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Meta-Analysis
. 2022 Feb;40(2):309-319.
doi: 10.55563/clinexprheumatol/8xj0b9. Epub 2022 Feb 25.

Defining anti-synthetase syndrome: a systematic literature review

Giovanni Zanframundo  1 , Sara Faghihi-Kashani  2 , Carlo Alberto Scirè  3 , Francesco Bonella  4 , Tamera J Corte  5 , Tracy J Doyle  6 , David Fiorentino  7 , Miguel A Gonzalez-Gay  8 , Marie Hudson  9 , Masataka Kuwana  10 , Ingrid E Lundberg  11 , Andrew Mammen  12 , Neil McHugh  13 , Frederick W Miller  14 , Carlomaurizio Monteccucco  1 , Chester V Oddis  2 , Jorge Rojas-Serrano  15 , Jens Schmidt  16 , Albert Selva-O'Callaghan  17 , Victoria P Werth  18 , Garifallia Sakellariou  19 , Rohit Aggarwal  2 , Lorenzo Cavagna  1
Affiliations
Meta-Analysis

Defining anti-synthetase syndrome: a systematic literature review

Giovanni Zanframundo et al. Clin Exp Rheumatol. 2022 Feb.

Abstract

Objectives: 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.

Methods: We searched 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.

Results: We 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.

Conclusions: The 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.

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Figures

Figure 1.
Figure 1.. Flow-chart showing the study selection process and numbers of publications identified.
* All 3 abstracts were included from 2017 and 2018 EULAR congress.
Figure 2.
Figure 2.. List of variables used to define ASSD.
ARS-Ab: anti aminoacyl-RNA-synthetase autoantibodies; ILD: interstitial lung disease; HRCT: high resolution computed tomography; NSIP: non-specific idiopathic pneumonia; OP: organizing pneumonia; UIP: usual interstitial pneumonia; GGO: ground glass opacities; LIP: lymphoid interstitial pneumonia; PFT: pulmonary function tests; EMG: electromyography; CPK: creatine phosphokinase; DM: dermatomyositis; PM: polymyositis; MRI: magnetic resonance imaging; MHC: major histocompatibility complex.
Figure 3.
Figure 3.. Available definitions of anti-synthetase syndrome, based on the combination of autoantibodies and other variables.
ARS-Ab: anti-synthetase autoantibodies; CTD: connective tissue disease.
Figure 4:
Figure 4:. Studies included in Q2, assessing the performance of muscle biopsy variables to diagnose ASSD.
95% CI: 95% confidence interval; TP: true positive; FP: false positive; FN: false negative; TN: true negative.
See this image and copyright information in PMC

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