Abstract
Connective tissue disease (CTD) related interstitial lung disease (CTD-ILD) is one of the leading causes of morbidity and mortality of CTD. Clinically, CTD-ILD is highly heterogenous and involves rheumatic immunity and multiple manifestations of respiratory complications affecting the airways, vessels, lung parenchyma, pleura, and respiratory muscles. The major pathological features of CTD are chronic inflammation of blood vessels and connective tissues, which can affect any organ leading to multi-system damage. The human lung is particularly vulnerable to such damage because anatomically it is abundant with collagen and blood vessels. The complex etiology of CTD-ILD includes genetic risks, epigenetic changes, and dysregulated immunity, which interact leading to disease under various ill-defined environmental triggers. CTD-ILD exhibits a broad spectra of clinical manifestations: from asymptomatic to severe dyspnea; from single-organ respiratory system involvement to multi-organ involvement. The disease course is also featured by remissions and relapses. It can range from stability or slow progression over several years to rapid deterioration. It can also present clinically as highly progressive from the initial onset of disease. Currently, the diagnosis of CTD-ILD is primarily based on distinct pathology subtype(s), imaging, as well as related CTD and autoantibodies profiles. Meticulous comprehensive clinical and laboratory assessment to improve the diagnostic process and management strategies are much needed. In this review, we focus on examining the pathogenesis of CTD-ILD with respect to genetics, environmental factors, and immunological factors. We also discuss the current state of knowledge and elaborate on the clinical characteristics of CTD-ILD, distinct pathohistological subtypes, imaging features, and related autoantibodies. Furthermore, we comment on the identification of high-risk patients and address how to stratify patients for precision medicine management approaches.
Highlights
Connective tissue disease (CTD) is a heterogeneous group of inflammatory disorders that can affect bone, cartilage, tendons, ligaments, muscle, joints, blood vessels, and even specific organs
The human lung is vulnerable to such damage because anatomically it is abundant with collagen and blood vessels
We focus on examining the pathogenesis of CTD-interstitial lung disease (ILD) with respect to genetics, environmental factors, and immunological factors
Summary
Connective tissue disease (CTD) is a heterogeneous group of inflammatory disorders that can affect bone, cartilage, tendons, ligaments, muscle, joints, blood vessels, and even specific organs. Patients with rare telomere-related variants TERT, TERC, PARN, or RTEL1 exhibit various forms of pulmonary fibrosis, ranging from IPF, interstitial pneumonia with autoimmune features (IPAF), to CTD-ILD. Driven MUC5B overexpression of MUC5B protein can hinder cilia clearance or disrupt normal lung repair mechanisms [25] These studies support that MUC5B is involved in the pathogenesis of CTD-ILD and may be a therapeutic target. Fingerlin et al reported that two HLA alleles in the high linkage disequilibrium are associated with pulmonary fibrosis (DRB1 * 15:01 and DQB1 * 06:02) [33, 34] These susceptibility genes are similar to the previous ILD-related loci associated with PM/DM [34,35,36].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
