Interstitial pneumonia with autoimmune features: challenges and controversies

Abstract

The presence of clinical, serological and/or radiological features suggestive, but not confirmatory, of a defined connective tissue disease in patients with interstitial lung disease is a relatively frequent occurrence. In 2015, the European Respiratory Society and the American Thoracic Society proposed classification criteria for the interstitial pneumonia with autoimmune features (IPAF) research entity to capture such patients in a standardised manner, with the intention of nurturing clinical research. This initiative resulted in the publication of several series of IPAF patients, with significant variation between cohorts in clinical characteristics, outcome and the application of IPAF criteria in patient selection. From this increasing body of published work, it has become apparent that revision of IPAF criteria is now required in order to justify the eventual designation of IPAF as a standalone diagnostic term, as opposed to a provisional entity put forward as a basis for clinical research. This review covers the current state of IPAF, conclusions that can and cannot be drawn from the IPAF evidence base, and ongoing uncertainties that require further expert group consideration.

FIGURE 1

Interstitial pneumonia with autoimmune features (IPAF) in the schema of clinical interstitial lung disease (ILD).

FIGURE 2

Histological patterns of interstitial pneumonia seen in interstitial pneumonia with autoimmune features. a) Fibrotic non-specific pneumonia (NSIP): there is diffuse uniform interstitial fibrosis associated with a mild patchy non-specific chronic inflammatory cell infiltrate. b) Organising pneumonia (right side) with progression to interstitial fibrosis (left side): buds of granulation tissue merge with established fibrosis. c) Lymphoid interstitial pneumonia (LIP) overlapping with cellular NSIP: in this field, the right-hand part of the image shows a density of interstitial inflammation characteristic of LIP.

FIGURE 3

Usual interstitial pneumonia (UIP) with features arguing against idiopathic pulmonary fibrosis (IPF). There are areas with established patchy interstitial fibrosis with an occasional fibroblastic focus characteristic of UIP, but also areas where interstitial chronic inflammation predominates, making this case indeterminate for UIP/IPF. Based on pathology alone, either fibrotic hypersensitivity pneumonitis or a connective tissue disease-related interstitial lung disease (interstitial pneumonia with autoimmune features) were favoured over IPF, and multidisciplinary review was recommended.

FIGURE 4

a and b) Interstitial pneumonia with autoimmune features (IPAF) in a 60-year-old male presenting with acute onset type 1 respiratory failure. Computed tomography (CT) demonstrates patchy consolidation with a bronchocentric distribution, and some lower lobe volume loss, suggestive of a pattern of fibrotic organising pneumonia. Positive serology for anti-OJ was identified. No clinical features of an idiopathic inflammatory myopathy were evident at presentation. The patient had an excellent response to prednisolone and tacrolimus. c and d) IPAF in an 80-year-old male. The CT demonstrates a usual interstitial pneumonia (UIP) pattern with right-sided pleural thickening/effusion suggestive of multi-compartment involvement. No known history of asbestos exposure was reported and no pleural plaques were evident on CT. The patient's anti-nuclear antibody (ANA) was low titre but in a nucleolar pattern and rheumatoid factor was elevated. The patient was treated with immunomodulation, but demonstrated an idiopathic pulmonary fibrosis-like disease trajectory and died within a few years of diagnosis. e) 84-year-old female presenting with gradually progressive dyspnoea with CT demonstrating a UIP pattern. ANA at presentation was speckled with titre of 1:320. The patient subsequently developed inflammatory arthritis and a positive anti-cyclic citrullinated peptide, resulting in an eventual diagnosis of rheumatoid arthritis and associated interstitial lung disease. Her rheumatoid arthritis was treated with sulfasalazine and the lung disease has remained under observation after the patient declined clinical trial participation. Over the first 12 months there was a 7% relative decline in forced vital capacity and a 26% relative decline in carbon monoxide diffusing capacity.

FIGURE 5

Interstitial pneumonia with autoimmune features (IPAF) in a 32-year-old male presenting with subacute cough and dyspnoea over 2 months. On presentation, he was in type 1 respiratory failure requiring supplemental oxygen. a) His computed tomography (CT) demonstrated upper zone ground glass opacity and fibrotic organising pneumonia in the lung bases. Anti-nuclear antibody was positive at 1:1280, although extended serology was negative. There were no clinical features of an autoimmune condition. IPAF criteria were met by morphological and serological domain. b) A significant response was observed with immunomodulation, with ongoing lung function improvement over a protracted period. FVC: forced vital capacity; i.v.: intravenous; KCOc: gas transfer coefficient, corrected for haemoglobin; MP: methylprednisolone; o.d.: once daily; TLCOc: transfer factor of the lung for carbon monoxide, corrected for haemoglobin.

FIGURE 6

Factors to consider in the management of patients fulfilling interstitial pneumonia with autoimmune features criteria. CTD: connective tissue disease; CT: computed tomography.