Question: I never know when to order an antinuclear antibody (ANA) or rheumatoid factor (RF) test on my interstitial lung disease (ILD) patients or what to do with a positive test. Please help!

Answer: Many pulmonary physicians choose to screen for occult connective tissue disease (CTD) with a variety of laboratory tests. The practice has evolved from the knowledge that 10% to 25% of ILD patients will eventually be diagnosed with a CTD; however, the frequency with which ILD is the only manifestation of a CTD remains unknown. Usually a CTD will evolve in the first 2 years following ILD presentation in these patients.

Older data has suggested that the frequency of ANA and RF positivity in idiopathic pulmonary fibrosis (IPF) is approximately 40%. More recent case series have suggested that many of these patients do not meet high resolution computed tomography (HRCT) or open lung biopsy criteria for usual interstitial pneumonitis (UIP), the pathologic correlate of IPF, and more typically have nonspecific interstitial pneumonitis (NSIP) in which lung fibrosis is more diffuse but less progressive.

Therefore, when a patient has a positive RF, particularly if arthritis is present, then further work must be done. A new test for anticyclic citrullinated peptide antibodies (Anti-CCP) is both more sensitive and specific for rheumatoid arthritis. Hand films and films of affected joints are obtained to solidify diagnosis. Importantly, if RA can be confirmed, anti-inflammatory therapy will be begin with a goal of reducing joint (and lung) inflammation. Most commonly, this will require a tumor necrosis factor (TNF) inhibitor when RA is advanced sufficiently to have ILD.

The utility of ANA is less well studied. ANA is almost always positive in systemic lupus erythematosis, scleroderma, CTD-associated Sjögren's syndrome, and often positive in polymyositis/dermatomyositis. If ANA is positive in ILD at a titer of 1:160 or higher, further characterization of an extractable nuclear antigen (ENA) panel is recommended. This panel can further characterize the disease and suggest the most appropriate anti-inflammatory therapy.

Although these laboratory tests are inexpensive and felt to be helpful, no prospective study has ever determined if the tests truly make a difference independent of a good history and physical exam.