Good outcome of interstitial lung disease in patients with scleroderma associated to anti-PM/Scl antibody
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.
References (43)
- et al.
Registry of the Spanish network for systemic sclerosis: clinical pattern according to cutaneous subsets and immunological status
Semin Arthritis Rheum
(2012) - et al.
African–American race and antibodies to topoisomerase I are associated with increased severity of scleroderma lung disease
Chest
(1998) - et al.
Mortality in systemic sclerosis: an international meta-analysis of individual patient data
Am J Med
(2005) Autoantibodies in systemic sclerosis
Semin Arthritis Rheum
(2005)- et al.
Survival, causes of death, and risk factors associated with mortality in Spanish systemic sclerosis patients: results from a single university hospital
Semin Arthritis Rheum
(2010) - et al.
Updated clinical classification of pulmonary hypertension
J Am Coll Cardiol
(2009) - et al.
Severe restrictive lung disease in systemic sclerosis
Arthritis Rheum
(1994) - et al.
Antinuclear antibody with distinct specificity for polymyositis
J Clin Invest
(1977) - et al.
Antibodies to a nuclear/nucleolar antigen in patients with polymyositis overlap syndromes
J Clin Immunol
(1984) - et al.
Immunolocalization and partial characterization of a nucleolar autoantigen (PM-Scl) associated with polymyositis/scleroderma overlap syndromes
J Immunol
(1986)
Immunogenetic associations of scleroderma-related antinuclear antibodies
Arthritis Rheum
Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic associations
Arthritis Rheum
The clinical and immunogenetic features of patients with autoantibodies to the nucleolar antigen PM-Scl
Medicine (Baltimore)
Clinical, serologic, and immunogenetic features in Polish patients with idiopathic inflammatory myopathies
Arthritis Rheum
Anti-pm/scl antibodies in connective tissue disease: clinical and biological assessment of 14 patients
Clin Exp Rheumatol
Myositis-specific and myositis-associated antibodies in a series of eighty-eight Mediterranean patients with idiopathic inflammatory myopathy
Arthritis Rheum
Interstitial lung disease associated with anti-PM/Scl or anti-aminoacyl-tRNA synthetase autoantibodies: a similar condition?
J Rheumatol
Anti-PM-Scl antibody in patients with systemic sclerosis
Clin Exp Rheumatol
Scleroderma (systemic sclerosis): classification, subsets and pathogenesis
J Rheumatol
2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative
Arthritis Rheum
Survival following the onset of scleroderma: results from a retrospective inception cohort study of the UK patient population
Br J Rheumatol
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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).