VANCOUVER, B.C. – Chest physicians must consider a slew of diagnostic possibilities when evaluating patients with rheumatoid arthritis who have developed pulmonary abnormalities, according to Dr. Kevin R. Flaherty.
"We have to keep in mind all the different things that can go wrong in these patients when we are trying to treat them: Is this progression of the underlying disease? Is this a complication of the therapy? Or is this the development of something new, like a cancer, that’s now causing the patient’s symptoms?" he commented.
"Trying to keep all those things in our mind to sort that out is difficult, and it’s an exercise that we have to go through each and every time we see one of these patients," he told attendees at the annual meeting of the American College of Chest Physicians.
Pulmonary Manifestations of RA
"The lung is a common site for extra-articular rheumatoid arthritis," noted Dr. Flaherty, who is a pulmonologist and associate professor at the University of Michigan Health System in Ann Arbor. Of the many pulmonary manifestations of RA, interstitial lung disease causes the greatest morbidity and mortality.
The lifetime risk of interstitial lung disease is nearly 8% in patients with RA, compared with 1% in the general population (Arthritis Rheum. 2010;62:1583-91). And this disease confers a poor prognosis, with a near tripling of the risk of death and with a median survival after diagnosis of only about 2.5 years.
High-resolution computed tomography (HRCT) and pulmonary functioning testing appear to be useful for identifying interstitial lung disease early in its course, according to Dr. Flaherty.
For example, among patients within 2 years of a RA diagnosis, 44% have been found to have HRCT, pulmonary function test, and other abnormalities consistent with interstitial lung disease in the absence of symptoms (Am. J. Respir. Crit. Care Med. 1997;156:528-35).
"The [HRCT] features were mild – reticular thickening, ground glass, and not much honeycombing – suggesting maybe that we might be able to impact the disease, because I think once you get to honeycomb lung and end-stage fibrosis, our ability to impact this disease is likely to be lower," he said.
Another study among patients with recent-onset RA found abnormalities on HRCT but normal results on pulmonary function tests (Scand. J. Rheumatol. 2007;36:338-44), "suggesting that symptoms and pulmonary screening are not going to be as sensitive as HRCT screening."
As for which patients to screen for interstitial lung disease, the predictors of abnormal pulmonary function testing in the RA population are respiratory symptoms, smoking, anti–cyclic citrullinated peptide positivity, and use of prednisone (Arthritis Res. Ther. 2010;12:R104).
When it comes to monitoring interstitial lung disease, HRCT appears to be more sensitive than pulmonary function testing for detecting disease progression (Arch. Intern. Med. 2008;168:159-66). And carbon monoxide diffusing capacity at diagnosis is the best predictor of progression (Ann. Rheum. Dis. 2002;61:517-21).
"We are starting ... to see data emerging that really mirrors what we see in idiopathic lung disease, that the histopathology and the CT appearance can help us in terms of stratifying patients for risk of subsequent mortality," Dr. Flaherty said.
For example, a study of patients with RA-associated interstitial lung disease found 50% mortality in those with a usual interstitial pneumonia (UIP) histology, compared with none in those with a nonspecific interstitial pneumonia (NSIP) histology after a similar median follow-up of about 4 years (Chest 2005;127:2019-27).
A honeycomb pattern on HRCT was found only in the UIP group, suggesting that this radiographic pattern is a good surrogate for this histology, Dr. Flaherty noted. And indeed, patients having a definite UIP radiographic appearance have poorer survival (Eur. Respir. J. 2010;35:1322-8).
Rigorous studies are lacking when it comes to treating interstitial lung disease in the RA population, according to Dr. Flaherty. Case reports, case series, and retrospective analyses have assessed many immunomodulating and immunosuppressive agents, but "what we are really begging for are some prospective, well done clinical trials to help us sort all of these potential treatments out," he said.
Pulmonary Adverse Effects of RA Therapy
Pneumonitis is often a concern in patients using methotrexate to treat RA. But with low-dose therapy, only 3% of patients develop this complication after a mean treatment duration of 23 months (Chest 1996;109:933-8). "So we worry about it, but yet it’s actually a very small number of patients that develop methotrexate toxicity," Dr. Flaherty pointed out.
Anti–tumor necrosis factor (TNF) agents such as infliximab have been associated with pulmonary adverse effects and complications, including infection, atypical presentation of tuberculosis, and pulmonary fibrosis. With the last, "patients have cough and dyspnea, it can occur within months of initiating treatment, and it can be associated with high mortality," he said.