Anti-synthetase syndrome (ASS) is a rare auto-immune disorder described for the first time in 1990 [1]. Clinical expression is miscellaneous and include inflammatory myopathy (IM), interstitial lung disease (ILD), polyarthritis, mechanic’s hands, Raynaud’s Phenomenon and unexplained fever [2]. The symptomatic presentation is highly variable as well as the clinical course of the disease [3]. Pulmonary manifestations mainly drive the overall prognosis and need to be carefully assessed in all patients. Initial presentation severity differs from asymptomatic forms to acute respiratory failure which can be responsible of an acute respiratory distress syndrome in a small number of patients [4]. A systematic blood analysis focusing on the specific antibodies assessment must be considered in the presence of any ILD. Each specific autoantibody is associated with variable clinical onset as well as the clinical evolution [5]. In the same line, treatment strategy has to be considered in an integrative way including immunological pattern, clinical onset as well as disease severity. Diagnosis of ASS associates a positive serologic testing for an anti-aminoacyl-transfer-RNA synthetase (anti-ARS) autoantibody and at least one pathognomonic clinical manifestation (Table 1) [6]. Ten specific antibodies are currently described in scientific literature. Anti-JO1 (anti-histidyl), anti-PL7 (anti-threonyl), anti-PL12 (anti-alanyl), anti-OJ (anti-isoleucyl) and anti-EJ (anti-glycyl) represent more than 90 percent of the detected ones [7]. They are now routinely tested in practice but clinician must consider that specific analysis in case of positive anti-cytoplasmic nuclear antibodies in patient suffering from ILD [8].
Table 1
Proposed criteria for myositis associated with anti-tRNA synthetase antibody according to :Connors, G. R., et al. (2010). Interstitial lung disease associated with the idiopathic inflammatory myopathies: What progress has been made in the past 35 years? Chest, 138 (6), 1464–1474. https://doi.org/10.1378/chest.10-0180
The patient must have positive tests for an anti-tRNA synthetase antibody Plus one major involvement: - Evidence of overt or hypomyopathic myositis (elevated CPK levels, myalgia, proximal muscular weakness, positive muscular biopsy, electromyographic triad of myositis or MRI muscular oedema) - Evidence of ILD according to ATS criteria - Evidence of articular involvement (symmetrical inflammatory arthralgia or overt arthritis) Or two minor involvements: - Unexplained, persistent fever - Raynaud’s phenomenon - Mechanic’s hands |
In order to assess respiratory disease severity, many tools have been developed. It is recommended to systematically evaluate pulmonary function tests (PFT), thoracic high-resolution CT scan (HRCT) as well as the potential desaturation occurring during exercises. Also blood gas analysis, bronchoalveolar lavage and exercise testing [9, 10] have been used as relevant indicators. ASS linked to interstitial lung disease is typically associated with restrictive lung function impairment and a reduced diffusing capacity of the lung for carbon monoxide (DLCO). DLCO is commonly reduced in patients with ILD, often at an earlier stage of the disease than total lung capacity (TLC) and forced vital capacity (FVC). PFT give important data to evaluate severity, as they only partially correlate with HRCT scores and pattern. In addition, PFT are more sensitive to changes upon therapy than HRCT abnormalities [11]. However, HRCT remains essential for the evaluation of lung involvement. The main CT findings with anti-ARS-ILD are areas of ground-glass attenuation and reticulation, predominantly distributed as lower and peribronchovascular lesions, which can be compatible with fibrosing non-specific interstitial pneumonia (NSIP) pattern. A combination of patchy areas of consolidation and reticulation is frequent and may suggest the presence of myositis in subjects with ILD, especially with a subacute or an acute onset. Honeycombing (areas of small cystic spaces with thickened walls), traction bronchiectasis (bronchial dilation due to traction by fibrous tissue) and subpleural bands are less frequently observed [12].
The treatment of patients with ASS is assessed on the presence or absence of ILD, its severity and/or its initial response to treatment [13]. The available medications are restricted and corticosteroids are generally regarded as the most effective choice. The usual recommendations highlight the benefit of the association of corticosteroids at the lowest efficient dose with another adjunctive immunosuppressive agent [14]. Currently, the most commonly used treatments have based on azathioprine, mycophenolate mofetil, calcineurin inhibitors, rituximab, intravenous cyclophosphamide or intravenous immunoglobulin [15]. The choice of the immunosuppressive drug regimen and when it should be started is left to the doctor’s experience. Despite these treatments, the overall mortality ratio for treated patients is significantly higher than in a standardized population of the same age and sex [16].
The aim of the present retrospective study is to analyze the ten-years clinical experience in ASS at CHU Liège (Belgium) and to confirm whether our clinical data are confident with the literature.