https://orcid.org/0000-0002-1294-6421
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ABSTRACT
Introduction
Pulmonary involvement is one of the most common extra-articular manifestations of rheumatoid arthritis (RA), a systemic inflammatory disease characterized by joint swelling and tenderness. All lung compartments can be interested in the course of RA, including parenchyma, airways, and, more rarely, pleura and vasculature.
Areas covered
The aim of this paper is to review the main RA lung manifestations, focusing on pathogenesis, clinical and therapeutic issues of RA-related interstitial lung disease (ILD). Despite an increasing number of studies in the last years, pathogenesis of RA-ILD remains largely debated and the treatment of RA patients with lung involvement is still challenging in these patients.
Expert opinion
Management of RA-ILD is largely based on expert-opinion. Due to the broad clinical manifestations, including both joints and pulmonary involvement, multidisciplinary discussion, including rheumatologist and pulmonologist, is essential, not only for diagnosis, but also to evaluate the best therapeutic approach and follow-up. In fact, the coexistence of different lung manifestations may influence the treatment response and safety. The identification of biomarkers and risk-factors for an early identification of RA patients at risk of developing ILD remains a need that still needs to be fulfilled, and that will require further investigation in the next years.
Article highlights
Rheumatoid arthritis-related lung involvement encompasses a heterogenous group of clinical conditions. All compartments can be affected, including airways, lung parenchyma, vasculature, and pleura.
Interstitial lung disease appears to be the most severe pulmonary complication, affecting the quality of life and contributing to significantly increase morbidity and mortality in rheumatoid arthritis patients.
Rheumatoid arthritis-associated usual interstitial pneumonia and idiopathic pulmonary fibrosis share several clinical, radiographic and genetic features. Moreover, myofibroblasts and macrophages play a key role in the pathogenesis of both diseases.
RA-ILD treatment is still challenging and ideally it should aim to control underlying disease activity and to prevent the progression of pulmonary damage, in particular fibrotic changes. A close collaboration between rheumatologist, pulmonologist, and radiologist in a multidisciplinary discussion might improve management and treatment for these patients.
Treatment of ILD should be decided according to the radiologic features of ILD, in particular, the presence of fibrosis and the progression of lung involvement, taking into account also lung function and respiratory symptoms.
In RA-ILD patients requiring a biologic DMARD, abatacept or rituximab are currently thought as the safest options and, in case of contraindication or inadequate response, an IL-6 antagonist or a targeted synthetic DMARD can be considered.
Abbreviations
| ACPA | = | Anti-cyclic citrullinated protein antibodies; |
| AE | = | Acute exacerbation; |
| CarP | = | Anti-carbamylated protein; |
| CI | = | Confidence interval; |
| COPD | = | Chronic obstructive pulmonary disease; |
| DMARDs | = | Disease modifying antirheumatic drugs; |
| ECM | = | Extracellular matrix; FB: follicular bronchiolitis; |
| FEV1 | = | Forced expiratory volume in the first second; |
| FVC | = | Forced vital capacity; |
| GC | = | Glucocorticoids; |
| HDAC3 | = | Histone deacetylase 3; |
| HRCT | = | High-resolution computed tomography; |
| ILD | = | Interstitial lung disease; |
| IPAF | = | Interstitial pneumonia with autoimmune features; |
| IPF | = | Idiopathic pulmonary fibrosis; |
| JK2 | = | Janus kinase 2; |
| KL-6 | = | Krebs von den Lungen-6; |
| LFTs | = | lung function tests; |
| MAA | = | Malondialdehyde-acetaldehyde; |
| MDD | = | Multidisciplinary discussion; |
| MMP-7 | = | Matrix metalloproteinase 7; |
| MTX | = | Methotrexate; |
| NK | = | Natural killer; |
| NSIP | = | Nonspecific interstitial pneumonia; |
| OB | = | Obliterative bronchiolitis; |
| OP | = | Organizing pneumonia; |
| RA | = | Rheumatoid arthritis; |
| RF | = | Rheumatoid factor; |
| SFTPC | = | Surfactant protein C gene; |
| SP | = | Surfactant protein; |
| TGF | = | Transforming growth factor; |
| UIP | = | Usual interstitial pneumonia; |
Declaration of interest
P Faverio and F Luppi were partially supported by the Grant: Italian MUR Dipartimenti di Eccellenza 2023–2027 (l. 232/2016, art. 1, commi 314–337). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Acknowledgments
We acknowledge Erica Keeling for revising the English language of the paper.