The Lung in a Cohort of Rheumatoid Arthritis Patients

An Overview of Different Types of Involvement and Treatment

Ana C. Duarte; Joanna C. Porter; Maria J. Leandro


Rheumatology. 2019;58(11):2031-2038. 

In This Article

Abstract and Introduction


Objectives: Lung involvement in RA has several manifestations and is a major cause of morbidity and mortality. The aim of this study was to characterize the different types of lung disease and response to treatment in a UK cohort of RA patients.

Methods: RA patients who had undergone high resolution CT scans of the lung were identified and scans reviewed. Demographic data, RA features, complementary exams and treatments were recorded for those with radiological evidence of lung involvement. Descriptive analysis was performed, and Mann–Whitney U and χ2 tests were used for comparison between different radiological subtypes.

Results: Lung disease was reported in 87 (7.7%) of 1129 RA patients, usually (97.7%) post-dating articular symptoms. Most patients had positive RF (74/84; 88.1%) and ACPA (72/82; 87.7%). Interstitial lung disease (ILD) was the most common pattern, reported in 45 (51.7%) patients. Drug-induced lung disease was reported in 2 of 64 (3.1%) patients treated with MTX. Rituximab was used in 26 (57.8%) patients with ILD, with evidence of disease improvement or stabilization in patients with non-specific interstitial pneumonia and organizing pneumonia. During lung disease follow-up (6.7 ± 4.1 years), 22 (25.3%) patients were admitted to hospital with respiratory infections, with 14 (63.6%) of them having underlying bronchiectasis. Lung disease-related mortality was estimated at 8%.

Conclusion: ILD was the most prevalent manifestation of lung involvement in RA and was associated with higher mortality. Immunosuppressive drugs used in RA were rarely associated with lung toxicity, and rituximab demonstrated promising results for the treatment of RA-ILD.


RA is a systemic inflammatory disease that most commonly affects the joints. However, a wide range of extra-articular manifestations have been described, including lung disease. Lung involvement is found in up to 60–80% of RA patients,[1] although lower prevalence rates (7–20%) have been reported in other studies.[2–5] This wide variation mainly reflects the different definitions of RA-associated lung disease,[2] as many of these patients are asymptomatic, despite radiographic or functional evidence of lung abnormalities, leading to misrepresentation of disease prevalence.

In most patients, lung disease occurs within the first 5 years of RA diagnosis.[6,7] However, respiratory symptoms may precede the articular ones in 10–20% of cases.[6,7] Lung disease in RA can affect the parenchyma, pleura, airways or vasculature and can result from direct involvement by the disease or as a result of RA treatment.[6] Secondary pulmonary infection is also an important cause of lung disease in RA patients.[2] Interstitial lung disease (ILD) is the most common manifestation of RA-associated lung disease, with an estimated prevalence of 4–50%.[5–7]

A large majority of RA patients need treatment with a DMARD. MTX is usually the first option and despite reports of induced lung disease, a recent study demonstrated a higher survival in patients with ILD treated with MTX when compared with those without MTX,[8] presumably due to control of underlying inflammation. Other drugs commonly used for RA treatment, such as leflunomide and anti-TNF agents, have also been rarely associated with the development of ILD.[6,9,10]

Despite new advances in RA diagnosis and treatment, including extra-articular manifestations, the incidence of ILD has remained fairly stable, if not increased,[6,11] and survival after RA-ILD diagnosis has changed very little for the last 30 years.[11] Pulmonary involvement is directly responsible for 10–20% of deaths in RA patients,[2,3,7] with most attributed to ILD.[2,12] Usual interstitial pneumonia (UIP) in particular is associated with median survival rates of just 3–4 years after diagnosis, similar to idiopathic pulmonary fibrosis.[13]

More recently, the anti-CD20 chimeric monoclonal antibody rituximab (RTX) has been proposed as an efficient rescue therapy for RA-ILD.[14]

In this study we aim to fully characterize the types of lung involvement in a cohort of RA patients and describe the potential lung toxicity associated with the DMARDs used. Secondly, we intend to share our experience regarding RTX use in patients with RA-ILD.