Thoracic Involvement in Systemic Autoimmune Rheumatic Diseases: Pathogenesis and Management

Abstract

Thoracic involvement is one of the main determinants of morbidity and mortality in patients with autoimmune rheumatic diseases (ARDs), with different prevalence and manifestations according to the underlying disease. Interstitial lung disease (ILD) is the most common pulmonary complication, particularly in patients with systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs) and rheumatoid arthritis (RA). Other thoracic manifestations include pulmonary arterial hypertension (PAH), mostly in patients with SSc, airway disease, mainly in RA, and pleural involvement, which is common in systemic lupus erythematosus and RA, but rare in other ARDs.In this review, we summarize and critically discuss the current knowledge on thoracic involvement in ARDs, with emphasis on disease pathogenesis and management. Immunosuppression is the mainstay of therapy, particularly for ARDs-ILD, but it should be reserved to patients with clinically significant disease or at risk of progressive disease. Therefore, a thorough, multidisciplinary assessment to determine disease activity and degree of impairment is required to optimize patient management. Nevertheless, the management of thoracic involvement-particularly ILD-is challenging due to the heterogeneity of disease pathogenesis, the variety of patterns of interstitial pneumonia and the paucity of randomized controlled clinical trials of pharmacological intervention. Further studies are needed to better understand the pathogenesis of these conditions, which in turn is instrumental to the development of more efficacious therapies.

Keywords: Airways disease; Autoimmune rheumatic disorders; Connective tissue diseases; Interstitial lung disease; Pleuritis; Pulmonary arterial hypertension.

Fig. 1

A pathogenetic model of parenchymal lung involvement in autoimmune rheumatic diseases. Environmental factors (cigarette smoke, pollutants and pathogens) in a genetically predisposed individual determine alveolar epithelial injury. This process results in damaged lung tissue, subsequent endothelial activation (in particular in systemic sclerosis) and release of self-antigens, which in turn lead to breakdown of self-tolerance and activation of the immune response. Multiple cellular compartments are involved: B-cells with production of autoantibodies, T-cells and monocytes–macrophages. Immune activation leads to the production of several cytokines such as IL-4, IL-5, IL-6, IL-13, TGF-β, TNF-α and VEGF that contribute to the initiation of repair pathways, including recruitment of fibroblasts and myofibroblasts. (ACPAs: anti-cyclic citrullinated peptide antibodies TGF-β: Transforming Growth Factor β, TNF-α: Tumor Necrosis Factor α, VEGF: Vascular Endothelial Growth Factor)

Fig. 2

HRCT images. a: Fibrosing NSIP pattern in a patient with SSc. b: UIP pattern in a patient with overlap SSc-RA; c and d: UIP pattern in a patient with RA: HRCT shows reticular opacities and subpleural honeycombing

Fig. 3

HRCT images. a: Fibrosing OP in a patient with dermatomyositis; b: NSIP pattern in a patient with anti-synthetase syndrome (Anti-Jo1 +); c: rapidly progressive ILD complicated by pneumomediastinum and subcutaneous emphysema in a patient with Clinically Amyopathic Dermatomyositis and anti-MDA5-antibodies positivity