Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations

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.

Clinical and radiological features of lung disorders related to connective-tissue diseases: a pictorial essay

“…All pulmonary compartments—such as airways, interstitium, pulmonary vessels and pleura may be interested, namely in RA, SSc and SS diseases. The heterogeneous lung involvement leads to “a broad spectra of clinical manifestations” [ 32 ], which may be not easily recognized by clinicians and radiologists.…”

“…Among patients with collagen vascular disease, those with SSc show the highest mortality, due to the development of pulmonary hypertension—which has a prevalence ranging from 10% up to 16% [ 31 ]. ILD development, which shows the highest prevalence in SSc than in other CTDs, represents the main cause of mortality in SSc, being responsible for up to 40% of the causes of death [ 32 , 33 ]. In other CTDs, the main cause of death is related to cardiovascular disease (RA and Sjogren’s syndrome) [ 34 , 35 ], infection or malignancy (IIMs) [ 36 ].…”

Hydroxychloroquine on the Pulmonary Vascular Diseases in Interstitial Lung Disease: Immunologic Effects, and Virus Interplay

“…The index date of a new virus infection is the date of the ILD cohort. Patients with an age <18 years or a history of PVD before entry into the study were excluded (The full names of the ICD-9-CM codes are listed in Table A1 and Table A2 in Appendix A ) ( Figure 1 and Figure 3 ) [ 9 , 19 , 20 , 21 ].…”

Therapeutic Potential of Janus Kinase Inhibitors for the Management of Interstitial Lung Disease

“…These conditions cause damage to the alveolar epithelium and lung parenchyma, ultimately leading to inflammation and extensive fibrosis. 1 ILD is characterized by varying degrees of inflammation or fibrosis in the pulmonary parenchyma. For instance, in inflammatory diseases, the histology of the pulmonary parenchyma is characterized by mechanical pneumonia or nonspecific interstitial pneumonia, while fibrotic diseases are characterized by common interstitial pneumonia.…”

“…Currently, the common treatment strategies include glucocorticoids and immunosuppressants such as cyclophosphamide. 1 However, occasionally the disease is refractory, rapidly progressive, and resistant to hormonal and immunosuppressive therapies. 15 As a result, it is necessary to develop alternative drug therapies based on the current understanding of ILD pathogenesis and the role of the JAK/STAT pathway in it.…”