Original articleEffect of glucocorticoid monotherapy on pulmonary function and survival in Japanese patients with scleroderma-related interstitial lung disease
Introduction
Systemic sclerosis (scleroderma, SSc) is an autoimmune connective tissue disorder characterized by microvascular injury, excessive fibrosis of the skin, and distinctive visceral changes that can involve the lungs, heart, kidneys, and gastrointestinal tract [1]. Forty percent of these patients have a restrictive ventilator defect that results from interstitial lung disease (ILD) and is the most common cause of premature death from pulmonary hypertension (PH) [2], [3], [4]. The mortality rate among patients with severe ILD is especially high, approximately 42–70% within 10 years [1], [2], [3], [4]. The most rapid decline in forced vital capacity (FVC) occurs within the initial 3 years after disease onset, indicating the presence of parenchymal lung injury and subsequent fibrosis [4].
At present, several agents have been evaluated as treatments for SSc-ILD. Daily oral ingestion or pulses of intravenous cyclophosphamide (CYC) were shown, in a large randomized, double-blinded, placebo-controlled trial, to suppress the decline of pulmonary function [5], [6]. Glucocorticoid has also been widely used to treat SSc-ILD, and a combination of both medications, with intravenous CYC administration, has been effective [6], [7]. However, given the lack of convincing benefit and the increased risk for SSc renal crisis, the use of glucocorticoid monotherapy is currently limited for individuals with SSc-ILD [8], and azathioprine is the alternative agent usually considered for patients with contraindications precluding the administration of CYC [9].
On the other hand, the majority of histopathological characteristics of SSc-ILD have been reported as a pattern of nonspecific interstitial pneumonia (NSIP), which includes varied degrees of alveolar wall inflammation and fibrosis with temporal homogeneity [10]. Patients' overall response to therapy directed toward ameliorating this pattern, and their related prognosis, are favorably related to those for idiopathic pulmonary fibrosis/usual interstitial pneumonitis (IPF/UIP) [10]. Accordingly, we usually manage idiopathic NSIP with immunosuppressive agents; that is, most of these patients' symptoms are controlled by glucocorticoid monotherapy [10], [11]. Hence, for SSc-ILD, glucocorticoid alone could be effective. Because its efficacy and safety have never been documented, we conducted a retrospective cohort analysis at 2 major Japanese medical institutions to assess the effect of glucocorticoid monotherapy on pulmonary function and survival in patients with SSc-ILD.
Section snippets
Study sample
For this retrospective review, we surveyed all cases that were diagnosed as SSc-ILD in the Department of Respiratory Medicine at Juntendo University Hospital and Kameda Medical Center, a 1000-bed tertiary care center, from April 1996 to March 2009. We identified 71 patients with SSc-ILD, all of whom had undergone both a pulmonary function test and chest computed tomography (CT). We excluded patients who lacked imaging or pulmonary function data, or whose follow-up period was not verified as
Patients' characteristics
The median follow-up period after the diagnosis of SSc-ILD was 9.8 years (SD, 3.3) for the entire sample of 71 individuals. Comparisons of patient characteristics between the non-treatment (n=50) and treatment groups (n=21) are shown in Table 1. The treatment group had a greater proportion of males (38.1% vs 10.0%, p<0.05), diffuse scleroderma-related disease (33.3% vs 10.0%, p<0.05), and patients with respiratory symptoms (71.4% vs 44.0%, p<0.05) than the non-treatment group. Mean age, smoking
Discussion
In this retrospective cohort study, we showed for the first time the efficacy of glucocorticoid monotherapy for SSc-ILD. We found that (1) the treatment group contained a higher proportion of patients with diffuse scleroderma-related disease and respiratory symptoms; (2) although FVC improved each year in the treatment group, 5- and 10-year survival rates were not different between the non-treatment and treatment groups; and (3) no serious adverse events, not even SSc renal crisis, were ever
Conflict of interest
The authors have no potential conflicts of interest.
Acknowledgment
We thank Phyllis Minick for excellent English-language assistance.
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