Interstitial lung disease in systemic sclerosis

Abstract

Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc) and mainly encountered in patients with diffuse disease and/or anti-topoisomerase 1 antibodies. ILD develops in up to 75% of patients with SSc overall. However, SSc-ILD evolves to end-stage respiratory insufficiency in only a few patients. Initial pulmonary function tests (PFT) with measurement of carbon monoxide diffusing capacity, together with high-resolution computed tomography, allows for early diagnosis of SSc-ILD, before the occurrence of dyspnea. Unlike idiopathic ILD, SSc-ILD corresponds to non-specific interstitial pneumonia in most cases, whereas usual interstitial pneumonia is less frequently encountered. Therefore, the prognosis of SSc-ILD is better than that for idiopathic ILD. Nevertheless, ILD represents one of the two main causes of death in SSc patients. To detect SSc-ILD early, PFT must be repeated regularly, every 6 months to 1 year, depending on disease worsening. Conversely, broncho-alveolar lavage is not needed to evaluate disease activity in SSc-ILD but may be of help in diagnosing opportunistic infection. The treatment of SSc-ILD is not well established. Cyclophosphamide, which has been used for 20 years, has recently been evaluated in two prospective randomized studies that failed to demonstrate a major benefit for lung function. Open studies reported mycophenolate mofetil, azathioprine and rituximab as alternatives to cyclophosphamide. On failure of immunosuppressive agent treatment, lung transplantation can be proposed in the absence of other major organ involvement or severe gastro-esophageal reflux.

Introduction

Systemic sclerosis (SSc) is a connective tissue disorder with microvascular involvement, excessive collagen deposition and autoimmunity that involves multiple organs [1], [2]. Women are more frequently affected than are men (3 to 8 women for one man) [3]. The peak frequency of disease is between 45 and 64 years [4]. The prevalence of SSc varies between 200 and 260 cases per million inhabitants in the United States and Australia, 20 and 50 per million in Asia and 100 and 200 per million in Europe [5], [6].

Patients with SSc are classified according to the extent of skin involvement: diffuse cutaneous SSc (dcSSc), characterized by sclerotic lesions extending above the elbows and the knees [7]; limited cutaneous SSc (lcSSc), with skin involvement essentially limited to the hands and face; and limited SSc, with no detectable skin involvement [8].

The finding of predominantly basal pulmonary fibrosis is one of the 3 minor criteria for the diagnosis of SSc according to the American College of Rheumatology [9], whereas the major criterion supporting the diagnosis of SSc is the presence of skin sclerosis extending above the metacarpo-phalangeal joints.

SSc is associated with a significant reduction in survival. Pulmonary involvement is common in the course of SSc, and interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are at present the two main causes of death in SSc patients [10]. In patients with lcSSc, visceral involvement is rare, and the prognosis is good, with the exception of the 8% to 12% of patients in whom PAH, ILD and/or bowel involvement eventually develop [11]. Patients with dcSSc experience visceral involvement, which is responsible for reduced life expectancy [12]. Although PAH and ILD are the two main pulmonary manifestations in SSc, other pulmonary manifestations include aspiration pneumonia, pleural effusion, spontaneous pneumothorax, drug-induced ILD, associated pneumoconiosis and neoplasms [13].