Interstitial lung disease in suggestive forms of connective tissue disease

Abstract

Patients with the characterizable forms of connective tissue disease (CTD) are at risk for developing interstitial lung disease (ILD), and there is a growing appreciation that ILD can be the first or only clinically relevant manifestation of an underlying CTD.(1-3) Less is understood— and there is far greater controversy—about ILD associated with suggestive or “undifferentiated” forms of CTD.(2,3) In the present issue of the Brazilian Journal of Pulmonology, Pereira et al. review the clinical scenario of autoantibody positivity in ILD and discuss how these serologic tests may be interpreted.(4) In addition, they provide useful insights into the evaluation of patients with ILD suspected of having occult forms of CTD. Finally, the authors argue in favor of implementing the concepts that have been put forth in a recent commentary on “lung-dominant CTD”(5): a proposed, provisional category that describes ILD patients with an autoimmune flavor that fall short of meeting established criteria of any of the characterizable forms of CTD. Identifying occult CTD in patients presenting with what is initially considered to be an idiopathic interstitial pneumonia (IIP) can be challenging. Sometimes patients that subsequently develop a classifiable CTD cannot be identified before the specific systemic manifestations of the CTD appear. There is no universally accepted approach to these evaluations, and current practice includes an assessment for extrathoracic features of CTD, testing of a broad array of circulating autoantibodies, and consideration of specific radiographic and histopathologic features.(2,6) Various centers have also found that a multidisciplinary evaluation—including rheumatologic consultation—can be useful.(7-9) A number of recent studies have shown that patients with IIP often have subtle extrathoracic or other clinical features suggestive of an underlying autoimmune process and yet do not meet established criteria for any of the characterizable forms of CTD.(9-17) Sometimes these subtle symptoms or signs occur in the absence of serologic abnormalities, or a serum autoantibody known to be highly specific for a certain CTD (e.g. anti-Jo-1 with the antisynthetase syndrome) may be present without typical systemic or extrathoracic features. Other scenarios exist whereby specific radiologic or histopathologic features are suggestive of an underlying CTD and yet the absence of extrathoracic or serologic findings precludes reliable classification as CTD-ILD. In an area without consensus regarding terminology, the terms “undifferentiated CTD” (UCTD),(10,16) “lung-dominant CTD”(5) and “autoimmune-featured ILD”(17) have been used to describe such patients with suggestive forms of CTD-ILD. Each of these categories has a unique set of proposed criteria, represent the ideas of investigative teams from distinct ILD referral centers, and have yet to be prospectively validated.