POS1298 INTERSTITIAL LUNG DISEASE IN ANTI-CENTROMERE ANTIBODY POSITIVE SYSTEMIC SCLEROSIS

Abstract

BackgroundDespite a lower risk of ILD and ILD progression in anti-centromere antibody (ACA) positive systemic sclerosis (SSc) patients, ILD may still occur and progress. Little is known regarding risk factors for ILD in ACA+ SSc patients to help guide screening with high-resolution computed tomography (HRCT), and risk of ILD progression in ACA+ SSc is understudied.ObjectivesTo determine prevalence and risk factors for ILD in ACA+ SSc, to classify radiographic ILD patterns, and to evaluate rate of progression of ILD in ACA+ SSc.MethodsA retrospective cohort of ACA+ SSc patients seen between 1/1/2007 and 12/31/2018, who met the 2013 ACR classification criteria or ≥3/5 CREST (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasias) criteria was identified. Subjects had to have ≥1 HRCT within 2 yrs. prior to or anytime following SSc diagnosis (dx). Two radiologists reviewed all HRCTs with interstitial abnormalities to classify by consensus into 9 radiographic patterns (1,2): confident usual interstitial pneumonitis (cUIP), probable UIP (pUIP), non-specific interstitial pneumonitis (NSIP), suggests hypersensitivity pneumonitis (sHP), lymphocytic interstitial pneumonia (LIP), organizing pneumonia (OP), not characteristic (NC) of a specific ILD pattern, too little fibrosis (LF) to characterize, and suggests sequelae of pulmonary arterial hypertension (PAH)/pulmonary venoocclusive disease (PVOD). Clinical and demographic characteristics were compared between ILD+ and no ILD (included PAH/PVOD sequelae) subjects using χ2tests of proportions for categorical data, and two-sample t-tests for continuous data. Kaplan-Meier curves estimated the risk of ILD progression, defined as a relative decline of 10% in forced vital capacity (FVC) from baseline PFT performed ±6 mo. of latter of SSc or ILD dx.Results99/480 (21%) of subjects had interstitial changes on HRCT: 5 cUIP, 7 pUIP, 28 NSIP, 14 sHP, 6 LIP, 2 OP, 11 NC, 17 LF, and 9 PAH/PVOD sequelae. There were no differences in time between SSc dx and HRCT between ILD+ and no ILD groups (median 6 yrs. (IQR 2, 14) vs. 6 yrs. (IQR 1, 15), respectively, p=0.44) or Raynaud’s phenomenon (RP) onset and HRCT (median 15 yrs. (8, 29) vs. 17 yrs. (9, 29), respectively, p=0.54). Older age at RP onset (median 55 yrs. (42, 62) vs. 44 yrs. (33, 55), ILD+ vs. no ILD, p<0.001) and at SSc dx (median 62 yrs. (55, 72) vs. 56 yrs. (45, 65), ILD+ vs. no ILD, p<0.001) were significantly associated with ILD. A positive SSA was more common in ILD+ vs. no ILD subjects (15/72 (21%) vs. 43/340 (13%), respectively, p<0.05). Sex, race/ethnicity, smoking status, cutaneous subtype, esophageal dysmotility, digital ischemia, abnormal nailfold capillaries, telangiectasias, calcinosis, and synovitis were not associated with ILD (p>0.05). In a subgroup analysis of UIP/NSIP (n=40) compared with no ILD (n=390), older age at RP onset was significantly associated with UIP/NSIP (median 55 yrs. (46, 61) vs. 44 yrs. (33, 55), p=0.042). There were no significant differences in baseline FVC% and DLCO% among ILD patterns (p>0.05). ILD progression was observed in 51% of patients with ILD by 72 mo. (Figure 1A). There was no significant difference in risk of ILD progression between the UIP/NSIP and sHP/LIP/OP/IP/LF subgroups (Figure 1B, p=0.67).ConclusionTo our knowledge, this is the largest study characterizing radiographic ILD patterns and assessing risk factors for prevalent ILD in ACA+ SSc patients. Older age at onset of RP and SSc dx, and a positive SSA, identifies a higher risk population for HRCT screening. UIP/NSIP accounted for close to half of ILD cases. Other radiographic patterns including sHP and IP require further study to determine potential underlying factors (e.g. exposure history, aspiration). The rate of ILD progression was similar between UIP/NSIP vs. other interstitial patterns, with half of subjects experiencing progression by 6 yrs. This underscores the role of HRCT screening for ILD detection and periodic PFTs for monitoring even in lower risk SSc populations.