Interstitial Pneumonia With Autoimmune Features: An Emerging Challenge at the Intersection of Rheumatology and Pulmonology

Abstract

Interstitial lung disease (ILD) remains a cause of significant morbidity and mortality in patients with connective tissue disease (CTD)-associated ILD. While some patients meet clear classification criteria for a systemic rheumatic disease, a subset of patients do not meet classification criteria but still benefit from immunosuppressive therapy. In 2015, the American Thoracic Society and European Respiratory Society described classification criteria for interstitial pneumonia with autoimmune features (IPAF) to identify patients with lung-predominant CTD who lack sufficient features of a systemic rheumatic disease to meet classification criteria. Although these criteria are imperfect, they are an important attempt to classify the patient with undifferentiated disease for future study. Rheumatologists play a key role in the evaluation of potential IPAF in patients, especially as many patients with a myositis-spectrum disease (e.g., non-Jo-1 antisynthetase syndrome, anti-melanoma differentiation-associated protein 5 antibody inflammatory myositis, or anti-PM/Scl antibody-associated inflammatory myositis) would be classified under IPAF using the currently available criteria for inflammatory myositis, and would therefore benefit from rheumatologic comanagement. The aim of this review was to describe the historical context that led to the development of these criteria and to discuss the limitations of the current criteria, diagnostic challenges, treatment options, and strategies for disease monitoring.

Figure 1.

Representative CT slices of various interstitial lung disease patterns. A. Organzing pneumonia (OP) showing scattered consolidation with areas of central lucency (reverse halo sign/Atoll sign) B. Non-specific interstitial pneumonia (NSIP) with traction bronchiectasis surrounded by ground glass in the absence of honeycombing. C. Usual interstitial pneumonia (UIP) with subpleural honeycombing and no ground glass. D. Lymphocytic interstitial pneumonia (LIP) with thin walled scattered cysts and no fibrosis.

Figure 2.

Kaplan-Meier survival curves of interstitial pneumonia with autoimmune features (IPAF), idiopathic pulmonary fibrosis (IPF), and connective tissue disease (CTD)-interstitial lung disease (ILD) cohorts. Overall, the IPAF cohort survival was significantly worse than the CTD-ILD cohort (p<0.001) and marginally better than the IPF cohort (p=0.07). After stratification of the IPAF cohort by the presence of usual interstitial pneumonia pattern on high-resolution computed tomography and/or surgical lung biopsy b) IPAF patients without usual interstitial pneumonia (UIP) demonstrated survival similar to those with CTD-ILD (p=0.45), while those with UIP demonstrate survival similar to those with IPF (p=0.51). Reproduced with permission from the ©ERS 2016. European Respiratory Journal Jun 2016, 47 (6) 1767–1775; DOI: 10.1183/13993003.01565-2015

Figure 3.

Proposed algorithm for the diagnosis of IPAF in patients with interstitial lung disease who do not meet criteria for a defined connective tissue disease. Comprehensive serologies should include anti-nuclear antibodies by indirect immunofluorescence, rheumatoid factor (RF), anti-cyclic citrillinated peptide (CCP), and a comprehensive myositis panel.