Background/Purpose:   Interstitial lung disease (ILD) can be idiopathic or associated with underlying etiologies including rheumatoid arthritis (RA). The purpose of this study is to determine the presence and significance of anti-CCP (and RF) in patients with ILD, whether or not they meet the diagnostic criteria for RA; supporting the notion that ILD as an extra articular manifestation of RA can develop prior to articular symptoms and that anti-CCP antibodies can be a prognostic marker for development of ILD in RA.

Methods: This is a retrospective chart review of 160 patients with ILD to identify and compare patients without articular manifestations whom had CCP antibodies (with or without RF) to those who met the diagnostic criteria for RA.  The data was abstracted from patients seen at the University of Kansas Medical Center Pulmonary ILD Clinic between January 2008 to June 2014. Each subject had serologic studies, pulmonary function testing (PFT), and thoracic computed tomography scan as part of the routine clinical evaluation.

Results:  Of the 160 patients, RF and/or anti-CCP were measured in 125 patients (78%). Of these 125 patients, 55 patients (44%) who had ILD along with positive RF and/or anti-CCP were identified. Of these 55 patients, only 4 patients who had ILD and anti-CCP positivity (median 94.7, range 36-138) did not have articular manifestations of RA, 3 of whom were male and one was female. The 3 male patients had a mean age of 65 at the time of diagnosis of ILD and only one had a history of smoking. The female patient was a 53 y/o cocaine abuser who also had a p-ANCA titer at 1:1280, MPO >8, and PR3 (0.4). One female patient died within 6 years of diagnosis of ILD and never developed articular manifestations of RA; the remaining 3 patients have not developed articular symptoms of RA yet. Nine patients with ILD had a positive RF but negative anti-CCP without articular findings of RA. Majority of these patients were female, and most were former cigarette smokers.  However, 6 of these 9 patients had elevated ANA (> 1:640) without features of a connective tissue disease. Among patients with ILD and RA, a positive anti-CCP antibody (28 patients) had a strong association with ILD (x²= 8.526, p=0.0035). Of these patients who had PFTs, 73% (30 of 41) already had moderate to severe restrictive lung disease or a severe impairment in diffusing capacity at the time of initial pulmonary evaluation.

Conclusion:   Our data indicates that the majority of patients with ILD and positive RF and/or anti CCP antibody in the ILD Clinic met the diagnostic criteria for RA. Consistent with other reports, there was a strong association with presence of anti-CCP antibody and development of interstitial lung disease. These findings highlight the prognostic value of anti-CCP antibody in patients with RA who may be at increased risk of developing ILD.  Hence, it is reasonable for CCP positive RA patients to undergo routine screening and surveillance for early detection and management of ILD at the time of diagnosis and thereafter. Further investigation and prospective studies are needed to fully assess the implications of a positive anti-CCP and RF in patients with ILD without articular manifestations of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/presence-and-significance-of-anti-ccp-antibody-in-patients-with-interstitial-lung-disease-with-and-without-clinically-apparent-rheumatoid-arthritis/