Good outcome of interstitial lung disease in patients with scleroderma associated to anti-PM/Scl antibody

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Abstract

Objective

The objective of this article was to establish the clinical course of interstitial lung disease (ILD) in scleroderma related to the presence of anti-PM/Scl antibody compared with anti-Scl-70 in a Spanish cohort. Furthermore, no study has thoroughly investigated the outcome of pulmonary function test in the first group of patients.

Methods

A total of 63 Spanish patients with scleroderma and ILD were selected in a retrospective observational study. Among them, 14 were positive for anti-PM/Scl antibodies and 49 for anti-Scl-70. Clinical assessments, including pulmonary function test, were collected. Variations equal or greater than 10% in forced vital capacity (FVC) were considered significant. Progression-free survival of disease was defined as the period of stable illness since pulmonary fibrosis diagnosis.

Results

Anti-Scl-70 patients had a higher frequency of diffuse SSc subset, peripheral vasculopathy, and gastrointestinal involvement. Inflammatory myopathy was associated to anti-PM/Scl antibody. Anti-PM/Scl patients presented more improvement in FVC during follow-up, 30.8% compared to a 7.1% in Scl-70 group (P = 0.04), with less worsening of this parameter (15.4% vs 52.4% in Scl-70 patients, P = 0.01), and secondary less frequency of severe restrictive pattern (FVC < 50%) (7.7% compared to 42.9% in the other group, P = 0.02). Regarding treatment, more anticalcineurinics were used in anti-PM/Scl patients, while cyclophosphamide and mycophenolate were mainly used in anti-Scl-70 patients. The progression-free survival of disease was higher in anti-PM/Scl patients, with 76% at 10 years from diagnosis of ILD against a 29% in the Scl-70 group.

Conclusions

Several features and prognosis of ILD in SSc may be modified depending on the identified immunological profile.

Introduction

Systemic sclerosis (SSc) is a multisystemic autoimmune disease, which has a wide clinical individual variability, causing substantial differences in the severity of skin and internal organ affection. Interstitial lung disease (ILD) is the most characteristic example of an organ fibrosis in this entity. The ILD is more severe and early in diffuse cutaneous subset (dcSSc), but patients with limited cutaneous systemic sclerosis (lcSSc) can evolve to it too [1]. Probably the ILD development and its severity are related to specific autoantibodies. The anti-topoisomerase I (anti-Scl-70) antibody׳s relation with ILD in scleroderma has been well documented [2], [3], [4]. Steen [5] proposed to consider scleroderma as seven or more distinct diseases because features of patients with lcSSc and with dcSSc differed depending on associated autoantibodies. In that article, anti-Scl-70 and PM/Scl antibodies were related to ILD, but there were important differences in the prognosis measured following the SSc diagnosis. Nevertheless, it was not possible to compare both groups directly, as the disease duration at the time of diagnosis was different, so the analysis was made following the classification regarding the cutaneous subset.

In 1977, Wolfe et al. [6] described for the first time a group of patients with polymyositis and an antibody precipitated by immunodiffusion. Later, Reichlin et al. [7] defined that antibody as anti-PM/Scl when in a group of patients with inflammatory myopathy half of them had features of scleroderma. The PM/Scl autoantibodies are mainly found in the scleromyositis overlap, although they are also present in polymyositis, dermatomyositis, other connective tissue diseases (CTD), and even SSc without features of myopathy involvement [5], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Since anti-PM/Scl was described, only a few studies have been focused on patients with SSc, in which the prevalence of ILD was between 30% and 78% [5], [8], [9], [10], [11], [16].

This article attempts to establish the clinical course of ILD in scleroderma related to the positivity against anti-PM/Scl antibody comparing with another well-characterized group with anti-Scl-70 antibody, with emphasis on the outcome of pulmonary function test (PFT) as an objective measure to indicate lung impairment. To our knowledge, this is the first time that the lung outcome is specifically analyzed in patients with ILD related with SSc and anti-PM/Scl antibodies.

Section snippets

Patients

A total of 159 patients with diagnosis of scleroderma and ILD were registered in the retrospective cohort from Vall d׳Hebron Hospital, from April 1980 to December 2012. All of them fulfilled the LeRoy and the ACR/EULAR 2013 classification criteria [17], [18]. Of them, 63 patients were selected for positivity against either anti-Scl-70 or anti-PM/Scl antibodies, another two patients were excluded for positivity to both antibodies. Among them, 49 had anti-Scl-70 antibodies and 14 had anti-PM/Scl

Baseline features

To assess the differences in clinical features between both groups of patients with ILD, we studied 63 patients with scleroderma and ILD with positivity either for anti-Scl-70 or anti-PM/Scl antibodies. There were 54 women and nine men (F:M ratio = 6:1). Median age (interquartile range, IQR) at disease onset was 43.0 (33.0–54.0) years (Table 1). The RP was the most frequent first symptom presented in the 71.4% of patients. Nevertheless, if we considered the non-RP symptoms, arthritis and puffy

Discussion

The current study is a retrospective analysis of ILD outcome related to SSc depending on its association to anti-PM/Scl or anti-Scl-70 antibodies. The anti-PM/Scl patients had a stabilization of FVC during follow-up. Even one-third of them had an improvement higher than 10% in FVC. This group presented better PFS and severe restrictive disease-free survival.

The age at first symptom of SSc was similar to other series in the literature [1], [5], [24], [36]. Although the most frequent symptom of

Conclusion

The autoantibodies associated to SSc are not only related with a typical organ involvement but also are markers capable of impacting and modifying the severity of the SSc condition itself.

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    Source of support: This study was supported by Secretaria d׳Universitats i Recerca del Departament d׳Economia i Coneixement de la Generalitat de Catalunya (FI-DGR 2014).

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