A Clue to Diagnosing Connective Tissue Disease-Associated Interstitial Lung Disease

Abstract

In a recent issue of CHEST (August 2010), Fischer and coworkers1Fischer A West SG Swigris JJ Brown KK du Bois RM Connective tissue disease-associated interstitial lung disease: a call for clarification.Chest. 2010; 138: 251-256Abstract Full Text Full Text PDF PubMed Scopus (249) Google Scholar discussed the dilemmas surrounding the classification of a patient with interstitial pneumonia (IP) whose clinical features suggested an associated connective tissue disease (CTD) but did not provide a clear diagnosis of CTD-associated interstitial lung disease (ILD) on the basis of current rheumatologic classification systems. Undeniably, current rheumatologic classification schemes are limiting because they do not allow CTD designation when IP is the lone manifestation. We agree with the authors that the detection of occult CTD in patients presenting with IP is optimized by multidisciplinary collaboration. It is very difficult to differentiate idiopathic pulmonary fibrosis from CTD-ILD before the appearance of their systematic manifestations. However, several autoantibodies have been identified as being of diagnostic significance for CTD and may serve as clues for a new CTD-ILD classification. We recently reported an elderly woman who presented with organizing pneumonia; anticyclic citrullinated peptide (anti-CCP) antibody positivity was the first manifestation of rheumatoid arthritis (RA).2Komiya K Teramoto S Kurosaki Y et al.Organizing pneumonia with a positive result for anti-CCP antibodies as the first clinical presentation of rheumatoid arthritis.Intern Med. 2010; 49: 1605-1607Crossref PubMed Scopus (13) Google Scholar Although she did not exhibit articular symptoms initially, representative RA manifestations developed 8 months later. Thus, anti-CCP antibody positivity may be a good indicator for RA-ILD diagnosis.2Komiya K Teramoto S Kurosaki Y et al.Organizing pneumonia with a positive result for anti-CCP antibodies as the first clinical presentation of rheumatoid arthritis.Intern Med. 2010; 49: 1605-1607Crossref PubMed Scopus (13) Google Scholar Anti-CCP antibodies are reportedly the best predictors of RA activity3van der Helm-van Mil AH Breedveld FC Huizinga TW Aspects of early arthritis. Definition of disease states in early arthritis: remission versus minimal disease activity.Arthritis Res Ther. 2006; 8: 216Crossref PubMed Scopus (37) Google Scholar; they can be detected very early in the disease and have been reported to predict erosive RA development.4van Venrooij WJ van Beers JJ Pruijn GJ Anti-ccp antibody, a marker for the early detection of rheumatoid arthritis.Ann N Y Acad Sci. 2008; 1143: 268-285Crossref PubMed Scopus (160) Google Scholar ILD as the first presentation of CTDs, particularly in RA, is rare5Sato T Fujita J Yamadori I et al.Non-specific interstitial pneumonia; as the first clinical presentation of various collagen vascular disorders.Rheumatol Int. 2006; 26: 551-555Crossref PubMed Scopus (47) Google Scholar; therefore, the examination of these antibodies may be important for the differential diagnosis of CTD-ILD. We also agree with the authors that specific antibodies are integral in CTD-ILD assessment, and practitioners should apply certain indicators in addition to antinuclear antibody and rheumatoid factor for more effective screening for CTD. In particular, anti-Scl-70, anti-tRNA synthetase antibodies (eg, Jo-1, PL-7, and PL-12), anti-Ro (SS-A), antiribonucleoprotein, and anti-CCP are highly specific to CTDs.6Fischer A Swigris JJ du Bois RM et al.Anti-synthetase syndrome in ANA and anti-Jo-1 negative patients presenting with idiopathic interstitial pneumonia.Respir Med. 2009; 103: 1719-1724Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar, 7Fischer A Meehan RT Feghali-Bostwick CA West SG Brown KK Unique characteristics of systemic sclerosis sine scleroderma-associated interstitial lung disease.Chest. 2006; 130: 976-981Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar The selection of the autoantibodies is critical for CTD-ILD diagnosis. The disease-specific antibodies should be examined extensively and carefully. Although the symptoms and extrapulmonary manifestation are not always specific for CTDs, an initial basic examination is important. The diagnostic and therapeutic outcomes are the ultimate determinants for the differential diagnosis and the further refinement of actual diagnosis. Nonetheless, several autoantibodies specific for CTDs are currently the strongest marker of the diseases and should be used wisely and actively for the early diagnosis and correction of the diagnosis of CTD-ILD. A Clue to Diagnosing Connective Tissue Disease-Associated Interstitial Lung Disease: ResponseCHESTVol. 139Issue 3PreviewWe appreciate the support of Teramoto and colleagues for the concepts outlined in our recent commentary in CHEST (August 2010),1 which include the importance of a multidisciplinary approach to evaluating interstitial pneumonia (IP) and emphasize the usefulness of specific autoantibodies, such as anti-cyclic citrullinated peptide (CCP), as part of the assessment for connective tissue disease-associated interstitial lung disease (CTD-ILD). Teramoto and colleagues also briefly describe a patient without synovitis who presented with organizing pneumonia and anti-CCP antibody positivity, who later developed the articular manifestations of rheumatoid arthritis (RA). Full-Text PDF