Arthritis Today

RA and Lung Disease: What You Need to Know

Respiratory problems are one of the most common – and serious – extra-articular complications of rheumatoid arthritis.


Rheumatoid arthritis (RA) doesn’t only affect your joints. In about 30 percent of people with RA, the same inflammatory process that erodes cartilage and bone damages other parts of the body, too. Although the skin, eyes, heart and blood vessels can all be affected, the lungs are the most common site of extra-articular disease.

RA can cause a variety of lung problems, ranging from small growths in the lungs (pulmonary nodules) to a buildup of fluid between the lung and chest wall (pleural effusion) and damage to the airways (bronchiectasis). But the condition most often associated with RA is interstitial lung disease (ILD), a broad group of serious disorders marked by inflammation and scarring of lung tissue. Over time, ILD can lead to a progressive loss of lung function and life-threatening complications.

“[ILD] is not routine, but it does occur, and we look for it every time we see a new patient. It should be part of routine screening for anyone newly diagnosed with RA,” says Brian Golden, MD, a clinical associate professor of rheumatology at New York University Langone Medical Center.

RA-ILD Risk Factors

Although the lifetime risk of ILD in people with RA is eight times that of the general population – most patients aren’t affected, says Dr. Golden.

Researchers have identified the risk factors that may trigger or contribute to it. They include:

  • Smoking. Study results on smoking have been mixed, but most evidence suggests that smoking injures lung cells and triggers the production of citrullinated proteins, which are specific markers for RA. In a study published in Thorax in 2001, researchers found that 75 percent of patients with diagnosed rheumatoid arthritis-associated ILD (RA-ILD) were current or former smokers.
  • High levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP) antibodies. ”Recent studies show that high anti-CCP and RF serologies predict the presence of ILD, likely because they are markers of more severe underlying RA,” explains Teng Moua, MD, a pulmonologist specializing in ILD at Mayo Clinic’s campus in Rochester, Minn.
  • Older age. People diagnosed with RA in their 60s are more likely to have RA-ILD than those diagnosed earlier.
  • Male gender. Although RA itself is two to three times more common in women, RA-ILD is two or three times more common in men.

Diagnosing RA-ILD

Diagnosing RA-ILD can be challenging. The disease rarely causes symptoms in the early stages; shortness of breath and a dry cough usually develop as the disease progresses. A proper evaluation includes a comprehensive clinical exam, X-rays and lung function tests. A high resolution CT should always performed if you have symptoms or risk factors for ILD or abnormal X-ray findings, Dr. Golden says.

ILD can even surface long before RA does, so a diagnosis of ILD sometimes leads to the discovery of RA, rather than the reverse. In a 2013 study published in Chest, more than half of 50 patients originally diagnosed with idiopathic ILD (meaning there was no known cause), were eventually found to have RA-ILD.

Also problematic is the lack of screening guidelines for RA-ILD, which can lead to wide variations in the way the disease is diagnosed. Complicating diagnosis even more is that many drugs commonly used to treat RA may cause or worsen lung disease. Methotrexate, a mainstay of RA treatment, can cause a type of lung inflammation called pneumonitis. Other disease-modifying antirheumatic drugs (DMARDs), including leflunomide and azathioprine, and biologics such as tumor necrosis factor (TNF) inhibitors have also been associated with RA-ILD.

A meta-analysis of methotrexate trials published in Arthritis &Rheumatism in 2013 found that methotrexate caused a “small but significant” increase in the risk of RA-associated lung disease in patients treated with it. And a literature review in the April 2014 issue of Seminars in Arthritis and Rheumatism found an association between RA-ILD and most DMARDS and biologics.

Still, the link between medications and RA-ILD is controversial. Teng Moua, MD, a pulmonologist specializing in ILD at Mayo Clinic’s campus in Rochester, Minn., says the risk of methotrexate-induced lung injury is low – less than 1 percent – and “it reverses or stabilizes once the drug is stopped.” He believes the benefits of methotrexate far outweigh its risks.

On the other hand, the American College of Rheumatology’s 2012 guidelines recommend against methotrexate for people with ILD or RA-ILD. Dr. Golden says using methotrexate in RA patients is “fraught with difficulty” and can also be confounding. “You don’t know which is the chicken and which is the egg,” he explains.

Experts do agree on one thing – ILD is hard to diagnose and rheumatologists, radiologists and pulmonologists should work together to ensure that patients receive a proper evaluation.

How Is RA-ILD Treated?

Few good treatments exist for RA-ILD. Corticosteroids and immunosuppressants are used for some patients but have their own side effects and aren’t always effective, especially later in the disease when the prognosis is poor. Drs. Golden and Moua both say it’s difficult to treat RA-ILD directly, and the best approach is usually to continue treating the underlying arthritis.

But even then, Dr. Moua says, “RA-ILD may progress despite well-controlled joint disease.”

Preventing Lung Disease

RA-associated lung disease is challenging to treat, so prevention is important. To help reduce your risk:

  • Don’t smoke. “Smoking may be the only modifiable risk factor for RA-ILD,” Dr. Golden points out.
  • Get flu and pneumonia vaccines. You’re more susceptible to infections when taking medications that suppress the immune system. Be sure to talk to your doctor before getting any vaccine.
  • Have regular checkups. Your doctor should listen to your lungs and monitor breathing at every visit. If you take methotrexate or other drugs associated with lung disease, you should be monitored even more closely. If you develop symptoms such as shortness of breath or coughing, see your doctor right away.