Clinical course of lung physiology in patients with scleroderma and interstitial lung disease: Analysis of the Scleroderma Lung Study Placebo Group

IntroductionAntisynthetase syndrome (ASyS) is a rare autoimmune connective tissue disease (CTD), associated with autoantibodies targeting tRNA synthetase enzymes, that can present to respiratory (interstitial lung disease (ILD)) or rheumatology (myositis, inflammatory arthritis and systemic features) services. The therapeutic management of CTD-associated ILD and idiopathic pulmonary fibrosis (IPF) differs widely, thus accurate diagnosis is essential.MethodsWe undertook a retrospective, multicentre observational cohort study designed to (1) evaluate differences between ASyS-associated ILD with IPF, (2) phenotypic differences in patients with ASyS-ILD presenting to respiratory versus rheumatology services, (3) differences in outcomes between ASySassociated with Jo-1 versus non-Jo-1 autoantibodies and (4) compare long-term outcomes between these groups.ResultsWe identified 76 patients with ASyS-ILD and 78 with IPF. Patients with ASyS were younger at presentation (57 vs 77 years, p<0.001) with a female predominance (57% vs 33%, p=0.006) compared with IPF. Cytoplasmic staining on indirect immunofluorescence was a differentiating factor between ASyS and IPF (71% vs 0%, p<0.0001). Patients with ASyS presenting initially to respiratory services (n=52) had a higher prevalence of ASyS non-Jo-1 antibodies and significantly fewer musculoskeletal symptoms/biochemical evidence of myositis, compared with those presenting to rheumatology services (p<0.05), although lung physiology was similar in both groups. There were no differences in high-resolution CT appearances or outcomes in those with Jo-1 versus non-Jo-1 ASyS-ILD.ConclusionsExtended autoimmune serology is needed to evaluate for ASyS autoantibodies in patients presenting with ILD, particularly in younger female patients. Musculoskeletal involvement is common in ASyS (typically Jo-1 autoantibodies) presenting to rheumatology but the burden of ILD is similar to those presenting to respiratory medicine.

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THU0305 PREVALENCE AND CLINICAL OUTCOME OF INTERSTITIAL LUNG DISEASE IN ANCA ASSOCIATED VASCULITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6211 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 381.2-381

Author(s):

J. Fernandes Serodio ◽

J. Hernández-Rodríguez ◽

G. Espígol-Frigolé ◽

M. Alba ◽

J. Marco-Hernández ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Interstitial Pneumonia ◽

Cox Regression ◽

Clinical Course ◽

Usual Interstitial Pneumonia ◽

Classification Criteria ◽

Lung Involvement ◽

Anca Associated Vasculitis ◽

Inflammatory Infiltrates

Background:Lung involvement is frequent in ANCA-associated vasculitis (AAV). Classical lung manifestations consist of capillaritis with lung haemorrhage, inflammatory infiltrates and nodules. Interstitial lung disease (ILD) is increasingly recognized among patients with AAV. However, little is known concerning risk factors and clinical course of these patients.Objectives:The aim of our study was to characterize the prevalence and clinical course of ILD in patients with AAV.Methods:We have performed a clinical retrospective single-centre observational analysis (1990-2019) of all patients with the diagnosis of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) diagnosed according to 2018 Draft Classification Criteria for GPA and MPA1. Demographic, clinical and immunologic data were reviewed. Radiologic pattern of ILD were assessed by high-resolution-CT. Main outcome evaluated was overall-all survival.Results:The study population consisted of 123 patients, 56% female, aged 59.3±18.2 years old at the time of diagnosis. Clinical diagnosis was of MPA in 54% of patients and GPA in 46%. While 108 (88%) ANCA positive patients had PR3 (n=25) or MPO (n=83), 15 (12%) patients had negative or atypical ANCA. Any lung involvement was present in 82 (71%) and ILD was identified in 24 (20%) of all patients. ILD pattern was of usual interstitial pneumonia (UIP) in 12 patients, non-specified interstitial pneumonia (NSIP) in 9 and chronic organizing pneumonia (OP) in 3. There was an association between the presence of ILD and ANCA specificity: MPO were present in 100% of patients with UIP and in 75% of patients with NSIP/OP (p=0.017). Bronchiectasis were more prevalent among patients with ILD (19/24; p<0.001). During the median follow-up time period of 68 (23-126) months, mortality was of 42% among patients with ILD-AAV compared with 11% in no ILD-AAV (log-rank p=0.0001). On the multivariate Cox regression model, ILD was an independent predictor of mortality HR 2.95 (95%CI 1.09-7.96; p=0.033).Conclusion:ILD is a frequent manifestation of MPA and GPA patients. The presence of ILD, particularly UIP, is associated with ANCA-MPO and is a predictor of mortality. Therefore, a better management of fibrotic lung involvement in AAV is warranted.References:[1]Robson JC, Grayson PC, Ponte C, et al. Draft classification criteria for the ANCA associated vasculitides. Ann Rheum Dis 2018;77 (suppl 2):60-1.Disclosure of Interests:João Fernandes Serodio: None declared, José Hernández-Rodríguez: None declared, Georgina Espígol-Frigolé: None declared, Marco Alba: None declared, Javier Marco-Hernández: None declared, Marcelo Sánchez: None declared, Fernanda Hernández-González: None declared, Jacobo Sellarés: None declared, Maria C. Cid Grant/research support from: Kiniksa Pharmaceuticals, Consultant of: Janssen, Abbvie, Roche, GSK, Speakers bureau: Vifor, Sergio Prieto-González: None declared

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Clinical course and outcomes of acute exacerbation of fibrosing interstitial lung disease

10.1183/13993003.congress-2021.pa2241 ◽

2021 ◽

Author(s):

Katsuyuki Furuta ◽

Daichi Fujimoto ◽

Atsushi Matsunashi ◽

Masanori Tanaka ◽

Ryota Shibaki ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Acute Exacerbation ◽

Clinical Course

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Interstitial lung disease caused by filamin A gene mutations: Clinical course of three paediatric cases

10.1183/13993003.congress-2016.pa3913 ◽

2016 ◽

Author(s):

Julia Carlens ◽

Timothy Price ◽

Eva Bültmann ◽

Florian Länger ◽

Ulrike Hehr ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Clinical Course ◽

Gene Mutations ◽

Filamin A

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Anti-aminoacyl-tRNA synthetase antibodies in clinical course prediction of interstitial lung disease complicated with idiopathic inflammatory myopathies

Autoimmunity ◽

10.1080/08916930600622884 ◽

2006 ◽

Vol 39 (3) ◽

pp. 233-241 ◽

Cited By ~ 123

Author(s):

Hajime Yoshifuji ◽

Takao Fujii ◽

Shio Kobayashi ◽

Yoshitaka Imura ◽

Yoshimasa Fujita ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Clinical Course ◽

Trna Synthetase ◽

Idiopathic Inflammatory Myopathies ◽

Inflammatory Myopathies ◽

Aminoacyl Trna Synthetase

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Hermansky–Pudlak syndrome pulmonary fibrosis: a rare inherited interstitial lung disease

European Respiratory Review ◽

10.1183/16000617.0193-2020 ◽

2021 ◽

Vol 30 (159) ◽

pp. 200193

Author(s):

Tadafumi Yokoyama ◽

Bernadette R. Gochuico

Keyword(s):

Interstitial Lung Disease ◽

Pulmonary Fibrosis ◽

Lung Disease ◽

Genetic Diseases ◽

Autosomal Recessive Disorder ◽

Oculocutaneous Albinism ◽

Excessive Bleeding ◽

Lung Physiology ◽

Hermansky Pudlak Syndrome ◽

Fibrotic Lung Disease

Pulmonary fibrosis is a progressive interstitial lung disease of unknown aetiology with a poor prognosis. Studying genetic diseases associated with pulmonary fibrosis provides insights into the pathogenesis of the disease. Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder characterised by abnormal biogenesis of lysosome-related organelles, manifests with oculocutaneous albinism and excessive bleeding of variable severity. Pulmonary fibrosis is highly prevalent in three out of 10 genetic types of HPS (HPS-1, HPS-2 and HPS-4). Thus, genotyping of individuals with HPS is clinically relevant. HPS-1 tends to affect Puerto Rican individuals due to a genetic founder effect. HPS pulmonary fibrosis shares some clinical features with idiopathic pulmonary fibrosis (IPF), including dyspnoea, cough, restrictive lung physiology and computed tomography (CT) findings of fibrosis. In contrast to IPF, HPS pulmonary fibrosis generally affects children (HPS-2) or middle-aged adults (HPS-1 or HPS-4) and may be associated with ground-glass opacification in CT scans. Histopathology of HPS pulmonary fibrosis, and not IPF, shows vacuolated hyperplastic type II cells with enlarged lamellar bodies and alveolar macrophages with lipofuscin-like deposits. Antifibrotic drugs approved as treatment for IPF are not approved for HPS pulmonary fibrosis. However, lung transplantation has been performed in patients with severe HPS pulmonary fibrosis. HPS pulmonary fibrosis serves as a model for studying fibrotic lung disease and fibrosis in general.

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