Publish date: October 4, 2016
Author(s): Kari Oakes
LAS VEGAS – Patients with rheumatoid arthritis who have pulmonary symptoms and a restrictive pulmonary function test pattern have a high likelihood for a diagnosis of interstitial lung disease, making it necessary to put it high on the differential and to begin working collaboratively with pulmonologists, according to Jon T. Giles, MD.
Overall, 8%-15% of RA patients will develop clinically significant interstitial lung disease (ILD), although radiographic evidence of ILD can be seen in up to half of RA patients, and in one study about one in four patients had evidence of ILD on CT scanning within 2 years of RA diagnosis. The overall risk for RA patients to develop ILD has been shown to be nine times higher than for matched controls (), Dr. Giles said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
Clinically evident RA-ILD is a serious diagnosis, with median survival of just 2.6 years after diagnosis; only about 20% of patients are still alive 8 years after diagnosis. One analysis found that ILD accounted for 13% of the excess mortality of RA, said, professor of medicine in the division of rheumatology at Columbia University, New York.
Relatively recently discovered risk factors for RA-ILD include higher levels of anti–citrullinated protein antibodies (ACPAs), and particularly antibodies against peptidylarginine deiminase (PAD), an enzyme that catalyzes arginine’s conversion to citrulline. Particularly for ever-smokers, the presence of the PAD3/4XR antibody has been highly correlated (P = .001) with having radiographic evidence of ILD. Besides currently smoking and ever smoking, other wide-ranging risk factors that have been associated with radiographic evidence of ILD include older age, being male, higher disease activity, and current use of prednisone or leflunomide, according to work that Dr. Giles conducted with his colleagues ().
An “alphabet soup” of ILD subtypes
Though there’s an “alphabet soup” of subtypes of ILD in RA, 90% of RA patients with ILD will have one of two conditions: usual interstitial pneumonitis (RA-UIP) or nonspecific interstitial pneumonitis (RA-NSIP). It’s not entirely clear whether one type of RA-ILD has a survival advantage over the other, Dr. Giles said.
Care for RA patients should include screening for ILD, said Dr. Giles. Physicians should ask about dry cough, dyspnea, and decreased exercise tolerance. Signs of ILD can include diminished oxygen saturation, a cardiac exam consistent with right heart disease, and rales. It’s not clear, he said, whether periodic chest radiographs or pulmonary function testing in asymptomatic RA patients is warranted.
Positive findings should prompt pulmonary function testing to include DLCO (diffusing capacity of lung for carbon monoxide), which may or may not be reduced in patients with clinically significant ILD. However, testing will show a restrictive pattern. A high-resolution chest CT should also be obtained.
Further evaluation should be done collaboratively with pulmonologists, and preferably with an ILD center, said Dr. Giles. A bronchoalveolar lavage and/or a lung biopsy may be considered.
Radiographic features of RA-UIP can include reticulation and honeycombing, predominantly seen in a subpleural and basilar distribution. Traction bronchiectasis may or may not be present. If a biopsy is performed, the histologic presentation of RA-UIP includes subpleural patches of dense fibrosis and honeycombing adjacent to healthy lung tissue; fibroblastic foci may be seen in the fibrotic regions.
In differentiating RA-UIP from interstitial pulmonary fibrosis (IPF), Dr. Giles said that lymphoid hyperplasia with germinal centers and peribronchial lesions are both more common in RA-UIP than in IPF. By contrast, fibroblastic foci are less common in RA-UIP than in IPF.
Sorting out the relationship between the use of disease-modifying antirheumatic drugs and ILD in RA is complicated by “complexities of attribution,” said Dr. Giles, since “RA patients with the most severe or refractory disease are more likely to both be exposed to a great number of RA therapies and higher doses and more combinations, and to have more risk factors for ILD.” Additionally, hypersensitivity pneumonitis can share some features with some subtypes of RA-ILD.
Beyond maximizing smoking-cessation intervention, which should be done for all currently smoking ILD patients, treatment goals for RA-ILD are “a balancing act,” Dr. Giles said. Immunizations should be up to date for all RA-ILD patients, and any concomitant pulmonary conditions, such as asthma or chronic obstructive pulmonary disorder, should also be optimally treated. An early evaluation for lung transplant is warranted for RA-ILD as well, he said.
If patients are symptomatic, then the goal is symptom reduction, with the extent of radiographically or histologically documented involvement and the rate of decline to be factored into treatment decisions.
Immunosuppressive treatments for RA-ILD, Dr. Giles said, “are not supported by any randomized clinical trials.” However, corticosteroids are often effective for RA-NSIP; “UIP is often not steroid responsive,” he said. Other agents can include azathioprine, which can give a “double whammy” effect by addressing joint and lung disease. However, azathioprine should not be used concurrently with corticosteroids, he said.
Mycophenolate mofetil (CellCept) has known antifibrotic effects, and there have been case reports of improvement in RA-ILD. Cyclophosphamide is also occasionally used. A host of other treatments have been attempted, including the antifibrotics pirfenidone (Esbriet) and nintedanib (Ofev), although these have been studied only in interstitial pulmonary fibrosis, said Dr. Giles. “Treating symptomatic RA-ILD is always a challenge,” he said.
Dr. Giles has been a consultant to Roche/Genentech and Proximagen and has received grant funding from Pfizer.
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