Interstitial lung disease in systemic sclerosis patients may benefit more from anti-reflux therapies than from immunosuppressants☆

L’atteinte interstitielle pulmonaire est présente chez presque un malade sur deux au cours de la sclérodermie systémique. Cette complication est fortement associée aux auto-anticorps anti-topoisomérase 1. Elle est toutefois évolutive chez seulement une faible proportion de ces patients et beaucoup d’initiatives actuellement cherchent à définir des facteurs prédictifs de progression. Les outils sont notamment la tomodensitométrie qui est très précise pour identifier des modifications du parenchyme et les explorations fonctionnelles respiratoires pour en définir les conséquences fonctionnelles. Les immunosuppresseurs synthétiques ont été beaucoup utilisés malgré la faible démonstration de leur efficacité. Si le cyclophosphamide oral a été le plus évalué, sa toxicité tend à imposer le mycophénolate mofétyl en traitement de première ligne. La sélection des malades à traiter reste l’objet de débat même si des critères simples basés sur le degré d’extension au scanner ont été proposés. Des traitements ciblés sont en cours d’évaluation notamment le tocilizumab et le rituximab. Des traitements anti-fibrosant sont également à l’étude, notamment la pirfénidone et le nintedanib qui sont autorisés dans la fibrose pulmonaire idiopathique. L’avenir pourrait être aux combinaisons de ces traitements qui apparaissent très complémentaires d’un point de vue physiopathologique.

Interstitial lung disease complicates systemic sclerosis in about one out of 2 patients. This event is strongly associated with the presence of auto-antibodies anti-topoisomerase type 1. However, it is progressing in a small proportion of the affected patients and several studies are ongoing to try to identify predictive factors. Tools are primarily computed tomography that can stringently depict any interstitial lung changes and also pulmonary functional tests that can identify any functional consequences of these defects. Synthetic immunosuppressants have mostly been offered to affected patients so far despite the weak scientific demonstration of efficacy. If oral cyclophosphamide has been mostly investigated, its high toxicity makes mycophenolate mofetyl frequently the preferred drug as a first line therapy. Criteria to select the patients to be treated remain a matter of debate although simple criteria based on the extent of damages on CT-scan have been published. Targeted therapies are under evaluation with in particular clinical trials assessing tocilizumab and rituximab. Anti-fibrotic drugs are also under development with specifically pirfenidone and nintedanib which are on the market for idiopathic lung fibrosis. The future might be the combination of the above molecules that would appear very complementary taking into account disease pathogenesis.

According to the existence of subclinical organ involvement pre-scleroderma should be divided into two subsets: very early and early disease. Pre-scleroderma patients included in the Spanish Scleroderma Registry (RESCLE) Cohort were reclassified into subsets. Differences were evaluated and the risk of progression to definite systemic sclerosis was estimated.

The characteristics of very early and early SSc patients were compared. A logistic regression model was used to determine the risk factors of progression.

1632 patients were included, 36 (2.2%) in the very early subset and 111 (6.8%) in the early subset. There were no differences in sex, age at disease onset, duration of Raynaud's phenomenon, antinuclear antibodies or capillaroscopic findings. Three (8.3%) very early SSc patients evolved to definite SSc, 2 (5.6%) of them meeting the ACR/EULAR 2013 criteria, unlike 31 (28%) early SSc patients, 20 (24%) of them meeting the criteria (p = 0.034). Digestive involvement was an independent risk factor of progression (OR 17; 95% CI, 6.1–47.2).

The classification of early forms of scleroderma identifies patients with different prognostic risk of progression. The evolution to definite SSc is more frequent in early than in very early SSc patients. Digestive involvement is a risk factor of progression. An active assessment of organ damage in preclinical stages allows a correct classification and risk stratification, with implications for monitoring and treatment.