What Rheumatologists Need to Know about Diagnosing and Managing Interstitial Lung Disease (ILD)

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Table 2: Useful Antibodies for CTD-ILD Assessment

Implications of a CTD-ILD Diagnosis

There are numerous implications of a CTD-ILD diagnosis. Most significantly, some data suggest that for a given histological pattern, subjects with CTD-ILD have a more favorable prognosis than subjects with idiopathic ILD. Other potential clinical implications of diagnosing a CTD include the following: 1) a CTD diagnosis could provide a context for extrathoracic disease manifestations (e.g., esophageal dysmotility); 2) if a CTD is diagnosed, the need for and timing of surveillance for certain extrathoracic features (e.g., pulmonary hypertension) is better defined; and 3) diagnosing a CTD may guide therapeutic decision making. As for research aimed at advancing the field of CTD-ILD, precisely phenotyping patients allows for greater validity of—and the ability to compare results across—studies of the pathobiology and natural history of CTD-ILD.

It is easy to confidently diagnose CTD—more specifically, RA—as the cause for the ILD in a 60-year-old male, former smoker with bilateral wrist synovitis, a high-titer anticyclic citrullinated peptide antibody, and a radiologic UIP pattern on HRCT, but there are a large number of patients with some features of a CTD (but not enough to satisfy ACR classification criteria) and ILD in a radiological or histological pattern commonly found in CTD-ILD. For example, we frequently encounter patients with ILD who are suspected of having a CTD based on the presence of circulating autoantibodies, certain autoimmune histopathologic features in SLBx specimens, or finding subtle extrathoracic manifestations. However, current CTD classification schemes do not accommodate these individuals, so they are labeled as having idiopathic ILD by default. This leaves them in limbo: they have a “flavor” of CTD and thus (perhaps appropriately) do not qualify for trials enrolling subjects with IIP, but they don’t meet criteria for the diagnosis of a CTD either. For example, a patient with idiopathic ILD and UIP-pattern histology would not be allowed in most therapeutic trials for IPF if, in addition to the UIP pattern, the SLBx revealed numerous lymphoid follicles with germinal centers; this is because the lymphoid follicles raise suspicion that such a patient may have CTD-ILD (even though they fulfill no ACR criteria for CTD) rather than IPF.

Further, despite the knowledge that ILD occurs commonly as a manifestation of CTD, current classification schemes—other than for SSc—do not consider ILD as a diagnostic criterion for CTD. Some experts have speculated that most patients with IIP (especially those with radiological or histological NSIP patterns) have an underlying CTD. This is because NSIP is the most common pattern in patients with CTD. Added to that, many patients with IIP have circulating autoantibodies, even those with reportedly high specificity for CTD (e.g., anti­cyclic citrullinated peptide). Song and colleagues observed that in subjects with IIP, the presence of circulating autoantibodies correlated with the presence of histologic features (mentioned above) of “autoimmune lung disease.”¹²