KEYSTONE, COLO. — The top diagnostic priorities when a lung problem is detected in a patient with underlying rheumatoid arthritis or another autoimmune disease are to rule out infection and drug reactions.

“The first 50 things on my list are infection and drug-induced disease. Almost all the drugs used to treat the autoimmune diseases put you at increased risk for infection—usually atypical infection. And all of the drugs used in treating autoimmune diseases have clearly been associated with the development of drug-induced lung disease, although some more than others,” Dr. Kevin K. Brown observed at a meeting on allergy and respiratory diseases.

Excluding infection up front is a high priority because it's the one type of interstitial lung disease (ILD) that's readily treatable. Also, a missed pulmonary infection spells trouble because efforts to treat nearly all other forms of ILD entail immunosuppression, which will make an infection worse, noted Dr. Brown, vice chairman of the department of medicine at National Jewish Health and professor of medicine at the University of Colorado, Denver.

Lung problems are extremely common in patients with autoimmune diseases. Chest abnormalities are present on high-resolution CT in 70%–90% of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, or other collagen vascular diseases, although the abnormalities often don't show up on a chest x-ray. Even though many of these patients report having no respiratory complaints, a careful history not uncommonly indicates that these patients have made lifestyle changes because of exertional shortness of breath or other symptoms.

“It used to be that patients with rheumatoid arthritis were not very active because if they were active they paid for it that night when their synovitis acted up. Now it's a rare patient whose synovitis can't be effectively managed. So we're seeing patients get off the couch, being very active, but having trouble getting up and down the stairs, not because of their arthritis but because of their lung disease,” he said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

One of the biggest offenders in terms of drug-induced ILD in patients with autoimmune disease is methotrexate. Probably 5%–7% of patients on methotrexate have drug-induced ILD. There are so many options available today for the treatment of collagen vascular diseases that, when Dr. Brown identifies ILD in a patient being treated for an autoimmune disease, he simply asks that the drug—whatever it is—be stopped and the patient be put on something else rather than trying to prove cause and effect by going through the complex exercise of drug discontinuation followed by rechallenge.

An ILD in the setting of autoimmune disease is associated with lower quality of life, more impaired functional status, greater health care costs, and markedly reduced survival over the next 4-5 years compared with the same autoimmune disease without ILD.

Dr. Brown and others have shown that the specific autoimmune disease doesn't matter: The prognosis for patients with an ILD and an autoimmune disease is significantly worse than for those with that autoimmune disease alone. Two factors that do matter in terms of prognosis are the extent of the lung disease on high-resolution CT and the degree to which spirometry results are preserved.

Dr. Brown and others use a prognostic algorithm in patients with autoimmune disease and ILD. If CT shows that not more than 10% of the lungs is involved in the disease process, that's classified as limited disease, with a prognosis similar to that of patients with the autoimmune disease without lung disease. If there's more than 30% involvement, that's categorized as extensive ILD, with a 3.5-fold greater mortality over the next 4-8 years than in patients with limited or no lung disease.

For patients with intermediate involvement on CT, spirometry serves as a tiebreaker. A patient whose forced vital capacity is at least 70% of predicted is classified as having limited disease, while an FVC less than 70% puts the patient in the extensive disease category.

The outcome of an ILD in the setting of underlying autoimmune disease is generally considerably better than for idiopathic interstitial pneumonia. For this reason, Dr. Brown goes to considerable lengths to make certain that patients initially diagnosed with idiopathic interstitial pneumonia don't have an underlying, previously undetected autoimmune disease.

Clinical symptoms suggestive of autoimmune disease in a patient with an ILD include weight loss, fever, onset of Raynaud's after about age 40 years, gastroesophageal reflux, rash, keratoconjunctivitis sicca, arthralgias, and myalgias.

A laboratory red flag that the ILD may be the first manifestation of an underlying autoimmune disease is the presence of nucleolar-staining antinuclear antibodies. Specific patterns of abnormal findings on CT and pathology also suggest rheumatologic disease, Dr. Brown noted.

Genetic conditions are another important cause of ILD.

Disclosures: Dr. Brown indicated that he has no financial interests relevant to his presentation.

Rule Out ILD in RA Patients' Lung Problems