoing large multicentre international effort funded by EULAR and ACR aiming to develop a validated criteria set for ASyS.…”