Background: Autoantibodies permit to classify and subgroup connective tissue diseases (CTD) in homogeneous groups of patients in terms of phenotype and prognosis. Anti PM-Scl antibodies have been associated with different CTD categories such as: idiopathic inflammatory myositis (IIM), systemic sclerosis (SSc), Sjögren’s syndrome (SjS), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD) or undifferentiated connective tissue disease (UCTD).

Objectives: To determine clinical spectrum of anti-PM-Scl associated disease and if it an homogenous condition.

Methods: This multicentric (four hospitals) observational and retrospective study included all consecutive patients with positive testing for anti PM-Scl antibodies on immunoblot assay and connective tissue disease (2011 -2020). Epidemiological, biological, clinical and radiological data were collected in standard form as well as patient’s outcome.

Results: One hundred twenty height patients (female n=96;75%) were included. Median [quartiles] age at diagnosis was 50 [18;84] (IQR) and follow-up duration of 7 [3.75-12] years. Seventy-six (59.3%) patients were simple anti-Pm-Scl positive, and 40.7% were associated with other antibodies: anti-SSA/Ro52 (n=13; 10.92%), SSc associated antibodies (n=21; 16.4%), anti-dsDNA for (n=9; 7%), anti-RNP (n=6; 4.7%) and anti-CCP antibodies (n=6; 4.7%). Most patients had cutaneous involvement (n=106; 83%) with skin thickening (n=47; 36%), mechanics hands (n= 28; 22%), calcinosis (n=26; 20.3%) and subcutaneous edema (n=20; 15.62%). Vascular involvement was frequent with Raynaud phenomenon (n= 89; 69%), telangiectasia (n=36; 28%), skin ulcers (n=27; 21%), pulmonary hypertension (n=8/120; 6.7%) and scleroderma renal crisis (n=2; 1.5%). A majority of patients also displayed an interstitial lung disease (ILD) (n=83; 65.8%); nonspecific interstitial pneumonia (92.7%) and/or organizing pneumonia (25.3%). ILD was characterized by a subacute onset in 37/81 (45.7%); median [quartiles] forced vital capacity (FVC) and total lung capacity (TLC) at diagnosis of 88% [73-105] and 79.5% [68.5-101] respectively. Sixty patients (47%) had muscular sign including myalgia (47%), elevated CPK (n=51; 40%) and muscular weakness (Medical Research Council score <4) (n=19/124;15%). Finally, fifty-three (41.7%) had gastroesophageal reflux. Thirty-nine patients (30.4%) experienced at least one muscular or ILD relapse and 6 (4.84%) died during follow-up (2 breast cancer, 1 pneumonia, 3 unknown etiology). Concerning patients’ prognosis, relapses were associated with skeletal (n=29, 74.4% vs n=32, 35.96%, p < 0.001) or cardiac muscle involvement (n=7, 18.4% vs n=2, 2.5%, p=0.007), and subacute ILD (n=19, 65.5% vs n=18, 34.62%, p= 0.05) with organized pneumonia pattern (n=11, 32.3% vs n=10, 13.9%, p=0.05). Strikingly, ILD occurred mainly in men (90.6% vs 57.2%, p < 0.001) and was associated with anti-Scl-70 positivity (n=14, 16.67% vs 0%, p= 0.01). Muscle involvement was associated arthralgia (n=46, 76.67% vs n=34, 50.75%, p=0.005), respiratory signs at diagnosis: dyspnea NYHA ≥3 (n=46, 75.41% vs n=30, 44.78%, p < 0.001), sub-acute ILD (n=24, 61.54% vs n=13, 30.95%, p=0.0111) with lower FVC (73% [64;88] vs 98 [76;105], p < 0.001). Ulcers were associated with Anti-Scl70 positivity (n=9, 33.33% vs n=5, 4.95%, p < 0.001), Raynaud phenomenon (n=27, 100% vs n=62, 61.39%, p < 0.001), digestive involvement (n=20, 74.07% vs n=34, 33.66%, p < 0.001), ILD with chronic onset (n=15, 78.95% vs n=29, 46.77%, p=0.027) and increased incidence of deaths (n=4, 16% vs n=2, 2.02%, p= 0.01).

Conclusion: Conducted on the largest cohort of Anti-PM-Scl patients, this study highlights two main phenotypes that determine different outcome and prognosis. One was associated with muscular disease and subacute onset ILD with more frequent relapses. The second with a vascular phenotype associated with chronic ILD, digestive involvement, chronic evolution and increased incidence of death. This could lead to a reclassification of PM-Scl associated auto immune diseases.

Disclosure of Interests: None declared