Current strategies for identifying and classifying patients with only some features of CTD are both controversial and inadequate. Proposed terms to describe them include “undifferentiated CTD,” “lung-dominant CTD,” and “autoimmune featured ILD.” Corte and colleagues retrospectively studied subjects with IIP who had undergone SLBx, 45 with NSIP- and 56 with UIP-pattern histology.13 They observed that features of CTD are common in patients with IIP: 31% of subjects with NSIP- and 13% of subjects with UIP-pattern histology fulfilled established diagnostic criteria for undifferentiated CTD (UCTD).14 Importantly, when a broader and less specific set of proposed criteria for UCTD was applied, they found an astounding 71% of subjects with NSIP-pattern histology and 36% of those with UIP could be “defined” as having UCTD!15 Because of its lack of specificity, they argued against further implementation of the broader set of UCTD criteria in patients with ILD. Moreover, although a diagnosis of UCTD was significantly associated with a pattern of NSIP, conveying a label of UCTD did not impact survival. Vij and colleagues considered subjects to have “autoimmune featured ILD” if they had a sign or symptom suggestive of a CTD—including at least one serologic marker—but did not meet criteria for definite CTD.16 Subjects with autoimmune featured ILD had survival rates no different from subjects with IPF, but worse than subjects with CTD-ILD. Interestingly, among subjects with autoimmune featured ILD, the presence of an antinuclear antibody with a titer of >1:1280 was associated with improved survival.
Well-organized prospective studies are needed to determine the true implications of finding serologic or histopathologic features of CTD in patients without a classifiable CTD. Productivity of such studies will be greatly enhanced if consensus is reached on terminology and a classification scheme for these patients.
Natural Progression of CTD-ILD
Like patients with other forms of ILD, patients with CTD-ILD most often present with the insidious onset and gradual progression of dyspnea. The heterogeneity among subjects has made large-scale natural history studies of ILD in RA, PM/DM, and each of the other CTDs challenging, so more intense research will be required to advance understanding of ILD behavior over time in those patients. In patients with SSc-ILD, a simple staging system (see Figure 4) has been recently proposed that incorporates HRCT and FVC, and results suggest it provides a more accurate prognostic separation across SSc-ILD than has been achieved with any single modality in isolation.17 We believe the application of this staging system could impact clinical management decisions as well as future clinical treatment trial design, although additional investigation of this staging system, and validation in additional study samples would add confidence in its wide-scale implementation. In contrast to initial beliefs, bronchoalveolar lavage (BAL) does not predict the likelihood of disease progression or treatment responsiveness in CTD-ILD, so its routine use as a diagnostic tool in patients evaluated for CTD-ILD should be discouraged. However, BAL is often indicated to exclude infection and may also be performed as a component of research protocols.
