Abstract and Introduction
Background/Objective: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF.
Methods: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models.
Results: We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77–11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome.
Conclusion: Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.
Interstitial lung diseases (ILDs) are a spectrum of parenchymal lung disorders that often occur in patients with connective tissue diseases (CTDs) and are associated with significant morbidity and mortality. Prompt recognition of ILD in these patients is critical, as certain CTD-ILDs improve with immunosuppression.[2,3] This is in contrast to idiopathic pulmonary fibrosis (IPF), a progressive ILD in which immunosuppression is associated with deleterious outcomes. Importantly, some patients with ILD have a subset of clinical features of systemic autoimmunity, but not enough to warrant a diagnosis of a specific CTD, thus prompting the therapeutically relevant question of whether these patients' ILD is truly idiopathic or instead represents an attenuated, lung-dominant version of a CTD.
In 2015, the American Thoracic Society (ATS) and European Respiratory Society proposed preliminary research classification criteria to identify this population of patients with ILD and features suggestive of, but not diagnostic for, a CTD, which they termed "interstitial pneumonia with autoimmune features" (IPAF). To be classified as IPAF, patients without a classifiable CTD must have ILD that is not attributable to a known cause and fulfill at least 2 of 3 IPAF domain criteria (Supplementary Figure 1, https://links.lww.com/RHU/A454). Subsequent studies characterizing these patients have demonstrated substantial heterogeneity in their findings, in part due to the variable role of rheumatologists in the multidisciplinary approach to ILD classification.[5–10] More recent data suggest that IPAF may represent a distinct entity from CTD-ILD, with few patients going on to develop classifiable CTD, but additional studies are needed to corroborate this concept given the different study methodologies, variable duration of follow-up, and heterogeneity in the comprehensiveness of serologic testing.[11–13] As a result, it remains unclear whether IPAF represents a unique population that is distinct from CTD-ILD and IPF, or an early form of CTD-ILD in which most patients will go on to develop a CTD. In addition, and particularly important given the heterogeneity of patients meeting criteria for IPAF, little is known about prognostic factors in this population.
We hypothesized that IPAF classification would identify patients with early or incompletely manifested CTD-ILD and would thus be associated with similar rates of transplant-free survival compared to CTD-ILD and with frequent development of overt CTD-ILD during follow-up. The goals of this study were to (1) carefully identify patients classifiable as IPAF, CTD-ILD, and IPF through a multidisciplinary approach that included rheumatologists; (2) compare prognosis among these 3 groups and identify factors associated with poor prognosis in patients with IPAF; and (3) assess risk of progression to CTD-ILD.
J Clin Rheumatol. 2022;28(5):257-264. © 2022 Lippincott Williams & Wilkins